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Sample records for macrolide resistance determinants

  1. Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi.

    Science.gov (United States)

    Anastasi, Elisa; Giguère, Steeve; Berghaus, Londa J; Hondalus, Mary K; Willingham-Lane, Jennifer M; MacArthur, Iain; Cohen, Noah D; Roberts, Marilyn C; Vazquez-Boland, Jose A

    2015-12-01

    The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomycete Rhodococcus equi, a major equine pathogen and zoonotic agent causing opportunistic infections in people. Macrolide-resistant (n = 62) and macrolide-susceptible (n = 62) clinical isolates of R. equi from foals in the USA were studied. WGS of 18 macrolide-resistant and 6 macrolide-susceptible R. equi was performed. Representative sequences of all known macrolide resistance genes identified to date were used to search the genome assemblies for putative homologues. PCR was used to screen for the presence of the identified resistance determinant in the rest of the isolates. Mating experiments were performed to verify mobility of the gene. A novel erm gene, erm(46), was identified in all sequenced resistant isolates, but not in susceptible isolates. There was complete association between macrolide resistance and the presence of erm(46) as detected by PCR screening of all 124 clinical isolates of R. equi. Expression of erm(46) in a macrolide-susceptible strain of R. equi induced high-level resistance to macrolides, lincosamides and streptogramins B, but not to other classes of antimicrobial agents. Transfer of erm(46) to macrolide-susceptible R. equi was confirmed. The transfer frequency ranged from 3 × 10(-3) to 1 × 10(-2). This is the first molecular characterization of resistance to macrolides, lincosamides and streptogramins B in R. equi. Resistance was due to the presence of a novel erm(46) gene mobilizable likely by conjugation, which has spread among equine isolates of R. equi in the USA. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Multiplex PCR to identify macrolide resistance determinants in Mannheimia haemolytica and Pasteurella multocida.

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    Rose, Simon; Desmolaize, Benoit; Jaju, Puneet; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

    2012-07-01

    The bacterial pathogens Mannheimia haemolytica and Pasteurella multocida are major etiological agents in respiratory tract infections of cattle. Although these infections can generally be successfully treated with veterinary macrolide antibiotics, a few recent isolates have shown resistance to these drugs. Macrolide resistance in members of the family Pasteurellaceae is conferred by combinations of at least three genes: erm(42), which encodes a monomethyltransferase and confers a type I MLS(B) (macrolide, lincosamide, and streptogramin B) phenotype; msr(E), which encodes a macrolide efflux pump; and mph(E), which encodes a macrolide-inactivating phosphotransferase. Here, we describe a multiplex PCR assay that detects the presence of erm(42), msr(E), and mph(E) and differentiates between these genes. In addition, the assay distinguishes P. multocida from M. haemolytica by amplifying distinctive fragments of the 23S rRNA (rrl) genes. One rrl fragment acts as a general indicator of gammaproteobacterial species and confirms whether the PCR assay has functioned as intended on strains that are negative for erm(42), msr(E), and mph(E). The multiplex system has been tested on more than 40 selected isolates of P. multocida and M. haemolytica and correlated with MICs for the veterinary macrolides tulathromycin and tilmicosin, and the newer compounds gamithromycin and tildipirosin. The multiplex PCR system gives a rapid and robustly accurate determination of macrolide resistance genotypes and bacterial genus, matching results from microbiological methods and whole-genome sequencing.

  3. Macrolide resistance determinants among Streptococcus pneumoniae isolates from carriers in Central Greece

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    Grivea Ioanna N

    2012-10-01

    Full Text Available Abstract Background We sought to characterize the temporal trends in nasopharyngeal carriage of macrolide-resistant pneumococci during a period with increased heptavalent pneumococcal conjugate vaccine (PCV7 coverage in Central Greece. Methods Streptococcus pneumoniae isolates were recovered from 2649 nasopharyngeal samples obtained from day-care center attendees in Central Greece during 2005–2009. A phenotypic and genotypic analysis of the isolates was performed, including the identification of macrolide resistance genes mef(A, subclasses mef(A and mef(E, as well as erm(B. Results Of the 1105 typeable S. pneumoniae isolates, 265 (24% were macrolide-resistant; 22% in 2005, 33.3% in 2006, 23.7% in 2007, and 20.5% in 2009 (P=0.398. Among these macrolide-resistant pneumococci, 28.5% possessed erm(B, 24.3% erm(B+mef(E, 41.8% mef(E, and 5.3% mef(A. A mef gene as the sole resistance determinant was carried by 31% of macrolide-resistant isolates belonging to PCV7 serotypes and 75.8% of the non-PCV7 serotypes. Across the 4 annual surveillances, pneumococci carrying mef(A gradually disappeared, whereas serotype 19F isolates carrying both erm(B and mef(E persisted without significant yearly fluctuations. Among isolates belonging to non-PCV7 serotypes, macrolide-resistance was observed in those of serotypes 6A, 19A, 10A, 15A, 15B/C, 35F, 35A, and 24F. In 2009, ie 5 years after the introduction of PCV7 in our country, 59% of macrolide-resistant pneumococci belonged to non-PCV7 serotypes. Conclusions Across the study period, the annual frequency of macrolide-resistant isolates did not change significantly, but in 2009 a marked shift to non-PCV7 serotypes occurred. Overall, more than half of the macrolide-resistant isolates possessed erm(B either alone or in combination with mef(E. erm(B dominated among isolates belonging to PCV7 serotypes, but not among those of non-PCV7 serotypes.

  4. Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida.

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    Desmolaize, Benoit; Rose, Simon; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

    2011-09-01

    Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella multocida. These infections can generally be successfully treated in the field with one of several groups of antibiotics, including macrolides. A few recent isolates of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product of the erm(42) gene. The second class shows no lincosamide resistance and lacks erm(42) and concomitant 23S rRNA methylation. Sequencing of the genome of a representative strain from this class, P. multocida 3361, revealed macrolide efflux and phosphotransferase genes [respectively termed msr(E) and mph(E)] that are arranged in tandem and presumably expressed from the same promoter. The third class exhibits the most marked drug phenotype, with high resistance to all of the macrolides tested, and possesses all three resistance determinants. The combinations of erm(42), msr(E), and mph(E) are chromosomally encoded and intermingled with other exogenous genes, many of which appear to have been transferred from other members of the Pasteurellaceae. The presence of some of the exogenous genes explains recent reports of resistance to additional drug classes. We have expressed recombinant versions of the erm(42), msr(E), and mph(E) genes within an isogenic Escherichia coli background to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants.

  5. Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Desmolaize, Benoit; Rose, Simon; Wilhelm, Cornelia

    2011-01-01

    Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella multocida. These infections can generally be successfully treated in the field with one of several groups of antibiotics, including macrolides. A few recent isolates...... of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product...

  6. Multiplex PCR To Identify Macrolide Resistance Determinants in Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Rose, Simon; Desmolaize, Benoit; Jaju, Puneet

    2012-01-01

    The bacterial pathogens Mannheimia haemolytica and Pasteurella multocida are major etiological agents in respiratory tract infections of cattle. Although these infections can generally be successfully treated with veterinary macrolide antibiotics, a few recent isolates have shown resistance...

  7. Multiplex PCR To Identify Macrolide Resistance Determinants in Mannheimia haemolytica and Pasteurella multocida

    OpenAIRE

    Rose, Simon; Desmolaize, Benoit; Jaju, Puneet; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

    2012-01-01

    The bacterial pathogens Mannheimia haemolytica and Pasteurella multocida are major etiological agents in respiratory tract infections of cattle. Although these infections can generally be successfully treated with veterinary macrolide antibiotics, a few recent isolates have shown resistance to these drugs. Macrolide resistance in members of the family Pasteurellaceae is conferred by combinations of at least three genes: erm(42), which encodes a monomethyltransferase and confers a type I MLSB ...

  8. Macrolide resistance determination and molecular typing of Mycoplasma pneumoniae by pyrosequencing.

    Science.gov (United States)

    Spuesens, Emiel B M; Hoogenboezem, Theo; Sluijter, Marcel; Hartwig, Nico G; van Rossum, Annemarie M C; Vink, Cornelis

    2010-09-01

    The first choice antibiotics for treatment of Mycoplasma pneumoniae infections are macrolides. Several recent studies, however, have indicated that the prevalence of macrolide (ML)-resistance, which is determined by mutations in the bacterial 23S rRNA, is increasing among M. pneumoniae isolates. Consequently, it is imperative that ML-resistance in M. pneumoniae is rapidly detected to allow appropriate and timely treatment of patients. We therefore set out to determine the utility of pyrosequencing as a convenient technique to assess ML-resistance. In addition, we studied whether pyrosequencing could be useful for molecular typing of M. pneumoniae isolates. To this end, a total of four separate pyrosequencing assays were developed. These assays were designed such as to determine a short genomic sequence from four different sites, i.e. two locations within the 23S rRNA gene, one within the MPN141 (or P1) gene and one within the MPN528a gene. While the 23S rRNA regions were employed to determine ML-resistance, the latter two were used for molecular typing. The pyrosequencing assays were performed on a collection of 108 M. pneumoniae isolates. The ML-resistant isolates within the collection (n=4) were readily identified by pyrosequencing. Moreover, each strain was correctly typed as either a subtype 1 or subtype 2 strain by both the MPN141 and MPN528a pyrosequencing test. Interestingly, two recent isolates from our collection, which were identified as subtype 2 strains by the pyrosequencing assays, were found to carry novel variants of the MPN141 gene, having rearrangements in each of the two repetitive elements (RepMP4 and RepMP2/3) within the gene. In conclusion, pyrosequencing is a convenient technique for ML-resistance determination as well as molecular typing of M. pneumoniae isolates.

  9. Prevalence of Genotypes That Determine Resistance of Staphylococci to Macrolides and Lincosamides in Serbia

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    Milena Mišić

    2017-08-01

    Full Text Available Macrolides, lincosamides, and streptogramins (MLS resistance genes are responsible for resistance to these antibiotics in Staphylococcus infections. The purpose of the study was to analyze the distribution of the MLS resistance genes in community- and hospital-acquired Staphylococcus isolates. The MLS resistance phenotypes [constitutive resistance to macrolide–lincosamide–streptogramin B (cMLSb, inducible resistance to macrolide–lincosamide–streptogramin B (iMLSb, resistance to macrolide/macrolide–streptogramin B (M/MSb, and resistance to lincosamide–streptogramin A/streptogramin B (LSa/b] were determined by double-disc diffusion method. The presence of the MLS resistance genes (ermA, ermB, ermC, msrA/B, lnuA, lnuB, and lsaA were determined by end-point polymerase chain reaction in 179 isolates of staphylococci collected during 1-year period at the Center for Microbiology of Public Health Institute in Vranje. The most frequent MLS phenotype among staphylococcal isolates, both community-acquired and hospital-acquired, was iMLSb (33.4%. The second most frequent was M/MSb (17.6% with statistically significantly higher number of hospital-acquired staphylococcal isolates (p < 0.05. MLS resistance was mostly determined by the presence of msrA/B (35.0% and ermC (20.8% genes. Examined phenotypes were mostly determined by the presence of one gene, especially by msrA/B (26.3% and ermC (14.5%, but 15.6% was determined by a combination of two or more genes. M/MSb phenotype was the most frequently encoded by msrA/B (95.6% gene, LSa/b phenotype by lnuA (56.3% gene, and iMLSb phenotype by ermC (29.4% and ermA (25.5% genes. Although cMLSb phenotype was mostly determined by the presence of ermC (28.9%, combinations of two or more genes have been present too. This pattern was particularly recorded in methicillin-resistant Staphylococcus aureus (MRSA (58.3% and methicillin-resistant coagulase-negative staphylococci (MRCNS (90.9% isolates with c

  10. New macrolides active against Streptococcus pyogenes with inducible or constitutive type of macrolide-lincosamide-streptogramin B resistance.

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    Fernandes, P B; Baker, W R; Freiberg, L A; Hardy, D J; McDonald, E J

    1989-01-01

    Macrolide-resistant bacteria can be classified as inducibly resistant or constitutively resistant. Inducibly resistant bacteria are resistant to 14-membered macrolides, such as erythromycin and clarithromycin (A-56268), but are susceptible to the 16-membered macrolides, such as tylosin and spiramycin, as well as to clindamycin. Constitutively resistant bacteria are resistant to macrolide-lincosamide-streptogramin B antibiotics. In this study, the MICs of several erythromycin and clarithromycin analogs against macrolide-susceptible and macrolide-resistant Streptococcus pyogenes strains were determined. Four 11,12-carbamate analogs of clarithromycin had lower MICs than erythromycin did against S. pyogenes with the inducible or constitutive type of macrolide-lincosamide-streptogramin B resistance. Five 11,12-carbonate analogs of erythromycin with modifications at the 4" position of cladinose had lower MICs than did erythromycin against S. pyogenes with the constitutive type of resistance, and one of these compounds, which had a naphthyl-glycyl substitution at the 4" position, had a lower MIC than erythromycin against both the inducibly resistant and constitutively resistant strains. Two analogs of erythromycin with a modification on the 4" position of cladinose had lower MICs than erythromycin did against the constitutively resistant organisms but not against the inducibly resistant organisms. Thus, 14-membered macrolides can be modified so as to confer a low MIC when tested in vitro.

  11. Macrolide resistance determination and molecular typing of mycoplasma pneumoniae in respiratory specimens collected between 1997 and 2008 in The Netherlands.

    NARCIS (Netherlands)

    Spuesens, E.B.M.; Meijer, A.; Bierschenk, D.; Hoogenboezem, T.; Donker, G.A.; Hartwig, N.G.; Koopmans, M.P.G.; Vink, C.; Rossum, A.M.C. van

    2012-01-01

    An important role in the treatment regimens for Mycoplasma pneumoniae infections is played by macrolide (ML) antibiotics. In the past few years, however, a steady increase has been detected in the worldwide prevalence of ML-resistant (MLr) M. pneumoniae strains. It is obvious that this increase nece

  12. Macrolides resistance of common bacteria isolated from Taiwan.

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    Chang, S C; Chen, Y C; Luh, K T; Hsieh, W C

    1995-12-01

    To determine the susceptibility to macrolides of common pathogenic bacteria isolated from Taiwan, the in vitro activities of erythromycin, roxithromycin, azithromycin, clarithromycin, and dirithromycin were tested against 492 clinical isolates of eight different bacteria, collected from the National Taiwan University Hospital. The results showed high minimum inhibitory concentrations (MICs) against most of the tested bacteria. The MIC90s for Staphylococcus aureus (both methicillin-resistant and -sensitive strains), coagulase-negative staphylococci (both methicillin-resistant and -sensitive strains), Streptococcus pyogenes, Streptococcus pneumoniae, enterococci, peptostreptococci, and Bacteroides fragilis were all > or = 256 micrograms/ml. The MIC50s for methicillin-resistant strains of S. aureus and coagulase-negative staphylococci, and enterococci were > or = 256 micrograms/ml. For S. pneumoniae, peptostreptococci, and B. fragilis, the MIC50s were > 8 micrograms/ml. The resistance rates to macrolides were 80% or more in methicillin-resistant staphylococci and about 30% in methicillin-sensitive staphylococci. Around 55% of S. pneumoniae strains and 37 approximately 42% of S. pyogenes strains were resistant to macrolides. Cross-resistance to different macrolides was clearly demonstrated in most of the resistant strains.

  13. New macrolides active against Streptococcus pyogenes with inducible or constitutive type of macrolide-lincosamide-streptogramin B resistance.

    OpenAIRE

    Fernandes, P B; Baker, W.R.; Freiberg, L A; Hardy, D. J.; McDonald, E J

    1989-01-01

    Macrolide-resistant bacteria can be classified as inducibly resistant or constitutively resistant. Inducibly resistant bacteria are resistant to 14-membered macrolides, such as erythromycin and clarithromycin (A-56268), but are susceptible to the 16-membered macrolides, such as tylosin and spiramycin, as well as to clindamycin. Constitutively resistant bacteria are resistant to macrolide-lincosamide-streptogramin B antibiotics. In this study, the MICs of several erythromycin and clarithromyci...

  14. Genotyping and serotyping of macrolide and multidrug resistant Streptococcus pneumoniae isolated from carrier children

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    S F Swedan

    2016-01-01

    Full Text Available Aims: Streptococcus pneumoniae, an opportunistic pathogen commonly carried asymptomatically in the nasopharynx of children, is associated with increasing rates of treatment failures due to a worldwide increase in drug resistance. We investigated the carriage of S. pneumoniae in children 5 years or younger, the identity of prevalent serotypes, the rates of resistance to macrolides and other antimicrobial agents and the genotypes responsible for macrolide resistance. Materials and Methods: Nasopharyngeal swabs were collected from 157 children under 5 years for cultural isolation of S. pneumoniae. Antibiogram of isolates  was determined using the disk diffusion test, and the minimal inhibitory concentration to macrolides was determined using the E-test. Isolate serotypes and macrolide resistance genes, erm(B and mef(E, were identified using multiplex polymerase chain reactions. Results: S. pneumoniae was recovered from 33.8% of children; 41.9% among males and 21.9% among females (P = 0.009. The highest carriage rate occurred among age groups 7-12 months and 49-60 months. Most frequent serotypes were 19F, 6A/B, 11A, 19A, 14 and 15B/C.  Resistance to macrolides was 60.4%. Resistance to oxacillin, trimethoprim/sulfamethoxazole and clindamycin was present among 90.6%, 54.7% and 32.1% of isolates, respectively. All isolates were susceptible to chloramphenicol, levofloxacin and vancomycin. Isolates resistant to one or more macrolide drugs were more likely to be multidrug resistant. Resistance to clindamycin or oxacillin coexisted with macrolide resistance. Among the erythromycin-resistant isolates, erm(B, mef(E and erm(B and mef(E genes were present at rates of 43.8%, 37.5% and 6.3%, respectively. Erm(B and mef(E were associated with very high level and moderate-to-high level resistance to macrolides, respectively. Conclusion: A significant proportion of children harboured macrolide and multidrug-resistant S. pneumoniae.

  15. Phenotypes and genotypes of macrolide-resistant Streptococcus pneumoniae in Serbia

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    Hadnađev Mirjana

    2014-01-01

    Full Text Available Although macrolides are widely used for treating pneumococcal infections, an increase in macrolide resistance might compromise their use. The objective of this study was to determine the prevalence of macrolide-resistant phenotypes and genotypes in macrolide-resistant S. pneumoniae isolates in Serbia. A total of 228 macrolide-resistant strains isolated during the period of 2009-2012, were analyzed. Macrolide resistance phenotypes were determined by a double disk diffusion test. The presence of macrolide resistance genes was detected by PCR. Antibiotics susceptibilities were tested using the VITEK2 system and E test. Among the examined isolates, the MLSB phenotype which is linked to the presence of the erm(B gene dominated (83.3%, while the mef(A gene which is associated with the M phenotype, was identified in 16.7% isolates. Over 40% of isolates expressed co-resistance to penicillin. A multiple-resistant pattern was found in 36.4% strains, more frequently in children. However, all strains were susceptible to telithromycin, vancomycin, linezolid, fluoroquinolones and rifampicin. [Projekat Ministarstva nauke Republike Srbije, br. 175039

  16. Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp. pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?

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    Šmajs, David; Paštěková, Lenka; Grillová, Linda

    2015-10-01

    Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent of yaws, affects about 2.5 million people. Although penicillin remains the drug of choice in the treatment of syphilis, in penicillin-allergic patients, macrolides have been used in this indication since the 1950s. Failures of macrolides in syphilis treatment have been well documented in the literature and since 2000, there has been a dramatic increase in a number of clinical samples with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide-resistant mutations in TPA suggest that although macrolide-resistance mutations have emerged independently several times, the increase in the proportion of TPA strains resistant to macrolides is mainly due to the spread of resistant strains, especially in developed countries. The emergence of macrolide resistance in TPA appears to require a two-step process including either A2058G or A2059G mutation in one copy of the 23S rRNA gene and a subsequent gene conversion unification of both rRNA genes. Given the enormous genetic similarity that was recently revealed between TPA and TPE strains, there is a low but reasonable risk of emergence and spread of macrolide-resistant yaws strains following azithromycin treatment.

  17. Molecular characterization of macrolide resistant Streptococcus pyogenes isolates from pharyngitis patients in Serbia.

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    Opavski, Natasa; Gajic, Ina; Borek, Anna L; Obszańska, Katarzyna; Stanojevic, Maja; Lazarevic, Ivana; Ranin, Lazar; Sitkiewicz, Izabela; Mijac, Vera

    2015-07-01

    A steady increase in macrolide resistance in Streptococcus pyogenes, group A streptococci (GAS) was reported in Serbia during 2004-2009 (9.9%). However, there are no data on the molecular epidemiology of pharyngeal macrolide resistance GAS (MRGAS) isolates. Therefore, the aims of this first nationwide study were to examine the prevalence of macrolide resistance in Serbian GAS and to determine their resistance phenotypes, genotypes and clonal relationships. Overall 3893 non-duplicate pharyngeal S. pyogenes isolates from outpatients with GAS infection were collected throughout country during 2008 and 2009. Among 486 macrolide resistant pharyngeal isolates collected, 103 were further characterized. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion test and PCR, respectively. Strain relatedness was determined by emm typing, multilocus sequence typing (MLST), multilocus variable tandem repeat analysis (MLVA), phage profiling (PP) and virulence factor profiling (VFP). Overall, macrolide resistance among GAS isolates in Serbia was 12.5%. M phenotype was the most common (71.8%), followed by iMLS (18.4%) and cMLS (9.7%). Three clonal complexes--emm75/mefA/ST49, emm12/mefA/ST36 and emm77/ermA/tetO/ST63 comprised over 90% of the tested strains. Although MLVA, PP and VFP distinguished 10, 20 and 12 different patterns, respectively, cluster analysis disclosed only small differences between strains which belonged to the same emm/ST type. Our data indicate dominance of three major internationally widely disseminated macrolide resistant clones and a high genetic homogeneity among the Serbian MRGAS population. Continued surveillance of macrolide resistance and clonal composition in MRGAS in Serbia in future is necessary to determine stability of MRGAS clones and to guide therapy strategies.

  18. Syphilis epidemiology in 1994-2013, molecular epidemiological strain typing and determination of macrolide resistance in Treponema pallidum in 2013-2014 in Tuva Republic, Russia.

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    Khairullin, Rafil; Vorobyev, Denis; Obukhov, Andrey; Kuular, Ural-Herel; Kubanova, Anna; Kubanov, Alexey; Unemo, Magnus

    2016-07-01

    The incidence of syphilis in the Tuva Republic (geographical centre of Asia), Russia has been exceedingly high historically. No detailed examinations and no molecular investigations of Treponema pallidum strains transmitted in the Tuva Republic, or in general, in Russia, were published internationally. We examined the syphilis epidemiology in 1994-2013, and the molecular epidemiology and macrolide resistance in T. pallidum strains in 2013-2014 in the Tuva Republic. Among 95 mainly primary or secondary syphilis patients, the arp, tpr, tp0548 and 23S rRNA genes in 85 polA gene-positive genital ulcer specimens were characterized. The syphilis incidence in Tuva Republic peaked in 1998 (1562), however declined to 177 in 2013. Among the 70 (82%) completely genotyped specimens, six molecular strain types were found. Strain type 14d/f accounted for 91%, but also 14c/f, 14d/g, 14b/f, 14i/f, 9d/f, and 4d/f were identified. Two (2.4%) specimens contained the 23S rRNA A2058G macrolide resistance mutation. This is the first internationally published typing study regarding T. pallidum in Russia, performed in the Tuva Republic with the highest syphilis incidence in Russia. The two molecular strain types 4d/f and 9d/f have previously been described only in Eastern and Northern China and for the first time, macrolide-resistant syphilis was described in Russia.

  19. Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

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    Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

    2017-02-01

    From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

  20. Macrolide resistance in Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany.

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    Brandt, C M; Honscha, M; Truong, N D; Holland, R; Hövener, B; Bryskier, A; Lütticken, R; Reinert, R R

    2001-01-01

    Macrolide-resistance was assessed in 216 consecutive Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany. Seventeen isolates were resistant to erythromycin: 12 isolates revealed a macrolide (M) phenotype and harbored mefA, and five strains expressed an inducible macrolide-lincosamide-streptogramin B (MLSB) phenotype of which four strains harbored ermA(TR) and one strain contained ermB(AM). Telithromycin (HMR 3647) and quinupristin/dalfopristin remained active particularly against the ermA(TR)-containing S. pyogenes isolates studied. Random amplified polymorphic DNA analysis identified multiple clones among erythromycin-resistant strains, but did not discriminate beyond the emm-type. mefA was present in three isolates either with emm2, emm12, or emm75, and in nine isolates with emm4. All four strains with ermA(TR) contained emm77, and the single strain with ermB(AM) harbored emm1. Despite the relative low rate of macrolide-resistance, these data suggest that at least three different macrolide-resistance determinants are prevalent in Germany and that mefA has spread rapidly into multiple clones of S. pyogenes.

  1. Macrolide-resistant phenotypes of invasive streptococcus pneumoniae isolates in Serbia

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    Gajić Ina

    2012-01-01

    Full Text Available Macrolide resistance in Streptococcus pneumoniae has emerged as an important worldwide problem over the past decade. The aim of this study was to investigate macrolide-resistant phenotypes and the antimicrobial susceptibility patterns of invasive pneumococci in Serbia. A total of 68 invasive pneumococcal strains, collected from 2009 to 2011, were sent from regional laboratories to the National Reference Laboratory. Susceptibility testing was performed using the VITEK2 system and phenotypes were determined by triple-test. Overall penicillin and erythromycin nonsusceptibility rates were 26% and 43%, respectively. Resistance rates were higher in children than in adults. Co-resistance to penicillin and erythromycin was detected in 18% strains. Resistance rates to the third generation of cephalosporins, TMP-SXT and tetracycline were 16%, 37% and 29%, respectively. All isolates were fully susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and rifampicin. Twenty-two isolates (79% an expressed macrolide-lincosamide-streptogramin B (MLSB resistance phenotype and M phenotype was found in 21% of macrolide resistant strains. [Projekat Ministarstva nauke Republike Srbije, br. 175039

  2. Macrolide-lincosamide-resistant phenotypes and genotypes of Staphylococcus aureus isolated from bovine clinical mastitis.

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    Wang, Yang; Wu, Cong-Ming; Lu, Li-Ming; Ren, Gao-Wa Na; Cao, Xing-Yuan; Shen, Jian-Zhong

    2008-07-27

    The present study aimed to determine the prevalence and mechanisms of macrolide-lincosamide (ML) resistance in 72 Staphylococcus aureus isolates from cows with clinical mastitis. Minimum inhibitory concentrations (MIC) of ML antibiotics were determined by the broth microdilution technique, inducible ML resistance phenotype by the D test, and ML resistance genes by PCR assay. The isolates showed a high level of resistance to erythromycin (93.1%), azithromycin (93.1%), spiramycin (41.7%), tylosin (40.3%), tilmicosin (27.8%), and clindamycin (36.1%). Macrolide-lincosamide MIC(90) values were > or = 128 mg/L. Inducible ML resistance (iML) phenotype was detected in 52.8% (38/72) of isolates. In erythromycin-resistant (ER-R) strains, methylase genes ermB and ermC, efflux gene msrA/msrB, and inactivating enzyme genes lnuA and mphC were present alone or in various combinations, with ermB and ermC genes predominating. This is the first report of ML resistance genes ermB, mrsA/mrsB and mphC in S. aureus isolated from bovine mastitis. The occurrence of high levels of resistance to ML antibiotics among the S. aureus isolates, and the high rate of iML phenotype, indicate that appropriate alternative antibiotics should be prescribed for treating bovine mastitis caused by S. aureus. Furthermore, significant differences in the conformations of lactone rings of 16- and 14-membered macrolides could explain why some isolates with a constitutive ML resistance (cML) phenotype were sensitive to 16-membered macrolides alone. The different interaction of the 16-membered macrolides with the 50S ribosomal subunit is also presumably the reason why the susceptibility results of tilmcosin differed from those of tylosin and spiramycin.

  3. Molecular resistance mechanisms of macrolide-resistant invasive Streptococcus pneumoniae isolates from Alaska, 1986 to 2010.

    Science.gov (United States)

    Rudolph, Karen; Bulkow, Lisa; Bruce, Michael; Zulz, Tammy; Reasonover, Alisa; Harker-Jones, Marcella; Hurlburt, Debby; Hennessy, Thomas

    2013-11-01

    The rapid emergence of antibiotic-resistant pneumococcal strains has reduced treatment options. The aim of this study was to determine antimicrobial susceptibilities, serotype distributions, and molecular resistance mechanisms among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to 2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to 2010 through statewide population-based laboratory surveillance. All invasive pneumococcal isolates submitted to the Arctic Investigations Program laboratory were confirmed by standard microbiological methods and serotyped by slide agglutination and the Quellung reaction. MICs were determined by the broth microdilution method, and macrolide-resistant genotypes were determined by multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to 2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin-nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%) were multidrug resistant. The most frequent serotypes among the macrolide-resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%), 19F (6.3%), 6A (5.6%), and 23F (4.8%). mef and erm(B) genes were detected in 207 (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the erythromycin-nonsusceptible isolates contained both mef and erm(B) genotypes; 15 were of serotype 19A. There was significant year-to-year variation in the proportion of isolates that were nonsusceptible to erythromycin (P resistance among pneumococcal isolates from Alaska is mediated predominantly by mef genes, and this has not changed significantly over time. However, there was a statistically significant increase in the proportion of isolates that possess both erm(B) and mef, primarily due to serotype 19A isolates.

  4. Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

    Science.gov (United States)

    Thornton, Christina S; Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2015-11-01

    The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone ( resistance to tetracycline (∼34%) and sulfamethoxazole/trimethoprim (∼45%). The highest rate of antibiotic resistance was to the macrolides [azithromycin (56.4%) and erythromycin (51.6%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome.

  5. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

    Science.gov (United States)

    Hare, K M; Grimwood, K; Chang, A B; Chatfield, M D; Valery, P C; Leach, A J; Smith-Vaughan, H C; Morris, P S; Byrnes, C A; Torzillo, P J; Cheng, A C

    2015-11-01

    Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.

  6. Evolution of macrolide resistance in Streptococcus pyogenes over 14 years in an area of central Italy.

    Science.gov (United States)

    Olivieri, Raffaela; Morandi, Matteo; Zanchi, Alessandra; Tordini, Giacinta; Pozzi, Gianni; De Luca, Andrea; Montagnani, Francesca

    2015-10-01

    We evaluated temporal fluctuations in macrolide resistance rates, analysing genetic determinants of resistance and clonal evolution in a population of 2744 S. pyogenes isolates collected in the period 2000-2013. The total resistance rate to erythromycin of the isolates was 17.9 %. A maximum of erythromycin resistance emerged in 2000 (38.6 %), followed by a significant decrease to 5.2 % in 2012 (P pyogenes. Continuous monitoring of microbiological epidemiology seems to be crucial for correct and effective management of streptococcal infections.

  7. Macrolide resistance conferred by rRNA mutations in field isolates of Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Olsen, Anders S; Warrass, Ralf; Douthwaite, Stephen Roger

    2014-01-01

    . haemolytica identified as being highly resistant (MICs >64 mg/L) to the macrolides erythromycin, gamithromycin, tilmicosin, tildipirosin and tulathromycin were screened by multiplex PCR for the previously identified resistance genes erm(42), msr(E) and mph(E). Strains lacking these determinants were analysed...

  8. Mycoplasma genitalium in Spain: prevalence of genital infection and frequency of resistance to macrolides.

    Science.gov (United States)

    Asenjo, Alejandra; Kusters, Johannes G; Severs, Tim T; Alós, Juan-Ignacio

    2017-03-11

    The aim of this study was to determine the prevalence of Mycoplasma genitalium infection and the resistance to macrolides within a general population in Madrid in 2015. We collected 359 urine samples from a general population with symptoms of sexually transmitted infections (STIs). All samples underwent a real-time PCR. For the detection of macrolide resistance, a 283bp fragment of region V of the 23S rRNA gene of M. genitalium was amplified and sequenced. We found a prevalence of 3.34% of M. genitalium and a macrolide resistance rate of 20%. In males, the prevalence was 6.62% and in women 0.96%, being significantly higher in males. The prevalence obtained shows that it is a pathogen to consider in our environment. These findings stress the need for routine testing of M. genitalium infections and would seem to suggest the advisability of resistance testing. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Mechanism of resistance to macrolide-lincosamide-streptogramin antibiotics in Streptococcus thermophilus

    Science.gov (United States)

    Resistance to macrolide-lincosamide-streptogramin (MLS) group antibiotics in the dairy bacterium Streptococcus thermophilus (ST) is documented but the mechanism of resistance has not been elucidated. MIC values for erythromycin (Erm), azithromycin (Azm), tylosin (Tyl), spiramycin (Spm), pristinamyci...

  10. [Macrolide resistance in Treponema pallidum subsp. pallidum in the Czech Republic and in other countries].

    Science.gov (United States)

    Grillová, L; Mikalová, L; Zákoucká, H; Židlická, J; Šmajs, D

    2015-03-01

    Treponema pallidum subsp. pallidum (TPA) is the causative agent of the sexually transmitted disease syphilis. In the Czech Republic, several hundred cases of syphilis are reported annually; e.g. in 2012, 696 syphilis cases were documented. In the last decades, an increasing prevalence of macrolide resistant TPA strains harboring A2058G or A2059G mutations in the 23S rRNA gene has been reported. Macrolides were used (and rarely are still being used) in the Czech Republic for the treatment of syphilis in patients allergic to penicillin. While 37% of TPA strains were resistant to macrolides between 2004 and 2010, this rate increased to 67% between 2011-2013. High prevalence of A2058G or A2059G mutations and increasing rates of macrolide resistant TPA strains have also been documented in other developed countries. Therefore, macrolides should not be used in the treatment of syphilis.

  11. Dominance of multidrug resistant CC271 clones in macrolide-resistant streptococcus pneumoniae in Arizona

    Directory of Open Access Journals (Sweden)

    Bowers Jolene R

    2012-01-01

    Full Text Available Abstract Background Rates of resistance to macrolide antibiotics in Streptococcus pneumoniae are rising around the world due to the spread of mobile genetic elements harboring mef(E and erm(B genes and post-vaccine clonal expansion of strains that carry them. Results Characterization of 592 clinical isolates collected in Arizona over a 10 year period shows 23.6% are macrolide resistant. The largest portion of the macrolide-resistant population, 52%, is dual mef(E/erm(B-positive. All dual-positive isolates are multidrug-resistant clonal lineages of Taiwan19F-14, mostly multilocus sequence type 320, carrying the recently described transposon Tn2010. The remainder of the macrolide resistant S. pneumoniae collection includes 31% mef(E-positive, and 9% erm(B-positive strains. Conclusions The dual-positive, multidrug-resistant S. pneumoniae clones have likely expanded by switching to non-vaccine serotypes after the heptavalent pneumococcal conjugate vaccine release, and their success limits therapy options. This upsurge could have a considerable clinical impact in Arizona.

  12. Impaired Fitness and Transmission of Macrolide-Resistant Campylobacter jejuni in Its Natural Host

    Science.gov (United States)

    Luangtongkum, Taradon; Shen, Zhangqi; Seng, Virginia W.; Sahin, Orhan; Jeon, Byeonghwa; Liu, Peng

    2012-01-01

    Campylobacter jejuni is a major zoonotic pathogen transmitted to humans via the food chain and is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance in Campylobacter has become a concern for public health. To facilitate the control of macrolide-resistant Campylobacter, it is necessary to understand if macrolide resistance affects the fitness and transmission of Campylobacter in its natural host. In this study we conducted pairwise competitions and comingling experiments in chickens using clonally related and isogenic C. jejuni strains, which are either susceptible or resistant to erythromycin (Ery). In every competition pair, Ery-resistant (Eryr) Campylobacter was consistently outcompeted by the Ery-susceptible (Erys) strain. In the comingling experiments, Eryr Campylobacter failed to transmit to chickens precolonized by Erys Campylobacter, while isogenic Erys Campylobacter was able to transmit to and establish dominance in chickens precolonized by Eryr Campylobacter. The fitness disadvantage was linked to the resistance-conferring mutations in the 23S rRNA. These findings clearly indicate that acquisition of macrolide resistance impairs the fitness and transmission of Campylobacter in chickens, suggesting that the prevalence of macrolide-resistant C. jejuni will likely decrease in the absence of antibiotic selection pressure. PMID:22183170

  13. Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Pettigrew, Melinda M; Tsuji, Brian T; Gent, Janneane F; Kong, Yong; Holden, Patricia N; Sethi, Sanjay; Murphy, Timothy F

    2016-07-01

    Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. Five of 27 (19%) strains developed 4-fold increases in azithromycin MICs and reached or exceeded the susceptibility breakpoint (≤4 μg/ml) during exposure. H. influenzae isolates were uniformly susceptible to ciprofloxacin, levofloxacin, and moxifloxacin (MIC90s of 0.015, 0.015, and 0.06, respectively); there were no mutations in quinolone resistance-determining regions. Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides (odds ratio [OR], 16.67; 95% confidence interval [CI], 2.67 to 104.09). There was no difference in H. influenzae eradication when comparing macrolide administration to no antibiotic (OR, 1.89; 95% CI, 0.43 to 8.30). Fluoroquinolones are effective in eradicating H. influenzae in individuals with COPD. Macrolides are ineffective in eradicating H. influenzae, and their use in COPD patients may lead to decreased macrolide susceptibility and resistance.

  14. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... resistance in Campylobacter and track resistance trends in human clinical isolates in relation to use of these agents in food animals. Susceptibility data suggest that erythromycin and other macrolides should remain the drugs of choice in most regions, with systematic surveillance and central measures...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  15. Mycoplasma genitalium Prevalence, Coinfection, and Macrolide Antibiotic Resistance Frequency in a Multicenter Clinical Study Cohort in the United States

    Science.gov (United States)

    Jiang, Alice; O'Donnell, Meghan; Cohen, Seth

    2016-01-01

    The prevalence rates of Mycoplasma genitalium infections and coinfections with other sexually transmitted organisms and the frequency of a macrolide antibiotic resistance phenotype were determined in urogenital specimens collected from female and male subjects enrolled in a multicenter clinical study in the United States. Specimens from 946 subjects seeking care from seven geographically diverse clinical sites were tested for M. genitalium and for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Sequencing was used to assess macrolide antibiotic resistance among M. genitalium-positive subjects. M. genitalium prevalence rates were 16.1% for females and 17.2% for males. Significant risk factors for M. genitalium infections were black race, younger age, non-Hispanic ethnicity, and female symptomatic status. Female M. genitalium infections were significantly more prevalent than C. trachomatis and N. gonorrhoeae infections, while the M. genitalium infection rate in males was significantly higher than the N. gonorrhoeae and T. vaginalis infection rates. The macrolide-resistant phenotype was found in 50.8% of females and 42% of males. These results show a high prevalence of M. genitalium single infections, a lower prevalence of coinfections with other sexually transmitted organisms, and high rates of macrolide antibiotic resistance in a diverse sample of subjects seeking care across a wide geographic area of the United States. PMID:27307460

  16. Detection of genetic mutations associated with macrolide resistance of Mycoplasma pneumoniae

    Directory of Open Access Journals (Sweden)

    Chi Eun Oh

    2010-02-01

    Full Text Available Purpose : The aim of this study was to identify mutations associated with macrolide resistance in Mycoplasma pneumoniae (MP and to establish a cultural method to determine antimicrobial susceptibility. Methods : Nasopharyngeal aspirates (NPAs were collected from 62 children diagnosed with MP pneumonia by a serologic method or polymerase chain reaction. The 23S rRNA and L4 ribosomal protein genes of MP were amplified and sequenced. To identify mutations in these 2 genes, their nucleotide sequences were compared to those of the reference strain M129. MP cultivation was carried out for 32 (28 frozen and 5 refrigerated NPAs and M129 strain using Chanock’s glucose broth and agar plate in a 5% CO2 incubator at 37?#608;and examined at 2-3 day intervals for 6 weeks. Results : Among the 62 specimens, 17 had M144V mutations in ribosomal protein L4. The A2064G mutation was observed in 1 specimen; its 23S rRNA gene was successfully sequenced. Culture for MP was successful from the M129 strain and 2 of the 5 NPAs that were refrigerated for no longer than 3 days. However, MP did not grow from the 28 NPAs that were kept frozen at -80?#608;since 2003. Conclusion : We found the M144V mutation of L4 protein to be common and that of domain V of 23S rRNA gene was relatively rare among MP. Studies on the prevalence of macrolide-resistant MP and the relationship between the mutations of 23S rRNA gene and ribosomal protein L4 will aid in understanding the mechanism of macrolide resistance in MP.

  17. In Vitro Activity of the New Ketolide Telithromycin Compared with Those of Macrolides against Streptococcus pyogenes: Influences of Resistance Mechanisms and Methodological Factors

    Science.gov (United States)

    Bemer-Melchior, Pascale; Juvin, Marie-Emmanuelle; Tassin, Sandrine; Bryskier, Andre; Schito, Gian Carlo; Drugeon, Henri-B.

    2000-01-01

    One hundred and seven clinical isolates of Streptococcus pyogenes, 80 susceptible to macrolides and 27 resistant to erythromycin A (MIC >0.5 μg/ml), were examined. The erythromycin A-lincomycin double-disk test assigned 7 resistant strains to the M-phenotype, 8 to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLSB) phenotype, and 12 to the constitutive MLSB resistance (cMLSB) phenotype. MICs of erythromycin A, clarithromycin, azithromycin, roxithromycin, and clindamycin were determined by a broth microdilution method. MICs of telithromycin were determined by three different methods (broth microdilution, agar dilution, and E-test methods) in an ambient air atmosphere and in a 5 to 6% CO2 atmosphere. Erythromycin A resistance genes were investigated by PCR in the 27 erythromycin A-resistant isolates. MICs of erythromycin A and clindamycin showed six groups of resistant strains, groups A to F. iMLSB strains (A, B, and D groups) are characterized by two distinct patterns of resistance correlated with genotypic results. A- and B-group strains were moderately resistant to 14- and 15-membered ring macrolides and highly susceptible to telithromycin. All A- and B-group isolates harbored erm TR gene, D-group strains, highly resistant to macrolides and intermediately resistant to telithromycin (MICs, 1 to 16 μg/ml), were all characterized by having the ermB gene. All M-phenotype isolates (C group), resistant to 14- and 15-membered ring macrolides and susceptible to clindamycin and telithromycin, harbored the mefA gene. All cMLSB strains (E and F groups) with high level of resistance to macrolides, lincosamide, and telithromycin had the ermB gene. The effect of 5 to 6% CO2 was remarkable on resistant strains, by increasing MICs of telithromycin from 1 to 6 twofold dilutions against D-E- and F-group isolates. PMID:11036012

  18. Development of macrolide-resistant Campylobacter in broilers administered subtherapeutic or therapeutic concentrations of tylosin.

    Science.gov (United States)

    Ladely, Scott R; Harrison, Mark A; Fedorka-Cray, Paula J; Berrang, Mark E; Englen, Mark D; Meinersmann, Richard J

    2007-08-01

    The use of antimicrobials in food animal production, particularly those commonly used to treat infections in humans, has become a source of debate in recent years. However, limited data are available regarding the development of resistance following the subtherapeutic or therapeutic administration of antimicrobials in animal production. The objective of this study was to evaluate the effect of the administration of therapeutic and subtherapeutic concentrations of tylosin on the erythromycin susceptibility of Campylobacter jejuni and Campylobacter coli isolated from the ceca of treated broilers. In three replicated studies, day-of-hatch chicks were exposed to macrolide-susceptible C. jejuni or C. coli. At 2 weeks of age, tylosin was administered at subtherapeutic (22 ppm, continuously in the diet) or therapeutic concentrations (529 ppm, in the drinking water for 5 days). Broilers were sacrificed weekly. Total and erythromycin-resistant Campylobacter spp. were enumerated from individual ceca plus cecal contents. Overall erythromycin resistance was observed at a higher frequency (P tylosin administration. Across Campylobacter species, erythromycin resistance was observed at a higher frequency (P tylosin was administered at subtherapeutic (62.7%) than at therapeutic (11.4%) concentrations. Subtherapeutic administration resulted in the recovery of 83.3 and 56.1% erythromycin-resistant isolates compared with only 33.3 and 7.9% of the isolates expressing erythromycin resistance following the administration of therapeutic concentrations for C. coli and C. jejuni, respectively. Further studies are needed to determine the factors involved in the apparent difference in the acquisition of macrolide resistance in C. coli compared with C. jejuni.

  19. Macrolides and lincosamides in cattle and pigs: use and development of antimicrobial resistance.

    Science.gov (United States)

    Pyörälä, Satu; Baptiste, Keith Edward; Catry, Boudewijn; van Duijkeren, Engeline; Greko, Christina; Moreno, Miguel A; Pomba, M Constança Matias Ferreira; Rantala, Merja; Ružauskas, Modestas; Sanders, Pascal; Threlfall, E John; Torren-Edo, Jordi; Törneke, Karolina

    2014-05-01

    Macrolides and lincosamides are important antibacterials for the treatment of many common infections in cattle and pigs. Products for in-feed medication with these compounds in combination with other antimicrobials are commonly used in Europe. Most recently approved injectable macrolides have very long elimination half-lives in both pigs and cattle, which allows once-only dosing regimens. Both in-feed medication and use of long-acting injections result in low concentrations of the active substance for prolonged periods, which causes concerns related to development of antimicrobial resistance. Acquired resistance to macrolides and lincosamides among food animal pathogens, including some zoonotic bacteria, has now emerged. A comparison of studies on the prevalence of resistance is difficult, since for many micro-organisms no agreed standards for susceptibility testing are available. With animal pathogens, the most dramatic increase in resistance has been seen in the genus Brachyspira. Resistance towards macrolides and lincosamides has also been detected in staphylococci isolated from pigs and streptococci from cattle. This article reviews the use of macrolides and lincosamides in cattle and pigs, as well as the development of resistance in target and some zoonotic pathogens. The focus of the review is on European conditions.

  20. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  1. Use of next generation sequence to investigate potential novel macrolide resistance mechanisms in a population of Moraxella catarrhalis isolates

    Science.gov (United States)

    Liu, Ya-Li; Li, Dong-Fang; Xu, He-Ping; Xiao, Meng; Cheng, Jing-Wei; Zhang, Li; Xu, Zhi-Peng; Chen, Xin-Xin; Zhang, Ge; Kudinha, Timothy; Kong, Fanrong; Gong, Yan-Ping; Wang, Xin-Ying; Zhang, Yin-Xin; Wu, Hong-Long; Xu, Ying-Chun

    2016-01-01

    Although previous studies have confirmed that 23S rRNA gene mutation could be responsible for most of macrolide resistance in M. catarrhalis, a recent study suggested otherwise. Next generation sequence based comparative genomics has revolutionized the mining of potential novel drug resistant mechanisms. In this study, two pairs of resistant and susceptible M. catarrhalis isolates with different multilocus sequence types, were investigated for potential differential genes or informative single nucleotide polymorphisms (SNPs). The identified genes and SNPs were evaluated in 188 clinical isolates. From initially 12 selected differential genes and 12 informative SNPs, 10 differential genes (mboIA, mcbC, mcbI, mboIB, MCR_1794, MCR_1795, lgt2B/C, dpnI, mcbB, and mcbA) and 6 SNPs (C619T of rumA, T140C of rplF, G643A of MCR_0020, T270G of MCR_1465, C1348A of copB, and G238A of rrmA) were identified as possibly linked to macrolide resistance in M. catarrhalis. Most of the identified differential genes and SNPs are related to methylation of ribosomal RNA (rRNA) or DNA, especially MCR_0020 and rrmA. Further studies are needed to determine the function and/or evolution process, of the identified genes or SNPs, to establish whether some novel or combined mechanisms are truly involved in M. catarrhalis macrolide resistance mechanism. PMID:27774989

  2. Macrolide-lincosamide-streptogramin B (MLS) resistance in cutaneous propionibacteria: definition of phenotypes.

    Science.gov (United States)

    Eady, E A; Ross, J I; Cove, J H; Holland, K T; Cunliffe, W J

    1989-04-01

    Erythromycin-resistant propionibacteria isolated from the skin of antibiotic-treated acne patients were found to express four different patterns of resistance to a set of eight MLS antibiotics. The majority of isolates (48/89 strains) were constitutively resistant to 14- and 16-membered ring macrolide, lincosamide and streptogramin B-type antibiotics. MICs of josamycin (0.5-16 mg/l) and spiramycin (0.5-128 mg/l) were lower than those of erythromycin, oleandomycin and tylosin (64 to less than 512 mg/l). Two strains of Propionibacterium granulosum exhibited inducible MLS resistance. Both 14- and 16-membered ring macrolides and virginiamycin S induced clindamycin resistance in these strains. Fifteen isolates demonstrated a similar phenotype to the inducible strains but were non-inducible by erythromycin. A fourth group of strains demonstrated high level resistance to all five macrolides tested (MIC greater than or equal to 128 mg/l) but were sensitive to virginiamycin S. The phenotype displayed by these strains is not compatible with the expression of methylase genes as currently known, nor with the action of an erythromycin esterase which hydrolyses only 14-membered ring macrolides. The resistance patterns of 12 isolates could not be classified into any of the above phenotypic classes. Therefore, the majority of erythromycin resistant propionibacteria express MLS resistance which is phenotypically similar to that coded for by several well characterized RNA methylase (erm) genes.

  3. Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes.

    Science.gov (United States)

    Zhang, Yan; Tatsuno, Ichiro; Okada, Ryo; Hata, Nanako; Matsumoto, Masakado; Isaka, Masanori; Isobe, Ken-ichi; Hasegawa, Tadao

    2016-01-01

    In Japan, the number of patients with streptococcal toxic shock syndrome is reported to be increasing. mef(A) gene-positive macrolide-resistant emm1 strains are thought to possibly contribute to the rise in the frequency of STSS. Although analyses of macrolide-resistant mechanisms, including mef(A) resistance, have been performed mainly in Streptococcus pneumoniae, the role of this gene in Streptococcus pyogenes has not been completely investigated. Therefore, to the best of our knowledge, we established the first mef(A)-knockout strain using an emm1-type S. pyogenes strain, and tested its susceptibility to erythromycin, clarithromycin and azithromycin. We found that the antimicrobial susceptibilities were almost identical to those of the parental strain. Hence, we established a knockout strain for another gene, msr(D), that is located immediately downstream of mef(A). The macrolide resistances of the resulting strain significantly decreased, and were further altered when both mef(A) and msr(D) were knocked out. The introduction of the msr(D) gene into a macrolide-sensitive strain conferred more resistance than the introduction of the mef(A) gene. The erythromycin susceptibilities of knockout strains were further dissected using two additional emm4- and emm75-type S. pyogenes strains. We found almost identical results for both strains except for the mef(A) knockout emm4 type, whose susceptibility was altered, although the change was less than that for the msr(D) knockout. These results suggest that both mef(A) and msr(D) are involved in macrolide resistance in S. pyogenes, and that the msr(D) gene plays a more predominant role in macrolide resistance than mef(A).

  4. The clinical characteristics,treatment and outcome of macrolide-resistant Mycoplasma pneumoniae pneumonia in children

    Institute of Scientific and Technical Information of China (English)

    鲍芳

    2013-01-01

    Objective To investigate the drug resistance of My-coplasma pneumoniae among children with community-acquired pneumonia (CAP) ,and to explore the clinical and radiological characteristics of and the role of azithromycin in the treatment of of macrolide-resistant (MR) Mycoplasma pneumoniae pneumonia.Methods Cases of CAP in children (n=179) were prospectively enrolled in

  5. Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry

    Directory of Open Access Journals (Sweden)

    Gerchman Irena

    2011-08-01

    Full Text Available Abstract The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18 of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS, detected 13 molecular types (I-XIII. Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01 and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides.

  6. Evaluation of macrolides for possible use against multidrug-resistant Mycobacterium tuberculosis

    NARCIS (Netherlands)

    van der Paardt, Anne-Fleur; Wilffert, Bob; Akkerman, Onno W.; de Lange, Wiel C. M.; van Soolingen, Dick; Sinha, Bhanu; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2015-01-01

    Multidrug-resistant tuberculosis (MDR-TB) is a major global health problem. The loss of susceptibility to an increasing number of drugs behoves us to consider the evaluation of non-traditional anti-tuberculosis drugs. Clarithromycin, a macrolide antibiotic, is defined as a group 5 anti-tuberculosis

  7. Failure of moxifloxacin treatment in Mycoplasma genitalium infections due to macrolide and fluoroquinolone resistance.

    Science.gov (United States)

    Couldwell, Deborah L; Tagg, Kaitlin A; Jeoffreys, Neisha J; Gilbert, Gwendolyn L

    2013-10-01

    Increasing azithromycin treatment failure in sexually transmitted Mycoplasma genitalium infection, is linked to macrolide resistance and second-line treatment relies on the fluoroquinolone, moxifloxacin. We recently detected fluoroquinolone and macrolide resistance-associated mutations in 15% and 43%, respectively, of 143 initial M. genitalium PCR-positive specimens. For a subset of 33 Western Sydney Sexual Health Centre patients, clinical information and results of sequence analysis of M. genitalium macrolide and fluoroquinolone target genes - the 23S rRNA gene, and parC and gyrA, respectively - were used to examine whether mutations were associated with treatment failure. Macrolide resistance-associated mutations correlated with microbiological (p = 0.013) and clinical (p = 0.024) treatment failure, and fluoroquinolone resistance-associated mutations with microbiological moxifloxacin treatment failure (p = 0.005). We describe the first reported cases of clinical and microbiological moxifloxacin treatment failure. Failure of first- and second-line antibiotic treatment of M. genitalium infection is occurring and likely to increase with current treatment strategies.

  8. Antimicrobial growth promoter ban and resistance to macrolides and vancomycin in enterococci from pigs

    DEFF Research Database (Denmark)

    Boerlin, P.; Wissing, A.; Aarestrup, Frank Møller;

    2001-01-01

    Ninety-six enterococcus isolates from fecal samples of pigs receiving tylosin as an antimicrobial growth promoter and 59 isolates obtained in the same farms 5 to 6 months after the ban of antimicrobial growth promoters in Switzerland were tested for susceptibility to nine antimicrobial agents. A ....... A clear decrease in resistance to macrolides, lincosamides, and tetracycline was visible after the ban. Vancomycin-resistant Enterococcus faecium belonged to the same clonal lineage as vancomycin-resistant isolates previously isolated from Danish pigs....

  9. Genotypic and phenotypic detection of macrolide and lincosamide resistance in Streptococcus uberis.

    Science.gov (United States)

    Schmitt-Van de Leemput, E; Zadoks, R N

    2007-11-01

    Streptococcus uberis isolates (n = 55) were obtained from milk samples of cases of mild clinical mastitis in 55 dairy cows from 35 herds serviced by one veterinary practice in Mayenne, France. Isolates were tested for macrolide and lincosamide resistance by using phenotypic and genotypic methods. Erythromycin resistance was detected in 12 of the 55 (22%) isolates based on agar disc diffusion testing and MIC measurements, and was encoded by ermB. This gene also conferred phenotypic resistance to pirlimycin based on MIC measurements, but the D-test was needed for detection of the resistance phenotype in the agar disc diffusion test. Isolates with ermB were also highly resistant to the macrolide antibiotic spiramycin. Seventeen of the 55 isolates (31%) were classified as resistant to spiramcyin only and as having intermediate susceptibility to spiramycin based on agar disc diffusion testing and MIC measurements, respectively. The genetic mechanism behind this phenotype and its clinical relevance are unknown. The efflux pump gene mefA was not detected in any of the 55 isolates in this study. Pirlimycin resistance without macrolide resistance was encoded by the lincosamide resistance gene linB in 4 isolates. Based on current guidelines, some linB-positive isolates would be classified as susceptible by using phenotypic tests, and alternative values for the interpretation of the agar disc diffusion test are suggested. We conclude that the agar disc diffusion test is a useful indicator for macrolide and lincosamide resistance of Strep. uberis in veterinary practice, provided that the D-test is used for detection of pirlimycin resistance.

  10. Antimicrobial susceptibility and macrolide resistance genes in Streptococcus pyogenes collected in Austria and Hungary.

    Science.gov (United States)

    Gattringer, Rainer; Sauermann, Robert; Lagler, Heimo; Stich, Karin; Buxbaum, Astrid; Graninger, Wolfgang; Georgopoulos, Apostolos

    2004-09-01

    A total of 341 clinical isolates of Streptococcus pyogenes from Vienna, Austria and three Hungarian cities were tested for susceptibility to four macrolides and 12 other antibiotics. All isolates were fully susceptible to penicillin and the other beta-lactams tested. A high level of tetracycline resistance was found in Austria (26.7%) and in Hungary (30.5%). The rate of resistance to erythromycin, clarithromycin and azithromycin was 4.7% in Vienna and 3.7% in the Hungarian communities. In both countries, the MIC(90) values of erythromycin and clarithromycin were 0.12 mg/L and the MIC(90) of josamycin was 0.5mg/L. The M phenotype of resistance conferred by the mefA genes was predominant (n = 9) among the macrolide-resistant isolates (n = 14).

  11. Macrolide, glycopeptide resistance and virulence genes in Enterococcus species isolates from dairy cattle.

    Science.gov (United States)

    Iweriebor, Benson C; Obi, Larry C; Okoh, Anthony I

    2016-07-01

    The genus Enterococcus is known to possess the capacity to acquire and disseminate antimicrobial resistant determinants alongside the ability to produce various virulence genes that enables it to establish infections. We assessed the prevalence and antibiogram profiles of Enterococcus spp. in faecal samples of dairy cattle. Faecal swab samples were collected from 400 dairy cattle from two commercial cattle farms in two rural communities in the Eastern Cape, South Africa. Confirmation of enterococci isolates was carried out by PCR targeting of the tuf gene. Species delineation was by species-specific primers targeting the superoxide dismutase (sod A) gene in a multiplex PCR assay. Isolates were screened for the presence of the following virulence genes (ace, gel E, esp, efa A, cyl A and hyl E) and antimicrobial resistance determinants to erythromycin, vancomycin and streptomycin were evaluated molecularly. A total of 340 isolates were confirmed as belonging to the genus Enterococcus . Species distribution among the isolates consisted of Enterococcus faecium (52.94 %) and Enterococcus durans (23.53 %) in preponderance compared to the three other species, namely Enterococcus faecalis (8.8 %), Enterococcus hirae (8.6 %) and Enterococcus casseliflavus (5.9 %). All were resistant to vancomycin, while 99 % showed resistance to aminoglycoside and 94 % to macrolide. Three virulence genes (ace, gel E and esp) were detected in almost all the confirmed isolates. The resistance determinants van B (19.7 %), van C1 (25 %), van C2/3 (26.3 %) erm B (40.29 %) and str A (50.88 %) were detected among the isolates. A high prevalence of multidrug-resistant enterococci isolates was detected in this study and the genetic repertoire to survive in the presence of antimicrobial agents was present in these organisms.

  12. Effect of subtherapeutic vs therapeutic administration of macrolides on antimicrobial resistance in Mannheimia haemolytica and enterococci isolated from beef cattle

    Directory of Open Access Journals (Sweden)

    Rahat eZaheer

    2013-05-01

    Full Text Available Macrolides are the first-line treatment against bovine respiratory disease, and are also used to treat infections in humans. The macrolide, tylosin phosphate, is often included in the diet of cattle as a preventative for liver abscesses in many regions of the world outside of Europe. This study investigated the effects of administering macrolides to beef cattle either systemically through a single subcutaneous injection (therapeutic or continuously in-feed (subtherapeutic, on the prevalence and antimicrobial resistance of Mannheimia haemolytica and Enterococcus spp. isolated from the nasopharynx and faeces, respectively. Nasopharyngeal and faecal samples were collected weekly over 28 days from untreated beef steers and from steers injected once with tilmicosin or tulathromycin or continuously fed tylosin phosphate at dosages recommended by manufacturers. Tilmicosin and tulathromycin were effective in lowering (P < 0.05 the prevalence of M. haemolytica, whereas subtherpeutic tylosin had no effect. M. haemolytica isolated from control- and macrolide-treated animals were susceptible to macrolides as well as to other antibiotics. Major bacteria co-isolated with M. haemolytica included Pasteurella multocida, Staphylococcus spp., Acinetobacter spp., E. coli and Bacillus spp. With the exception of M. haemolytica and P. multocida, erythromycin resistance was frequently found in other isolated species. Both methods of macrolide administration increased (P < 0.05 the levels erythromycin-resistance enterococci in faeces. Development of resistance to injectable macrolides in bacteria isolated from the nasopharynx was species dependent. Therapeutic administration of tilmicosin and tularthromycin selected for macrolide resistant bacteria within both the respiratory and intestinal tract, whereas suptherapeutic administration of tylosin only selected for macrolide resistance in enteric bacteria.

  13. Resistance to the macrolide antibiotic tylosin is conferred by single methylations at 23S rRNA nucleotides G748 and A2058 acting in synergy

    Science.gov (United States)

    Liu, Mingfu; Douthwaite, Stephen

    2002-01-01

    The macrolide antibiotic tylosin has been used extensively in veterinary medicine and exerts potent antimicrobial activity against Gram-positive bacteria. Tylosin-synthesizing strains of the Gram-positive bacterium Streptomyces fradiae protect themselves from their own product by differential expression of four resistance determinants, tlrA, tlrB, tlrC, and tlrD. The tlrB and tlrD genes encode methyltransferases that add single methyl groups at 23S rRNA nucleotides G748 and A2058, respectively. Here we show that methylation by neither TlrB nor TlrD is sufficient on its own to give tylosin resistance, and resistance is conferred by the G748 and A2058 methylations acting together in synergy. This synergistic mechanism of resistance is specific for the macrolides tylosin and mycinamycin that possess sugars extending from the 5- and 14-positions of the macrolactone ring and is not observed for macrolides, such as carbomycin, spiramycin, and erythromycin, that have different constellations of sugars. The manner in which the G748 and A2058 methylations coincide with the glycosylation patterns of tylosin and mycinamycin reflects unambiguously how these macrolides fit into their binding site within the bacterial 50S ribosomal subunit. PMID:12417742

  14. Genetic analysis of a pediatric clinical isolate of Moraxella catarrhalis with resistance to macrolides and quinolones.

    Science.gov (United States)

    Iwata, Satoshi; Sato, Yoshitake; Toyonaga, Yoshikiyo; Hanaki, Hideaki; Sunakawa, Keisuke

    2015-04-01

    During the surveillance conducted in 2012 by the Drug-resistant Pathogen Surveillance Group in Pediatric Infectious Disease, we isolated a strain of Moraxella catarrhalis that demonstrated resistance to both macrolides and quinolones from a male pediatric patient aged 1.5 years who had developed acute bronchitis. Then we evaluated the susceptibility of this strain to different types of antibacterial agents and conducted a genetic analysis. The results of the susceptibility evaluation showed that the MIC values of azithromycin, clarithromycin, and rokitamycin were >64 μg/mL, >64 μg/mL, and 4 μg/mL, respectively; clearly demonstrating resistance to macrolides. The MIC values of the quinolones levofloxacin, tosufloxacin, and garenoxacin were 4 μg/mL, 2 μg/mL, and 1 μg/mL, respectively; indicating decreased susceptibility. The genetic analysis of this strain revealed one mutation in 23s rRNA with a replacement of adenine by thymine at nucleotide position 2330 (A2330T) and another mutation in gyrB at nucleotide position 1481 by replacement of adenine with guanine (A1481G) that caused a substitution of the 494 th asparagine acid by glycine, as being associated with the observed resistance to macrolides and quinolones, respectively. Similar to drug-resistant bacteria Streptococcus pneumoniae and Haemophilus influenzae, the prevalence of which has recently increased, the treatment of drug-resistant M. catarrhalis infections is considered difficult due to the development of resistance to different types of antibacterial agents. It is vital to maintain an unwavering focus on the trend toward an increasing number of drug-resistant M. catarrhalis strains and ensure the proper use of each antibacterial agent.

  15. Transmission and selection of macrolide resistant Mycoplasma genitalium infections detected by rapid high resolution melt analysis.

    Directory of Open Access Journals (Sweden)

    Jimmy Twin

    Full Text Available BACKGROUND: Mycoplasma genitalium (MG causes urethritis, cervicitis and pelvic inflammatory disease. The MG treatment failure rate using 1 g azithromycin at an Australian Sexual Health clinic in 2007-9 was 31% (95%CI 23-40%. We developed a rapid high resolution melt analysis (HRMA assay targeting resistance mutations in the MG 23S rRNA gene, and validated it against DNA sequencing by examining pre- and post-treatment archived samples from MG-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Available MG-positive pre-treatment (n = 82 and post-treatment samples from individuals with clinical treatment failure (n = 20 were screened for 23S rRNA gene mutations. Sixteen (20% pre-treatment samples possessed resistance mutations (A2058G, A2059G, A2059C, which were significantly more common in patients with symptomatic azithromycin-treatment failure (12/26; 44% than in those clinically cured (4/56; 7%, p<0.001. All 20 patients experiencing azithromycin-failure had detectable mutations in their post-treatment samples. In 9 of these cases, the same mutational types were present in both pre- and post-treatment samples indicating transmitted resistance, whilst in 11 of these cases (55%, mutations were absent in pre-treatment samples indicating likely selection of resistant isolates have occurred. HRMA was able to detect all mutational changes determined in this study by DNA sequencing. An additional HRMA assay incorporating an unlabelled probe was also developed to detect type 4 single-nucleotide polymorphisms found in other populations, with a slightly lower sensitivity of 90%. CONCLUSIONS/SIGNIFICANCE: Treatment failure is associated with the detection of macrolide resistance mutations, which appear to be almost equally due to selection of resistant isolates following exposure to 1 g azithromycin and pre-existing transmitted resistance. The application of a rapid molecular assay to detect resistance at the time of initial detection of infection allows

  16. Relationship between copper, glycopeptide, and macrolide resistance among Enterococcus faecium strains isolated from pigs in Denmark between 1997 and 2003

    DEFF Research Database (Denmark)

    Hasman, Henrik; Aarestrup, Frank Møller

    2005-01-01

    A significant relationship between copper resistance (tcrB), glycopeptide resistance (Tn1546), and macrolide resistance [erm(B)] in Enterococcus faecium isolated from pigs was found. The tcrB gene was located closely upstream of the Tn1546 element. However, the continued use of copper sulfate has...

  17. Spectrophotometric determination of acidity constants of some macrolides in acetonitrile-water binary mixtures.

    Science.gov (United States)

    Sanli, Senem; Sanli, Nurullah; Alsancak, Güleren

    2010-12-01

    The acidity constants of eight macrolides (erythromycin, roxithromycin, oleandomycin, azithromycin, josamycin, tylosin tartrate, tilmicosin and spiramycin) have been determined in acetonitrile-water binary mixtures (30%, 40% and 50% (v/v)) by spectrophotometric method. The pKa's available in literature determined by various methods are compiled in comparison with the value of this work. These results are expected to essentially facilitate the research on occurrence, fate and effects, analysis method development, and control of antibiotics in various treatment occurrences.

  18. Acquired resistance to the 16-membered macrolides tylosin and tilmicosin by Mycoplasma bovis.

    Science.gov (United States)

    Lerner, Uri; Amram, Eytan; Ayling, Roger D; Mikula, Inna; Gerchman, Irena; Harrus, Shimon; Teff, Dina; Yogev, David; Lysnyansky, Inna

    2014-01-31

    The molecular mechanism of acquired resistance to the 16-membered macrolides tylosin (Ty) and tilmicosin (Tm) was investigated in Mycoplasma bovis field isolates. Sequence analysis of domains II and V of the two 23S rRNA alleles and ribosomal proteins L4 and L22 was performed on 54 M. bovis isolates showing different minimal inhibitory concentrations (MIC). The presence of any one of the point mutations G748A, C752T, A2058G, A2059G or A2059C (Escherichia coli numbering) in one or both alleles of the 23S rRNAs was correlated with decreased susceptibility to Ty (8-1024 μg/ml) and to Tm (32 to >256 μg/ml) in 27/27 and 27/31 M. bovis isolates, respectively. Although a single mutation in domain II or V could be sufficient to cause decreased susceptibility to Ty, our data imply that a combination of mutations in two domains is necessary to achieve higher MICs (≥ 128 μg/ml). The influence of a combination of mutations in two domains II and V on enhancement of resistance to Tm was less clear. In addition, the amino acid (aa) substitution L22-Q90H was found in 24/32 representative M. bovis isolates with different MICs, but no correlation with decreased susceptibility to Ty or Tm was identified. Multiple aa substitutions were also identified in the L4 protein, including at positions 185-186 (positions 64 and 65 in E. coli) which are adjacent to the macrolide-binding site. This is the first description of the molecular mechanism of acquired resistance to the 16-membered macrolides in M. bovis. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Determination of macrolide antibiotics in chicken tissues by liquid chromatography-electrospray mass spectrometry

    Science.gov (United States)

    Salikin, Jamilah; Abdullah, Aminah

    2013-11-01

    A methodusingliquid chromatography-electrospray mass spectrometry (LC-(ESI)MS) for the simultaneous determination of three macrolides (tylosin, spiramycin and tilmicosin) in poultry muscle has been developed. The drugs were extracted with EDTA McIlvaine buffer, filter through celite 545 and the extracts were cleaned up by SPE Oasis HLB cartridge. Separation was carried out in end-capped silica-based C18 column and mobile phases containing trifluoroacetic acid-acetonitrile with a binary gradient system at a flow rate 0.5 ml/min. Detection was performed by single mass spectrometry with electrospray ionization in the positive mode. Several parameters affecting the mass spectra were studied. Chicken samples from the market were analyzed to check the residue of macrolide antibiotics.

  20. In vitro activity of telithromycin against Spanish Streptococcus pneumoniae isolates with characterized macrolide resistance mechanisms.

    Science.gov (United States)

    Morosini, M I; Cantón, R; Loza, E; Negri, M C; Galán, J C; Almaraz, F; Baquero, F

    2001-09-01

    The susceptibilities to telithromycin of 203 Streptococcus pneumoniae isolates prospectively collected during 1999 and 2000 from 14 different geographical areas in Spain were tested and compared with those to erythromycin A, clindamycin, quinupristin-dalfopristin, penicillin G, cefotaxime, and levofloxacin. Telithromycin was active against 98.9% of isolates (MICs, MICs at which 90% of isolates are inhibited being 0.06 microg/ml, irrespective of the resistance genotype. The corresponding values for erythromycin were 61.0% (MICs, 64 microg/ml. The erm(B) gene (macrolide-lincosamide-streptogramin B resistance phenotype) was detected in 36.4% (n = 74) of the isolates, which corresponded to 93.6% of erythromycin-intermediate and -resistant isolates, whereas the mef(A) gene (M phenotype [resistance to erythromycin and susceptibility to clindamycin and spiramycin without blunting]) was present in only 2.4% (n = 5) of the isolates. One of the latter isolates also carried erm(B). Interestingly, in one isolate for which the erythromycin MIC was 2 microg/ml, none of these resistance genes could be detected. Erythromycin MICs for S. pneumoniae erm(B)-positive isolates were higher (range, 0.5 to >64 microg/ml) than those for erm(B)- and mef(A)-negative isolates (range, 0.008 to 2 microg/ml). The corresponding values for telithromycin were lower for both groups, with ranges of 0.004 to 1 and 0.002 to 0.06 microg/ml, respectively. The erythromycin MIC was high for a large number of erm(B)-positive isolates, but the telithromycin MIC was low for these isolates. These results indicate the potential usefulness of telithromycin for the treatment of infections caused by erythromycin-susceptible and -resistant S. pneumoniae isolates when macrolides are indicated.

  1. Insights into resistance mechanism of the macrolide biosensor protein MphR(A) binding to macrolide antibiotic erythromycin by molecular dynamics simulation

    Science.gov (United States)

    Feng, Tingting; Zhang, Yanjun; Ding, Jing-Na; Fan, Song; Han, Ju-Guang

    2015-12-01

    Macrolide biosensor protein MphR(A) has been known as a key regulatory protein in metabolite sensing and genetic expression regulating. MphR(A) protein binds to macrolide antibiotic erythromycin (Ery) and releases the gene operon, thus activates expression of the mphA gene and initiates Ery resistance. The two mutant amino acid residues (V66L and V126L) might potentially disrupt Ery binding to MphR(A). In these studies, the binding of macrolide antibiotic Ery to wild type (Wt) MphR(A) and double mutant (V66L/V126L) MphR(A) are explored by molecular dynamics simulations. Compared to the Apo-MphR(A) protein and Wt-MphR(A)-Ery complex, many interesting effects owing to the double mutant (V66L/V126L) are discovered. In the case of Ery, Helix I which plays an important role in transcription shows itself a right-hand α helix in Wt-MphR(A)-Ery, whereas the activated helix is broken down in double mutant-V66L/V126L-MphR(A)-Ery. The calculated results exhibit that the double mutant V66L/V126L reduces the binding affinity of the V66L/V126L-MphR(A) to Ery, resulting in the block of Ery resistance. The binding free energy decomposition analysis reveals that the decrease of the binding affinity for the variant V66L/V126L-MphR(A)-Ery is mainly attributed to the gas phase electrostatic energies. The residue Leu66, Thr154, and Arg122 enhance the binding affinity of V66L/V126L-MphR(A) to Ery. The residues Tyr103 and His147 contributes mainly to binding energies in the Wt-MphR(A)-Ery complex, whereas the two residues have no contribution to the binding free energy inV66L/V126L-MphR(A)-Ery complex. Our study gives useful insights into the nature of amino acids mutation effect, the mechanism of blocking drug resistance at the atomic level and the characteristics in binding affinity for Ery to double mutant (V66L/V126L) MphR(A), which will contribute to the design of more effective macrolide antibiotics.

  2. Insights into resistance mechanism of the macrolide biosensor protein MphR(A) binding to macrolide antibiotic erythromycin by molecular dynamics simulation.

    Science.gov (United States)

    Feng, Tingting; Zhang, Yanjun; Ding, Jing-Na; Fan, Song; Han, Ju-Guang

    2015-12-01

    Macrolide biosensor protein MphR(A) has been known as a key regulatory protein in metabolite sensing and genetic expression regulating. MphR(A) protein binds to macrolide antibiotic erythromycin (Ery) and releases the gene operon, thus activates expression of the mphA gene and initiates Ery resistance. The two mutant amino acid residues (V66L and V126L) might potentially disrupt Ery binding to MphR(A). In these studies, the binding of macrolide antibiotic Ery to wild type (Wt) MphR(A) and double mutant (V66L/V126L) MphR(A) are explored by molecular dynamics simulations. Compared to the Apo-MphR(A) protein and Wt-MphR(A)-Ery complex, many interesting effects owing to the double mutant (V66L/V126L) are discovered. In the case of Ery, Helix I which plays an important role in transcription shows itself a right-hand α helix in Wt-MphR(A)-Ery, whereas the activated helix is broken down in double mutant-V66L/V126L-MphR(A)-Ery. The calculated results exhibit that the double mutant V66L/V126L reduces the binding affinity of the V66L/V126L-MphR(A) to Ery, resulting in the block of Ery resistance. The binding free energy decomposition analysis reveals that the decrease of the binding affinity for the variant V66L/V126L-MphR(A)-Ery is mainly attributed to the gas phase electrostatic energies. The residue Leu66, Thr154, and Arg122 enhance the binding affinity of V66L/V126L-MphR(A) to Ery. The residues Tyr103 and His147 contributes mainly to binding energies in the Wt-MphR(A)-Ery complex, whereas the two residues have no contribution to the binding free energy inV66L/V126L-MphR(A)-Ery complex. Our study gives useful insights into the nature of amino acids mutation effect, the mechanism of blocking drug resistance at the atomic level and the characteristics in binding affinity for Ery to double mutant (V66L/V126L) MphR(A), which will contribute to the design of more effective macrolide antibiotics.

  3. Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027.

    Science.gov (United States)

    Wieczorkiewicz, Jeffrey T; Lopansri, Bert K; Cheknis, Adam; Osmolski, James R; Hecht, David W; Gerding, Dale N; Johnson, Stuart

    2015-11-02

    Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Macrolide and clindamycin resistance in Streptococcus milleri group isolates from the airways of cystic fibrosis patients.

    Science.gov (United States)

    Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Eshaghurshan, Christina S; Rabin, Harvey R; Surette, Michael G

    2010-07-01

    Organisms belonging to the Streptococcus milleri group (SMG) are known for their role in pyogenic infections but have recently been implicated as etiological agents of pulmonary exacerbation in adult patients with cystic fibrosis (CF). The prolonged exposure of CF patients to antibiotics prompted us to investigate the susceptibility profiles of 118 SMG isolates from the airways of CF patients to 12 antibiotics compared to 43 SMG isolates from patients with invasive infections. We found that approximately 60% of all isolates failed to grow using the standard medium for disc diffusion, Mueller-Hinton blood agar (MHBA), so we explored the usefulness of brain heart infusion (BHI) agar for susceptibility testing. Zone-of-inhibition comparisons between BHI and MHBA showed strong correlations for six antibiotics, and interpretations were similar for both medium types. For ceftriaxone and cefepime, both groups of isolates were highly susceptible. Tetracycline resistance levels were comparable between the two groups (22% in CF isolates and 17.4% in invasive isolates). However, more than half of the CF isolates were not susceptible to azithromycin, erythromycin, and clindamycin, compared to 11%, 13%, and 6.5% of invasive isolates, respectively. There were 5-fold and 8-fold increased risks of azithromycin and clindamycin resistance, respectively, for the isolates from the airways of CF patients relative to the invasive isolates. Macrolide resistance was strongly linked to chronic azithromycin therapy in CF patients. This study shows that BHI agar is a suitable alternative for antimicrobial susceptibility testing for the SMG and that SMG isolates from the airways of CF patients are more resistant to macrolides and clindamycin than strains isolated from patients with invasive infections.

  5. Synergy of four macrolide antibiotics with chloroquine against chloroquine-resistant Plasmodium falciparum in vitro.

    Science.gov (United States)

    Gershon, P; Howells, R E

    1986-01-01

    The antimalarial activity of four macrolide antibiotics was investigated against the multidrug resistant K1 strain of Plasmodium falciparum in vitro. ID50 (50% inhibitory concentration) values for erythromycin, spiramycin, tylosin tartrate and oleandomycin phosphate in 48-hour assays were 1.6 X 10(-4)M, 2.5 X 10(-5)M, 1.2 X 10(-5)M and 9 X 10(-6)M respectively, and in 96 hour assays were 10(-5)M, 2.6 X 10(-6)M, 2.6 X 10(-6) and 3 X 10(-6)M, respectively. Comparable values were obtained in assays in which drug effect was quantified from either parasite counts or 14C isoleucine incorporation. Each of the four macrolides displayed synergy with chloroquine at the IC90 (90% inhibitory concentration) level, but at the IC50 level synergy was either less pronounced or absent. For each combination this difference in the degree of synergy was significant at the 95% level of confidence. In replicate assays in which 3H hypoxanthine was the marker of drug effect, synergy between chloroquine and either erythromycin or spiramycin could not be detected.

  6. Phenotypic and genotypic study of macrolide, lincosamide and streptogramin B (MLSB) resistance in clinical isolates of Staphylococcus aureus in Tehran, Iran

    OpenAIRE

    Saderi, Horieh; Emadi, Behzad; Owlia, Parviz

    2011-01-01

    Summary Background Resistance to antimicrobial agents among Staphylococcus aureus is an increasing problem. Two common genes responsible for resistance to macrolide, lincosamide and streptogramin B (MLSB) antibiotics are the ermA and ermC genes. Three resistance phenotypes have been detected to these antibiotics: strains containing cMLSB (constitutive MLSB) and iMLSB (inducible MLSB), which are resistant to macrolide, lincosamide and streptogramin B antibiotics, and MS, which is only resistan...

  7. Fluoroquinolone and macrolide resistance in Campylobacter jejuni isolated from broiler slaughterhouses in southern Brazil.

    Science.gov (United States)

    Sierra-Arguello, Yuli M; Perdoncini, G; Morgan, R B; Salle, C T P; Moraes, H L S; Gomes, Marcos J P; do Nascimento, Vladimir Pinheiro

    2016-01-01

    Campylobacter jejuni is recognized as a leading cause of acute bacterial gastroenteritis in humans. The over-use of antimicrobials in the human population and in animal husbandry has led to an increase in antimicrobial-resistant infections, particularly with fluoroquinolones and macrolides. The aim of the present study was to provide information of the current status of antimicrobial resistance patterns in Campylobacter jejuni from poultry sources. Fifty strains were recovered from broiler slaughterhouses in Rio Grande do Sul state, Brazil, 2012. The strains were investigated for antimicrobial susceptibility against three agents (ciprofloxacin, nalidixic acid and erythromycin) by minimal inhibitory concentrations. The strains were analysed by polymerase chain reaction-restriction fragment length polymorphism for detection of the Thr-86 mutation that confers resistance to ciprofloxacin. In addition, all the strains were tested for the presence of efflux systems (cmeB gene) conferring antimicrobial resistance. The minimum inhibitory concentrations results showed that 98% of isolates were sensitive to erythromycin and most isolates were resistant to ciprofloxacin (94%) and nalidixic acid (90%). A complete correlation was observed between the minimum inhibitory concentrations and PCR-RFLP assay. Finally, the cmeB gene that is responsible for multidrug resistance was detected in 16 isolates out the 50 strains (32%).

  8. The macrolide antibiotic renaissance.

    Science.gov (United States)

    Dinos, George P

    2017-09-01

    Macrolides represent a large family of protein synthesis inhibitors of great clinical interest due to their applicability to human medicine. Macrolides are composed of a macrocyclic lactone of different ring sizes, to which one or more deoxy-sugar or amino sugar residues are attached. Macrolides act as antibiotics by binding to bacterial 50S ribosomal subunit and interfering with protein synthesis. The high affinity of macrolides for bacterial ribosomes, together with the highly conserved structure of ribosomes across virtually all of the bacterial species, is consistent with their broad-spectrum activity. Since the discovery of the progenitor macrolide, erythromycin, in 1950, many derivatives have been synthesised, leading to compounds with better bioavailability and acid stability and improved pharmacokinetics. These efforts led to the second generation of macrolides, including well-known members such as azithromycin and clarithromycin. Subsequently, in order to address increasing antibiotic resistance, a third generation of macrolides displaying improved activity against many macrolide resistant strains was developed. However, these improvements were accompanied with serious side effects, leading to disappointment and causing many researchers to stop working on macrolide derivatives, assuming that this procedure had reached the end. In contrast, a recent published breakthrough introduced a new chemical platform for synthesis and discovery of a wide range of diverse macrolide antibiotics. This chemical synthesis revolution, in combination with reduction in the side effects, namely, 'Ketek effects', has led to a macrolide renaissance, increasing the hope for novel and safe therapeutic agents to combat serious human infectious diseases. © 2017 The British Pharmacological Society.

  9. Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Alison H Skalet

    Full Text Available BACKGROUND: It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. METHODS AND FINDINGS: In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9% at baseline, to 46.9% (37.5%-57.5% at month 12 (p = 0.003. In control communities, azithromycin resistance was 9.2% (95% CI 6.7%-13.3% at month 12, significantly lower than the treated group (p < 0.0001. Penicillin resistance was identified in 0.8% (95% CI 0%-4.2% of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. CONCLUSIONS: This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting

  10. Molecular characterization of macrolide resistance of a Mycoplasma pneumoniae strain that developed during therapy of a patient with pneumonia

    Directory of Open Access Journals (Sweden)

    Roger Dumke

    2014-12-01

    Full Text Available The development of macrolide resistance that occurred during 3 days of therapy with azithromycin to treat Mycoplasma pneumoniae pneumonia in a paediatric patient is reported. After extended molecular characterization of strains, the parallel occurrence of clones showing the non-mutated wild-type 23S rRNA sequence as well as mutations A2063G and A2064G, which are both responsible for phenotypic resistance, was confirmed for the first time.

  11. In vitro activity of beta-lactams, macrolides, telithromycin, and fluoroquinolones against clinical isolates of Streptococcus pneumoniae: correlation between drug resistance and genetic characteristics.

    Science.gov (United States)

    Yamaguchi, Toshiyuki; Hashikita, Giichi; Takahashi, Shun; Itabashi, Akira; Yamazaki, Tsutomu; Maesaki, Shigefumi

    2005-10-01

    The in vitro activity of antimicrobial agents against Streptococcus pneumoniae was determined using 16 strains of penicillin-susceptible S. pneumoniae (PSSP) and 26 strains of penicillin intermediately resistant S. pneumoniae (PISP) + penicillin-resistant S. pneumoniae (PRSP) in Japan. The minimum inhibitory concentrations (MICs) of potent antibiotics, including eight beta-lactams (benzylpenicillin, ampicillin, cefotiam, cefepime, cefditoren, faropenem, panipenem, and biapenem), three macrolides (erythromycin, clarithromycin, and azithromycin), telithromycin, and three fluoroquinolones (ciprofloxacin, levofloxacin, and gatifloxacin), were determined. Twenty-three strains exhibited genetic variations at pbp1a + pbp2x + pbp2b, which are genetic-PRSP (g-PRSP). g-PISP strains accounted for 62.5% (10/16) of the PSSP strains. The existence of an abnormal pbp gene conferred not only penicillin resistance but resistance to cephems; however, panipenem and biapenem had potent in vitro efficacy against alterations. Regarding the macrolide resistance mechanisms (mefA or ermB): 16 isolates had only mefA, 18 isolates had ermB, and 2 isolates had both mefA and ermB. There was no correlation between the existence of an abnormal pbp gene and the existence of the mefA gene or the ermB gene.

  12. Prevalence of macrolide and fluoroquinolone resistance-mediating mutations in Mycoplasma genitalium in five cities in Russia and Estonia.

    Science.gov (United States)

    Shipitsyna, Elena; Rumyantseva, Tatiana; Golparian, Daniel; Khayrullina, Guzel; Lagos, Amaya C; Edelstein, Inna; Joers, Kai; Jensen, Jörgen S; Savicheva, Alevtina; Rudneva, Natalia; Sukhanova, Larisa; Kozlov, Roman; Guschin, Alexander; Unemo, Magnus

    2017-01-01

    Resistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date, internationally reported resistance surveillance data for M. genitalium strains circulating in Eastern Europe are entirely lacking. The aim of this study was to estimate the prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium in four cities in Russia and one in Estonia, 2013-2016. Consecutive urogenital samples found positive for M. genitalium during diagnostic testing were retrospectively analyzed for resistance-associated mutations in the 23S rRNA and parC genes using pyrosequencing and conventional Sanger sequencing, respectively. In total, 867 M. genitalium positive samples from 2013-2016 were analyzed. Macrolide resistance-associated mutations were detected in 4.6% of the samples from Russia (0.7-6.8% in different cities) and in 10% of the samples from Estonia. The mutations A2059G and A2058G were highly predominating in both Russia and Estonia, accounting together for 90.9% of the cases positive for nucleotide substitutions in the 23S rRNA gene. The rates of possible fluoroquinolone resistance-associated mutations were 6.2% in Russia (2.5-7.6% in different cities) and 5% in Estonia. The mutations S83I and S83N were the most frequent ones in Russia (24.4% each), whereas D87N highly predominated in Estonia (83.3% of all fluoroquinolone resistance-associated mutations). Approximately 1% of the samples in both countries harbored both macrolide and possible fluoroquinolone resistance-associated mutations, with A2058G and S83I being the most frequent combination (37.5%). The prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium was 4.6% and 6.2%, respectively, in Russia, and 10% and 5%, respectively, in Estonia. Despite the relatively low rates of macrolide and fluoroquinolone resistance in these countries, antimicrobial resistance

  13. Molecular basis of resistance to macrolides, lincosamides and streptogramins in Staphylococcus saprophyticus clinical isolates.

    Science.gov (United States)

    Le Bouter, Anne; Leclercq, Roland; Cattoir, Vincent

    2011-02-01

    The aim of this study was to evaluate the prevalence of resistance to macrolide-lincosamide-streptogramin (MLS) antibiotics as well as to assess the molecular basis of this resistance amongst 72 Staphylococcus saprophyticus urinary isolates collected from 2005 to 2009 in University Hospital of Caen (France). Of the 72 strains studied, 33 (45.8%) were resistant to at least one MLS antibiotic, including 24 (72.7%) with an M phenotype, 5 (15.2%) with an inducible MLS(B) phenotype, 3 (9.1%) with a combined M+L phenotype and 1 (3.0%) with an L phenotype. All isolates were susceptible to the combination of streptogramins A and B. The resistance genes erm(A), erm(B), erm(C), msr(A) and lnu(A) were detected alone in 0, 0, 5 (15.2%), 24 (72.7%) and 1 (3.0%) of the 33 MLS-resistant isolates, respectively, whereas 2 strains (6.1%) were positive for both msr(A) and lnu(A). All msr(A)-positive isolates exhibited an M phenotype, whereas all five erm(C)-positive and all three lnu(A)-positive strains displayed, respectively, an inducible MLS(B) phenotype and an L phenotype with a positive Hodge test. Plasmid analysis indicated that erm(C) and lnu(A) genes were borne by small-size plasmids (ca. 2.5 kb), whereas larger plasmids (30-90 kb) harboured msr(A). In conclusion, these findings show a high prevalence of MLS resistance in S. saprophyticus, which was mainly associated with the presence of the msr(A) gene. Since S. saprophyticus colonises the gastrointestinal tract, it may constitute an unexpected reservoir for MLS resistance genes, in particular msr(A), amongst coagulase-negative staphylococci.

  14. Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in pediatric patients

    Science.gov (United States)

    Koseki, Naoko; Kaiho, Miki; Ariga, Tadashi; Kikuta, Hideaki; Togashi, Takehiro; Oba, Koji; Morita, Keisuke; Nagano, Naoko; Nakanishi, Masanori; Hara, Kazuya; Hazama, Kyosuke; Watanabe, Toru; Yamanaka, Tatsuru; Sasaki, Satoshi; Furuyama, Hideto; Shibata, Mutsuo; Shida, Satoru; Ishizaka, Akihito; Tabata, Yuichi; Aoyagi, Hayato; Naito, Hiroyuki; Yoshioka, Mikio; Horino, Atsuko; Kenri, Tsuyoshi

    2017-01-01

    Objective To clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients. Methods A prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured. Results Mean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were <0.000125 and 0.001 μg/ml, respectively. The MIC90s of minocycline and tosufloxacin among the 27 isolates of MRMP were 1.0 and 0.25 μg/ml, respectively, and those among the 23 isolates of MSMP were 1.0 and 0.5 μg/ml, respectively. Conclusion Both minocycline and tosufloxacin showed good in vitro activities against MRMP. Minocycline, but not tosufloxacin, shortened the duration of fever in pediatric patients infected with MRMP compared to the duration of fever in patients treated with macrolides. PMID:28288170

  15. Macrolides from a Marine-Derived Fungus, Penicillium meleagrinum var. viridiflavum, Showing Synergistic Effects with Fluconazole against Azole-Resistant Candida albicans.

    Science.gov (United States)

    Okabe, Miki; Sugita, Takashi; Kinoshita, Kaoru; Koyama, Kiyotaka

    2016-04-22

    Two new 13-membered macrolides (1, 7), along with known 13-membered macrolides PF1163A, B, D, H, and F (2-6), were isolated from a strain of a marine-derived fungus, Penicillium meleagrinum var. viridiflavum. The structures of 1 and 7 were elucidated from spectroscopic data (NMR, MS, IR). Compounds 1-7 showed synergistic effects with fluconazole against azole-resistant Candida albicans by a checkerboard assay.

  16. Fate and transport of tylosin-resistant bacteria and macrolide resistance genes in artificially drained agricultural fields receiving swine manure.

    Science.gov (United States)

    Luby, Elizabeth M; Moorman, Thomas B; Soupir, Michelle L

    2016-04-15

    Application of manure from swine treated with antibiotics introduces antibiotics and antibiotic resistance genes to soil with the potential for further movement in drainage water, which may contribute to the increase in antibiotic resistance in non-agricultural settings. We compared losses of antibiotic-resistant Enterococcus and macrolide-resistance (erm and msrA) genes in water draining from plots with or without swine manure application under chisel plow and no till conditions. Concentrations of ermB, ermC and ermF were all >10(9)copies g(-1) in manure from tylosin-treated swine, and application of this manure resulted in short-term increases in the abundance of these genes in soil. Abundances of ermB, ermC and ermF in manured soil returned to levels identified in non-manured control plots by the spring following manure application. Tillage practices yielded no significant differences (p>0.10) in enterococci or erm gene concentrations in drainage water and were therefore combined for further analysis. While enterococci and tylosin-resistant enterococci concentrations in drainage water showed no effects of manure application, ermB and ermF concentrations in drainage water from manured plots were significantly higher (p<0.01) than concentrations coming from non-manured plots. ErmB and ermF were detected in 78% and 44%, respectively, of water samples draining from plots receiving manure. Although ermC had the highest concentrations of the three genes in drainage water, there was no effect of manure application on ermC abundance. MsrA was not detected in manure, soil or water. This study is the first to report significant increases in abundance of resistance genes in waters draining from agricultural land due to manure application.

  17. Progress on macrolide-resistant Streptcoccus pneumoniae%肺炎链球菌对大环内酯类抗生素耐药的现状

    Institute of Scientific and Technical Information of China (English)

    刘学欣; 胡志东

    2014-01-01

    Streptococcus pneumoniae is one of the main pathogenic bacteria of community acquired pneumonia.With the wide use of macrolide antibiotics,infection of macrolide-resistant Streptococcus pneumoniae is rising.The article reviews the macrolide-resistance status quo,the resistance mechanism,and the genotyping methods of Streptococcus pneumoniae.%肺炎链球菌是社区获得性肺炎的主要致病菌之一.随着大环内酯类抗生素的广泛应用,耐大环内酯类肺炎链球菌的感染日趋上升.现就目前临床肺炎链球菌对大环内酯类抗生素耐药的现状、机制及其分型方法作一综述.

  18. Invasive pneumococci before the introduction of pneumococcal conjugate vaccine in Turkey: antimicrobial susceptibility, serotype distribution, and molecular identification of macrolide resistance.

    Science.gov (United States)

    Altun, Hatice Uludag; Hascelik, Gülsen; Gür, Deniz; Eser, Özgen Köseoglu

    2015-02-01

    This study evaluates the antimicrobial susceptibilities and serotype distributions of invasive Streptococcus pneumoniae (SP) isolates identified in a Turkish hospital before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The susceptibilities of all isolates were determined by evaluating six antibiotics: penicillin (PEN), ceftriaxone (CRO), levofloxacin (LEV), erythromycin (ERY), clindamycin (CD), and vancomycin (VAN). Serotyping and amplification of macrolide resistance genes were performed. Sixteen (50%) and four (2%) isolates were resistant to PEN and LEV, respectively. No isolates demonstrated VAN resistance. Intermediate resistance to CRO was found in 4% of all invasive isolates. Twenty-three (12.6%) isolates were resistant to ERY. Four (2%) invasive SP isolates demonstrated multidrug resistance. Serogroups 3, 5, 6, 8, 9, and 23 were the most common in both age groups. The potential coverage rates of PCV7 and PCV13 were 44.1 and 66.1% in children and 39.8 and 71.5% in adults, respectively. Continuous surveillance of antimicrobial resistance is required.

  19. Treponema pallidum pallidum Genotypes and Macrolide Resistance Status in Syphilitic Lesions among Patients at 2 Sexually Transmitted Infection Clinics in Lima, Peru.

    Science.gov (United States)

    Flores, Juan Antonio; Vargas, Silver Keith; Leon, Segundo Ramos; Perez, Danny Giancarlo; Ramos, Lourdes Beatriz; Chow, Jeremy; Konda, Kelika Anne; Calvo, Gino Mauricio; Salvatierra, Hector J; Klaussner, Jeffrey D; Caceres, Carlos Fernando

    2016-07-01

    We report the circulating genotypes and the frequency of macrolide-resistance patterns among Treponema pallidum pallidum DNA isolated from syphilitic lesions from patients who attended 2 sexual health clinics in Lima, Peru. We implemented and used a molecular typing scheme to describe local T. pallidum pallidum strains. Among 14 specimens, subtype 14d/f was the most prevalent strain in 7 fully typed T. pallidum DNA specimens obtained from men who have sex with men and transgender women presenting with chancre-like lesions. No macrolide-resistance mutations were found in T. pallidum DNA from 10 lesions.

  20. Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000-2013.

    Science.gov (United States)

    Grad, Yonatan H; Harris, Simon R; Kirkcaldy, Robert D; Green, Anna G; Marks, Debora S; Bentley, Stephen D; Trees, David; Lipsitch, Marc

    2016-11-15

     Treatment of Neisseria gonorrhoeae infection is empirical and based on population-wide susceptibilities. Increasing antimicrobial resistance underscores the potential importance of rapid diagnostic tests, including sequence-based tests, to guide therapy. However, the usefulness of sequence-based diagnostic tests depends on the prevalence and dynamics of the resistance mechanisms.  We define the prevalence and dynamics of resistance markers to extended-spectrum cephalosporins, macrolides, and fluoroquinolones in 1102 resistant and susceptible clinical N. gonorrhoeae isolates collected from 2000 to 2013 via the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project.  Reduced extended-spectrum cephalosporin susceptibility is predominantly clonal and associated with the mosaic penA XXXIV allele and derivatives (sensitivity 98% for cefixime and 91% for ceftriaxone), but alternative resistance mechanisms have sporadically emerged. Reduced azithromycin susceptibility has arisen through multiple mechanisms and shows limited clonal spread; the basis for resistance in 36% of isolates with reduced azithromycin susceptibility is unclear. Quinolone-resistant N. gonorrhoeae has arisen multiple times, with extensive clonal spread.  Quinolone-resistant N. gonorrhoeae and reduced cefixime susceptibility appear amenable to development of sequence-based diagnostic tests, whereas the undefined mechanisms of resistance to ceftriaxone and azithromycin underscore the importance of phenotypic surveillance. The identification of multidrug-resistant isolates highlights the need for additional measures to respond to the threat of untreatable gonorrhea. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  1. Mutations determining mitomycin resistance in Bacillus subtilis.

    Science.gov (United States)

    Iyer, V N

    1966-12-01

    Iyer, V. N. (Microbiology Research Institute, Canada Department of Agriculture, Ottawa, Canada). Mutations determining mitomycin resistance in Bacillus subtilis. J. Bacteriol. 92:1663-1669. 1966.-The pattern of development of genetic resistance in Bacillus subtilis to mitomycin C was studied, and spontaneous single and multistep mutants were obtained. The transmission and expression of these mutations in sensitive strains proved possible by means of genetic transformation. The mutations were genetically studied in relation to a chromosomal mutation, mac-1, which confers resistance to the macrolide antibiotic erythromycin and which has been previously localized in the early-replicating segment of the B. subtilis chromosome. The results indicate that all of three primary mutations studied in this manner, as well as a secondary and tertiary mutation derived from one of the primary mutations, are clustered in this early-replicating segment. It appears that the secondary and tertiary mutations enhance the resistance conferred by the primary mutation, apparently without themselves conferring any resistance.

  2. Direct Detection of Macrolide Resistance in Mycoplasma genitalium Isolates from Clinical Specimens from France by Use of Real-Time PCR and Melting Curve Analysis

    Science.gov (United States)

    Touati, Arabella; Peuchant, Olivia; Jensen, Jorgen S.; Bébéar, Cécile

    2014-01-01

    Mycoplasma genitalium is a sexually transmitted organism commonly treated with azithromycin. However, macrolide resistance has been reported and is associated with point mutations in the 23S rRNA gene. To evaluate the prevalence of macrolide resistance in M. genitalium isolates from clinical specimens from France, we first used a previously reported high-resolution melting assay. Because susceptible and resistant M. genitalium isolates were hardly discriminated in M. genitalium-positive clinical specimens, we developed a new molecular assay for the rapid detection of macrolide resistance. An assay using real-time PCR based on fluorescence resonance energy transfer (FRET) coupled with melting curve analysis was designed. The assay was first validated on characterized macrolide-resistant M. genitalium isolates and then applied to 202 urogenital M. genitalium-positive specimens collected from 178 patients from France in 2011 and 2012. Resistant genotypes were confirmed by 23S rRNA gene sequencing. Among the 202 M. genitalium-positive specimens, 155 were amplified, demonstrating a sensitivity of 76.7%. A substitution in the 23S rRNA gene was found in 14.2% of the patient samples. Nine and six patients had M. genitalium isolates with a substitution at positions 2059 and 2058, respectively. In four cases, a mixed population of wild-type and mutated M. genitalium isolates was observed. The prevalence of M. genitalium macrolide resistance has been stable in France since its detection in 2006. Our FRET PCR assay is able to discriminate between wild-type and resistant genotypes directly from clinical specimens. This assay will allow clinicians to shorten the time to the initiation of effective disease treatment. PMID:24574291

  3. Development of an endpoint genotyping assay to detect the Mycoplasma pneumoniae 23S rRNA gene and distinguish the existence of macrolide resistance-associated mutations at position 2063.

    Science.gov (United States)

    Suzuki, Yu; Seto, Junji; Shimotai, Yoshitaka; Ikeda, Tatsuya; Yahagi, Kazue; Mizuta, Katsumi; Matsuzaki, Yoko; Hongo, Seiji

    2016-12-01

    The prevalence of macrolide-resistant Mycoplasma pneumoniae harboring a mutation in the 23S rRNA gene is increasing, and rapid detection assays are needed for clinical management. We developed an endpoint genotyping assay to detect the M. pneumoniae 23S rRNA gene and determine the existence of macrolide resistance-associated mutations at position 2063 (A2063G, A2063T and A2063C mutations). This A2063B genotyping assay detected more than 50 copies/reaction of the M. pneumoniae gene in every nucleotide mutation at position 2063. Of 42 clinical specimens, 3 were positive without mutation, 6 were positive with the A2063G mutation, and 33 were negative. The results were confirmed using nested PCR with the sequencing of the M. pneumoniae 23S rRNA gene, and a high sensitivity (90%), specificity (100%), and coincidence ratio (kappa coefficient=0.93) were obtained. Therefore, the A2063B genotyping assay is useful for the rapid discrimination of macrolide resistance mutations at position 2063.

  4. Emergence of macrolide resistance gene mph(B) in Streptococcus uberis and cooperative effects with rdmC-like gene.

    Science.gov (United States)

    Achard, Adeline; Guérin-Faublée, Véronique; Pichereau, Vianney; Villers, Corinne; Leclercq, Roland

    2008-08-01

    Streptococcus uberis UCN60 was resistant to spiramycin (MIC = 8 microg/ml) but susceptible to erythromycin (MIC = 0.06 microg/ml), azithromycin (MIC = 0.12 microg/ml), josamycin (MIC = 0.25 microg/ml), and tylosin (MIC = 0.5 microg/ml). A 2.5-kb HindIII fragment was cloned from S. uberis UCN60 DNA on plasmid pUC18 and introduced into Escherichia coli AG100A, where it conferred resistance to spiramycin by inactivation. The sequence analysis of the fragment showed the presence of an rdmC-like gene that putatively encoded a protein belonging to the alpha/beta hydrolase family and of the first 196 nucleotides of the mph(B) gene putatively encoding a phosphotransferase known to inactivate 14-, 15-, and 16-membered macrolides in E. coli. The entire mph(B) gene was then identified in S. uberis UCN60. The two genes were expressed alone or in combination in E. coli, Staphylococcus aureus, and Enterococcus faecalis. Analysis of MICs revealed that rdmC-like alone did not confer resistance to erythromycin, tylosin, and josamycin in those three hosts. It conferred resistance to spiramycin in E. coli and E. faecalis but not in S. aureus. mph(B) conferred resistance in E. coli to erythromycin, tylosin, josamycin, and spiramycin but only low levels of resistance in E. faecalis and S. aureus to spiramycin (MIC = 8 microg/ml). The combination of mph(B) and rdmC-like genes resulted in a resistance to spiramycin and tylosin in the three hosts that significantly exceeded the mere addition of the resistance levels conferred by each resistance mechanism alone.

  5. Simple methods for the qualitative identification and quantitative determination of macrolide antibiotics.

    Science.gov (United States)

    Danielson, N D; Holeman, J A; Bristol, D C; Kirzner, D H

    1993-02-01

    Pyrolysis-gas chromatography is shown to be a rapid straightforward method for the qualitative differentiation of the macrolide antibiotics erythromycin, oleandomycin, troleandomycin, spiramycin and tylosin. Organic salts do not interfere and identification of erythromycin and troleandomycin in commercial products is viable. Spectrophotometric quantitation of these same five antibiotics after reaction with concentrated sulphuric acid is studied at about 470 nm. Reaction conditions such as acid concentration, time and temperature are provided. The sugar moieties of the antibiotics are proposed as the reactive sites. Detection limits are about 0.2-1.0 microg ml-1 [corrected] and analysis of pharmaceutical products should be possible.

  6. In vivo spread of macrolide-lincosamide-streptogramin B (MLSB) resistance--a model study in chickens.

    Science.gov (United States)

    Marosevic, D; Cervinkova, D; Vlkova, H; Videnska, P; Babak, V; Jaglic, Z

    2014-07-16

    The influence of specific and non-specific antibiotic pressure on in vivo spread of macrolide-lincosamide-streptogramin B (MLSB) resistance was evaluated in this study. Chickens repeatedly inoculated with Enterococcus faecalis harbouring the plasmid pAMβ1 carrying the erm(B) gene were perorally treated for one week with tylosin, lincomycin (both specific antibiotic pressure) and chlortetracycline (non-specific antibiotic pressure). Antibiotic non-treated but E. faecalis inoculated chickens served as a control. To quantify the erm(B) gene and characterise intestinal microflora, faecal DNA was analysed by qPCR and 454-pyrosequencing. Under the pressure of antibiotics, a significant increase in erm(B) was observed by qPCR. However, at the final stage of the experiment, an increase in erm(B) was also observed in two out of five non-treated chickens. In chickens treated with tylosin and chlortetracycline, the increase in erm(B) was accompanied by an increase in enterococci. However, E. faecalis was at the limit of detection in all animals. This suggests that the erm(B) gene spread among the gut microbiota other than E. faecalis. Pyrosequencing results indicated that, depending on the particular antibiotic pressure, different bacteria could be responsible for the spread of MLSB resistance. Different species of MLSB-resistant enterococci and streptococci were isolated from cloacal swabs during and after the treatment. PFGE analysis of MLSB-resistant enterococci revealed four clones, all differing from the challenge strain. All of the MLSB-resistant isolates harboured a plasmid of the same size as pAMβ1. This study has shown that MLSB resistance may spread within the gut microbiota under specific and non-specific pressure and even in the absence of any antimicrobial pressure. Finally, depending on the particular antibiotic pressure, different bacterial species seems to be involved in the spread of MLSB resistance.

  7. Determination of Macrolide Antibiotics Using Dispersive Liquid-Liquid Microextraction Followed by Surface-Assisted Laser Desorption/Ionization Mass Spectrometry

    Science.gov (United States)

    Chen, Kuan-Yu; Yang, Thomas C.; Chang, Sarah Y.

    2012-06-01

    A novel method for the determination of macrolide antibiotics using dispersive liquid-liquid microextraction coupled to surface-assisted laser desorption/ionization mass spectrometric detection was developed. Acetone and dichloromethane were used as the disperser solvent and extraction solvent, respectively. A mixture of extraction solvent and disperser solvent were rapidly injected into a 1.0 mL aqueous sample to form a cloudy solution. After the extraction, macrolide antibiotics were detected using surface-assisted laser desorption/ionization mass spectrometry (SALDI/MS) with colloidal silver as the matrix. Under optimum conditions, the limits of detection (LODs) at a signal-to-noise ratio of 3 were 2, 3, 3, and 2 nM for erythromycin (ERY), spiramycin (SPI), tilmicosin (TILM), and tylosin (TYL), respectively. This developed method was successfully applied to the determination of macrolide antibiotics in human urine samples.

  8. Regimen analysis of children infected by macrolide-resistant mycoplasma pneumoniae%耐药肺炎支原体感染患儿的用药分析

    Institute of Scientific and Technical Information of China (English)

    王穗琼; 王豫; 邓文喻; 张琳

    2013-01-01

    Objective To explore the regimen of children infected by macrolide - resistant mycoplasma pneumoniae. Methods The regimens were analyzed of children whose throat swab mycoplasma pneumoniae cultures were positive, from November 2010 to May 2012 in our hospital. And the courses of medications were returned visits. Results There were 116 children whose throat swab mycoplasma pneumoniae cultures were positive. All of them took macrolide antibacterial agents. In addition to three children combined (3-lactam antibacterials, there were 49 children in the drug - resistant group of 52 children infected by macrolide - resistant mycoplasma pneumoniae. There were 64 children in the drug - susceptive group. No significant differences were found in sex, age, usage rates of macrolide antibacterial agents, antipyretic drugs, antihistamines and phlegm drugs, P > 0. 05. Compared to drug - susceptive group, the courses of macrolide antibacterial agents were shorter, and antipyretic drugs, antihistamine drugs and apophlegmatisants were longer in the drug -resistant group, P < 0. 05. Conclusions The children infected by macrolide - resistant mycoplasma pneumoniae treated by antipyretic drugs, antihistamine drugs and apophlegmatisants. Compared to the children infected by macrolide - susceptive mycoplasma pneumoniae, the children infected by macrolide - resistant had shorter course of macrolide antibacterial agents, and longer courses of antipyretic drugs, antihistamine drugs and apophlegmatisants.%目的 探讨耐大环内酯类抗菌药的肺炎支原体感染患儿的用药方案.方法 分析2010年11月至2012年5月广东省妇幼保健院收治的咽拭子肺炎支原体培养阳性患儿的用药方案,并回访用药疗程.结果 MP培养阳性患儿116例均使用了大环内酯类抗菌药抗感染治疗,其中耐药52例,除去3例联合了β内酰胺类抗菌药,耐药组为49例;敏感组为64例,没有联合β内酰胺类抗菌药病例.两组

  9. Associations between capsular serotype, multilocus sequence type, and macrolide resistance in Streptococcus agalactiae isolates from Japanese infants with invasive infections.

    Science.gov (United States)

    Morozumi, M; Wajima, T; Kuwata, Y; Chiba, N; Sunaoshi, K; Sugita, K; Sakata, H; Iwata, S; Ubukata, K

    2014-04-01

    SUMMARY Streptococcus agalactiae (group B streptococcus; GBS) isolates (n = 150) from infants with invasive infections between 2006 and 2011 were analysed for capsular serotype, multilocus sequence type, and antibiotic susceptibility. In cases with late-onset disease (n = 115), primary meningitis was predominant (62.6%), but represented only 39.1% in cases with early-onset disease (n = 23). The most common serotype was III (58.7%), followed by Ia (21.3%) and Ib (12.7%). Sequence types (STs) of serotype III strains included ST17 (50.0%), ST19 (26.1%), ST335 (18.2%), ST27 (4.5%), and ST1 (1.1%). Predominant STs of serotypes Ia and Ib were ST23 (81.3%) and ST10 (84.2%), respectively. No penicillin-resistant strains were detected, but 22·0% of strains had mef(A/E), erm(A), or erm(B) genes, which mediate macrolide resistance. A new ST335, possessing an mef(A/E) gene belonging to clonal complex 19 gradually increased in frequency. Improved prevention of invasive GBS infections in infants requires timely identification, and ultimately vaccine development.

  10. Rapid assay of A2058T-mutated 23S rRNA allelic profiles associated with high-level macrolide resistance in Moraxella catarrhalis.

    Science.gov (United States)

    Saito, Ryoichi; Kasai, Ayako; Ogihara, Shinji; Yamada, Kageto; Tao, Kazuyuki

    2015-09-01

    We report on a restriction fragment-length polymorphism (HpyCH4III) assay for profile analysis of 23S rRNA gene A2058T-mutated alleles associated with high-level macrolide resistance in Moraxella catarrhalis. Our assay results were supported by DNA sequencing analysis, allowed for simultaneous testing of many strains, and produced results from pure-cultured colonies within 4 h.

  11. A Novel erm(44) Gene Variant from a Human Staphylococcus saprophyticus Isolate Confers Resistance to Macrolides and Lincosamides but Not Streptogramins.

    Science.gov (United States)

    Strauss, Christian; Hu, Yanmin; Coates, Anthony; Perreten, Vincent

    2017-01-01

    A novel erm(44) gene variant, erm(44)v, has been identified by whole-genome sequencing in a Staphylococcus saprophyticus isolate from the skin of a healthy person. It has the particularity to confer resistance to macrolides and lincosamides but not to streptogramin B when expressed in S. aureus The erm(44)v gene resides on a 19,400-bp genomic island which contains phage-associated proteins and is integrated into the chromosome of S. saprophyticus.

  12. Study on mechanism of macrolide resistance in Streptococcus pneumoniae%肺炎链球菌对大环内酯类的耐药机制研究

    Institute of Scientific and Technical Information of China (English)

    余素飞; 厉世笑; 傅鹰; 陈慧红; 朱海燕; 陈文娴; 张慧娜

    2012-01-01

    OBJECTIVE To investigate the antimicrobial susceptibility of Streptococcus pneumaniae isolated in Taizhou Hospital and their mechanisms of resistance to erythromycin so as to guide the rational use of drug in clinic. METHODS Antimicrobial susceptibility of 31 strains of S. Pneumoniae was determined by KB disk diffusion method and VITEK identification system. Phenotypes of macrolide-resistant S. Pneumoniae were determined using double disk test with erythromycin. ermB, mefA genes were amplified by PCR and sent for sequencing. RESULTS The antimicrobial susceptibility results showed that of the 31 S, pneumoniae isolates, the resistance rates to erythromycin, sulfamethoxazole, and tetracycline were 100. 0% , 64. 5% , 32. 2%, respectively. No strain was resistant to penicillin, vancomycin and teicoplanin. 31 clinical isolates were of the constitutive resistance phenotype. All erythromycin-resistant isolates had ermB ( + )/me/A( + ) genes. CONCLUSION The resistance of S. Pneumoniae to erythromycin is serious in Taizhou Hospital. Target modification by erm rnethylase and gene modification by mef efflux pump are the main mechanism of macrolide-resistance in S. Pneumoniae isolates.%目的 探讨台州医院肺炎链球菌临床分离株的耐药性及对红霉素的耐药机制,为临床用药提供依据.方法 收集临床分离的肺炎链球菌31株,运用K-B纸片法及VITEK细菌鉴定仪检测其对抗菌药物的药敏谱;通过纸片法筛选对大环内酯类抗菌药物(红霉素)的耐药表型,PCR扩增红霉素耐药基因:ermB、mefA,并送测序鉴定.结果 K-B法纸片药敏结果显示,肺炎链球菌临床分离株主要对红霉素、磺胺甲噁唑/甲氧苄啶和四环素耐药,耐药率分别为:100.0%、64.5%、32.2%;未发现有对青霉素、万古霉素及替考拉宁耐药的菌株;31株肺炎链球菌临床分离株耐药表型均为组成型耐药;31株红霉素耐药菌株的基因均为ermB(+)/mefA(+),测序结果正确.结论

  13. High Prevalence of Macrolide-resistance and Molecular Characterization of Streptococcus pyogenes Isolates Circulating in China from 2009 to 2016.

    Science.gov (United States)

    Lu, Binghuai; Fang, Yujie; Fan, Yanyan; Chen, Xingchun; Wang, Junrui; Zeng, Ji; Li, Yi; Zhang, Zhijun; Huang, Lei; Li, Hongxia; Li, Dong; Zhu, Fengxia; Cui, Yanchao; Wang, Duochun

    2017-01-01

    Streptococcus pyogenes, or group A Streptococcus, is a pathogen responsible for a wide range of clinical manifestations, from mild skin and soft tissue infections and pharyngitis to severe diseases. Its epidemiological characteristics should be comprehensively under surveillance for regulating the national prevention and treatment practice. Herein, a total of 140 S. pyogenes, including 38 invasive and 102 noninvasive isolates, were collected from infected patients in 10 tertiary general hospitals from 7 cities/provinces in China during the years 2009-2016. All strains were characterized by classical and molecular techniques for its emm types/subtypes, virulent factors and antibiotic resistance profiling. Of 140 isolates, 15 distinct emm types and 31 subtypes were detected, dominated by emm12 (60 isolates, 42.9%), emm1(43, 30.7%), and emm89 (10, 7.1%), and 8 new emm variant subtypes were identified. All strains, invasive or not, harbored the superantigenic genes, speB and slo. The other virulence genes, smeZ, speF, and speC accounted for 96.4, 91.4, and 87.1% of collected isolates, respectively. Further multilocus sequence typing (MLST) placed all strains into 22 individual sequence types (STs), including 4 newly-identified STs (11, 7.9%). All isolates were phenotypically susceptible to penicillin, ampicillin, cefotaxime, and vancomycin, whereas 131(93.5%), 132(94.2%), and 121(86.4%) were resistant to erythromycin, clindamycin, and tetracycline, respectively. Our study highlights high genotypic diversity and high prevalence of macrolide resistance of S. pyogenes among clinical isolates circulating in China.

  14. High Prevalence of Macrolide-resistance and Molecular Characterization of Streptococcus pyogenes Isolates Circulating in China from 2009 to 2016

    Directory of Open Access Journals (Sweden)

    Binghuai Lu

    2017-06-01

    Full Text Available Streptococcus pyogenes, or group A Streptococcus, is a pathogen responsible for a wide range of clinical manifestations, from mild skin and soft tissue infections and pharyngitis to severe diseases. Its epidemiological characteristics should be comprehensively under surveillance for regulating the national prevention and treatment practice. Herein, a total of 140 S. pyogenes, including 38 invasive and 102 noninvasive isolates, were collected from infected patients in 10 tertiary general hospitals from 7 cities/provinces in China during the years 2009–2016. All strains were characterized by classical and molecular techniques for its emm types/subtypes, virulent factors and antibiotic resistance profiling. Of 140 isolates, 15 distinct emm types and 31 subtypes were detected, dominated by emm12 (60 isolates, 42.9%, emm1(43, 30.7%, and emm89 (10, 7.1%, and 8 new emm variant subtypes were identified. All strains, invasive or not, harbored the superantigenic genes, speB and slo. The other virulence genes, smeZ, speF, and speC accounted for 96.4, 91.4, and 87.1% of collected isolates, respectively. Further multilocus sequence typing (MLST placed all strains into 22 individual sequence types (STs, including 4 newly-identified STs (11, 7.9%. All isolates were phenotypically susceptible to penicillin, ampicillin, cefotaxime, and vancomycin, whereas 131(93.5%, 132(94.2%, and 121(86.4% were resistant to erythromycin, clindamycin, and tetracycline, respectively. Our study highlights high genotypic diversity and high prevalence of macrolide resistance of S. pyogenes among clinical isolates circulating in China.

  15. Biofilm formation by Rhodococcus equi and putative association with macrolide resistance

    Directory of Open Access Journals (Sweden)

    Letícia T. Gressler

    2015-10-01

    Full Text Available Abstract: Rhodococcus equi is a facultative intracellular pathogen, which cause severe pyogranulomatous pneumonia in foals and tuberculosis-like lesions in humans. Its ability to form biofilm was described in strains isolated from chronic diseases associated to treatment failures in humans. This study aimed to verify the biofilm formation by 113 R. equi isolated from equine samples (clinical and fecal using two different methods (biofilm-culturing with and without additional glucose and epifluorescence microscopy. We also aimed to determine the efficacy of azithromycin, clarithromycin and erythromycin on R. equi in established biofilm. We found 80.5% (26/41 and 63% (58/72 biofilm-positive isolates, in fecal and clinical samples, respectively. The additional glucose increased the biofilm formation by R. equi fecal samples, but not by clinical samples. The antimicrobials tested herein were not able to eradicate R. equi in biofilm even at higher concentrations. This is the first study showing the biofilm formation by R. equi isolated from equine samples. Our findings indicate that R. equi biofilm-producers may be more resistant to the antimicrobials evaluated. Further studies are warranted to test this hypothesis.

  16. Characterization and transfer studies of macrolide resistance genes in Streptococcus pneumoniae from Denmark

    DEFF Research Database (Denmark)

    Nielsen, Karen L; Hammerum, Anette M; Lambertsen, Lotte M

    2010-01-01

    Over the last decade, erythromycin resistance has been increasing in frequency in Streptococcus pneumoniae in Denmark. In the present study, 49 non-related erythromycin-resistant S. pneumoniae isolates from invasive sites and 20 isolates from non-invasive sites were collected; antimicrobial...

  17. Streptococcus pneumoniae: the evolution of antimicrobial resistance to beta-lactams, fluoroquinolones and macrolides.

    Science.gov (United States)

    Cornick, J E; Bentley, S D

    2012-07-01

    Multi drug resistant Streptococcus pneumoniae constitute a major public health concern worldwide. In this review we discuss how the transformable nature of the pneumococcus, in parallel with antimicrobial induced stress, contributes to the evolution of antimicrobial resistance; and how the introduction of the pneumococcal conjugate vaccine has affected the situation.

  18. The lactococcal secondary multidrug transporter LmrP confers resistance to lincosamides, macrolides, streptogramins and tetracyclines

    NARCIS (Netherlands)

    Putman, M; van Veen, HW; Degener, JE; Konings, WN

    2001-01-01

    The active efflux of toxic compounds by (multi)drug transporters is one of the mechanisms that bacteria have developed to resist cytotoxic drugs. The authors describe the role of the lactococcal secondary multidrug transporter LmrP in the resistance to a broad range of clinically important antibioti

  19. Antimicrobial resistance determinant microarray for analysis of multi-drug resistant isolates

    Science.gov (United States)

    Taitt, Chris Rowe; Leski, Tomasz; Stenger, David; Vora, Gary J.; House, Brent; Nicklasson, Matilda; Pimentel, Guillermo; Zurawski, Daniel V.; Kirkup, Benjamin C.; Craft, David; Waterman, Paige E.; Lesho, Emil P.; Bangurae, Umaru; Ansumana, Rashid

    2012-06-01

    The prevalence of multidrug-resistant infections in personnel wounded in Iraq and Afghanistan has made it challenging for physicians to choose effective therapeutics in a timely fashion. To address the challenge of identifying the potential for drug resistance, we have developed the Antimicrobial Resistance Determinant Microarray (ARDM) to provide DNAbased analysis for over 250 resistance genes covering 12 classes of antibiotics. Over 70 drug-resistant bacteria from different geographic regions have been analyzed on ARDM, with significant differences in patterns of resistance identified: genes for resistance to sulfonamides, trimethoprim, chloramphenicol, rifampin, and macrolide-lincosamidesulfonamide drugs were more frequently identified in isolates from sources in Iraq/Afghanistan. Of particular concern was the presence of genes responsible for resistance to many of the last-resort antibiotics used to treat war traumaassociated infections.

  20. Macrolide susceptibility in Streptococcus pyogenes: monitoring of isolates collected from throat swabs for the period november 2003 to september 2006

    Directory of Open Access Journals (Sweden)

    Maria Gabriella Mazzarello

    2008-03-01

    Full Text Available Background: Streptococcus pyogenes can cause acute suppurative infections (tonsillitis and pharyngitis and serious complications like rheumatic fever or acute post-streptococcal glomerulonephritis. Antibiotic treatment of streptococcal infections is recommended and penicillin is the therapy of choice, moreover, macrolides represent an important alternative particularly for patients with ß-lactam-associated allergies. However, increasing resistance of S. pyogenes to macrolides has been observed in some European countries (especially in Spain and Italy in the last decade.This study was conducted to update our knowledge on this evolution. Materials and methods: A total of 128 clinical strains of S. pyogenes isolated from 933 throat swabs collected in the Clinical Microbiological Laboratory of Ovada (ASL 22 between November 2003 and September 2006 were tested for their susceptibility to erythromycin, clindamycin and rokitamycin. The phenotype of macrolide resistance was determined by the triple-disc diffusion test method (Giovanetti et al, 1999. Results: S. pyogenes strains isolated between November 2003 and December 2005 showed a percentage of macrolide-resistance of 15%; more precisely 9% with phenotype M and 6% with phenotype iMLS. Only 3 of the 28 isolates (10.7% collected between January-September 2006 were macrolide-resistant (phenotype M.All 128 isolates were fully susceptible to rokitamycin. Conclusion: Macrolide resistance rates determined in the present study were relatively low in comparison to the values registered in our country in the last decade. Efflux of the drug (phenotype M is the predominating mechanism. This type of resistance does not affect the activity of macrolides 16-membered (e.g. rokitamicin.However, changes of resistance rates and their prevailing mechanisms can occur rapidly. For safe empirical prescription of macrolides, further surveillance studies that include the identification of resistance mechanisms are required

  1. In vitro activity of six macrolides, clindamycin and tetracycline on Streptococcus pneumoniae with different penicillin susceptibilities.

    Science.gov (United States)

    Poulsen, R L; Knudsen, J D; Petersen, M B; Fuursted, K; Espersen, F; Frimodt-Møller, N

    1996-03-01

    A collection of 99 clinical isolates of Streptococcus pneumoniae, chosen due to their different susceptibilities to penicillin, were investigated with respect to their susceptibility to the macrolides azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin, and to clindamycin and tetracycline by the agar dilution method. We found complete cross resistance among the macrolides. The pneumococci were either susceptible, MIC MIC > or = 16 micrograms/ml, to the tested macrolides, giving a bimodal distribution. In addition, complete cross resistance was observed between clindamycin and macrolides. Pneumococci resistant to macrolides were also resistant to tetracycline, and 26% of the macrolide-susceptible strains were tetracycline resistant.

  2. In Vitro Activity of Telithromycin against Spanish Streptococcus pneumoniae Isolates with Characterized Macrolide Resistance Mechanisms

    OpenAIRE

    Morosini, María-Isabel; Cantón, Rafael; Loza, Elena; Negri, María-Cristina; Galán, Juan-Carlos; Almaraz, Felisa; Baquero, Fernando

    2001-01-01

    The susceptibilities to telithromycin of 203 Streptococcus pneumoniae isolates prospectively collected during 1999 and 2000 from 14 different geographical areas in Spain were tested and compared with those to erythromycin A, clindamycin, quinupristin-dalfopristin, penicillin G, cefotaxime, and levofloxacin. Telithromycin was active against 98.9% of isolates (MICs, ≤0.5 μg/ml), with MICs at which 90% of isolates are inhibited being 0.06 μg/ml, irrespective of the resistance genotype. The corre...

  3. Antimicrobial susceptibility of Mycoplasma pneumoniae and drug resistance mechanisms to macrolides%肺炎支原体对抗菌药物敏感性及对大环内酯类的耐药机制研究

    Institute of Scientific and Technical Information of China (English)

    赵茂茂; 宋波; 蒲增惠; 于红霞

    2014-01-01

    OBJECTIVE To investigate the prevalence of Mycoplasma pneumoniae infection in the adults and teenagers with community-acquired pneumonia (CAP) ,observe the drug susceptibility to the commonly used antibiotics ,and define the drug resistance mechanisms to the macrolides .METHODS From Oct 2010 to Mar 2012 , the throat swab specimens were collected during the acute stage to isolate and culture the M .pneumoniae .The molecular identification of the clinical isolates was performed by using polymerase-chain-reaction , the minimal inhibitory concentrations (MICs) of macrolides ,quinolones ,and tetracyclines were determined with the use of microdilution method .The 23S rRNA gene sequencing was performed for the macrolides-resistant strains and was compared with the gene sequencing of the standard strain MPFH (ATCC 15531) .RESULTS A total of 20 strains of M .pneumoniae have been isolated from the throat swab specimens obtained from the 129 CAP patients ,with the isolation rate of 15 .50% ;the strains were highly susceptible to tetracyclines and fluoroquinolones and were resistant to all the macrolides ,and both of the resistance mechanisms were the mutation of locus 2063 of 23 rRNA from A to G .CONCLUSIONS The situation of the drug resistance of M .pneumoniae to macrolides is harsh ,and the mutation of locus of the 23S rRNA is the major drug resistance mechanism .%目的:了解成人及青少年社区获得性肺炎(CAP)中肺炎支原体(MP)感染状况及其对常用抗菌药物的敏感性,明确M P对大环内酯类的耐药机制。方法2010年10月-2012年3月129例C A P患者取急性期咽拭子标本进行肺炎支原体分离培养,应用聚合酶链反应(PC R )对临床分离株进行分子鉴定;采用微量稀释法测定肺炎支原体对大环内酯类、喹诺酮类及四环素类抗菌药物的最低抑菌浓度(M IC );对大环内酯类耐药株进行23S rRNA 基因测序,并与标准菌株MPFH (ATCC 15531)基

  4. Evaluation of macrolide resistance and enhanced molecular typing of Treponema pallidum in patients with syphilis in Taiwan: a prospective multicenter study.

    Science.gov (United States)

    Wu, Hsiu; Chang, Sui-Yuan; Lee, Nan-Yao; Huang, Wen-Chi; Wu, Bing-Ru; Yang, Chia-Jui; Liang, Shiou-Haur; Lee, Chen-Hsiang; Ko, Wen-Chien; Lin, Hsi-Hsun; Chen, Yen-Hsu; Liu, Wen-Chun; Su, Yi-Ching; Hsieh, Chia-Yin; Wu, Pei-Ying; Hung, Chien-Ching

    2012-07-01

    Studies of macrolide resistance mutations and molecular typing using the newly proposed enhanced typing system for Treponema pallidum isolates obtained from HIV-infected patients in the Asia-Pacific region are scarce. Between September 2009 and December 2011, we conducted a survey to detect T. pallidum using a PCR assay using clinical specimens from patients with syphilis at six major designated hospitals for HIV care in Taiwan. The T. pallidum strains were genotyped by following the enhanced molecular typing methodology, which analyzed the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and the sequence of base pairs 131 to 215 in the tp0548 open reading frame of T. pallidum. Detection of A2058G and A2059G point mutations in the T. pallidum 23S rRNA was performed with the use of restriction fragment length polymorphism (RFLP). During the 2-year study period, 211 clinical specimens were obtained from 136 patients with syphilis. T. pallidum DNA was isolated from 105 (49.8%) of the specimens, with swab specimens obtained from chancres having the highest yield rate (63.2%), followed by plasma (49.4%), serum (35.7%), and cerebrospinal fluid or vitreous fluid (18.2%) specimens. Among the 40 fully typed specimens, 11 subtypes of T. pallidum were identified. Subtype 14f/f (18 isolates) was the most common isolates, followed by 14f/c (3), 14b/c (3), and 14k/f (3). Among the isolates examined for macrolide resistance, none had the A2058G or A2059G mutation. In conclusion, we found that type 14 f/f was the most common T. pallidum strain in this multicenter study on syphilis in Taiwan and that none of the isolates exhibited 23S rRNA mutations causing resistance to macrolides.

  5. 23S rRNA gene mutations contributing to macrolide resistance in Campylobacter jejuni and Campylobacter coli

    Science.gov (United States)

    Operon specific 23S rRNA mutations affecting minimum inhibitory concentrations (MICs) of macrolides (erythromycin [ERY], azithromycin [AZM], tylosin [TYL]) and a lincosamide (clindamycin [CLI]) were examined in a collection of Campylobacter jejuni and C. coli isolates. The three copies of the Campy...

  6. Novel spectrophotometric method for determination of some macrolide antibiotics in pharmaceutical formulations using 1,2-naphthoquinone-4-sulphonate

    Science.gov (United States)

    Ashour, Safwan; Bayram, Roula

    2012-12-01

    New, simple and rapid spectrophotometric method has been developed and validated for the assay of two macrolide drugs, azithromycin (AZT) and erythromycin (ERY) in pure and pharmaceutical formulations. The proposed method was based on the reaction of AZT and ERY with sodium 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline medium at 25 °C to form an orange-colored product of maximum absorption peak at 452 nm. All variables were studied to optimize the reaction conditions and the reaction mechanism was postulated. Beer's law was obeyed in the concentration range 1.5-33.0 and 0.92-8.0 μg mL-1 with limit of detection values of 0.026 and 0.063 μg mL-1 for AZT and ERY, respectively. The calculated molar absorptivity values are 4.3 × 104 and 12.3 × 104 L mol-1 cm-1 for AZT and ERY, respectively. The proposed methods were successfully applied to the determination of AZT and ERY in formulations and the results tallied well with the label claim. The results were statistically compared with those of an official method by applying the Student's t-test and F-test. No interference was observed from the concomitant substances normally added to preparations.

  7. Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France.

    Directory of Open Access Journals (Sweden)

    Claire Janoir

    Full Text Available In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7 lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002-2003 to the PCV13 era (2010-2011, both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315, which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter.

  8. The change of macrolide resistance rates in group A Streptococcus isolates from children between 2002 and 2013 in Asahikawa city.

    Science.gov (United States)

    Sakata, Hiroshi

    2015-05-01

    This study targeted patients in the Department of Pediatrics, Asahikawa Kosei Hospital, between January 2002 and December 2013. In patients suspected of having hemolytic streptococcal infection, Group A Streptococcus (GAS) strains isolated from a throat swab were examined for antimicrobial susceptibility testing. The MICs were measured by the broth microdilution method. The annual number of GAS strains examined for antimicrobial susceptibility testing ranged from 28 to 65 strains, for a total of 574 strains. Some of the isolates obtained from 2006 to 2009 and from 2011 to 2013 were analyzed to determine their emm types. An erythromycin (EM) resistant strain was not detected until 2004, but one EM-resistant strain appeared in 2005. Subsequently, EM-resistant strains rapidly increased, and 48 of 65 strains (73.8%) examined in 2009 were resistant. In 2010, the number of EM-resistant strains decreased to 12 of 36 strains (33.3%). However, it gradually increased afterwards, and 37 of 60 strains (61.7%) were resistant in 2013. Out of 574 strains examined, 184 exhibited EM-resistance, and the overall resistance rate was 31.9%. Partitioning the 124 strains examined between 2006 and 2008 according to emm types, only emm28 strains, which exhibited a high resistance rate, and emm12 strains demonstrated resistance. For the 142 strains examined between 2011 and 2013, the resistance rate of emm28 strains was similarly high; the resistance of emm12 strains significantly increased, and emm1 strains exhibited a high resistance rate. The number of emm types associated with the resistant strains increased. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Comparison of pyrosequencing, Sanger sequencing, and melting curve analysis for detection of low-frequency macrolide-resistant mycoplasma pneumoniae quasispecies in respiratory specimens.

    Science.gov (United States)

    Chan, Kwok-Hung; To, Kelvin K W; Chan, Betsy W K; Li, Clara P Y; Chiu, Susan S; Yuen, Kwok-Yung; Ho, Pak-Leung

    2013-08-01

    Macrolide-resistant Mycoplasma pneumoniae (MRMP) is emerging worldwide and has been associated with treatment failure. In this study, we used pyrosequencing to detect low-frequency MRMP quasispecies in respiratory specimens, and we compared the findings with those obtained by Sanger sequencing and SimpleProbe PCR coupled with a melting curve analysis (SimpleProbe PCR). Sanger sequencing, SimpleProbe PCR, and pyrosequencing were successfully performed for 96.7% (88/91), 96.7% (88/91), and 93.4% (85/91) of the M. pneumoniae-positive specimens, respectively. The A-to-G transition at position 2063 was the only mutation identified. Pyrosequencing identified A2063G MRMP quasispecies populations in 78.8% (67/88) of the specimens. Only 38.8% (26/67) of these specimens with the A2063G quasispecies detected by pyrosequencing were found to be A2063G quasispecies by Sanger sequencing or SimpleProbe PCR. The specimens that could be detected by SimpleProbe PCR and Sanger sequencing had higher frequencies of MRMP quasispecies (51% to 100%) than those that could not be detected by those two methods (1% to 44%). SimpleProbe PCR correctly categorized all specimens that were identified as wild type or mutant by Sanger sequencing. The clinical characteristics of the patients were not significantly different when they were grouped by the presence or absence of MRMP quasispecies, while patients with MRMP identified by Sanger sequencing more often required a switch from macrolides to an alternative M. pneumoniae-targeted therapy. The clinical significance of mutant quasispecies should be investigated further with larger patient populations and with specimens obtained before and after macrolide therapy.

  10. Surface-coated wooden-tip electrospray ionization mass spectrometry for determination of trace fluoroquinolone and macrolide antibiotics in water.

    Science.gov (United States)

    Deng, Jiewei; Yu, Tiantian; Yao, Yao; Peng, Qi; Luo, Lijuan; Chen, Baowei; Wang, Xiaowei; Yang, Yunyun; Luan, Tiangang

    2017-02-15

    In this study, a surface-coated wooden-tip electrospray ionization mass spectrometry (SCWT-ESI-MS) method was developed for rapid and sensitive analysis of trace fluoroquinolone and macrolide antibiotics in water. First, a SCWT solid-phase microextration (SPME) probe was prepared, via silanization and sulfonation for modification of a layer of adsorbent containing both C8-chain and sulfo group on the surface of wooden tips. Then, the SCWT-SPME probe was applied for extraction of trace fluoroquinolone and macrolide antibiotics in water. The specially designed adsorbent gave the probe desirable enrichment capacity towards fluoroquinolone and macrolide antibiotics, with enrichment factors of approximately 100-500 folds for six target analytes. After extraction, the loaded SCWT-SPME probe was directly applied for ambient MS analysis. With the application of a high voltage and some spray solvent on the SCWT-SPME probe, analytes enriched on the probe was desorbed and ionized for mass spectrometric analysis under ambient and open-air conditions. The method was sensitive, with limits of detection and quantification of 1.8-4.5 ng/L and 5.9-15.1 ng/L, respectively. The method also showed good linearity, with correlation coefficient values (r(2)) of no less than 0.9940 for six target analytes. The developed method was successfully applied for the analysis of six fluoroquinolone and macrolide antibiotics in tap and river water samples, and no antibiotic was found in tap water but some antibiotics were detected in river water with concentrations at dozens to hundreds nanogram-per-liter level. Standard addition experiments were also performed, and the obtained recoveries were 89-102% for tap waters and 82-92% for river waters, respectively. All the experimental results demonstrated that our proposed SCWT-ESI-MS method was rapid, sensitive, and reliable for analyzing trace antibiotics in water.

  11. High prevalence of erythromycin resistance and macrolide-resistance genes, mefA and ermB, in Streptococcus pneumoniae isolates from the upper respiratory tracts of children in the Sapporo district, Japan.

    Science.gov (United States)

    Harimaya, Atsushi; Yokota, Shin-ichi; Sato, Kiyoshi; Yamazaki, Norikazu; Himi, Tetsuo; Fujii, Nobuhiro

    2007-08-01

    Our previous study demonstrated that the frequency of penicillin-resistant Streptococcus pneumoniae (PRSP) was lower in our district than in districts in other Japanese studies. In this study, we investigated the prevalence of erythromycin resistance. The susceptibility to erythromycin and the distribution of the macrolide-resistance genes, mefA and ermB, were examined in S. pneumoniae isolates from the upper respiratory tracts of children in four cities in the Sapporo district, Hokkaido prefecture, Japan. Of the 156 isolates, 27 (17.3%) were erythromycin-sensitive, 6 (3.9%) were erythromycin-intermediately resistant, and 123 (78.9%) were erythromycin-resistant. Fifty-nine (37.8%) had the mefA gene, 89 (57.1%) had the ermB gene, and 129 (82.7%) had the mefA and/or the ermB gene. The ermB-positive isolates tended to show high resistance to erythromycin. Erythromycin-resistant isolates and the macrolide-resistance genes were often present in infants or younger children. The frequency of erythromycin-resistant isolates in the four cities was very high, ranging from 76.3% to 83. 3%, as high as the national average. Although erythromycin-resistant isolates generally tend to show cross-resistance to penicillin, the frequency of PRSP was very low in this study, as compared with other Japanese studies. Erythromycin resistance was frequently recognized not only in PRSP but also in penicillin-sensitive S. pneumoniae (PSSP) as well. In Japan, erythromycin resistance may have already become widespread, even in local areas where penicillin resistance is not especially prevalent.

  12. Characterization of Enterococcus faecium with macrolide resistance and reduced susceptibility to quinupristin/dalfopristin in a Japanese hospital: detection of extensive diversity in erm(B)-regulator regions.

    Science.gov (United States)

    Isogai, Nayuta; Urushibara, Noriko; Kawaguchiya, Mitsuyo; Ghosh, Souvik; Suzaki, Keisuke; Watanabe, Naoki; Quiñones, Dianelys; Kobayashi, Nobumichi

    2013-08-01

    Cross-resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics is mainly mediated by the erm (erythromycin ribosome methylation) genes that encode 23S rRNA methylases in enterococi, and various mechanisms are involved in the streptogramin B resistance. Prevalence of MLSB resistance and its genetic mechanisms were analyzed for a total of 159 strains of Enterococcus faecium isolated from clinical specimens in a university hospital in Japan from 1997 to 2006. Resistance to erythromycin (EM) and clindamycin was detected in 88.1% and 89.9% of all the strains examined, respectively, and expression of resistance was totally constitutive. Although none of the strain was resistant to quinupristin/dalfopristin (Q/D), 28 strains (17.6%) showed intermediate resistance to Q/D (MIC: 2 μg/ml). The erm(B) gene was detected in 139 strains (87.4%), and msrC was found in all the strains examined, whereas no other known MLSB resistance genes were identified. The erm(B) regulator region (RR) containing a coding region of the leader peptide was classified into 13 genetic variations (L1-L3, M, S1-S7, D, and R genotypes) in 56 strains. However, no relatedness was identified between the erm(B) RR genotype and EM resistance, or reduced susceptibility to Q/D, although most of Q/D-intermediate strains were assigned to the L1, L2, and S1 genotypes. Q/D-intermediate strains were classified into five multiple-locus variable-number tandem-repeat analysis (MLVA) types, including four types of clonal complex (CC)-C1, five sequence types (STs), including four STs of CC-17, and several resistance gene/virulence factor profiles. The present study revealed the occurrence of Q/D-intermediate E. faecium, which are composed of heterogeneous strains in Japan, and more genetic diversity in the erm(B) RRs than those reported previously.

  13. ANALYSIS OF STREPTOCOCCUS PNEUMONIA 'S DRUG RESISTANCE TO MACROLIDES%肺炎链球菌对大环内酯类耐药性分析

    Institute of Scientific and Technical Information of China (English)

    郁宝慧

    2015-01-01

    目的 探索郯城县区肺炎链球菌分离株对大环内酯类耐药性及其治疗情况.方法 收集郯城县社区和临床分离的肺炎链球菌 ,根据CLSI标准,用K-B法、Etest法检测肺炎链球菌对红霉素和克林霉素的耐药性及对红霉素的耐药表型.结果 493株肺炎链球菌中红霉素不敏感菌株489株 ,对克林霉素不敏感菌株482株,其中 ermB基因介导的红霉素耐药菌株482株 ,占98.6% , mefE基因介导的红霉素耐药菌株7株,占1.4%.结论 郯城县区对红霉素和克林霉素近乎全部耐药 ,ermB基因介导的靶位改变是郯城县区肺炎链球菌对大环内酯类抗菌药物的主要耐药机制.%Objective To explore streptococcus pneumonia's drug resistance to macrolides . Methods Samples of streptococcus pneumonia were collected from the communities in Tancheng County and the iso-lated ones from clinical treatment .According to the CLSI standard ,K-B method and Etest were used to detect streptococcus pneumonia ' s drug resistance to erythromycin and clindamycin and the resistance phenotype of erythromycin . Results In the 493 strains of streptococcus pneumonia ,489 strains were not sensi-tive to erythromycin ,482 strains were not sensitive to clindamycin .482 drug-resistant strains were mediated by ermB gene ,accounting for 98 .6% of all the strains .7 drug-resistant strains were mediated by mefE gene ,accounting for 1 .4% .Conclusion Erythro-mycin and clindamycin has no obvious effect on streptococcus pneumoniae in this county . T he target change of mediating by ErmB gene is the main mechanism of streptococcus pneumonia 's resistance to mac-rolides .

  14. Characterization of glycopeptide-resistant Enterococcus faecium (GRE) from broilers and pigs in Denmark: Genetic evidence that persistence of GRE in pig herds is associated with coselection by resistance to macrolides

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller

    2000-01-01

    Glycopeptide-resistant enterococci (GRE) from broilers and pigs were characterized to investigate the background for the persistence of GRE in pig herds. All porcine isolates belonged to closely related pulsed-field gel electrophoretic (PFGE) types, with the ermB and vanA genes located on the same...... transferable genetic element. Broiler isolates belonged to different PFGE types. The persistence of GRE in Danish pig herds after the ban of glycopeptides may be explained by the genetic link between ermB and vanA and coselection by use of macrolides for treatment and growth promotion....

  15. Technical note: Occurrence in fecal microbiota of genes conferring resistance to both macrolide-lincosamide-streptogramin B and tetracyclines concomitant with feeding of beef cattle with tylosin.

    Science.gov (United States)

    Chen, J; Fluharty, F L; St-Pierre, N; Morrison, M; Yu, Z

    2008-09-01

    Development of antimicrobial resistance in food animals receiving antimicrobials has been well documented among bacterial isolates, especially pathogens, but information on development of antimicrobial resistance at the microbial community level during long-term feeding of antimicrobials is lacking. The objective of this study was to examine the association between inclusion of tylosin in feed and occurrence of resistance to macrolide-lincosamide-streptogramin B (MLS(B)) in the entire fecal microbial communities of beef cattle over a feeding study of 168 d. A completely randomized design included 6 pens housed together in 1 barn, with each pen housing 10 to 11 steers. The control and tylosin groups each had 3 pens, with the former receiving no antimicrobial whereas the latter received both tylosin and monensin (11 and 29.9 mg/ kg of feed, respectively, DM) in feed. The abundance of genes conferring resistance to MLS(B) (erm genes) and tetracyclines (tet genes) were quantified using class-specific, real-time PCR assays. The abundances of erm and tet genes were analyzed with pens as experimental units using the MIXED procedure of SAS. Correlations between abundance of different resistance genes were calculated using the CORR procedure of SAS. We identified 4 classes (B, F, T, and X) of erm genes in fresh fecal samples collected at wk 2, 17, and 21 of feeding. From wk 2 to 17, the abundance of erm(T) and erm(X) increased (P tylosin feeding. Such co-selection of multiresistance at community level by one antimicrobial drug used in animals has the important implication that future studies should examine resistance to not only the antimicrobials used in animals, but also other antimicrobials, especially those used in human medicine, to fully assess the potential risk associated with antimicrobial use in animals. Both the erm and tet genes appeared to be disseminated among the microbial populations in all steers housed together.

  16. Synthesis of novel 15-membered macrolide derivatives

    Institute of Scientific and Technical Information of China (English)

    Rui Qing Xian; Shu Tao Ma; Bo Jiao

    2008-01-01

    In order to develop new antibiotics effective against resistant bacteria,a series of novel 15-membered macrolide derivatives were designed and synthesized by the modification of hydroxyl groups at C-11,C-12 and C-4" positions.Their structures were confirmed by MS,IR,1H NMR or 13C NMR.

  17. Synthesis of novel 15-membered macrolide dimers

    Institute of Scientific and Technical Information of China (English)

    Shu Tao Ma; Rui Xin Ma; Rui Qing Xian; Bo Jiao

    2009-01-01

    A series of novel dimers of 15-memhered macrolides was synthesized and evaluated. The directs exhibited excellent activity against erythromycin-susceptible S. pneumonia, but did not show any improved activity against erythromycin-resistant S. pneumoniae encoded by erm gene.

  18. Fate and transport of tylosin and macrolide-resistance genes following manure applications in tile-drained landscapes

    Science.gov (United States)

    The use of antibiotics in swine production leads to antibiotic-resistance in gastrointestinal bacteria. Application of swine manure to drained agricultural fields introduces elevated levels of antibiotic-resistant bacteria and residual antibiotics. The persistence and transport of these agents are g...

  19. [In vitro activity of roxithromycin, new semisynthetic macrolide against obligate anaerobes].

    Science.gov (United States)

    Dubreuil, L; Devos, J; Romond, C; Bryskier, A

    1986-05-01

    The "in vitro" susceptibility to roxithromycin and three other macrolides of 236 anaerobes isolated from clinical samples in 1984/1985 was determined by an agar-dilution method on Wilkins Chalgren medium. 90% of Gram positive cocci were susceptible to both roxithromycin and josamycin (MIC less than 1 mg/l, whereas 1 mg/l erythromycin and 2 mg/l spiramycin were able to inhibit respectively 46 and 86% of the same tested strains. No resistance to the four macrolides was observed among Eubacterium, propionibacterium and Bifidobacterium. Two C. perfringens strains and one C. difficile strain were resistant to all four macrolides, while 97% of Clostridium sp. strains were inhibited by 4 mg/l erythromycin, josamycin or roxithromycin. Against Gram positive anaerobes, roxithromycin was equal or superior to erythromycin and spiramycin. At a concentration of 4 mg/l, roxithromycin inhibited 82% of B. fragilis strains. Roxithromycin and josamycin were more active against Gram negative bacilli that erythromycin and spiramycin. Macrolides had no effect on Fusobacterium strains. In this study, 4 mg/l roxithromycin inhibited 217 of the 236 anaerobic strains investigated (92%).

  20. Emergence of Macrolide Resistance Gene mph(B) in Streptococcus uberis and Cooperative Effects with rdmC-Like Gene▿

    OpenAIRE

    Achard, Adeline; Guérin-Faublée, Véronique; Pichereau, Vianney; Villers, Corinne; Leclercq, Roland

    2008-01-01

    Streptococcus uberis UCN60 was resistant to spiramycin (MIC = 8 μg/ml) but susceptible to erythromycin (MIC = 0.06 μg/ml), azithromycin (MIC = 0.12 μg/ml), josamycin (MIC = 0.25 μg/ml), and tylosin (MIC = 0.5 μg/ml). A 2.5-kb HindIII fragment was cloned from S. uberis UCN60 DNA on plasmid pUC18 and introduced into Escherichia coli AG100A, where it conferred resistance to spiramycin by inactivation. The sequence analysis of the fragment showed the presence of an rdmC-like gene that putatively ...

  1. Tylosin Resistance in Arcanobacterium pyogenes Is Encoded by an Erm X Determinant

    Science.gov (United States)

    Jost, B. Helen; Field, Adam C.; Trinh, Hien T.; Songer, J. Glenn; Billington, Stephen J.

    2003-01-01

    Arcanobacterium pyogenes, a commensal on the mucous membranes of many economically important animal species, is also a pathogen, causing abscesses of the skin, joints, and visceral organs as well as mastitis and abortion. In food animals, A. pyogenes is exposed to antimicrobial agents used for growth promotion, prophylaxis, and therapy, notably tylosin, a macrolide antibiotic used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Of 48 A. pyogenes isolates, 11 (22.9%) exhibited inducible or constitutive resistance to tylosin (MIC of ≥128 μg/ml). These isolates also exhibited resistance to other macrolide and lincosamide antibiotics, suggesting a macrolide-lincosamide resistance phenotype. Of the 11 resistant isolates, genomic DNA from nine hybridized to an erm(X)-specific probe. Cloning and nucleotide sequencing of the A. pyogenes erm(X) gene indicated that it was >95% similar to erm(X) genes from Corynebacterium and Propionibacterium spp. Eight of the erm(X)-containing A. pyogenes isolates exhibited inducible tylosin resistance, which was consistent with the presence of a putative leader peptide upstream of the erm(X) open reading frame. For at least one A. pyogenes isolate, 98-4277-2, erm(X) was present on a plasmid, pAP2, and was associated with the insertion sequence IS6100. pAP2 also carried genes encoding the repressor-regulated tetracycline efflux system determinant Tet 33. The repA gene from pAP2 was nonfunctional in Escherichia coli and at least one A. pyogenes isolate, suggesting that there may be host-encoded factors required for replication of this plasmid. PMID:14576111

  2. A platform for the discovery of new macrolide antibiotics

    Science.gov (United States)

    Seiple, Ian B.; Zhang, Ziyang; Jakubec, Pavol; Langlois-Mercier, Audrey; Wright, Peter M.; Hog, Daniel T.; Yabu, Kazuo; Allu, Senkara Rao; Fukuzaki, Takehiro; Carlsen, Peter N.; Kitamura, Yoshiaki; Zhou, Xiang; Condakes, Matthew L.; Szczypiński, Filip T.; Green, William D.; Myers, Andrew G.

    2016-05-01

    The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

  3. A Second Tylosin Resistance Determinant, Erm B, in Arcanobacterium pyogenes

    Science.gov (United States)

    Jost, B. Helen; Trinh, Hien T.; Songer, J. Glenn; Billington, Stephen J.

    2004-01-01

    Arcanobacterium pyogenes, a common inhabitant of the mucosal surfaces of livestock, is also a pathogen associated with a variety of infections. In livestock, A. pyogenes is exposed to antimicrobial agents used for prophylaxis and therapy, notably tylosin, a macrolide used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Many, but not all, tylosin-resistant A. pyogenes isolates carry erm(X), suggesting the presence of other determinants of tylosin resistance. Oligonucleotide primers designed for conserved regions of erm(B), erm(C), and erm(T) were used to amplify a 404-bp fragment from a tylosin-resistant A. pyogenes isolate, OX-7. DNA sequencing revealed that the PCR product was 100% identical to erm(B) genes, and the erm(B) gene region was cloned in Escherichia coli. The A. pyogenes Erm B determinant had the most DNA identity with an Erm B determinant carried by the Clostridium perfringens plasmid pIP402. However, the A. pyogenes determinant lacked direct repeat DR1 and contained a deletion in DR2. Flanking the A. pyogenes erm(B) gene were partial and entire genes similar to those found on the Enterococcus faecalis multiresistance plasmid pRE25. This novel architecture suggests that the erm(B) element may have arisen by recombination of two distinct genetic elements. Ten of 32 tylosin-resistant isolates carried erm(B), as determined by DNA hybridization, and all 10 isolates carried a similar element. Insertion of the element was site specific, as PCR and Southern blotting analysis revealed that the erm(B) element was inserted into orfY, a gene of unknown function. However, in three strains, this insertion resulted in a partial duplication of orfY. PMID:14982756

  4. New Spectrophotometric and Conductometric Methods for Macrolide Antibiotics Determination in Pure and Pharmaceutical Dosage Forms Using Rose Bengal

    Directory of Open Access Journals (Sweden)

    Rania A. Sayed

    2013-01-01

    Full Text Available Two Simple, accurate, precise, and rapid spectrophotometric and conductometric methods were developed for the estimation of erythromycin thiocyanate (I, clarithromycin (II, and azithromycin dihydrate (III in both pure and pharmaceutical dosage forms. The spectrophotometric procedure depends on the reaction of rose bengal and copper with the cited drugs to form stable ternary complexes which are extractable with methylene chloride, and the absorbances were measured at 558, 557, and 560 nm for (I, (II, and (III, respectively. The conductometric method depends on the formation of an ion-pair complex between the studied drug and rose bengal. For the spectrophotometric method, Beer's law was obeyed. The correlation coefficient ( for the studied drugs was found to be 0.9999. The molar absorptivity (, Sandell’s sensitivity, limit of detection (LOD, and limit of quantification (LOQ were also calculated. The proposed methods were successfully applied for the determination of certain pharmaceutical dosage forms containing the studied drugs

  5. Laboratory investigation of the macrolide-resistant Streptococcus pneumoniae strains isolated from adults%成人耐大环内酯类抗生素肺炎链球菌的实验研究

    Institute of Scientific and Technical Information of China (English)

    康悦; 吴菊芳; 徐晓刚; 叶信予

    2012-01-01

    Objective To investigate the resistance profile of S. Pneumoniae strains isolated from adults in China and provide useful information for rational treatment of community acquired respiratory tract infections. Methods S. Pneumoniae strains were isolated from adults with confirmed community-acquired pneumonia or acute exacerbation of chronic bronchitis. Microdilution method was used to test the sensitivity of S. Pneumoniae to 15 commonly used antimicrobial agents. The resistant phenotype was identified by erythromycin and clindamycin double disk diffusion method. PCR was used to amplify the relevant resistant genes. Results Seventy-one strains of S. Pneumoniae were included in this study. About 98. 6% (70/71) of the strains were susceptible to penicillin. One strain (1.4%, 1/71) was intermediate to penicillin. Most of the strains (84.5%, 60/71) were resistant to macrolides. Majority (90%, 54/60) of these strains were cMLSb phenotype. Five (8. 3%, 5/60) strains showed iMLSB phenotype and 1 (1. 7%, 1/60) strain belonged to M phenotype. ermB gene was identified in 59 (98. 3%) of the 60 strains of macrolide-resistant S. Pneumoniae. Conclusions S. Pneumoniae strains associated with community acquired respiratory infections isolated from Chinese adults are highly resistant to macrolides. Macrolides should be used cautiously in community acquired respiratory infections according to the results of susceptibility testing or in combination with (β-lactam antibiotics.%目的 了解近年我国成人患者中分离的肺炎链球菌的耐药现状,为社区获得性呼吸道感染的抗菌药物选用提供依据.方法 对临床明确诊断为社区获得性肺炎(CAP)及慢性气管炎急性加重(AECB)患者中分离获得肺炎链球菌;采用微量稀释法测定15种常用抗菌药物对肺炎链球菌的体外药敏结果;进行克林霉素诱导耐药性D试验;PCR扩增方法检测耐药基因.结果 71株肺炎链球菌中,青霉素敏感肺炎链球菌(PSSP)70

  6. tcrB, a gene conferring transferable copper resistance in Enterococcus faecium: occurrence, transferability, and linkage to macrolide and glycopeptide resistance

    DEFF Research Database (Denmark)

    Hasman, Henrik; Aarestrup, Frank Møller

    2002-01-01

    B protein from Enterococcus hirae. The tcrB gene was found in E. faecium isolated from pigs (75%), broilers (34%), calves (16%), and humans (10%) but not in isolates from sheep. Resistant isolates, containing the tcrB gene, grew on brain heart infusion agar plates containing up to 28 mM CuSO4 compared...

  7. Determining the specific electric resistance of rock

    Energy Technology Data Exchange (ETDEWEB)

    Persad' ko, V.Ia.

    1982-01-01

    Data are presented on perfecting the method of laboratory determination of the specific electric resistance of a rock formation. The average error in determining the specific electric resistance of the core at various locations is no more than two percent with low resistance values (2-5 ohms).

  8. Antibiotic resistance determinants in a Pseudomonas putida strain isolated from a hospital.

    Directory of Open Access Journals (Sweden)

    Lázaro Molina

    Full Text Available Environmental microbes harbor an enormous pool of antibiotic and biocide resistance genes that can impact the resistance profiles of animal and human pathogens via horizontal gene transfer. Pseudomonas putida strains are ubiquitous in soil and water but have been seldom isolated from humans. We have established a collection of P. putida strains isolated from in-patients in different hospitals in France. One of the isolated strains (HB3267 kills insects and is resistant to the majority of the antibiotics used in laboratories and hospitals, including aminoglycosides, ß-lactams, cationic peptides, chromoprotein enediyne antibiotics, dihydrofolate reductase inhibitors, fluoroquinolones and quinolones, glycopeptide antibiotics, macrolides, polyketides and sulfonamides. Similar to other P. putida clinical isolates the strain was sensitive to amikacin. To shed light on the broad pattern of antibiotic resistance, which is rarely found in clinical isolates of this species, the genome of this strain was sequenced and analysed. The study revealed that the determinants of multiple resistance are both chromosomally-borne as well as located on the pPC9 plasmid. Further analysis indicated that pPC9 has recruited antibiotic and biocide resistance genes from environmental microorganisms as well as from opportunistic and true human pathogens. The pPC9 plasmid is not self-transmissible, but can be mobilized by other bacterial plasmids making it capable of spreading antibiotic resistant determinants to new hosts.

  9. 肺炎链球菌对β-内酰胺类及大环内酯类抗生素耐药基因的研究进展%Update on study of resistance genes of Streptococcus pneumoniae to β-lactam and macrolide antibiotics

    Institute of Scientific and Technical Information of China (English)

    石燕华; 李昌崇

    2009-01-01

    In recent years, resistance to β-lactam and macrolide antibiotics has been increasingly observed in Streptococcus pneumoniae. At present,about its resistance gene studies have aroused widespread public concern. This review describes update on the study of resistance genes of Streptococcus pneumoniae to β-lactam and macrolide antibiotics.%近年来,肺炎链球菌对β-内酰胺类及大环内酯类抗生素的耐药率在逐渐上升,目前关于其耐药基因的研究已引起广泛关注,现就肺炎链球菌对β-内酰胺类及大环内酯类抗生素耐药基因的研究进展作一综述.

  10. The determinants of the antibiotic resistance process

    Directory of Open Access Journals (Sweden)

    Beatriz Espinosa Franco

    2009-04-01

    Full Text Available Beatriz Espinosa Franco1, Marina Altagracia Martínez2, Martha A Sánchez Rodríguez1, Albert I Wertheimer31Facultad de Estudios Superiores Zaragoza (UNAM, Mexico; 2Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico; 3Temple University, Philadelphia, Pennsylvania, USABackground: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community.Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem.Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded.Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance.Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals.Keywords: antibiotic drug resistance

  11. Phenotypic and Molecular Antibiotic Resistance Determination of Airborne Coagulase Negative Staphylococcus spp. Strains from Healthcare Facilities in Southern Poland.

    Science.gov (United States)

    Lenart-Boroń, Anna; Wolny-Koładka, Katarzyna; Stec, Joanna; Kasprowic, Andrzej

    2016-10-01

    This study assessed the antimicrobial resistance of airborne Staphylococcus spp. strains isolated from healthcare facilities in southern Poland. A total of 55 isolates, belonging to 10 coagulase-negative staphylococci (CoNS) species, isolated from 10 healthcare facilities (including hospitals and outpatient units) were included in the analysis. The most frequently identified species were Staphylococcus saprophyticus and Staphylococcus warneri, which belong to normal human skin flora, but can also be the cause of common and even severe nosocomial infections. Disk diffusion tests showed that the bacterial strains were most frequently resistant to erythromycin and tetracycline and only 18% of strains were susceptible to all tested antimicrobials. Polymerase chain reaction amplification of specific gene regions was used to determine the presence of the Macrolide-Lincosamide-Streptogramin resistance mechanisms in CoNS. The molecular analysis, conducted using specific primer pairs, identified the msrA1 gene, encoding active efflux pumps in bacterial cells, as the most frequent resistance gene. As many as seven antibiotic resistance genes were found in one isolate, whereas the most common number of resistance genes per isolate was five (n = 17). It may be concluded that drug resistance was widely spread among the tested strains, but the resulting antimicrobial resistance profile indicates that in the case of infection, the use of antibiotics from the basic antibiogram group will be effective in therapy. However, before administering treatment, determination of the specific antimicrobial resistance should be conducted, particularly in the case of hospitalized patients.

  12. Relationship of macrolide-resistant phenotypes with biofilm formation and icaA-genetypes of clinically isolated Staphylococcus epidermidis%临床分离表皮葡萄球菌的大环内酯耐药性与生物膜形成能力、icaA基因型的关系

    Institute of Scientific and Technical Information of China (English)

    枉前; 孙凤军; 夏培元

    2009-01-01

    Objective To study the macrolide-resistance, ability of biofilm formation and icaA-genetypes of 68 stains of clinically isolated Staphylococcus epidermidis (S. epidermidis) so as to explore the efficacy of ma-crolide to prevent biofilm-associated infections caused by S. epidermidis. Methods Minimum inhibitory con-centration (MIC) were detected by agar-plate dilution method, and microtiter-plate assay was used to investi-gate the ability of biofilm formation, and icaA genetype was identified by PCR. Results High macrolide-re-sistant rate (88.2%) was showed for clinical isolated S. epidermidis, and biofilms for macrolide-resistant strains were significantly stronger than that of macrolide-sensitive strains, but there was no dependability found between these two for icaA positive rate. Conclusion Frequently-used macrolide such as erythromycin, azithro-mycin, and clarithromycin may incompetence to prevent biofilm-associated infections caused by S. epidermidis.%目的 研究68株临床分离表皮葡萄球菌大环内酯耐药性与生物膜形成能力、icaA基因型之间的关系,初步预测采用大环内酯抗菌药物预防表皮葡萄球菌生物膜感染的有效性.方法 以琼脂平板稀释法测定菌株的最小抑菌浓度,采用微孔测定法考察临床分离表皮衙萄球菌生物膜形成能力,通过PCR法测定icaA基因型,探讨三者之间的关系.结果 临床分离表皮葡萄球菌对大环内酯耐药程度较高(88.2%),且耐药菌生物膜形成能力较敏感菌显著增强(P0.05).结论 红霉素、阿奇霉素、克拉霉素等常用的大环内酯类药物可能难以有效地预防表皮葡萄球菌生物膜感染.

  13. Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

    Science.gov (United States)

    Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

    2017-01-01

    Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. PCR ribotype prevalence and molecular basis of macrolide-lincosamide-streptogramin B (MLSB) and fluoroquinolone resistance in Irish clinical Clostridium difficile isolates.

    LENUS (Irish Health Repository)

    Solomon, Katie

    2011-09-01

    Antimicrobial use is recognized as a risk factor for Clostridium difficile infection (CDI) and outbreaks. We studied the relationship between PCR ribotype, antimicrobial susceptibility and the genetic basis of resistance in response to exposure to antimicrobial agents.

  15. Research of macrolide resistant phenotype and resistant gene and antimicrobial susceptibility in streptococcus pneumonia isolated from children in Yueqing%乐清地区儿童肺炎链球菌耐药性及大环内酯类耐药表型和耐药基因型

    Institute of Scientific and Technical Information of China (English)

    林雪峰; 朱旭阳; 江丹英; 王兵勇; 陈静

    2015-01-01

    Objective To investigate the distribution of macrolide resistant phenotype and resistant gene, and antimicro-bial susceptibility in streptococcus pneumonia isolated from children in Yueqing. Methods A total of 124 streptococcus pneumonia isolates from children in Yueqing was analyzed for detecting minimal inhibitory concentration. Then the macrolide resistance phenotypes were identified by double disc test with erythromycin and clindamycin discs. The ermB and mefE genes were amplified by PCR. Results In 124 strains of streptococcus pneumonia, the resistance rates to ery-thromycin, clindamycin, tetracycline, and sulfamethoxazole were 96.77%, 93.55%, 84.68%and 81.45%respectively. The resistance rate to penicillin, chloromycetin and levofloxacin were lower which were 20.16%, 5.65%and 0.81%respectively. No strain was found that resistant to amoxicillin and vancomycin. Majority(96.67%) of 120 streptococcus pneumonia strains of macrolide were cMLS phenotype. One (0.83%) strain showed iMLS phenotype and 3 (2.5%) strains belonged to macrolide resistance phenotype. The ermB gene was identified in 97.50%and mefE gene was 6.67%. Conclusion The re-sistance of streptococcus pneumonia to macrolide is serious in children from Yueqing. The ermB-mediated cMLS is the most prevalent phenotype among macrolide resistance streptococcus pneumonia isolates. Obviously, the macrolide antibiotic is not effective on streptococcus pneumonia infection.%目的:了解乐清地区儿童患者分离的肺炎链球菌耐药性及大环内酯类耐药表型和耐药基因型分布情况。方法对2014年乐清地区儿童患者分离的124株肺炎链球菌采用细菌鉴定分析仪进行9种抗菌药物的最低抑菌浓度(MIC)检测,同时对大环内酯类耐药肺炎链球菌用红霉素和克林霉素双纸片协同试验确定其耐药表型,用聚合酶链反应(PCR)扩增这些菌株的耐药基因ermB和mefE。结果124株肺炎链球菌中,红霉素、克林霉素、四

  16. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

    Directory of Open Access Journals (Sweden)

    Euna eOh

    2015-10-01

    Full Text Available The increasing resistance of Campylobacter to clinically-important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN. Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux.

  17. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds.

    Science.gov (United States)

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

    The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux.

  18. Macrolide treatment failure in streptococcal pharyngitis resulting in acute rheumatic fever.

    Science.gov (United States)

    Logan, Latania K; McAuley, James B; Shulman, Stanford T

    2012-03-01

    Macrolide resistance (MR) in group A Streptococcus (GAS) has been well documented in several countries and has become clinically significant since the large increases in macrolide usage during the 1970s. Macrolides are recommended as an alternative therapy for GAS pharyngitis, the most common cause of bacterial pharyngitis. Macrolide resistance has been associated with certain emm types, a sequence-based typing system of the hypervariable region of the GAS M-protein gene. Clinical failure of macrolide treatment of GAS infections can be associated with complications including acute rheumatic fever and rheumatic heart disease, the leading cause of acquired heart disease in children worldwide. Here we report 2 pediatric cases of MR and/or treatment failure in the treatment of GAS pharyngitis with the subsequent development of acute rheumatic fever. We also review the literature on worldwide MR rates, molecular classifications, and emm types, primarily associated with GAS pharyngeal isolates between the years of 2000 and 2010. The use of macrolides in the management of GAS pharyngitis should be limited to patients with significant penicillin allergy.

  19. Prevalence of macrolide-non-susceptible isolates among β-lactamase-negative ampicillin-resistant Haemophilus influenzae in a tertiary care hospital in Japan.

    Science.gov (United States)

    Wajima, Takeaki; Seyama, Shoji; Nakamura, Yuka; Kashima, Chihiro; Nakaminami, Hidemasa; Ushio, Masanobu; Fujii, Takeshi; Noguchi, Norihisa

    2016-09-01

    β-Lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae account for a large portion of H. influenzae clinical isolates in Japan. The aim of this study was to clarify the antimicrobial susceptibility of BLNAR H. influenzae clinical isolates as well as the annual changes in susceptibility. BLNAR H. influenzae isolates were collected from a tertiary care hospital from 2007 to 2012. Antimicrobial susceptibility testing was performed and resistance mechanisms were analysed. All of the isolates (n=304) had amino acid substitutions in penicillin-binding protein 3 (PBP3) and isolates were classified by these amino acid substitutions: R517H or N526K (class I); S385T and R517H (class II); and S385T and N526K (class III). Classes I, II and III represented 8.2% (n=25), 9.5% (n=29) and 81.6% (n=248) of the isolates, respectively; 2 isolates could not be classified because they had a PBP3 with a substantially mutated FtsI transpeptidase domain. All of the isolates were highly susceptible to fluoroquinolones and carbapenems. The number of clarithromycin (CAM)-non-susceptible [minimum inhibitory concentration (MIC) ≥16μg/mL] H. influenzae isolates increased significantly between 2010 and 2012. Moreover, CAM-non-susceptible H. influenzae isolates were prevalent among class II and class III BLNAR H. influenzae. Multilocus sequence typing (MLST) of the CAM-resistant (MIC ≥32μg/mL) H. influenzae isolates showed that they were not specific sequence types, suggesting that CAM resistance may occur in any isolates. These results raise concern regarding the occurrence of multidrug-resistant BLNAR H. influenzae.

  20. Direct Detection of Helicobacter pylori Mutations Associated with Macrolide Resistance in Gastric Biopsy Material Taken from Human Immunodeficiency Virus-Infected Subjects

    Science.gov (United States)

    Scarpellini, Paolo; Carrera, Paola; Cavallero, Annalisa; Cernuschi, Massimo; Mezzi, Gianni; Testoni, Pier Alberto; Zingale, Anna; Lazzarin, Adriano

    2002-01-01

    One hundred forty gastric biopsies were tested by microbiological methods and by amplifying a sequence of 23S rRNA and identifying mutations associated to clarithromycin resistance. Seventy-six specimens were positive for Helicobacter pylori. Mutational analysis revealed alterations in 18 (39.1%) of 46 and 2 (8.7%) of 23 samples from human immunodeficiency virus-seropositive and -seronegative persons, respectively. The results of the mutational analysis fully correlated with those of the susceptibility tests. PMID:12037095

  1. [In vitro antibacterial activity of a new macrolide: miokamycin. Comparison with erythromycin and josamycin].

    Science.gov (United States)

    Soussy, C J; Leclercq, R; Duval, J

    1988-05-01

    Minimal inhibitory concentrations (MIC) of miokamycin (M) were evaluated by agar dilution, comparatively with erythromycin (E) and josamycin (J) for 81 bacterial strains chosen as a function of susceptibility and resistance to Macrolides-Lincosamides-Streptogramins group (MLS). On Gram positive cocci, mode MIC of E, J, and M for strains sensitive to MLS were respectively (micrograms/ml): Staphylococci: 0.25; 1; 2-Streptococci and Pneumococci: 0.016; 0.03-0.12; 0.06-0.25-Enterococci: 0.5; 0.5-1; 1-2. Activity of the three antibiotics was similar against Staphylococci resistant to lincomycin and streptogramin A, those resistant to streptogramins A and B, on Staphylococci and Streptococci only resistant to lincosamides by inactivation. M, as J, was active on coagulase negative (Staphylococci resistant to E by inactivation and on MLBB inducible Staphylococci; on these strains, M is a resistance non-inducible macrolide. Activity of E, J and M was reduced on MLSB inducible Streptococci. The three antibiotics were inactive on Staphylococci Streptococci and Enterococci MLSB resistant constitutive. On Haemophilus, E (2-8 micrograms/ml) was more active than J (2-16) and M (8-32). Thus, M, as J, was shown to be among macrolide antibiotics of resistance non-inducing type on MLSB inducible resistant Staphylococci; its activity was slightly inferior to that of J, but very similar to that of spiramycin, other macrolide of this group.

  2. Quantitative determination of the macrolide antibiotics erythromycin, roxithromycin, azithromycin and clarithromycin in human serum by high-performance liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl chloride and fluorescence detection.

    Science.gov (United States)

    Sastre Toraño, J; Guchelaar, H J

    1998-12-11

    A validated, highly sensitive and precise high-performance liquid chromatographic (HPLC) method for the determination of the macrolides erythromycin, azithromycin, clarithromycin and roxithromycin in human serum is described. A diethyl ether extract, obtained from serum using a saturated sodium carbonate solution, was treated with 9-fluorenylmethyl-oxycarbonyl chloride (FMOC-Cl) for 40 min at 40 degrees C and chromatographed on a base-deactivated octadecyl column, maintained at 50 degrees C during elution, using an eluent composed of acetonitrile-hydrogenphosphate buffer, pH 7.5, with 0.125% triethylamine (3:2, v/v). Fluorescence detection was used at an excitation wavelength of 255 nm and an emission wavelength of 315 nm. Erythromycin, clarithromycin, roxithromycin and azithromycin were found to have retention times of 8.8, 15.7, 17.1 and 20.7 min, respectively. Recoveries ranging from 93 to 104% were found with reproducibility coefficients of variation of 1.1-5%. Mean correlation coefficients of 0.9997, 0.9998, 0.9996 and 0.9994 were found for the linear calibration curves (n = 2) of erythromycin (0.320-16.1 mg/l), roxithromycin (3.24-19.4 mg/l), clarithromycin (0.190-19.4 mg/l) and azithromycin (0.0988-4.94 mg/l), respectively.

  3. The determinants of the antibiotic resistance process

    OpenAIRE

    Espinosa, Beatriz

    2009-01-01

    Beatriz Espinosa Franco1, Marina Altagracia Martínez2, Martha A Sánchez Rodríguez1, Albert I Wertheimer31Facultad de Estudios Superiores Zaragoza (UNAM), Mexico; 2Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico; 3Temple University, Philadelphia, Pennsylvania, USABackground: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a se...

  4. Analysis of macrolide antibiotics, using liquid chromatography-mass spectrometry, in food, biological and environmental matrices.

    Science.gov (United States)

    Wang, Jian

    2009-01-01

    Macrolides are a group of antibiotics that have been widely used in human medical and veterinary practices. Analysis of macrolides and related compounds in food, biological, and environmental matrices continue to be the focus of scientists for the reasons of food safety, pharmacokinetic studies, and environmental concerns. This article presents an overview on the primary biological properties of macrolides and their associated analytical issues, including extraction, liquid chromatography-mass spectrometry (LC-MS), method validation, and measurement uncertainty. The main techniques that have been used to extract macrolides from various matrices are solid-phase extraction and liquid-liquid extraction. Conventional liquid chromatography (LC) with C18 columns plays a dominant role for the determination of macrolides, whereas ultra-performance liquid chromatography (UPLC) along with sub-2 microm particle C18 columns reduces run time and improves sensitivity. Mass spectrometry (MS), serving as a universal detection technique, has replaced ultraviolet (UV), fluorometric, and electrochemical detection for multi-macrolide analysis. The triple-quadrupole (QqQ), quadrupole ion trap (QIT), triple-quadrupole linear ion trap, time-of-flight (TOF), and quadrupole time-of-flight (QqTOF) mass spectrometers are current choices for the determination of macrolides, including quantification, confirmation, identification of their degradation products or metabolites, and structural elucidation. LC or UPLC coupled to a triple-quadrupole mass spectrometer operated in the multiple-reaction monitoring (MRM) mode (LC/MS/MS) is the first choice for quantification. UPLC-TOF or UPLC-QqTOF has been recognized as an emerging technique for accurate mass measurement and unequivocal identification of macrolides and their related compounds.

  5. Molecular determinants of resistance to Verticillium dahliae in potato

    Science.gov (United States)

    A constant evolutionary arms race between host resistance genes and pathogen effectors determine adaptive fitness. Therefore, identification of both host resistance genes and pathogen effectors is important in devising effective strategies to control disease. In tomato, resistance to Verticillium da...

  6. Macrolides in Chronic Inflammatory Skin Disorders

    Directory of Open Access Journals (Sweden)

    Abdullateef A. Alzolibani

    2012-01-01

    Full Text Available Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents.

  7. Effect of different pH on antibacterial activity and drug resistance of macrolide antibiotics%不同pH值条件下3种大环内酯类抗菌药物的抗菌活性及耐药性

    Institute of Scientific and Technical Information of China (English)

    高慧莉; 罗光明

    2015-01-01

    目的:不同 pH 值条件下3种大环内酯类药物对金黄色葡萄球菌和化脓性链球菌的耐药性和最小抑菌浓度(MIC)。方法在 pH6.0、pH7.0和 pH8.0条件下,采用肉汤稀释法分别检测大环内酯类抗菌药物对临床分离金黄色葡萄球菌和化脓性链球菌 MIC 及细菌耐药性。结果随着 pH 值的增加,大环内酯类抗菌药物对金黄色葡萄球菌和化脓性链球菌的 MIC 值均有不同程度的降低,并呈一定的依赖效应,其中罗红霉素和阿奇霉素的抑菌活性强于红霉素;体外诱导试验表明,在所有试验 pH 值条件下,MIC 值均有所增加,但是随着 pH 值的增加细菌的 MIC 值逐渐降低。结论大环内酯类抗菌药物的 MIC 随培养基 pH 值升高而逐渐降低,在一定 pH 值范围内大环内酯类抗菌药物可提高金黄色葡萄球菌和化脓性链球菌的抗菌作用。%Objective To investigate the effect of staphylococcus aureus and streptococcus pyogenes on the drug resistance and the minimal inhibition concentration (MIC) of macrolide antibiotics under the different pH value conditions .Methods The broth dilution method was used to detect the drug resistance and MIC of macrolide antibi‐otics to clinically isolated staphylococcus aureus and streptococcus pyogenes .Results The drug resistance and MIC of macrolide antibiotics to staphylococcus aureus and streptococcus pyogenes were decreased with enhance of pH val‐ue in certainly dose‐dependent manner .In addition ,the inhibition activity of roxithromycin and azithromycin were stronger than that of erythromycin .The in vitro study indicated that the MIC values were increased in all the experi‐ment pH conditions ,but the MIC values gradually were decreased with augment of pH values .Conclusion The MIC values of macrolide antibiotics are gradually decreased with augment of pH values in culture medium ,and macrolide antibiotics can improve the antibacterial

  8. The non-antibacterial effects and possible clinical applications of macrolide antibiotics

    Institute of Scientific and Technical Information of China (English)

    TONG Shi-liang; WANG Yuan-liang; GAO Wen-juan

    2006-01-01

    As one group of the most widely used oral antibacterial drugs, macrolides have been clinically applied for more than 50 years because of their safety and efficacy. Recently, the non-antibacterial applications of macrolides are frequently reported, such as the therapy of malignant tumor, exudative pleurisy, pulmonary fibrosis, rheumatoid arthritis, bronchiectasis, asthma, gastrointestinal peristalsis disorders, and so on with new pharmacological effects, including reverse of tumor resistance, anti-chemical adherence, anti-fibrosis, and modulations of gastrointestinal motility as well as immune activity. The in-depth research of marcolides' non-antibiotic actions can not only extend the application fields of macrolides, but provide a new way to treat some refractory diseases.

  9. Inference of Antibiotic Resistance and Virulence Among Diverse Group A Streptococcus Strains Using emm Sequencing and Multilocus Genotyping Methods

    Science.gov (United States)

    2009-09-04

    pneumonia . Less frequently, it can cause severe symptoms such as toxic shock syndrome, necrotizing fasciitis, and sterile rheumatic sequelae [1]. Penicillin ... Pneumonia outbreak associated with group A Streptococcus at a military training facility. Clin Infect Dis 40: 511–518. 17. Lamagni TL, Neal S, Keshishian C...Macrolide resistance and erythromycin resistance determinants among Belgian Streptococcus pyogenes and Streptococcus pneumoniae isolates. J Antimicrob

  10. Timcodar (VX-853 Is a Non-FKBP12 Binding Macrolide Derivative That Inhibits PPARγ and Suppresses Adipogenesis

    Directory of Open Access Journals (Sweden)

    Terry D. Hinds

    2016-01-01

    Full Text Available Nutrient overload and genetic factors have led to a worldwide epidemic of obesity that is the underlying cause of diabetes, atherosclerosis, and cardiovascular disease. In this study, we used macrolide drugs such as FK506, rapamycin, and macrolide derived, timcodar (VX-853, to determine their effects on lipid accumulation during adipogenesis. Rapamycin and FK506 bind to FK506-binding proteins (FKBPs, such as FKBP12, which causes suppression of the immune system and inhibition of mTOR. Rapamycin has been previously reported to inhibit the adipogenic process and lipid accumulation. However, rapamycin treatment in rodents caused immune suppression and glucose resistance, even though the mice lost weight. Here we show that timcodar (1 μM, a non-FKBP12-binding drug, significantly (p<0.001 inhibited lipid accumulation during adipogenesis. A comparison of the same concentration of timcodar (1 μM and rapamycin (1 μM showed that both are inhibitors of lipid accumulation during adipogenesis. Importantly, timcodar potently (p<0.01 suppressed transcriptional regulators of adipogenesis, PPARγ and C/EBPα, resulting in the inhibition of genes involved in lipid accumulation. These studies set the stage for timcodar as a possible antiobesity therapy, which is rapidly emerging as a pandemic.

  11. Prevalence and determinants of resistant hypertension among ...

    African Journals Online (AJOL)

    ... 1/3 of patients receiving treatment. Such patients with poor BP control fall in the category of resistant hypertension [4]. ... including old age, alcohol consumption, obesity, sodium intake, adherence and knowledge of therapy and limitation of ...

  12. Determination of antimicrobial resistance in Salmonella spp.

    Science.gov (United States)

    Harish, Belgode N; Menezes, Godfred A

    2015-01-01

    Infections with Salmonella are an important public health problem worldwide. Salmonella are one of the most common causes of food-borne illness in humans. There are many types of Salmonella but they can be divided into two broad categories: those that cause typhoid and those that do not. The typhoidal Salmonella (TS), such as S. enterica subsp. enterica serovars Typhi and S. Paratyphi only colonize humans and are usually acquired by the consumption of food or water contaminated with human fecal material. The much broader group of non-typhoidal Salmonella (NTS) usually results from improperly handled food that has been contaminated by animal or human fecal material. Antimicrobials are critical to the successful outcome of invasive Salmonella infections and enteric fever. Due to resistance to the older antimicrobials, ciprofloxacin [fluoroquinolone (FQ)] has become the first-line drug for treatment. Nevertheless, switch to FQ has led to a subsequent increase in the occurrence of salmonellae resistant to this antimicrobial agent. The exact mechanism of this FQ resistance is not fully understood. FQ resistance has driven the use of third-generation cephalosporins and azithromycin. However, there are sporadic worldwide reports of high level resistance to expanded-spectrum cephalosporins (such as ceftriaxone) in TS and in NTS it has been recognized since 1988 and are increasing in prevalence worldwide. Already there are rare reports of azithromycin resistance leading to treatment failure. Spread of such resistance would further greatly limit the available therapeutic options, and leave us with only the reserve antimicrobials such as carbapenem and tigecycline as possible treatment options. Here, we describe the methods involved in the genotypic characterization of antimicrobial resistance in clinical isolates of salmonellae.

  13. Macrolides: A Canadian Infectious Disease Society Position Paper

    Directory of Open Access Journals (Sweden)

    S McKenna

    2001-01-01

    Full Text Available Since the introduction of erythromycin in 1965, no new compounds from the macrolide antimicrobial class were licensed in Canada until the 1990s. Clarithromycin and azithromycin, since their introduction, have become important agents for treating a number of common and uncommon infectious diseases. They have become prime agents in the treatment of respiratory tract infections, and have revolutionized the management of both genital chlamydial infections, by the use of single-dose therapy with azithromycin, and nontuberculous mycobacterial infections, by the use of clarithromycin. The improvement of clarithromycin and azithromycin over the gastrointestinal intolerability of erythromycin has led to supplanting the use of the latter for many primary care physicians. Unfortunately, the use of these agents has also increased the likelihood for misuse and has raised concerns about a resultant increase in the rates of macrolide resistance in many important pathogens, such as Streptococcus pneumoniae. This paper reviews the pharmacology and evidence for the current indications for use of these newer agents, and provides recommendations for appropriate use.

  14. Molecular epidemiology, antimicrobial susceptibilities and resistance mechanisms of Streptococcus pyogenes isolates resistant to erythromycin and tetracycline in Spain (1994–2006

    Directory of Open Access Journals (Sweden)

    Rubio-López Virginia

    2012-09-01

    Full Text Available Abstract Background Group A Streptococcus (GAS causes human diseases ranging in severity from uncomplicated pharyngitis to life-threatening necrotizing fasciitis and shows high rates of macrolide resistance in several countries. Our goal is to identify antimicrobial resistance in Spanish GAS isolates collected between 1994 and 2006 and to determine the molecular epidemiology (emm/T typing and PFGE and resistance mechanisms of those resistant to erythromycin and tetracycline. Results Two hundred ninety-five out of 898 isolates (32.8% were erythromycin resistant, with the predominance of emm4T4, emm75T25, and emm28T28, accounting the 67.1% of the 21 emm/T types. Spread of emm4T4, emm75T25 and emm28T28 resistant clones caused high rates of macrolide resistance. The distribution of the phenotypes was M (76.9%, cMLSB (20.3%, iMLSB (2.7% with the involvement of the erythromycin resistance genes mef(A (89.5%, msr(D (81.7%, erm(B (37.3% and erm(A (35.9%. Sixty-one isolates were tetracycline resistant, with the main representation of the emm77T28 among 20 emm/T types. To note, the combination of tet(M and tet(O tetracycline resistance genes were similar to tet(M alone reaching values close to 40%. Resistance to both antibiotics was detected in 19 isolates of 7 emm/T types, being emm11T11 and the cMLSB phenotype the most frequent ones. erm(B and tet(M were present in almost all the strains, while erm(A, mef(A, msr(D and tet(O appeared in less than half of them. Conclusions Spanish GAS were highly resistant to macrolides meanwhile showed minor resistance rate to tetracycline. A remarkable correlation between antimicrobial resistance and emm/T type was noticed. Clonal spread of emm4T4, emm75T25 and emm28T28 was the main responsable for macrolide resistance where as that emm77T28 clones were it to tetraclycline resistance. A wide variety of macrolide resistance genes were responsible for three macrolide resistance phenotypes.

  15. Trends in antibacterial resistance among Streptococcus pneumoniae isolated in the USA: update from PROTEKT US Years 1–4

    Directory of Open Access Journals (Sweden)

    Brown Steven D

    2008-01-01

    Full Text Available Abstract Background The increasing prevalence of resistance to established antibiotics among key bacterial respiratory tract pathogens, such as Streptococcus pneumoniae, is a major healthcare problem in the USA. The PROTEKT US study is a longitudinal surveillance study designed to monitor the susceptibility of key respiratory tract pathogens in the USA to a range of commonly used antimicrobials. Here, we assess the geographic and temporal trends in antibacterial resistance of S. pneumoniae isolates from patients with community-acquired respiratory tract infections collected between Year 1 (2000–2001 and Year 4 (2003–2004 of PROTEKT US. Methods Antibacterial minimum inhibitory concentrations were determined centrally using the Clinical and Laboratory Standards Institute (CLSI broth microdilution method; susceptibility was defined according to CLSI interpretive criteria. Macrolide resistance genotypes were determined by polymerase chain reaction. Results A total of 39,495 S. pneumoniae isolates were collected during 2000–2004. The percentage of isolates resistant to erythromycin, penicillin, levofloxacin, and telithromycin were 29.3%, 21.2%, 0.9%, and 0.02%, respectively, over the 4 years, with marked regional variability. The proportion of isolates exhibiting multidrug resistance (includes isolates known as penicillin-resistant S. pneumoniae and isolates resistant to ≥ 2 of the following antibiotics: penicillin; second-generation cephalosporins, e.g. cefuroxime; macrolides; tetracyclines; and trimethoprim-sulfamethoxazole remained stable at ~30% over the study period. Overall mef(A was the most common macrolide resistance mechanism. The proportion of mef(A isolates decreased from 68.8% to 62.3% between Year 1 and Year 4, while the percentage of isolates carrying both erm(B and mef(A increased from 9.7% to 18.4%. Over 99% of the erm(B+mef(A-positive isolates collected over Years 1–4 exhibited multidrug resistance. Higher than previously

  16. [Comparison of the in vitro post-antibiotic effect of C14 macrolides (erythromycin and roxithromycin) and C16 macrolides (josamycin and spiramycin) against Staphylococcus aureus].

    Science.gov (United States)

    Rolin, O; Bouanchaud, D H

    1989-05-01

    In vitro post-antibiotic effect (PAE) induced by erythromycin, roxithromycin, josamycin and spiramycin has been compared on Staphylococcus aureus. Three MLSB sensitive and three MLSB inducible resistant S. aureus strains have been used. delta t was the time required for culture to increase by 1 log10 after drug removal in comparison with controls. For erythromycin and roxithromycin delta t ranged from 6 minutes at 1 x MIC to 48 minutes at 4 x MIC (average of the six strains at 4 x MIC: 33 minutes). For josamycin and spiramycin, delta t ranged from 36 at 1/2 x MIC to 138 minutes at 4 x MIC (average at 4 x MIC: 101 minutes). No difference was observed between MLSB sensitive and MLSB inducible resistant S. aureus strains. In our experimental conditions, PAEs observed with josamycin and spiramycin (16-membered-ring macrolides) were 2.5 to 3 times longer than those observed with erythromycin and roxithromycin (14-membered-ring macrolides). These results added to biological differences previously observed between 14-membered-ring and 16-membered-ring macrolides.

  17. Determining of antibiotic resistance profile inStaphylococcus aureus isolates

    Institute of Scientific and Technical Information of China (English)

    Hossein Motamedi; Hadis Mirzabeigi; Tahere Shirali

    2010-01-01

    Objective:To determine the pattern of antibiotic resistance amongStaphylococcus aureus (S. aureus) isolates from clinical specimens and to identify community-acquired methicillin-resistantStaphylococcus aureus(CA-MRSA)in specimens that have been collected from patients referring to one of the hospitals of Ahvaz.Methods:S. aureus isolates from a hospital in Ahvaz were screened for resistance to various antibiotics including methicillin. The susceptibility of the isolates was determined by Kirby-Bauer disc diffusion method. TheMRSA was also treated with ethidium bromide to find the origin of resistance.Results: Among the bacterial isolates, all of 11S. aureus were resistant to methicillin and cefixime,2 were resistant to ciprofloxacine,6 were resistant to tetracycline and the reminder were sensitive or intermediate to other antibiotics. The treated isolates were reminded resistant to methicillin and this suggested that the plasmid was not the origin of resistance in these isolates.Conclusions: These results showed that infection due toMRSA is widespread in Ahvaz and with respect to the spread of vancomycin resistance among MRSA and appearance of overwhelming infections. It is necessary to identify continuously the profile of antibiotic resistance amongS. aureus isolates in other regions and finding appropriate antibiotic for infection control and eradication.

  18. In vitro susceptibility of Ureaplasma urealyticum clinical isolates to new macrolides.

    Science.gov (United States)

    Kanamoto, Y; Miyake, Y; Suginaka, H; Usui, T

    1991-01-01

    Nine antimicrobial agents, the new macrolides, rokitamycin and midecamycin acetate, and seven other antibiotics, tetracycline, minocycline, doxycycline, josamycin, erythromycin, spiramycin, and norfloxacin, were studied for their antimicrobial activity against 100 strains of Ureaplasma urealyticum, using a microtiter broth dilution technique. The new macrolides, rokitamycin and midecamycin acetate, had the highest activity, with the MIC against 90% of isolates tested (MIC90) being less than or equal to 0.05 microgram/ml. MICs90 of erythromycin, josamycin, doxycycline, minocycline and tetracycline ranged from 0.1 to 0.78 micrograms/ml. Norfloxacin was least active, with a MIC90 of 12.5 micrograms/ml. Five of 100 strains tested were resistant (MIC greater than or equal to 12.5 micrograms/ml) to tetracycline, and two were resistant to minocycline and doxycycline; all of these were susceptible to rokitamycin and midecamycin acetate.

  19. Methylation of 23S rRNA caused by tlrA (ermSF), a tylosin resistance determinant from Streptomyces fradiae.

    Science.gov (United States)

    Zalacain, M; Cundliffe, E

    1989-01-01

    Ribosomes from Streptomyces griseofuscus expressing tlrA, a resistance gene isolated from the tylosin producer Streptomyces fradiae, are resistant to macrolide and lincosamide antibiotics in vitro. The tlrA product was found to be a methylase that introduces two methyl groups into a single base within 23S rRNA, generating N6,N6-dimethyladenine at position 2058. This activity is therefore similar to the ermE resistance mechanism in Saccharopolyspora erythraea (formerly Streptomyces erythraeus). Images PMID:2753855

  20. Antimicrobial susceptibility and tetracycline resistance determinant genotyping of Gallibacterium anatis

    DEFF Research Database (Denmark)

    Bojesen, Anders M.; Vazquez, Maria E.; Bager, Ragnhild J.;

    2011-01-01

    these figures were 67% and 42%, respectively, for the reference strains.Genotyping of tetracycline resistance determinants was performed with primers specific for tet(A–E, H, K–M, O). Strains positive for tet(B), tet(H) and tet(L) were identified, however, in 20 out of 49 tetracycline resistant strains...

  1. Molecular characterization of multidrug resistant hospital isolates using the antimicrobial resistance determinant microarray.

    Directory of Open Access Journals (Sweden)

    Tomasz A Leski

    Full Text Available Molecular methods that enable the detection of antimicrobial resistance determinants are critical surveillance tools that are necessary to aid in curbing the spread of antibiotic resistance. In this study, we describe the use of the Antimicrobial Resistance Determinant Microarray (ARDM that targets 239 unique genes that confer resistance to 12 classes of antimicrobial compounds, quaternary amines and streptothricin for the determination of multidrug resistance (MDR gene profiles. Fourteen reference MDR strains, which either were genome, sequenced or possessed well characterized drug resistance profiles were used to optimize detection algorithms and threshold criteria to ensure the microarray's effectiveness for unbiased characterization of antimicrobial resistance determinants in MDR strains. The subsequent testing of Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae hospital isolates revealed the presence of several antibiotic resistance genes [e.g. belonging to TEM, SHV, OXA and CTX-M classes (and OXA and CTX-M subfamilies of β-lactamases] and their assemblages which were confirmed by PCR and DNA sequence analysis. When combined with results from the reference strains, ~25% of the ARDM content was confirmed as effective for representing allelic content from both Gram-positive and -negative species. Taken together, the ARDM identified MDR assemblages containing six to 18 unique resistance genes in each strain tested, demonstrating its utility as a powerful tool for molecular epidemiological investigations of antimicrobial resistance in clinically relevant bacterial pathogens.

  2. Correlation between macrolide lung pharmacokinetics and therapeutic efficacy in a mouse model of pneumococcal pneumonia.

    Science.gov (United States)

    Veber, B; Vallée, E; Desmonts, J M; Pocidalo, J J; Azoulay-Dupuis, E

    1993-09-01

    The correlation between the pharmacokinetics of erythromycin, roxithromycin, clarithromycin, spiramycin and azithromycin and their efficacy was investigated in two pneumococcal pneumonia models. Female Swiss and C57B1/6 mice were infected with Streptococcus pneumoniae strain P4241 by the intratracheal per oral route. This virulent strain produces acute pneumonia with death within 3-4 days (Swiss mice), or subacute pneumonia with death within 10 days (C57B1/6 mice) in untreated mice and the outcome of the disease is closely related to progressive weight loss. Swiss mice received three doses of each macrolide 50 mg/kg bd beginning 18 h post-infection. C57B1/6 mice received three doses of each macrolide 25 mg/kg, bd (except azithromycin was 12.5 mg/kg bd) beginning 48 h post-infection. Cure rates were evaluated on the basis of body weight variations recorded daily after the end of treatment. Pharmacokinetic parameters were determined in infected and non-infected mice after a single dose of each macrolide 50 mg/kg sc. The pharmacokinetics of azithromycin was also determined in leucopenic Swiss mice. We observed a hierarchy of in-vivo efficacy as follows: azithromycin > spiramycin = clarithromycin > roxithromycin = erythromycin which did not correlate with in-vitro MIC or MBC. The same hierarchy was found in terms of the lung T1/2. Lung T1/2s of macrolides could thus be predictive of their efficacy in respiratory tract infections. A reduced tissue AUC of azithromycin was seen in leucopenic mice suggesting leucocytes may help transport macrolides to sites of infection.

  3. Erythromycin-resistant genes in group A β-haemolytic Streptococci in Chengdu, Southwestern China

    Directory of Open Access Journals (Sweden)

    W Zhou

    2014-01-01

    Full Text Available Context: The management of Group A β-haemolytic Streptococci (Streptococcus pyogenes or GAS infection include the use of penicillins, cephalosporins or macrolides for treatment. A general increase in macrolides resistance in GAS has been observed in recent years. Differences in rates of resistance to these agents have existed according to geographical location and investigators. Aims: To investigate the antibiotic pattern and erythromycin-resistant genes of GAS isolates associated with acute tonsillitis and scarlet fever in Chengdu, southwestern China. Settings and Design: To assess the macrolide resistance, phenotype, and genotypic characterization of GAS isolated from throat swabs of children suffering from different acute tonsillitis or scarlet fever between 2004 and 2011 in the city of Chengdu, located in the southwestern region of China. Materials and Methods: Minimal inhibitory concentration with seven antibiotics was performed on 127 GAS isolates. Resistance phenotypes of erythromycin-resistant GAS isolates were determined by the double-disk test. Their macrolide-resistant genes (mefA, ermB and ermTR were amplified by PCR. Results: A total of 98.4% (125/127 of the isolates exhibited resistance to erythromycin, clindamycin and tetracycline. All isolates were sensitive to penicillin G and cefotaxime. Moreover, 113 ermB-positive isolates demonstrating the cMLS phenotype of erythromycin resistance were predominant (90.4% and these isolates showed high-level resistance to both erythromycin and clindamycin (MIC 90 > 256 μg/ml; 12 (9.6% isolates demonstrating the MLS phenotype of erythromycin resistance carried the mefA gene, which showed low-level resistance to both erythromycin (MIC 90 = 8 μg/ml and clindamycin (MIC 90 = 0.5 μg/ml; and none of the isolates exhibited the M phenotype. Conclusions: The main phenotype is cMLS, and the ermB gene code is the main resistance mechanism against macrolides in GAS. Penicillin is the most beneficial

  4. In vitro activities of eight macrolide antibiotics and RP-59500 (quinupristin-dalfopristin) against viridans group streptococci isolated from blood of neutropenic cancer patients.

    Science.gov (United States)

    Alcaide, F; Carratala, J; Liñares, J; Gudiol, F; Martin, R

    1996-09-01

    From January 1988 to December 1994, 66 consecutive blood culture isolates of viridans group streptococci collected from febrile neutropenic cancer patients were tested for antimicrobial susceptibilities by the agar dilution method. The antibiotics studied were erythromycin, clarithromycin, roxithromycin, dirithromycin, azithromycin, josamycin, diacetyl-midecamycin, spiramycin, and quinupristin-dalfopristin. A total of 26 (39.4%) strains were resistant to erythromycin with an MIC range of 0.5 to > 128 micrograms/ml. The strains were classified into three groups according to their penicillin susceptibility: 42 (63.6%) were susceptible, 8 (12.1%) were intermediately resistant, and 16 (24.3%) were highly resistant. The percentages of erythromycin-resistant strains in each group were 23.8, 62.5, and 68.8%, respectively. Streptococcus mitis was the species most frequently isolated (83.3%) and showed the highest rates of penicillin (40%) and erythromycin (43.6%) resistance. MICs of all macrolide antibiotics tested and of quinupristin-dalfopristin were higher for penicillin-resistant strains than for penicillin-susceptible strains. All macrolide antibiotics tested had cross-resistance to erythromycin, which was not observed with quinupristin-dalfopristin. Our study shows a high rate of macrolide resistance among viridans group streptococci isolated from blood samples of neutropenic cancer patients, especially those infected with penicillin-resistant strains. These findings make macrolides unsuitable prophylactic agents against viridans group streptococcal bacteremia in this patient population.

  5. Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains in Italy and heterogeneity of inducibly resistant strains.

    Science.gov (United States)

    Giovanetti, E; Montanari, M P; Mingoia, M; Varaldo, P E

    1999-08-01

    A total of 387 clinical strains of erythromycin-resistant (MIC, >/=1 microg/ml) Streptococcus pyogenes, all isolated in Italian laboratories from 1995 to 1998, were examined. By the erythromycin-clindamycin double-disk test, 203 (52.5%) strains were assigned to the recently described M phenotype, 120 (31.0%) were assigned to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS) phenotype, and 64 (16.5%) were assigned to the constitutive MLS resistance (cMLS) phenotype. The inducible character of the resistance of the iMLS strains was confirmed by comparing the clindamycin MICs determined under normal testing conditions and those determined after induction by pregrowth in 0.05 microg of erythromycin per ml. The MICs of erythromycin, clarithromycin, azithromycin, josamycin, spiramycin, and the ketolide HMR3004 were then determined and compared. Homogeneous susceptibility patterns were observed for the isolates of the cMLS phenotype (for all but one of the strains, HMR3004 MICs were 0.5 to 8 microg/ml and the MICs of the other drugs were >128 microg/ml) and those of the M phenotype (resistance only to the 14- and 15-membered macrolides was recorded, with MICs of 2 to 32 microg/ml). Conversely, heterogeneous susceptibility patterns were observed in the isolates of the iMLS phenotype, which were subdivided into three distinct subtypes designated iMLS-A, iMLS-B, and iMLS-C. The iMLS-A strains (n = 84) were highly resistant to the 14-, 15-, and 16-membered macrolides and demonstrated reduced susceptibility to low-level resistance to HMR3004. The iMLS-B strains (n = 12) were highly resistant to the 14- and 15-membered macrolides, susceptible to the 16-membered macrolides (but highly resistant to josamycin after induction), and susceptible to HMR3004 (but intermediate or resistant after induction). The iMLS-C strains (n = 24) had lower levels of resistance to the 14- and 15-membered macrolides (with erythromycin MICs increasing two to four times after

  6. [Susceptibility of Streptococcus pyogenes to macrolides and quinolones in Guadalajara, Spain].

    Science.gov (United States)

    Rodríguez-Zurita, M E; Solís del Baño, S; Robres Guillén, P; González Praetorius, A; Gimeno Fernández, C; Pérez Pomata, M T; Bisquert Santiago, J

    2003-03-01

    We carried out a retrospective study of the susceptibility of 104 Streptococcus pyogenes strains, which were isolated in 2000 and 2001 from clinical samples of different origins, to penicillin, erythromycin, clindamycin, ofloxacin and levofloxacin. The susceptibility testing was performed using the agar difusion method according to the guidelines of the NCCLS. All of the isolates showed susceptibility to penicillin and clindamycin. However, we detected 11 strains that were resistant to erythromycin (10.6%) and 4 strains resistant to ofloxacin (3.8%). We studied the resistance phenotypes of macrolides and lincosamides using erythromycin and clindamycin discs. Nine of the eleven strains that were resistant to erythromycin showed an M phenotype, while the remaining two showed inducible resistance to clindamycin, thus suggesting an MLS(B) inducible phenotype. No strains with constitutive resistance to erythromycin or clindamycin (MLS(B) constitutive phenotype) were identified. While penicillin is still uniformly active against S. pyogenes, in Guadalajara, there are 10.6% strains that are resistant to 14- and 15-atoms macrolides.

  7. Prevalence of plasmid-mediated quinolone resistance determinants among oxyiminocephalosporin-resistant Enterobacteriaceae in Argentina

    Directory of Open Access Journals (Sweden)

    Giovanna Rincon Cruz

    2013-11-01

    Full Text Available High quinolone resistance rates were observed among oxyiminocephalosporin-resistant enterobacteria. In the present study, we searched for the prevalence of plasmid-mediated quinolone resistance (PMQR genes within the 55 oxyiminocephalosporin-resistant enterobacteria collected in a previous survey. The main PMQR determinants were aac(6'-Ib-cr and qnrB, which had prevalence rates of 42.4% and 33.3%, respectively. The aac(6'-Ib-cr gene was more frequently found in CTX-M-15-producing isolates, while qnrB was homogeneously distributed among all CTX-M producers.

  8. Resistance Genes and Genetic Elements Associated with Antibiotic Resistance in Clinical and Commensal Isolates of Streptococcus salivarius.

    Science.gov (United States)

    Chaffanel, Fanny; Charron-Bourgoin, Florence; Libante, Virginie; Leblond-Bourget, Nathalie; Payot, Sophie

    2015-06-15

    The diversity of clinical (n = 92) and oral and digestive commensal (n = 120) isolates of Streptococcus salivarius was analyzed by multilocus sequence typing (MLST). No clustering of clinical or commensal strains can be observed in the phylogenetic tree. Selected strains (92 clinical and 46 commensal strains) were then examined for their susceptibilities to tetracyclines, macrolides, lincosamides, aminoglycosides, and phenicol antibiotics. The presence of resistance genes tet(M), tet(O), erm(A), erm(B), mef(A/E), and catQ and associated genetic elements was investigated by PCR, as was the genetic linkage of resistance genes. High rates of erythromycin and tetracycline resistance were observed among the strains. Clinical strains displayed either the erm(B) (macrolide-lincosamide-streptogramin B [MLSB] phenotype) or mef(A/E) (M phenotype) resistance determinant, whereas almost all the commensal strains harbored the mef(A/E) resistance gene, carried by a macrolide efflux genetic assembly (MEGA) element. A genetic linkage between a macrolide resistance gene and genes of Tn916 was detected in 23 clinical strains and 5 commensal strains, with a predominance of Tn3872 elements (n = 13), followed by Tn6002 (n = 11) and Tn2009 (n = 4) elements. Four strains harboring a mef(A/E) gene were also resistant to chloramphenicol and carried a catQ gene. Sequencing of the genome of one of these strains revealed that these genes colocalized on an IQ-like element, as already described for other viridans group streptococci. ICESt3-related elements were also detected in half of the isolates. This work highlights the potential role of S. salivarius in the spread of antibiotic resistance genes both in the oral sphere and in the gut. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field

    Energy Technology Data Exchange (ETDEWEB)

    Topp, Edward, E-mail: ed.topp@agr.gc.ca; Renaud, Justin; Sumarah, Mark; Sabourin, Lyne

    2016-08-15

    The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1 mg kg{sup −1} soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10 mg kg{sup −1} macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1 mg kg{sup −1} macrolides. Rapid mineralization of {sup 14}C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance. - Highlights: • The impact of field exposure on persistence of macrolide antibiotics was evaluated. • Soil samples were incubated in the laboratory with macrolides. • Field exposure resulted in more rapid dissipation of all macrolides. • Radiolabelled erythromycin and clarithromycin were rapidly mineralized

  10. The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection.

    Science.gov (United States)

    Kasetty, Gopinath; Bhongir, Ravi K V; Papareddy, Praveen; Herwald, Heiko; Egesten, Arne

    2017-09-01

    Macrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to β-lactam antibiotics for treatment of severe community-acquired pneumonia. However, a beneficial effect of macrolides in treating Gram-negative bacterial airway infections, e.g., those caused by Pseudomonas aeruginosa, remains to be shown. Macrolide antibiotics have significant side effects, in particular, motility-stimulating activity in the gastrointestinal tract and promotion of bacterial resistance. In this study, EM703, a modified macrolide lacking antibiotic and motility-stimulating activities but with retained anti-inflammatory properties, was used as an adjunct treatment for experimental P. aeruginosa lung infection, in combination with a conventional antibiotic. Airway infections in BALB/cJRj mice were induced by nasal instillation of P. aeruginosa; this was followed by treatment with the quinolone levofloxacin in the absence or presence of EM703. Survival, inflammatory responses, and cellular influx to the airways were monitored. Both pretreatment and simultaneous administration of EM703 dramatically improved survival in levofloxacin-treated mice with P. aeruginosa airway infections. In addition, EM703 reduced the levels of proinflammatory cytokines, increased the numbers of leukocytes in bronchoalveolar lavage fluid, and reduced the numbers of neutrophils present in lung tissue. In summary, the findings of this study show that the immunomodulatory properties of the modified macrolide EM703 can be important when treating Gram-negative pneumonia, as exemplified by P. aeruginosa infection in this study. Copyright © 2017 American Society for Microbiology.

  11. Survey of strain distribution and antibiotic resistance pattern of group B streptococci (Streptococcus agalactiae isolated from clinical specimens

    Directory of Open Access Journals (Sweden)

    Mousavi, Seyed Masoud

    2016-09-01

    Full Text Available Aim: The aims of the present study were to determine the antibiotic susceptibility profils with particular emphasis on susceptible or resistant strains to macrolides and lincosamids antibiotics and to determine possible antibiotic resistance mechanisms occurring in group B streptococci (GBS strains using PCR assay and disk diffusion method.Methods: A total of 62 clinical GBS strains were investigated. Antibacterial susceptibility testing was performed using the disk diffusion method and inducible resistance test for clindamycin by standard double disk diffusion or D-zone test for all isolates to differentiate macrolide resistance phenotype (M, constitutive macrolide-lincosamide-streptogramin B phenotype (cMLS and induced macrolide-lincosamide-streptogramin B phenotype (iMLS. In addition, minimum inhibitory concentrations (MIC of penicillin were determined for all isolates. Finally, possible existence of antibiotic resistance genes for erythromycin , and and for clindamycin were examined among isolates using PCR assay.Results: All 62 isolates were susceptible to penicillin, ampicillin, linezolid, cefazoline and vancomycin. However, 93.5% (n=58 of isolates showed an increased MIC to penicillin. The overall rate of erythromycin resistance was 35.5% (n=22. All erythromycin-resistant isolates displayed the M phenotype (100%, n=22. All three erythromycin resistance genes (i.e. , and were found in erythromycin-resistant isolates.Conclusion: It was concluded that prescribing antibiotic without antibacterial susceptibility tests should be prevented because of the high prevalence of erythromycin-resistant GBS strains and the fact that erythromycin-resistant GBS strains has shown an increased MIC to penicillin, as the drug of choice for treating GBS infections.

  12. Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm

    Directory of Open Access Journals (Sweden)

    Lutz Larissa

    2012-09-01

    Full Text Available Abstract Background Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF patients. Results A total of 64 isolates were analysed. The biofilm inhibitory concentration (BIC results were consistently higher than those obtained by the conventional method, minimal inhibitory concentration, (MIC for most anti-pseudomonal agents tested (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P P = 0.005. When macrolides were associated with the anti-pseudomonal agents, the BIC values were reduced significantly for ceftazidime (P  0.001 and tobramycin (P  0.001, regardless the concentration of macrolides. Strong inhibitory quotient was observed when azithromycin at 8 mg/L was associated with all anti-pseudomonal agents tested in biofilm conditions. Conclusions P. aeruginosa from CF patients within biofilms are highly resistant to antibiotics but macrolides proved to augment the in vitro activity of anti-pseudomonal agents.

  13. Characterization of antibiotic resistance determinants in oral biofilms.

    Science.gov (United States)

    Kim, Seon-Mi; Kim, Hyeong C; Lee, Seok-Woo S

    2011-08-01

    Oral biofilms contain numerous antibiotic resistance determinants that can be transferred within or outside of the oral cavity. The aim of this study was to evaluate the prevalence and the relative level of antibiotic resistance determinants from oral biofilms. Oral biofilm samples that were collected from healthy subjects and periodontitis patients were subjected to qualitative and quantitative analyses for selected antibiotic resistance determinants using PCR. The prevalence of tet(Q), tet(M), cfxA, and bla ( TEM ) was very high both in the patient and the healthy subject group, with a tendency toward higher values in the patient group, with the exception of erm(F), which was more prevalent in the healthy group. The two extended spectrum β-lactam (ESBL) resistance determinants bla ( SHV ) and bla ( TEM ) showed a dramatic difference, as bla ( TEM ) was present in all of the samples and bla ( SHV ) was not found at all. The aacA-aphD, vanA, and mecA genes were rarely detected, suggesting that they are not common in oral bacteria. A quantitative PCR analysis showed that the relative amount of resistance determinants present in oral biofilms of the patient group was much greater than that of the healthy group, exhibiting 17-, 13-, 145-, and 3-fold increases for tet(Q), tet(M), erm(F), and cfxA, respectively. The results of this study suggest that the oral antibiotic resistome is more diverse and abundant in periodontitis patients than in healthy subjects, suggesting that there is a difference in the diversity and distribution of antibiotic resistance in oral biofilms associated with health and disease.

  14. Mobile antibiotic resistance - the spread of genes determining the resistance of bacteria through food products.

    Science.gov (United States)

    Godziszewska, Jolanta; Guzek, Dominika; Głąbski, Krzysztof; Wierzbicka, Agnieszka

    2016-07-07

    In recent years, more and more antibiotics have become ineffective in the treatment of bacterial nfections. The acquisition of antibiotic resistance by bacteria is associated with circulation of genes in the environment. Determinants of antibiotic resistance may be transferred to pathogenic bacteria. It has been shown that conjugation is one of the key mechanisms responsible for spread of antibiotic resistance genes, which is highly efficient and allows the barrier to restrictions and modifications to be avoided. Some conjugative modules enable the transfer of plasmids even between phylogenetically distant bacterial species. Many scientific reports indicate that food is one of the main reservoirs of these genes. Antibiotic resistance genes have been identified in meat products, milk, fruits and vegetables. The reason for such a wide spread of antibiotic resistance genes is the overuse of antibiotics by breeders of plants and animals, as well as by horizontal gene transfer. It was shown, that resistance determinants located on mobile genetic elements, which are isolated from food products, can easily be transferred to another niche. The antibiotic resistance genes have been in the environment for 30 000 years. Their removal from food products is not possible, but the risks associated with the emergence of multiresistant pathogenic strains are very large. The only option is to control the emergence, selection and spread of these genes. Therefore measures are sought to prevent horizontal transfer of genes. Promising concepts involve the combination of developmental biology, evolution and ecology in the fight against the spread of antibiotic resistance.

  15. [In vitro antibacterial activity of a new macrolide, miokamycin. Results of a multicenter study].

    Science.gov (United States)

    Soussy, C J; Thabaut, A; Bismuth, R; Morel, C; Berthelot, G; Chanal, M; Derlot, E

    1989-05-01

    Minimal inhibitory concentration (MIC) of miokamycin (M) were evaluated by agar dilution for 1,024 bacterial strains isolated in 6 hospitals and classed as a function of susceptibility and resistance to macrolides, lincosamides, streptogramins group (MLS). MIC of M ranged from 0.25 to 4 micrograms/ml (mode MIC 1-2) on Staphylococcus susceptible to MLS and on MLSB inducible strains; M was inactive on MLSB constitutive strains. MIC of M ranged from 0.016 to 4 micrograms/ml (mode MIC 0.12 to 0.5) for Streptococci and Pneumococci susceptible to erythromycin (E) and from 0.12 to greater than 128 for strains resistant to E. Enterococci susceptible to E were inhibited by 0.5 to 2 micrograms/ml (mode MIC 1) and strains resistant to E by 4 to greater than 128. Haemophilus were inhibited by 2 to 64 micrograms/ml (mode MIC 32), Neisseria by 0.12 to 4 (mode MIC 0.5-1) and B. catarrhalis by 0.12 to 8 (mode MIC 1). L. pneumophila was very susceptible to M: MIC 0.016 to 0.12 (mode MIC 0.06). MIC of M ranged generally from 0.5 to 2 micrograms/ml (mode MIC 1) for C. perfringens and from 0.03 to 2 (mode MIC 1) for B. fragilis. Thus, M was shown to be among macrolide antibiotics of resistance non-inducing type on MLSB inducible resistance strains. Its activity was similar to that of spiramycin slightly superior on Staphylococci, slightly inferior on Streptococci and Enterococci, similar on Pneumococci, very superior on Neisseria, Legionella and anaerobes. M had a good activity on Branhamella and, as others macrolides, was poorly active on Haemophilus.

  16. In-vitro activities of 14-, 15- and 16-membered macrolides against gram-positive cocci.

    Science.gov (United States)

    Hamilton-Miller, J M

    1992-02-01

    The in-vitro activities of the 14-membered macrolides erythromycin, dirithromycin, roxithromycin, clarithromycin, the 15-membered compound azithromycin and the 16-membered macrolides (16 MM) josamycin, spiramycin and midecamycin acetate (MOM) have been compared against staphylococci, enterococci and streptococci. Results have been analysed separately according to the sensitivity status of the tested strains to erythromycin, namely sensitive (S), inducibly resistant (IR) or constitutively resistant (CR). 14- and 15-membered macrolides were active only against S strains; the order of potency in vitro was clarithromycin = erythromycin greater than azithromycin = roxithromycin greater than dirithromycin. The 16 MM were slightly less active against S strains than were the 14- and 15-membered compounds, and inhibited most IR strains; MOM and josamycin were about twice as potent as spiramycin. IR and S Staphylococcus aureus strains were equally sensitive to 16 MM, while IR strains of coagulase-negative staphylococci were less sensitive than were S strains. All CR strains of S. aureus were resistant to 16 MM, as were most of the other CR strains. However, 5/21 CR coagulase-negative staphylococci and 2/20 CR enterococci tested were sensitive to 16 MM. The seven CR strains showing anomalous sensitivity to the 16 MM (five Staphylococcus haemolyticus and two enterococci) were only 'moderately resistant' to erythromycin (MIC 8-64 mg/L), while all the other CR strains were 'highly resistant' (MIC greater than 128 mg/L). These results indicate that it may be difficult to predict the sensitivity of Gram-positive cocci to 16 MM, and therefore individual sensitivity testing to specific compounds is essential.

  17. Macrolide antibiotics and the risk of cardiac arrhythmias.

    Science.gov (United States)

    Albert, Richard K; Schuller, Joseph L

    2014-05-15

    Randomized, controlled trials have demonstrated that chronic therapy with macrolide antibiotics reduces the morbidity of patients with cystic fibrosis, non-cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease, and nontuberculous mycobacterial infections. Lower levels of evidence indicate that chronic macrolides are also effective in treating patients with panbronchiolitis, bronchiolitis obliterans, and rejection after lung transplant. Macrolides are known to cause torsade des pointes and other ventricular arrhythmias, and a recent observational study prompted the FDA to strengthen the Warnings and Precautions section of azithromycin drug labels. This summary describes the electrophysiological effects of macrolides, reviews literature indicating that the large majority of subjects experiencing cardiac arrhythmias from macrolides have coexisting risk factors and that the incidence of arrhythmias in absence of coexisting risk factors is very low, examines recently published studies describing the relative risk of arrhythmias from macrolides, and concludes that this risk has been overestimated and suggests an approach to patient evaluation that should reduce the relative risk and the incidence of arrhythmias to the point that chronic macrolides can be used safely in the majority of subjects for whom they are recommended.

  18. Determination of slope failure using 2-D resistivity method

    Science.gov (United States)

    Muztaza, Nordiana Mohd; Saad, Rosli; Ismail, Nur Azwin; Bery, Andy Anderson

    2017-07-01

    Landslides and slope failure may give negative economic effects including the cost to repair structures, loss of property value and medical costs in the event of injury. To avoid landslide, slope failure and disturbance of the ecosystem, good and detailed planning must be done when developing hilly area. Slope failure classification and various factors contributing to the instability using 2-D resistivity survey conducted in Selangor, Malaysia are described. The study on landslide and slope failure was conducted at Site A and Site B, Selangor using 2-D resistivity method. The implications of the anticipated ground conditions as well as the field observation of the actual conditions are discussed. Nine 2-D resistivity survey lines were conducted in Site A and six 2-D resistivity survey lines with 5 m minimum electrode spacing using Pole-dipole array were performed in Site B. The data were processed using Res2Dinv and Surfer10 software to evaluate the subsurface characteristics. 2-D resistivity results from both locations show that the study areas consist of two main zones. The first zone is alluvium or highly weathered with the resistivity of 100-1000 Ωm at 20-70 m depth. This zone consists of saturated area (1-100 Ωm) and boulders with resistivity value of 1200-3000 Ωm. The second zone with resistivity values of > 3000 Ωm was interpreted as granitic bedrock. The study area was characterized by saturated zones, highly weathered zone, highly contain of sand and boulders that will trigger slope failure in the survey area. Based on the results obtained from the study findings, it can be concluded that 2-D resistivity method is useful method in determination of slope failure.

  19. Antibiotic resistance determinants of a group of multidrug-resistant Acinetobacter baumannii in China.

    Science.gov (United States)

    Xiao-Min, Xu; You-Fen, Fan; Wei-Yun, Feng; Zu-Huang, Mi; Xing-Bei, Weng

    2014-06-01

    A group of Acinetobacter baumannii confers multidrug resistance, but the molecular epidemiology and multidrug resistance mechanisms are poorly understood. Nineteen isolates were identified, and the antimicrobial susceptibility profile was determined using the disc diffusion method. Then, PCR of 78 kinds of resistance-associated genes were performed. A novel variant of blaADC gene: blaADC-67 gene (Genbank accession No. JX169789) was prevalent in all 19 isolates. Moreover, ISAba1 could also provide strong promoter to upregulate the expression of blaADC67 to confer resistance to beta-lactam. This is the first report of emergence of blaADC-67 in A. baumannii worldwide, which might confer resistance to beta-lactam.

  20. Macrolides vs. quinolones for community-acquired pneumonia: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Skalsky, K; Yahav, D; Lador, A; Eliakim-Raz, N; Leibovici, L; Paul, M

    2013-04-01

    The relative efficacy, safety and ecological implications of macrolides vs. quinolones in the treatment of community-acquired pneumonia (CAP) are debatable. We performed a systematic review and meta-analysis of randomized controlled trials comparing any macrolide vs. any quinolone for the treatment of CAP among adult inpatients or outpatients, as monotherapy or both in combination with a beta-lactam. We did not limit inclusion by pneumonia severity, publication status, language or date of publication. The primary outcomes assessed were 30-day all-cause mortality and treatment failure. Two authors independently extracted the data. Fixed effect meta-analysis of risk ratios (RRs) with 95% confidence intervals was performed. Sixteen trials (4989 patients) fulfilling inclusion criteria were identified, mostly assessing outpatients with mild to moderate CAP. All-cause mortality was not significantly different for macrolides vs. quinolones, RR 1.03 (0.63-1.68, seven trials), with a low event rate (2%). Treatment failure was significantly lower with quinolones, RR 0.78 (0.67-0.91, 16 trials). The definition of failure used in the primary studies was not clearly representative of patients' benefit. Microbiological failure was lower with quinolones, RR 0.63 (0.49-0.81, 13 trials). All adverse events, adverse events requiring discontinuation and any premature antibiotic discontinuation were significantly more frequent with macrolides, mainly on account of gastrointestinal adverse events. Resistance development was not assessed in the trials. Randomized controlled trials show an advantage of quinolones in the treatment of CAP with regard to clinical cure without need for antibiotic modification at end of treatment and gastrointestinal adverse events. The clinical significance of this advantage is unclear.

  1. Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria.

    Science.gov (United States)

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2016-07-01

    Any pathogen population sufficiently large is expected to harbor spontaneous drug-resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer, exacerbating their predominance in the final mutant subpopulation. Here, we investigate the extent to which this reduction in evenness can constrain the genetic diversity of spontaneous drug resistance in bacteria. Combining theory and experiments, we show that even small variations in growth rate between resistant mutants and the wild type result in orders-of-magnitude differences in genetic diversity. Indeed, only a slight fitness advantage for the mutant is enough to keep diversity low and independent of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population's capacity to cope with future challenges (i.e., second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multidrug-resistant microbes, as well as contribute to theories aimed at predicting cancer evolution.

  2. [In vitro antibacterial activity of rokitamycin, a new macrolide antibiotic. Results of a multicenter study].

    Science.gov (United States)

    Soussy, C J; Le Van Thoi, J; Meyran, M; Joly, B; Derlot, E; Morel, C

    1990-05-01

    Minimal inhibitory concentrations (MIC) of rokitamycin (R) were evaluated by agar dilution for 914 bacterial strain isolated in 4 hospitals and classed as a function of susceptibility and resistance to Macrolides-Lincosamides-Streptogramines group (MLS). MICs of R ranged from 0.06 to 1 microgram/ml (mode MIC 0.25-0.5) on Staphylococci susceptible to MLS and on MLSB inducible strains; R was inactive on MLSB constitutive strains. MICs of R ranged from 0.008 to 0.5 microgram/ml (mode MIC 0.06 to 0.25) for Streptococci and Pneumococci susceptible to erythromycin (E) and from 0.06 to greater than 128 for strains resistant to E. Enterococci susceptible to E were inhibited by 0.06 to 0.5 microgram/ml (mode MIC 0.5) and strains resistant to E by 0.25 to greater than 128. Haemophilus were inhibited by 0.5 to 0.65 microgram/ml (mode MICs of R ranged generally from 0.016 to 0.5 microgram/ml (mode MIC 0.12) for C. perfringens and from 0.016 to 1 (mode MIC 0.06) for B. fragilis. Thus, R was shown to be among macrolide antibiotics of resistance strains. Its activity was superior to that of other products of this group spiramycin, josamycin, miokamycin, particularly on Gram positive cocci. R had a good activity on Neisseria, Branhamella, anaerobes and, as others macrolides, was poorly active on Haemophilus.

  3. Standard test method for determination of resistance to staining

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2004-01-01

    1.1 This test method is intended to determine the resistance to staining of ceramic tile surfaces. 1.2 The resistance to staining is determined by maintaining test solutions in contact with ceramic tile surfaces for a specified period of time. After exposure, the surface is cleaned in a defined manner, and the test specimens are inspected visually for change. 1.3 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.

  4. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS: Study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Uzun Sevim

    2012-06-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. Methods/design The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. Discussion We investigate whether

  5. Method of separate determination of high-ohmic sample resistance and contact resistance

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    Vadim A. Golubiatnikov

    2015-09-01

    Full Text Available A method of separate determination of two-pole sample volume resistance and contact resistance is suggested. The method is applicable to high-ohmic semiconductor samples: semi-insulating gallium arsenide, detector cadmium-zinc telluride (CZT, etc. The method is based on near-contact region illumination by monochromatic radiation of variable intensity from light emitting diodes with quantum energies exceeding the band gap of the material. It is necessary to obtain sample photo-current dependence upon light emitting diode current and to find the linear portion of this dependence. Extrapolation of this linear portion to the Y-axis gives the cut-off current. As the bias voltage is known, it is easy to calculate sample volume resistance. Then, using dark current value, one can determine the total contact resistance. The method was tested for n-type semi-insulating GaAs. The contact resistance value was shown to be approximately equal to the sample volume resistance. Thus, the influence of contacts must be taken into account when electrophysical data are analyzed.

  6. Determining the resistance of X-pinch plasma

    Institute of Scientific and Technical Information of China (English)

    Zhao Shen; Xue Chuang; Zhu Xin-Lei; Zhang Ran; Luo Hai-Yun; Zou Xiao-Bing; Wang Xin-Xin

    2013-01-01

    The current and the voltage of an X-pinch were measured.The inductance of the X-pinch was assumed to be a constant and estimated by the calculation of the magnetic field based on the well-known Biot-Savart's Law.The voltage of the inductance was calculated with L.di/dt and subtracted from the measured voltage of the X-pinch.Then,the resistance of the X-pinch was determined and the following results were obtained.At the start of the current flow the resistance of the exploding wires is several tens of Ohms,one order of magnitude,higher than the metallic resistance of the wires at room temperature,and then it falls quickly to about 1 Ω,which reflects the physical processes occurring in the electrically exploding wires,i.e.,a current transition from the highly resistive wire core to the highly conductive plasma.It was shown that the inductive contribution to the voltage of the X-pinch is less than the resistive contribution.For the wires we used,the wires' material and diameter have no strong influence on the resistance of the X-pinch,which may be explained by the fact that the current flows through the plasma rather than through the metallic wire itself.As a result,the current is almost equally divided between two parallel X-pinches even though the diameter and material of the wires used for these two X-pinches are significantly different.

  7. Are Sewage Treatment Plants Promoting Antibiotic Resistance?

    Science.gov (United States)

    1. Introduction 1.1. How bacteria exhibit resistance 1.1.1. Resistance to -lactams 1.1.2. Resistance to sulphonamides and trimethoprim 1.1.3. Resistance to macrolides 1.1.4. Resistance to fluoroquinolones 1.1.5. Resistance to tetracyclines 1.1.6. Resistance to nitroimidaz...

  8. Are Sewage Treatment Plants Promoting Antibiotic Resistance?

    Science.gov (United States)

    1. Introduction 1.1. How bacteria exhibit resistance 1.1.1. Resistance to -lactams 1.1.2. Resistance to sulphonamides and trimethoprim 1.1.3. Resistance to macrolides 1.1.4. Resistance to fluoroquinolones 1.1.5. Resistance to tetracyclines 1.1.6. Resistance to nitroimidaz...

  9. Gallium maltolate as an alternative to macrolides for treatment of presumed Rhodococcus equi pneumonia in foals.

    Science.gov (United States)

    Cohen, Noah D; Slovis, Nathan M; Giguère, Steeve; Baker, Samantha; Chaffin, M Keith; Bernstein, Lawrence R

    2015-01-01

    Macrolide-resistant isolates of Rhodococcus equi are emerging, prompting the search for clinically effective alternative antimicrobials. The proportion of foals with ultrasonographic evidence of pneumonia presumed to be caused by R. equi that had a successful outcome when administered gallium maltolate (GaM) PO would not be more than 10% inferior (ie, lower) than that of foals receiving standard treatment. Fifty-four foals with subclinical pulmonary abscesses among 509 foals at 6 breeding farms in Kentucky. Controlled, randomized, prospective noninferiority study. Foals with ultrasonographic lesions >1 cm in diameter (n = 54) were randomly allocated to receive per os either clarithromycin combined with rifampin (CLR+R) or GaM, and followed up for 28 days by daily physical inspections and weekly (n = 1 farm) or biweekly (n = 4 farms) thoracic ultrasound examinations by individuals unaware of treatment-group assignments. Treatment success was defined as resolution of ultrasonographically identified pulmonary abscesses within 28 days of initiating treatment. Noninferiority was defined as a 90% confidence interval for the observed difference in CLR+R minus GaM that was ≤10%. The proportion of GaM-treated foals that resolved (70%; 14/20) was similar to that of foals treated with CLR+R (74%; 25/34), but we failed to demonstrate noninferiority for GaM relative to CLR+R; however, GaM was noninferior to CLR+R treatment when results from a noncompliant farm were excluded. Gallium maltolate is not inferior to macrolides for treating foals with subclinical pneumonia. Use of GaM might reduce pressure for macrolide-resistance in R. equi. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  10. Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância Anti-inflammatory effects of macrolides in childhood lung diseases

    Directory of Open Access Journals (Sweden)

    Fernanda Luisi

    2012-12-01

    Full Text Available Os macrolídeos são fármacos com efeitos antimicrobianos especialmente contra patógenos intracelulares. Vários estudos têm demonstrado possíveis efeitos anti-inflamatórios dos macrolídeos. Esses medicamentos inibem a produção de algumas interleucinas e podem reduzir a inflamação neutrofílica pulmonar. Ensaios clínicos têm demonstrado efeitos benéficos dos macrolídeos em diversas doenças pulmonares crônicas. O objetivo deste estudo foi revisar os dados recentes da literatura médica sobre os efeitos anti-inflamatórios dos macrolídeos nas doenças respiratórias da infância, através da pesquisa da base de dados Medline (PubMed dos seguintes termos em inglês: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; e "macrolide and acute bronchiolitis" Foram selecionados artigos publicados em revistas científicas internacionais entre 2001 e 2012. Estudos clínicos e evidências in vitro comprovam o efeito anti-inflamatório dos macrolídeos em doenças respiratórias. Alguns ensaios clínicos demonstram benefícios na administração de macrolídeos em pacientes com fibrose cística; porém, o risco de resistência bacteriana deve ser considerado na análise desses benefícios. Tais benefícios são controversos em outras doenças respiratórias, e seu uso rotineiro não está indicado. Mais estudos clínicos controlados são necessários para avaliar a eficácia desses medicamentos como anti-inflamatórios. Dessa forma, poderemos definir melhor os benefícios dos macrolídeos no tratamento de cada uma das situações clínicas especificadas.Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have anti-inflammatory effects. Macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. Clinical trials have demonstrated beneficial effects of

  11. Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies.

    Science.gov (United States)

    Caffrey, Patrick; De Poire, Eimear; Sheehan, James; Sweeney, Paul

    2016-05-01

    The polyene macrolide group includes important antifungal drugs, to which resistance does not arise readily. Chemical and biological methods have been used in attempts to make polyene antibiotics with fewer toxic side effects. Genome sequencing of producer organisms is contributing to this endeavour, by providing access to new compounds and by enabling yield improvement for polyene analogues obtained by engineered biosynthesis. This recent work is also enhancing bioinformatic methods for deducing the structures of cryptic natural products from their biosynthetic enzymes. The stereostructure of candicidin D has recently been determined by NMR spectroscopy. Genes for the corresponding polyketide synthase have been uncovered in several different genomes. Analysis of this new information strengthens the view that protein sequence motifs can be used to predict double bond geometry in many polyketides.Chemical studies have shown that improved polyenes can be obtained by modifying the mycosamine sugar that is common to most of these compounds. Glycoengineered analogues might be produced by biosynthetic methods, but polyene glycosyltransferases show little tolerance for donors other than GDP-α-D-mycosamine. Genome sequencing has revealed extending glycosyltransferases that add a second sugar to the mycosamine of some polyenes. NppY of Pseudonocardia autotrophica uses UDP-N-acetyl-α-D-glucosamine as donor whereas PegA from Actinoplanes caeruleus uses GDP-α-D-mannose. These two enzymes show 51 % sequence identity and are also closely related to mycosaminyltransferases. These findings will assist attempts to construct glycosyltransferases that transfer alternative UDP- or (d)TDP-linked sugars to polyene macrolactones.

  12. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62,993), and A-56268) on Toxoplasma gondii

    Energy Technology Data Exchange (ETDEWEB)

    Chang, H.R.; Pechere, J.C.

    1988-04-01

    The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with (/sup 3/H)uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

  13. 应用HPLC-MS/MS对鸡组织中三种大环内酯类抗生素残留的同时检测%Simultaneous determination of three macrolide antibiotics residues in chicken by HPLC-MS/MS

    Institute of Scientific and Technical Information of China (English)

    杨娜; 汤春莲; 欧俊秀; 王中宝; 曾明华

    2012-01-01

    In order to establish the high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS) for the determination of there macrolide antibiotics(tylosin,tilmicosin and azithromycin) in chicken,samples were extracted with acetonitrile and cleaned-up by MCX cartridge.The three antibiotics were separated with luna C8 column by a gradient elution program with 1 mL/L formic acid-acetonitrile and 1 mL/L formic acid-water as the mobile phase.The identification of three drugs was carried out by positive electrospray ionization(ESI+) in multiple reaction monitoring(MRM) mode.In result,the calibration curves showed good linearity for 3 antibiotics in the range from 1 ng/mL to 100 ng/mL,with correlation coefficient greater than 0.998.The limits of detection(LOD) were 0.1,0.2 and 0.3 μg/kg,respectively and the limits of quantification(LOQ) were 0.3,0.7,1.0 μg/kg for AZI,TILM and TYL,respectively.The average recoveries varied from 83.5% to 108.0% at three spiked levels of 0.5,5 and 20 μg/kg.The intra-RSDS were in the range from 4.3% to 15.2% and inter-RSDS were from 4.8% to 11.3%.The result showed that the method is simple,rapid,sensitive and suitable for the simultaneous determination of 3 macrolide antibiotics in chicken.%为建立鸡体内阿奇霉素(AZI)、替米考星(TILM)、泰乐菌素(TYL)三种大环内酯类抗生素残留的高效液相色谱-串联质谱检测方法,样品经乙腈提取,MCX柱净化,Luna C8色谱柱分离,以1mL/L的甲酸-乙腈和1mL/L甲酸-水作为流动相进行梯度洗脱以及电喷雾正离子多反应模式检测。结果显示,3种抗生素在1~100ng/mL范围内呈现良好的线性关系,相关系数R2均大于0.998,AZI、TILM、TYL的检测限分别为0.1、0.2、0.3μg/kg,定量限依次为0.3、0.7、1.0μg/kg。以0.5、5、20μg/kg共3个水平进行添加回收试验,3种药物的回收率为83.5%~108.0%,日内相对标准偏差为4.3%~15.2%,日间相对标准偏差为4.8%~11.3%。结果表明,

  14. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations

    Directory of Open Access Journals (Sweden)

    Couldwell DL

    2015-05-01

    failure, due to bacteria with coexistent macrolide-associated and fluoroquinolone-associated resistance mutations, were recently published by Australian investigators. Pristinamycin and solithromycin may be of clinical benefit for such multidrug-resistant infections. Further clinical studies are required to determine the optimal therapeutic dosing schedules for both agents to effect clinical cure and minimize the risk of emergent antimicrobial resistance. Continual inappropriate M. genitalium treatments will likely lead to untreatable infections in the future. Keywords: Mycoplasma genitalium, non-gonococcal urethritis, macrolide, fluoroquinolone, resistance, treatment failure

  15. Antipneumococcal activities of two novel macrolides, GW 773546 and GW 708408, compared with those of erythromycin, azithromycin, clarithromycin, clindamycin, and telithromycin.

    Science.gov (United States)

    Matic, Vlatka; Kosowska, Klaudia; Bozdogan, Bulent; Kelly, Linda M; Smith, Kathy; Ednie, Lois M; Lin, Gengrong; Credito, Kim L; Clark, Catherine L; McGhee, Pamela; Pankuch, Glenn A; Jacobs, Michael R; Appelbaum, Peter C

    2004-11-01

    The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with erm(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were >/=0.5 microg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No mef(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two mef(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 microg/ml. Single-step studies showed mutation frequencies 4.3 x 10(-3) for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h.

  16. Antimicrobial resistance of thermophilic Campylobacter

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Engberg, J.

    2001-01-01

    Campylobacter has become the leading cause of zoonotic enteric infections in developed and developing countries world-wide. Antimicrobial resistance has emerged among Campylobacter mainly as a consequence of the use of antimicrobial agents in food animal production. Resistance to drugs of choice...... for the treatment of infections, macrolides and fluoroquinolones has emerged as a clinical problem and interventions to reduce this are recommended. Resistance to fluoroquinolones and macrolides is mediated by chromosomal mutations. Resistance to other relevant antimicrobial agents, mediated by acquired resistance...

  17. Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants

    Science.gov (United States)

    Blanco, Paula; Hernando-Amado, Sara; Reales-Calderon, Jose Antonio; Corona, Fernando; Lira, Felipe; Alcalde-Rico, Manuel; Bernardini, Alejandra; Sanchez, Maria Blanca; Martinez, Jose Luis

    2016-01-01

    Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy. In this regard, it is worth mentioning that efflux pumps can extrude a wide range of substrates that include, besides antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals or bacterial metabolites, among others. In the current review, we present information on the different functions that multidrug efflux pumps may have for the bacterial behaviour in different habitats as well as on their regulation by specific signals. Since, in addition to their function in non-clinical ecosystems, multidrug efflux pumps contribute to intrinsic, acquired, and phenotypic resistance of bacterial pathogens, the review also presents information on the search for inhibitors of multidrug efflux pumps, which are currently under development, in the aim of increasing the susceptibility of bacterial pathogens to antibiotics. PMID:27681908

  18. Remarkable increase in fluoroquinolone-resistant Mycoplasma genitalium in Japan.

    Science.gov (United States)

    Kikuchi, Mina; Ito, Shin; Yasuda, Mitsuru; Tsuchiya, Tomohiro; Hatazaki, Kyoko; Takanashi, Masaki; Ezaki, Takayuki; Deguchi, Takashi

    2014-09-01

    We determined the prevalence of macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium DNA specimens from men with non-gonococcal urethritis (NGU) and analysed their effects on antibiotic treatments of M. genitalium infections. In this retrospective study, we examined antibiotic resistance-associated mutations in the 23S rRNA, gyrA and parC genes of M. genitalium and the association of the mutations with microbiological outcomes of antibiotic treatments in men with M. genitalium-positive NGU. No macrolide resistance-associated mutations in the 23S rRNA gene were observed in 27 M. genitalium DNA specimens in 2011 and in 24 in 2012. However, 5 of 17 in 2013 had 23S rRNA mutations. Three of 15 in 2011, 6 of 19 in 2012 and 8 of 17 in 2013 had fluoroquinolone resistance-associated alterations in ParC. Three in 2013 had both the antibiotic resistance-associated alterations coincidentally. In two men with M. genitalium harbouring 23S rRNA mutations, the mycoplasma persisted after treatment with a regimen of 2 g of extended-release azithromycin (AZM-SR) once daily for 1 day. All nine men with mycoplasma harbouring ParC alterations were microbiologically cured with a regimen of 100 mg of sitafloxacin twice daily for 7 days. Macrolide- or fluoroquinolone-resistant M. genitalium appears to be increasing, and the increase in fluoroquinolone-resistant mycoplasmas is especially remarkable in Japan. Mycoplasmas harbouring 23S rRNA mutations would be resistant to the AZM-SR regimen, but those harbouring ParC alterations would still be susceptible to the sitafloxacin regimen. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Standard practice for determining rail-to-Earth resistance

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    1999-01-01

    1.1 This practice covers the procedures necessary to follow for measuring resistance-to-earth of the running rails which are used as the conductors for returning the train operating current to the substation in electric mass transit systems. 1.2 The values stated in SI units are to be regarded as the standard. The values given in parentheses are for information only. 1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.

  20. Determinants of virological failure and antiretroviral drug resistance in Mozambique.

    Science.gov (United States)

    Rupérez, María; Pou, Christian; Maculuve, Sonia; Cedeño, Samandhy; Luis, Leopoldina; Rodríguez, Judith; Letang, Emilio; Moltó, José; Macete, Eusébio; Clotet, Bonaventura; Alonso, Pedro; Menéndez, Clara; Naniche, Denise; Paredes, Roger

    2015-09-01

    The objective of this study was to inform public health actions to limit first-line ART failure and HIV drug resistance in Mozambique. This was a cross-sectional study. HIV-1-infected adults on first-line ART for at least 1 year attending routine visits in the Manhiça District Hospital, in a semi-rural area in southern Mozambique with no HIV-1 RNA monitoring available, were evaluated for clinical, socio-demographic, therapeutic, immunological and virological characteristics. Factors associated with HIV-1 RNA ≥1000 copies/mL and HIV drug resistance were determined using multivariate logistic regression. The study included 334 adults on first-line ART for a median of 3 years, of which 65% (214/332) had suppressed viraemia, 11% (37/332) had low-level viraemia (HIV-1 RNA 150-999 copies/mL) and 24% (81/332) had overt virological failure (HIV-1 RNA ≥1000 copies/mL). HIV drug resistance was detected in 89% of subjects with virological failure, but in none with low-level viraemia. Younger age [OR = 0.97 per additional year (95% CI = 0.94-1.00), P = 0.039], ART initiation at WHO stage III/IV [OR = 2.10 (95% CI = 1.23-3.57), P = 0.003] and low ART adherence [OR = 2.69 (95% CI = 1.39-5.19), P = 0.003] were associated with virological failure. Longer time on ART [OR = 1.55 per additional year (95% CI = 1.00-2.43), P = 0.052] and illiteracy [OR = 0.24 (95% CI = 0.07-0.89), P = 0.033] were associated with HIV drug resistance. Compared with HIV-1 RNA, clinician's judgement of ART failure, based on clinical and immunological outcomes, only achieved 29% sensitivity and misdiagnosed 1 out of every 4.5 subjects. Public health programmes in Mozambique should focus on early HIV diagnosis, early ART initiation and adherence support. Virological monitoring drastically improves the diagnosis of ART failure, enabling a better use of resources. © The Author 2015. Published by Oxford University Press on behalf of the British

  1. Plasmid-determined resistance to fosfomycin in Serratia marcescens.

    Science.gov (United States)

    Mendoza, C; Garcia, J M; Llaneza, J; Mendez, F J; Hardisson, C; Ortiz, J M

    1980-08-01

    Multiple-antibiotic-resistant strains of Serratia marcescens isolated from hospitalized patients were examined for their ability to transfer antibiotic resistance to Escherichia coli by conjugation. Two different patterns of linked transferable resistance were found among the transconjugants. The first comprised resistance to carbenicillin, streptomycin, and fosfomycin; the second, and more common, pattern included resistance to carbenicillin, streptomycin, kanamycin, gentamicin, tetracycline, chloramphenicol, sulfonamide, and fosfomycin. The two types of transconjugant strains carried a single plasmid of either 57 or 97 megadaltons in size. Both of these plasmids are present in parental S. marcescens strains resistant to fosfomycin. The 57-megadalton plasmid was transformed into E. coli.

  2. Balticolid: A New 12-Membered Macrolide with Antiviral Activity from an Ascomycetous Fungus of Marine Origin

    Directory of Open Access Journals (Sweden)

    Ulrike Lindequist

    2011-05-01

    Full Text Available A new 12-membered macrolide, balticolid (1 was isolated from the EtOAc extract of the culture broth of fungal strain 222 belonging to the Ascomycota, which was found on driftwood collected from the coast of the Greifswalder Bodden, Baltic Sea, Germany. The structure of balticolid was determined to be (3R,11R, (4E,8E-3-hydroxy-11-methyloxacyclododeca-4,8-diene-1,7-dione using extensive spectral data as well as the modified Mosher ester method. Balticolid (1 displayed anti-HSV-1 activity with an IC50 value of 0.45 µM.

  3. Determinants of carriage of resistant Escherichia coli in the Indonesian population inside and outside hospitals

    NARCIS (Netherlands)

    O.D. Duerink (Offra); E.S. Lestari (Endang Sri); U. Hadi (Usman); N.J.D. Nagelkerke (Nico); J.A. Severin (Juliëtte); H.A. Verbrugh (Henri); M. Keuter (Monique); I.C. Gyssens (Inge); P. van den Broek (Peterhans)

    2007-01-01

    textabstractObjectives: Antibiotic resistance is a worldwide healthcare problem exacerbated by antibiotic use and transmission of resistant bacteria. Not much is known about resistance in commensal flora and about determinants for resistance in Indonesia. This study analysed recent antibiotic use as

  4. Topical macrolide immunomodulators: a role in the treatment of vitiligo?

    NARCIS (Netherlands)

    Tjioe, M.; Vissers, W.H.P.M.; Gerritsen, M.J.P.

    2006-01-01

    Recently, topical macrolide immunomodulators have been successfully introduced in the treatment of atopic dermatitis. With the growing interest in this new line of topical immunosuppressants, research into the efficacy of these medicines in other T-cell-mediated skin diseases, such as psoriasis, lic

  5. Phenotypic and molecular assessment of antimicrobial resistance profile of airborne Staphylococcus spp. isolated from flats in Kraków.

    Science.gov (United States)

    Lenart-Boroń, Anna; Wolny-Koładka, Katarzyna; Juraszek, Katarzyna; Kasprowicz, Andrzej

    2017-01-01

    Bacteria of the genus Staphylococcus were isolated from air sampled from living spaces in Kraków (Poland). In total, 55 strains belonging to the genus Staphylococcus were isolated from 45 sites, and 13 species of coagulase-negative staphylococci were identified. The species composition of studied airborne microbiota contains Staphylococcus species that are rarely infectious to humans. Most commonly isolated species comprised S. hominis and S. warneri. The disk-diffusion tests showed that the collected isolates were most frequently resistant to erythromycin. The PCR technique was employed to search for genes conferring the resistance in staphylococci to antibiotics from the group of macrolides, lincosamides and streptogramins. The analyzed Staphylococcus isolates possessed simultaneously 4 different resistance genes. The molecular analysis with the use of specific primers allowed to determine the most prevalent gene which is mphC, responsible for the resistance to macrolides and for the enzymatic inactivation of the drug by phosphotransferase. The second most often detected gene was msrA1, which confers the resistance of staphylococci to macrolides and is responsible for active pumping of antimicrobial particles out of bacterial cells.

  6. Determination of Resistance to Lodging by Stem Strength in Wheat

    Institute of Scientific and Technical Information of China (English)

    XIAO Shi-he; ZHANG Xiu-ying; YAN Chang-sheng; ZHANG Wen-xiang; HAI Lin; GUO Hui-jun

    2002-01-01

    Stem strength affects directly the resistance of wheat plant to lodging. Unfortunately, the determination of the stem strength is not perfect for wheat breeding and genetics up to now. In this study a prostrate tester was engaged for testing the stem strength of 661 wheat varieties and of 1183 single plants from a F2 population. The results showed that the suitable time to determine the stem strength should be from milk stage to dough ripe stage. The stem strength at the maturity would decrease and it was not easy to distinguish the difference among the varieties. The single plant with a strong stem could be judged using the prostrate tester from the F2 population. By testing the stem strength and anatomic characters of 30 varieties, a significant negative relationship between the pith diameter of the upper internodes and the stem strength was observed. On the other hand, there was a significant positive relationship between the stem diameter of the lower internodes and stem strength. It was suggested that a wheat breeder should breed the cuitivar with a strong stem, because the spike weight and biomass yield were significantly related to the stem strength.

  7. Crack resistance curves determination of tube cladding material

    Science.gov (United States)

    Bertsch, J.; Hoffelner, W.

    2006-06-01

    Zirconium based alloys have been in use as fuel cladding material in light water reactors since many years. As claddings change their mechanical properties during service, it is essential for the assessment of mechanical integrity to provide parameters for potential rupture behaviour. Usually, fracture mechanics parameters like the fracture toughness KIC or, for high plastic strains, the J-integral based elastic-plastic fracture toughness JIC are employed. In claddings with a very small wall thickness the determination of toughness needs the extension of the J-concept beyond limits of standards. In the paper a new method based on the traditional J approach is presented. Crack resistance curves (J-R curves) were created for unirradiated thin walled Zircaloy-4 and aluminium cladding tube pieces at room temperature using the single sample method. The procedure of creating sharp fatigue starter cracks with respect to optical recording was optimized. It is shown that the chosen test method is appropriate for the determination of complete J-R curves including the values J0.2 (J at 0.2 mm crack length), Jm (J corresponding to the maximum load) and the slope of the curve.

  8. Cloning of a lincosamide resistance determinant from Streptomyces caelestis, the producer of celesticetin, and characterization of the resistance mechanism.

    OpenAIRE

    1990-01-01

    Self-resistance has been investigated in Streptomyces caelestis (producer of the lincosamide antibiotic celesticetin), from which a lincosamide resistance determinant (clr) has been isolated on a 1-kilobase DNA fragment and cloned in Streptomyces lividans. The clr product is a specific methylase which produces a single residue of N6-monomethyladenine in 23S rRNA at position 2058, thereby rendering the 50S ribosmal subunit resistant to the action of lincosamides.

  9. Cloning of a lincosamide resistance determinant from Streptomyces caelestis, the producer of celesticetin, and characterization of the resistance mechanism.

    Science.gov (United States)

    Calcutt, M J; Cundliffe, E

    1990-01-01

    Self-resistance has been investigated in Streptomyces caelestis (producer of the lincosamide antibiotic celesticetin), from which a lincosamide resistance determinant (clr) has been isolated on a 1-kilobase DNA fragment and cloned in Streptomyces lividans. The clr product is a specific methylase which produces a single residue of N6-monomethyladenine in 23S rRNA at position 2058, thereby rendering the 50S ribosmal subunit resistant to the action of lincosamides. PMID:2376570

  10. Identification of a New Tetracycline Resistance Determinant tet47 from Fish Intestine.

    Science.gov (United States)

    Huang, Ying; Zhang, Lu; Wang, Hua H

    2015-08-01

    To better understand food safety risks, functional genomic analysis was conducted to identify undescribed antibiotic resistance genes in fish samples from an aquaculture fish farm in Ohio. A fosmid genomic library from pooled DNA of antibiotic-resistant isolates was used to screen for resistance genes against tetracycline (Tet). A new Tet-resistant determinant designated as tet 47 was identified, with the original hosts being Providencia spp. from fish intestine. The new gene was also found to confer Tet resistance in Escherichia coli. Fish and byproducts were shown to be possible carriers that may disseminate new, functional, and potentially transmissible antibiotic resistance determinants through food, feed, and environmental contacts.

  11. Genetic determinants of resistance to gastrointestinal nematodes in ruminants

    Science.gov (United States)

    Genetic markers for host resistance to gastrointestinal parasites have long been sought by the livestock industry as a way to select more resistant individuals, and alternatively, to help farmers with parasite control because high egg shedders will be removed from the flock and reduce parasite trans...

  12. Past, present and future of macrolide therapy for chronic rhinosinusitis in Japan.

    Science.gov (United States)

    Shimizu, Takeshi; Suzaki, Harumi

    2016-04-01

    In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

  13. Determination of Characteristics of Erythromycin Resistant Streptococcus pneumoniae with Preferred PCV Usage in Iran

    Science.gov (United States)

    Talebi, Malihe; Azadegan, Azadeh; Sadeghi, Javad; Ahmadi, Ali; Katouli, Mohammad

    2016-01-01

    Amongst 100 Streptococcus pneumoniae isolated from clinical cases and nasopharynx of healthy individuals, 60 erythromycin resistant strains were isolated and characterized using MLST, PFGE, transposon analysis and Quellung reaction. Most of the S. pneumoniae erythromycin resistant (80%) were found to be attributable to the ermB-edncoded ribosome methylase activity which differs from the dominant mechanism of macrolide resistance seen in North America. The most predominant transposons were; Tn1545/6003 (27%), Tn6002 (22%), Tn2009 (20%), Tn2010 (17%). Number of the clinical isolates carrying Tn2010 was more significant than the normal flora. The serotypes found were; 14 (33%), 3 (22%), 23F (15%), 19F (15%), 19A (7%), 6A (3%), 9V (3%) and 6B (2%). The most prevalent serotypes among the clinical (n = 28) and normal flora (n = 32) isolates were serotypes 14 (46%) and 3 (31%), respectively. The most prevalent vaccine serotypes amongst the clinical isolates and the healthy individuals were pneumococcal conjugate vaccines (PCV) 13 and PCV10, respectively. PFGE revealed 34 pulsotypes with 9 common and 25 single types. Significant number of the normal isolates belonged to CT5 and CT6. On the other hand, significant number of clinical isolates belonged to CT8 as compared to the normal flora isolates. MLST showed 2 dominant sequence types. ST3130 (23%) and ST180 (22%) were the most predominant sequence types in the clinical and normal isolates, respectively. There was no significant difference in other sequence types between clinical and normal flora isolates. Three polyclonal complexes including Sweden15A -25, Spain23F-1 and Spain9V-3 constituted 58% of the isolates. Our results suggest that the genetic diversity and transposon distribution were high among S. pneumoniae, particularly in the isolates containing erm(B) and double antibiotic resistant genes (erm/mef). The results presented here could influence the change in the current vaccination practices in Iran which

  14. The tetracycline resistance determinant Tet 39 and the sulphonamide resistance gene sulII are common among resistant Acinetobacter spp. isolated from integrated fish farms in Thailand

    DEFF Research Database (Denmark)

    Agersø, Yvonne; Petersen, Andreas

    2007-01-01

    Objectives: To determine the genetic basis for tetracycline and sulphonamide resistance and the prevalence of class I and II integrons in oxytetracycline-resistant Acinetobacter spp. from integrated fish farms in Thailand. Methods: A total of 222 isolates were screened for tetracycline resistance...... genes [tet(A), tet(B), tet(H), tet(M) and tet(39)] and class II integrons by PCR. One hundred and thirty-four of these isolates were also sulphonamide resistant and these isolates were screened for sulphonamide resistance genes (sulII and sulIII) as well as class I integrons. Plasmid extraction...

  15. The rarely reported tet(31) tetracycline resistance determinant is common in Gallibacterium anatis

    DEFF Research Database (Denmark)

    Bojesen, Anders M.; Bager, Ragnhild J.; Ifrah, Dan

    2011-01-01

    prevalent tetracycline resistance determinant in a larger collection of G. anatis field strains from Mexico and Denmark. However, in 41% of the tetracycline resistant strains no determinant could be assigned. Here we demonstrate that tet(31) is a common determinant in G. anatis originating from chickens...

  16. In vitro impact of macrolide antibiotics on the viability of selected mammalian cell lines

    Directory of Open Access Journals (Sweden)

    Eva Tvrdá

    2016-10-01

    Full Text Available The aim of this study was to evaluate the in vitro cytotoxicity of different concentrations of macrolide  antibiotics (tilmicosin-TILM, tylosin-TYL and spiramycin-SPI on selected animal cell cultures. VERO cells (kidney cells from Macacus rhesus, FE cells (feline embryonal cells and BHK 21 cells (cell line from young hamster kidneys were used in the study and subjected to concentrations of macrolides ranging 50-1000 µg/mL, depending on the specific antibiotic and cell line. The cell viability expressed as the mitochondrial activity of living cells was assessed using the metabolic mitochondrial MTT test. The effect of tilmicosin: FE cells were the most sensitive with a significant decrease of mitochondrial activity at 100-150 µg/mL (P<0.001 TILM. VERO cells were the most resistant, as no significant decrease of viability was observed at any TILM dose. The effect of tylosin: FE cells showed the highest sensitivity to TYL, as 1000 µg/mL reduced the cell viability to a half (P<0.001 when compared to the untreated control. Similarly, a decreased viability of BHK 21 cells was observed following the supplementation of 1500 (P<0.001 and 900 (P<0.05 µg/mL TYL. VERO cells exhibited the highest resilience to the TYL treatment, with no significant differences of viability in comparison to the control. The effect of spiramycin: BHK 21 cells exhibited the highest sensitivity to the antibiotic, as all concentrations (150, 200, 300 µg/mL SPI led to a significant decrease (P<0.001 of the mitochondrial activity.  Similarly, the viability of FE cells significantly (P<0.05 decreased after the administration of 350 and 540 µg/mL SPI. On the other hand, VERO cells revealed the highest resistance to the antibiotic, with no significant effects in comparison to the control. Our data reveal that macrolides have a significant adverse negative effect on the cell viability, and may provide more information to our knowledge on the specific effects medication has on

  17. Ecological approach of macrolide-lincosamides-streptogramin producing actinomyces from Cuban soils.

    Science.gov (United States)

    González, I; Niebla, A; Lemus, M; González, L; Iznaga, I O; Pérez, M E; Vallin, C

    1999-09-01

    We report in this study the frequency of Streptomyces strains to produce macrolide-lincosamide-streptogramin (MLS) antibiotics isolated from Cuban soils. The screening assay is based on the induction of MLS-resistance phenotype in a clinical isolated strain of Staphylococcus aureus S-18. Our results suggest that of 800 Streptomyces strains isolated from different soil samples, 6% were positives in the screening test used. The ferralitic red soil from Pinar del Río (north) provided the major percentage (3.6%) of MLS producing strains. The other soil samples tested belonging to Guira de Melena and Bauta in Havana, Matanzas City, Topes De Collantes (Villa Clara), and Soroa Mountains (Pinar del Rio) hill reached very low percentages.

  18. Neutral Complex Extraction and Synergistic Extraction of Macrolide Antibiotics

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Based on the theory of reactive extraction, new solvent systems were developed to replace butylacetate for extraction of macrolide antibiotics (erythromycin, kitasamycin, spiramycin meleumycin etc.). A new neutral complex solvent extraction system, fatty alcohol-kerosene (marked by E1), was used for extraction of erythromycin, one of the macrolide antibiotics. The extraction equilibrium equation is obtained, and the extraction distribution is as follows The effects of several parameters on extraction equilibrium were investigated. Furthermore, a new synergistic extraction system (marked by E2) was developed, in which another solvent was used as synergistic agent to replace the diluent kerosene in the neutral complex extraction system. Based on these new extraction systems, an improved process for extraction of erythromycin was developed, showing remarkable advantages in technology and economics owing to its low solvent consumption of 3kg per billion unit compared with 9-10 for butylacetate. The recovery process of solvent from raffinate may be eliminated.

  19. 78 FR 15376 - Determinations: Corrosion-Resistant Carbon Steel Flat Products From Germany and Korea

    Science.gov (United States)

    2013-03-11

    ... COMMISSION Determinations: Corrosion-Resistant Carbon Steel Flat Products From Germany and Korea On the basis... Korea and the antidumping duty orders on corrosion-resistant carbon steel flat products from Germany and... Corrosion-Resistant Carbon Steel Flat Products from Germany and Korea: Investigation Nos. 701-TA-350 and...

  20. Hydrolysis of amphenicol and macrolide antibiotics: Chloramphenicol, florfenicol, spiramycin, and tylosin.

    Science.gov (United States)

    Mitchell, Shannon M; Ullman, Jeffrey L; Teel, Amy L; Watts, Richard J

    2015-09-01

    Antibiotics that enter the environment can present human and ecological health risks. An understanding of antibiotic hydrolysis rates is important for predicting their environmental persistence as biologically active contaminants. In this study, hydrolysis rates and Arrhenius constants were determined as a function of pH and temperature for two amphenicol (chloramphenicol and florfenicol) and two macrolide (spiramycin and tylosin) antibiotics. Antibiotic hydrolysis rates in pH 4-9 buffer solutions at 25°C, 50°C, and 60°C were quantified, and degradation products were characterized. All of the antibiotics tested remained stable and exhibited no observable hydrolysis under ambient conditions typical of aquatic ecosystems. Acid- and base-catalyzed hydrolysis occurred at elevated temperatures (50-60°C), and hydrolysis rates increased considerably below pH 5 and above pH 8. Hydrolysis rates also increased approximately 1.5- to 2.9-fold for each 10°C increase in temperature. Based on the degradation product masses found, the functional groups that underwent hydrolysis were alkyl fluoride, amide, and cyclic ester (lactone) moieties; some of the resultant degradation products may remain bioactive, but to a lesser extent than the parent compounds. The results of this research demonstrate that amphenicol and macrolide antibiotics persist in aquatic systems under ambient temperature and pH conditions typical of natural waters. Thus, these antibiotics may present a risk in aquatic ecosystems depending on the concentration present.

  1. Crack resistance curve determination of zircaloy-4 cladding

    Energy Technology Data Exchange (ETDEWEB)

    Bertsch, J.; Alam, A.; Zubler, R

    2009-03-15

    Fracture mechanics properties of fuel claddings are of relevance with respect to fuel rod integrity. The integrity of a fuel rod, in turn, is important for the fuel performance, for the safe handling of fuel rods, for the prevention of leakages and subsequent dissemination of fuel, for the avoidance of unnecessary dose rates, and for safe operation. Different factors can strongly deteriorate the mechanical fuel rod properties: irradiation damage, thermo-mechanical impact, corrosion or hydrogen uptake. To investigate the mechanical properties of fuel rod claddings which are used in Swiss nuclear power plants, PSI has initiated a program for mechanical testing. A major issue was the interaction between specific loading devices and the tested cladding tube, e.g. in the form of bending or friction. Particular for Zircaloy is the hexagonal closed packed structure of the zirconium crystallographic lattice. This structure implies plastic deformation mechanisms with specific, preferred orientations. Further, the manufacturing procedure of Zircaloy claddings induces a specific texture which plays a salient role with respect to the embrittlement by irradiation or integration of hydrogen in the form of hydrides. Both, the induced microstructure as well as the plastic deformation behaviour play a role for the mechanical properties. At PSI, in a first step inactive thin walled Zircaloy tubes and, for comparison reasons, plates were tested. The validity of the mechanical testing of the non standard tube and plate geometries had to be verified. The used Zircaloy-4 cladding tube sections and small plates of the same wall thickness have been notched, fatigue pre-cracked and tensile tested to evaluate the fracture toughness properties at room temperature, 300 {sup o}C and 350 {sup o}C. The crack propagation has been determined optically. The test results of the plates have been further used to validate FEM calculations. For each sample a complete crack resistance (J-R) curve could

  2. Multicenter cross-sectional observational study of antibiotic resistance and the genotypes of Propionibacterium acnes isolated from Chinese patients with acne vulgaris.

    Science.gov (United States)

    Fan, Yukun; Hao, Fei; Wang, Weizhen; Lu, Yonghong; He, Li; Wang, Gang; Chen, Wenchieh

    2016-04-01

    Antibiotics are widely applied in management of acne vulgaris, which raises the issue of antibiotic resistance. Due to improper application and supervision of antibiotics, antibiotic resistance has become a serious problem in China. So, the efficacy of antimicrobial therapy in acne is unclear without an objective monitor of antibiotic resistance of Propionibacterium acnes. This cross-sectional, multicenter observational study is aimed at understanding the status of antibiotic resistance in P. acnes, investigating the measures of acne management in China and analyzing the genotypes of antibiotic-resistant strains of P. acnes. Altogether, 312 strains of P. acnes were collected from patients in five medical centers across central China after reviewing the corresponding medical history in detail. The samples underwent antibiotic susceptibility assays by agar dilution method with a total of 11 classes of antibiotics being tested. The antibiotic-resistant strains were screened and further analyzed by investigation of the genotypes regarding 23S rRNA, 16S rRNA and erm(X). The predominant resistance occurred in macrolides and lincomycin with an overall resistance rate of 47.8%. The resistance to tetracyclines was scarce with only two cases identified. The emergence of minimum inhibitory concentration elevation for tetracyclines is associated with its application history (P resistance strains were also spotted in Chinese subjects while other resistance determinants may also exist. The tetracyclines have been proved to be vastly susceptible while macrolides and lincomycin face a serious resistance status in China. © 2015 Japanese Dermatological Association.

  3. Mycobacterium tuberculosis pyrazinamide resistance determinants: a multicenter study.

    Science.gov (United States)

    Miotto, Paolo; Cabibbe, Andrea M; Feuerriegel, Silke; Casali, Nicola; Drobniewski, Francis; Rodionova, Yulia; Bakonyte, Daiva; Stakenas, Petras; Pimkina, Edita; Augustynowicz-Kopeć, Ewa; Degano, Massimo; Ambrosi, Alessandro; Hoffner, Sven; Mansjö, Mikael; Werngren, Jim; Rüsch-Gerdes, Sabine; Niemann, Stefan; Cirillo, Daniela M

    2014-10-21

    Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZA(r)). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the development of a molecular test. We performed a large multicenter study assessing pncA sequence variations in 1,950 clinical isolates, including 1,142 multidrug-resistant (MDR) strains and 483 fully susceptible strains. The results of pncA sequencing were correlated with phenotype, enzymatic activity, and structural and phylogenetic data. We identified 280 genetic variants which were divided into four classes: (i) very high confidence resistance mutations that were found only in PZA(r) strains (85%), (ii) high-confidence resistance mutations found in more than 70% of PZA(r) strains, (iii) mutations with an unclear role found in less than 70% of PZA(r) strains, and (iv) mutations not associated with phenotypic resistance (10%). Any future molecular diagnostic assay should be able to target and identify at least the very high and high-confidence genetic variant markers of PZA(r); the diagnostic accuracy of such an assay would be in the range of 89.5 to 98.8%. Importance: Conventional phenotypic testing for pyrazinamide resistance in Mycobacterium tuberculosis is technically challenging and often unreliable. The development of a molecular assay for detecting pyrazinamide resistance would be a breakthrough, directly overcoming both the limitations of conventional testing and its related biosafety issues. Although the main mechanism of pyrazinamide resistance involves mutations inactivating the pncA enzyme, the highly diverse genetic variants scattered over the full length of the pncA gene and the lack of a reliable phenotypic gold standard hamper the development of molecular diagnostic

  4. Environmental pollution by antibiotics and by antibiotic resistance determinants

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Jose Luis, E-mail: jlmtnez@cnb.csic.e [Departamento de Biotecnologia Microbiana, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Darwin 3, Cantoblanco, 28049 Madrid, and CIBERESP (Spain)

    2009-11-15

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  5. A review of macrolide treatment of atherosclerosis and abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Stovring, Jette; Andersen, Paul Lehm;

    2003-01-01

    groups, a significant reduction in serious end-points were noticed in patients receiving macrolide. Similarly, two other minor randomized trials showed that macrolide treatment inhibited growth of small AAA. Macrolide therapy thus seems potential to improve the outcome of severe ischaemic heart disease......, and growth of AAA. If true, it not known whether this is transient because of macrolide's non-specific anti-inflammatory effect or latent infection, or permanent because of eradicating C. pneumoniae organisms. In order to clarify this, large and long term randomized trials are needed, as well as diagnostic...

  6. Chemical modification of antifungal polyene macrolide antibiotics

    Science.gov (United States)

    Solovieva, S. E.; Olsufyeva, E. N.; Preobrazhenskaya, M. N.

    2011-02-01

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  7. Chemical modification of antifungal polyene macrolide antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Solovieva, S E; Olsufyeva, E N; Preobrazhenskaya, M N [G.F.Gause Institute of New Antibiotics, Russian Academy of Medical Sciences (Russian Federation)

    2011-02-28

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  8. Determination of the Antibiotic Resistance Profile of Student Cell Phones

    Directory of Open Access Journals (Sweden)

    Lisa Ann Blankinship

    2012-08-01

    Full Text Available Sampling of common use items (e.g., student cell phones for bacterial presence, identification, and antibiotic resistance profiling helps students to recognize the need for routine cleaning of personal items and encourages thoughtful use of currently available medications. This multilab period project can be used to teach or reinforce several methods from general microbiology including aseptic technique, isolation streak, serial dilution, spread plating, Kirby Bauer testing, unknown identification, and media production. The data generated can be saved and added to each semester, thus providing a data set that reflects a local trend of antibiotic resistance.      

  9. Antibiotic resistance profiles of Campylobacter species in the South Africa private health care sector.

    Science.gov (United States)

    Shobo, Christiana O; Bester, Linda Antionette; Baijnath, Sooraj; Somboro, Anou M; Peer, Abdool K C; Essack, Sabiha Y

    2016-11-24

    There is a dearth of surveillance data on clinical Campylobacter in South Africa, particularly in the private healthcare environment. We investigated the prevalence of resistance to first-line antibiotics used to treat campylobacterioses in clinical Campylobacter isolates from a private pathology laboratory. Identification of the Campylobacter specific genes were confirmed by PCR. Minimum inhibitory concentrations were determined using the broth micro-dilution method against macrolides (erythromycin, azithromycin), fluoroquinolones (ciprofloxacin, gatifloxacin) and tetracycline. Seventy-two Campylobacter isolates were identified by PCR, with 54 (75%) being classified as C. jejuni and 18 (25%) as C. coli. Of these, 11 (20.4%) C. jejuni and six (33.3%) C. coli strains were resistant to ciprofloxacin and three (7.41%) C. jejuni and three (16.7%) C. coli strains were resistant to gatifloxacin. The number of C. jejuni strains resistant to erythromycin and azithromycin was 17 (31.5%) and 36 (50%) respectively, while the resistance of C. coli strains to erythromycin and azithromycin were seven (38.9%) and 14 (77.8%) respectively. Resistance to tetracycline was detected in 10 (55.6%) C. coli and 14 (25.9%) C. jejuni strains. In the light of these resistant profiles, the lack of a South African Campylobacter surveillance program is of concern. Relatively high prevalence of resistance in clinical isolates of C. jejuni and C. coli to the fluoroquinolones, macrolides and tetracycline used in first line treatment is of great concern. The efficacy treating human campylobacteriosis should thus be revisited.

  10. Specific multilocus variable-number tandem-repeat analysis genotypes of Mycoplasma pneumoniae are associated with diseases severity and macrolide susceptibility.

    Directory of Open Access Journals (Sweden)

    Jiuxin Qu

    Full Text Available Clinical relevance of multilocus variable-number tandem-repeat (VNTR analysis (MLVA in patients with community-acquired pneumonia (CAP by Mycoplasma pneumoniae (M. pneumoniae is unknown. A multi-center, prospective study was conducted from November 2010 to April 2012. Nine hundred and fifty-four CAP patients were consecutively enrolled. M. pneumoniae clinical isolates were obtained from throat swabs. MLVA typing was applied to all isolates. Comparison of pneumonia severity index (PSI and clinical features among patients infected with different MLVA types of M. pneumoniae were conducted. One hundred and thirty-six patients were positive with M. pneumoniae culture. The clinical isolates were clustered into 18 MLVA types. One hundred and fourteen (88.3% isolates were resistant to macrolide, covering major MLVA types. The macrolide non-resistant rate of M. pneumoniae isolates with Mpn13-14-15-16 profile of 3-5-6-2 was significantly higher than that of other types (p ≤ 0.001. Patients infected with types U (5-4-5-7-2 and J (3-4-5-7-2 had significantly higher PSI scores (p<0.001 and longer total duration of cough (p = 0.011. Therefore it seems that there is a correlation between certain MLVA types and clinical severity of disease and the presence of macrolide resistance.

  11. Mechanisms, molecular and sero-epidemiology of antimicrobial resistance in bacterial respiratory pathogens isolated from Japanese children

    Directory of Open Access Journals (Sweden)

    Sunakawa Keisuke

    2007-08-01

    Full Text Available Abstract Background The clinical management of community-acquired respiratory tract infections (RTIs is complicated by the increasing worldwide prevalence of antibacterial resistance, in particular, β-lactam and macrolide resistance, among the most common causative bacterial pathogens. This study aimed to determine the mechanisms and molecular- and sero-epidemiology of antibacterial resistance among the key paediatric respiratory pathogens in Japan. Methods Isolates were collected at 18 centres in Japan during 2002 and 2003 from children with RTIs as part of the PROTEKT surveillance programme. A proportion of Haemophilus influenzae isolates was subjected to sequencing analysis of the ftsI gene; phylogenetic relatedness was assessed using multilocus sequence typing. Streptococcus pneumoniae isolates were screened for macrolide-resistance genotype by polymerase chain reaction and serotyped using the capsular swelling method. Susceptibility of isolates to selected antibacterials was performed using CLSI methodology. Results and Discussion Of the 557 H. influenzae isolates collected, 30 (5.4% were β-lactamase-positive [BL+], 115 (20.6% were BL-nonproducing ampicillin-resistant (BLNAR; MIC ≥ 4 mg/L and 79 (14.2% were BL-nonproducing ampicillin-intermediate (BLNAI; MIC 2 mg/L. Dabernat Group III penicillin binding protein 3 (PBP3 amino acid substitutions in the ftsI gene were closely correlated with BLNAR status but phylogenetic analysis indicated marked clonal diversity. PBP mutations were also found among BL+ and BL-nonproducing ampicillin-sensitive isolates. Of the antibacterials tested, azithromycin and telithromycin were the most active against H. influenzae (100% and 99.3% susceptibility, respectively. A large proportion (75.2% of the 468 S. pneumoniae isolates exhibited macrolide resistance (erythromycin MIC ≥ 1 mg/L; erm(B was the most common macrolide resistance genotype (58.8%, followed by mef(A (37.2%. The most common pneumococcal

  12. Isolation, Identification of Heat Resistant Moulds in Margarine and Determination of Their Heat Resistance

    Directory of Open Access Journals (Sweden)

    A. S. Demirci

    2006-09-01

    Full Text Available In this study, moulds that cause problems in a margarine production plant which is located in Trakyaregion have been isolated and identified. In addition to, their heat resistance and lipolytic activity werestudied. For this purpose, margarine samples from various production lots and process water samples fromproduction plant were taken aseptically, transported immediately to the laboratory and analyzed. In thisresearch, two different heat resistant mould strains have been isolated from margarines and process water.After identification of this moulds, their heat resistances at different temperatures have been investigated.Mould isolates were identified as heat resistant Aspergillus fumigatus, Paecilomyces variotii based onmacroscopic and microscopic features. To this analyses results about thermal resistance, Aspergillusfumigatus and Paecilomyces variotii were ability to survive heat treatment at 95oC 10 minutes and 90oC 10minutes, respectively.

  13. A molecular analysis of quinolone-resistant Haemophilus influenzae: validation of the mutations in Quinolone Resistance-Determining Regions.

    Science.gov (United States)

    Shoji, Hisashi; Shirakura, Tetsuro; Fukuchi, Kunihiko; Takuma, Takahiro; Hanaki, Hideaki; Tanaka, Kazuo; Niki, Yoshihito

    2014-04-01

    The mechanism of quinolone-resistance is considered to be amino acid mutations in the type II topoisomerase. We validated the genetic mechanisms of quinolone resistance in Haemophilus influenzae. We obtained 29 H. influenzae strains from a nationwide surveillance program in Japan (including 11 quinolone-resistant strains [moxifloxacin: MFLX or levofloxacin MIC ≥2 μg/ml]). We analyzed the sequences of the Quinolone Resistance-Determining Regions (QRDRs) in GyrA, GyrB, ParC and ParE. Furthermore, we induced resistance in susceptible strains by exposing them to quinolone, and investigated the relationship between mutations in the QRDRs and the MICs. Five amino acid substitutions in GyrA (at Ser84 and Asp88) and ParC (at Gly82, Ser84 and Glu88) were found to be closely related to the MICs. The strains with a MFLX MIC of 0.125-1 and 2-4 μg/ml had one and two mutations, respectively. The strains with a MFLX MIC of ≥8 μg/ml had three or more mutations. The strains with induced resistance with MFLX MICs of 0.5-1 and ≥2 μg/ml also had one and two mutations, respectively. We confirmed that these five mutations strongly contribute to quinolone resistance and found that the degree of resistance is related to the number of the mutations. In addition, the three strains of 18 susceptible strains (16.7%) also had a single mutation. These strains may therefore be in the initial stage of quinolone resistance. Currently, the frequency of quinolone-resistant H. influenzae is still low. However, as has occurred with β-lactams, an increase in quinolone use may lead to more quinolone-resistant strains.

  14. [Estimation of Probiotic Lactobacilli Drug Resistance].

    Science.gov (United States)

    Bruslik, N L; Akhatova, D R; Toimentseva, A A; Abdulkhakov, S R; Ilyinskaya, O N; Yarullina, D R

    2015-01-01

    An actual problem of analysis of probiotic lactobacilli resistance to antibiotics and other drugs used in the treatment of gastro-intestinal disturbances has been for the first time solved. The levels of resistance of 19 strains of Lactobacillus (14 strains of L. fermentum, 4 strains of L.plantarum and 1 strain of L.rhamnosus) isolated from commercial probiotics and sour milk products to 14 antibiotics of various nature, i.e. β-lactams, aminoglycosides, macrolides, clindamycin, vancomycin, rifampicin, ciprofloxacin, tetracycline and chloramphenicol were determined. All the isolates were practically susceptible to the drugs of the first line antihelicobacterial therapy, i.e. amoxicillin and clarithromycin, that makes inexpedient the parallel use of the probiotics containing the above lactobacilli in the treatment of gastritis and gastric ulcer, despite the lactobacilli antagonism with respect to Helicobacter pylory. Lactobacilli are as well resistant to mesalazin and can be used for correction of dysbiosis in inflammatory affections of the intestine.

  15. Resistance to hepatitis C virus: potential genetic and immunological determinants.

    Science.gov (United States)

    Mina, Michael M; Luciani, Fabio; Cameron, Barbara; Bull, Rowena A; Beard, Michael R; Booth, David; Lloyd, Andrew R

    2015-04-01

    Studies of individuals who were highly exposed but seronegative (HESN) for HIV infection led to the discovery that homozygosity for the Δ32 deletion mutation in the CCR5 gene prevents viral entry into target cells, and is associated with resistance to infection. Additionally, evidence for protective immunity has been noted in some HESN groups, such as sex workers in The Gambia. Population studies of individuals at high risk for hepatitis C virus infection suggest that an HESN phenotype exists. The body of evidence, which suggests that protective immunity allows clearance of hepatitis C virus without seroconversion is growing. Furthermore, proof-of-principle evidence from in-vitro studies shows that genetic polymorphisms can confer resistance to establishment of infection. This Review discusses the possibility that genetic mutations confer resistance against hepatitis C virus, and also explores evidence for protective immunity, including via genetically programmed variations in host responses. The data generally strengthens the notion that investigations of naturally arising polymorphisms within the hepatitis C virus interactome, and genetic association studies of well characterised HESN individuals, could identify potential targets for vaccine design and inform novel therapies.

  16. Determination of internal series resistance of PV devices: repeatability and uncertainty

    Science.gov (United States)

    Trentadue, Germana; Pavanello, Diego; Salis, Elena; Field, Mike; Müllejans, Harald

    2016-05-01

    The calibration of photovoltaic devices requires the measurement of their current-voltage characteristics at standard test conditions (STC). As the latter can only be reached approximately, a curve translation is necessary, requiring among others the internal series resistance of the photovoltaic device as an input parameter. Therefore accurate and reliable determination of the series resistance is important in measurement and test laboratories. This work follows standard IEC 60891 ed 2 (2009) for the determination of the internal series resistance and investigates repeatability and uncertainty of the result in three aspects for a number of typical photovoltaic technologies. Firstly the effect of varying device temperature on the determined series resistance is determined experimentally and compared to a theoretical derivation showing agreement. It is found that the series resistance can be determined with an uncertainty of better than 5% if the device temperature is stable within  ±0.1 °C, whereas the temperature range of  ±2 °C allowed by the standard leads to much larger variations. Secondly the repeatability of the series resistance determination with respect to noise in current-voltage measurement is examined yielding typical values of  ±5%. Thirdly the determination of the series resistance using three different experimental set-ups (solar simulators) shows agreement on the level of  ±5% for crystalline Silicon photovoltaic devices and deviations up to 15% for thin-film devices. It is concluded that the internal series resistance of photovoltaic devices could be determined with an uncertainty of better than 10%. The influence of this uncertainty in series resistance on the electrical performance parameters of photovoltaic devices was estimated and showed a contribution of 0.05% for open-circuit voltage and 0.1% for maximum power. Furthermore it is concluded that the range of device temperatures allowed during determination of series

  17. [Determination of insecticide-resistance and resistance mechanisms of Blattella germanica (Dictyoptera: Blattellidae)].

    Science.gov (United States)

    Díaz, Pantoja Cristina; Alvarez Gavilán, Yudelmis; de Armas Rodríguez, Yaxsier; Bisset Lazcano, Juan A

    2007-01-01

    In this paper, the level of resistance to four insecticides of 3 Blatella germanica strains collected from various places in the City of Havana province was evaluated. These strains were resistant to two pyrethroids (cypermethrin and lambda-cyalothrine) and to organophosphorate malathion but susceptible to carbamate propoxur. The values of alpha and beta esterases, acetylcholinesterase and gluthatione-S-transferase were estimated in three strains involved in the study. The results of the study showed high esterase activity in all the strains, mainly beta esterases and two of the three strains presented with high gluthation-S-transferase enzyme. No changes in acetylcholinesterase were demonstrated in relation to the reference strain. The association of levels of resistance to insecticides, the possible resistance mechanisms in each strain and the results of the enzymatic activity were also analyzed.

  18. Antibiotic resistance among Ureaplasma spp. isolates: cause for concern?

    Science.gov (United States)

    Beeton, M L; Spiller, O B

    2017-02-01

    There is growing global concern regarding the rise of antibiotic-resistant organisms. Many of these reports have focused on various Gram-positive and Gram-negative pathogens, with little attention to the genus Ureaplasma. Ureaplasma spp. are associated with numerous infectious diseases affecting pregnant women, neonates and the immunocompromised. Treatment options are extremely limited due to high levels of intrinsic resistance resulting from the unique physiology of these organisms and further restricted in cases of the developing fetus or neonate, often limiting therapeutic options to predominantly macrolides or rarely fluoroquinolones. The increasing presence of macrolide- and fluoroquinolone-resistant strains among neonatal infections may result in pan-drug resistance and potentially untreatable conditions. Here, we review the requirements for accurate measurement of antimicrobial susceptibility, provide a comprehensive review of the antimicrobial resistance (AMR) for Ureaplasma species in the literature and contextualize these results relative to some investigators' reliance on commercial kits that are not CLSI compliant when determining AMR. The dramatic variation in the resistance patterns and impact of high levels of AMR amongst neonatal populations suggests the need for continued surveillance. Commercial kits represent an excellent tool for initial antibiotic susceptibility determination and screening. However, AMR reporting must utilize internationally standardized methods, as high-titre samples, or Mycoplasma hominis-contaminated samples routinely give false AMR results. Furthermore, there is a requirement for future reports to determine the underlying AMR mechanisms and determine whether expanding AMR is due to spontaneous mutation, transmission of resistance genes on mobile elements or selection and expansion of resistant clones. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy

  19. Antimicrobial resistance in Campylobacter coli selected by tylosin treatment at a pig farm.

    Science.gov (United States)

    Juntunen, P; Heiska, H; Olkkola, S; Myllyniemi, A-L; Hänninen, M-L

    2010-11-20

    Limited knowledge is available regarding the dynamics of macrolide resistance under farm conditions with natural Campylobacter populations. We examined the dynamics of antimicrobial resistance in Campylobacter coli at a large pig farm. Faeces were sampled from untreated sows and piglets (n=57), weaned pigs treated with tylosin (n=68) and pigs of the same group 3-5 weeks after withdrawal of tylosin (n=15). Additionally, 48 weaned pigs were sampled after tylosin had not been administered for 7 months at the farm. MICs for seven antimicrobials were determined, isolates were genotyped by PFGE and mutations conferring macrolide resistance were identified. Resistance to at least one antimicrobial agent was higher (Ptylosin had not been administered for 7 months. Resistance to erythromycin and streptomycin also decreased (Ptylosin treatment. In conclusion, tylosin treatment of pigs selected for a high-level of resistance to erythromycin and resistance to ciprofloxacin, nalidixic acid and streptomycin also increased in C. coli isolates within a few days. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Antimicrobial Resistance Trends among Community-Acquired Respiratory Tract Pathogens in Greece, 2009–2012

    Directory of Open Access Journals (Sweden)

    Sofia Maraki

    2014-01-01

    Full Text Available The aim of the present study was to determine the antimicrobial resistance trends of respiratory tract pathogens isolated from patients with community-acquired respiratory tract infections (CARTIs in Crete, Greece, over a 4-year period (2009–2012. A total of 588 community-acquired respiratory pathogens were isolated during the study period. Streptococcus pneumoniae was the most common organism responsible for 44.4% of CARTIs, followed by Haemophilus influenzae (44.2% and Moraxella catarrhalis (11.4%. Among S. pneumoniae, the prevalence of isolates with intermediate- and high-level resistance to penicillin was 27.2% and 12.3%, respectively. Macrolide resistance slightly decreased from 29.4% over the period 2009-2010 to 28.8% over the period 2011-2012. Multiresistance was observed among 56 (54.4% penicillin nonsusceptible isolates. A nonsignificant increase in resistance of H. influenzae isolates was noted for β-lactams, cotrimoxazole, and tetracycline. Among the 67 M. catarrhalis tested, 32 produced beta-lactamase and were resistant to ampicillin. Macrolide resistance decreased over the study period. All isolates were susceptible to amoxicillin + clavulanic acid, chloramphenicol, rifampicin, and the fluoroquinolones. Although a decreasing trend in the prevalence of resistance of the three most common pathogens involved in CARTIs was noted, continuous surveillance of antimicrobial susceptibility at the local and national level remains important, in order to guide appropriate empirical antimicrobial therapy.

  1. Molecular basis of NDM-1, a new antibiotic resistance determinant.

    Directory of Open Access Journals (Sweden)

    Zhongjie Liang

    Full Text Available The New Delhi Metallo-β-lactamase (NDM-1 was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat.In this study, we performed modeling studies to obtain its 3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic mechanisms are highly conserved. In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which had the ability to slow down the hydrolysis velocity of meropenem by NDM-1. Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E, which displayed down-regulation on meropenem catalysis, proved the accuracy of our model.At present, there are no effective antibiotics against NDM-1 positive pathogen. Our study will provide clues to investigate the molecular basis of extended antibiotics resistance of NDM-1 and then accelerate the search for new antibiotics against NDM-1 positive strain in clinical studies.

  2. Molecular basis of NDM-1, a new antibiotic resistance determinant.

    Science.gov (United States)

    Liang, Zhongjie; Li, Lianchun; Wang, Yuanyuan; Chen, Limin; Kong, Xiangqian; Hong, Yao; Lan, Lefu; Zheng, Mingyue; Guang-Yang, Cai; Liu, Hong; Shen, Xu; Luo, Cheng; Li, Keqin Kathy; Chen, Kaixian; Jiang, Hualiang

    2011-01-01

    The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat.In this study, we performed modeling studies to obtain its 3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic mechanisms are highly conserved. In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which had the ability to slow down the hydrolysis velocity of meropenem by NDM-1. Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E, which displayed down-regulation on meropenem catalysis, proved the accuracy of our model.At present, there are no effective antibiotics against NDM-1 positive pathogen. Our study will provide clues to investigate the molecular basis of extended antibiotics resistance of NDM-1 and then accelerate the search for new antibiotics against NDM-1 positive strain in clinical studies.

  3. Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases.

    Science.gov (United States)

    Hodge, Sandra; Tran, Hai B; Hamon, Rhys; Roscioli, Eugene; Hodge, Greg; Jersmann, Hubertus; Ween, Miranda; Reynolds, Paul N; Yeung, Arthur; Treiberg, Jennifer; Wilbert, Sibylle

    2017-05-01

    We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H. influenzae We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5-1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll

  4. Determination of radiation resistant of electronic components in robot system

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hee Dong [Kyungpook National University, Taegu (Korea); Kim, Do Sung [Taegu University, Taegu (Korea); Woo, Hong [Kyungsan University, Kyungsan (Korea)

    1998-04-01

    We investigated the characteristic change for the electronic components of the systems which were used in radiation area, when those were exposured by gamma rays. Bipolar transistor, FET, TTL, CMOS, operational amplifier, some capacitors, and several electronic components were selected for experiment. We applied irradiated gamma ray to the electronic components in the range of 10{sup 6} rad, by {sup 6}0Co(KAERI). We made up appropriate assessment circuit for each electronic component during the performance test, and assessed the reliability and radiation-resistance of them for the each radiation irradiation. (author). 59 refs., 35 figs., 8 tabs.

  5. Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro

    Directory of Open Access Journals (Sweden)

    Toshikazu Shimane

    2001-01-01

    Full Text Available Background: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood.

  6. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides

    DEFF Research Database (Denmark)

    Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf

    2012-01-01

    on the ribosome (50% inhibitory concentration [IC(50)], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal...

  7. Glycopeptide resistance determinants from the teicoplanin producer Actinoplanes teichomyceticus.

    Science.gov (United States)

    Serina, Stefania; Radice, Francesca; Maffioli, Sonia; Donadio, Stefano; Sosio, Margherita

    2004-11-01

    In enterococci and other pathogenic bacteria, high-level resistance to vancomycin and other glycopeptide antibiotics requires the action of the van genes, which direct the synthesis of peptidoglycan terminating in the depsipeptide D-alanyl-D-lactate, in place of the usual D-Ala-D-Ala. The Actinoplanes teichomyceticus tcp cluster, devoted to the biosynthesis of the glycopeptide antibiotic teicoplanin, contains van genes associated to a murF-like sequence (murF2). We show that A. teichomyceticus contains also a house-keeping murF1 gene, capable of complementing a temperature sensitive Escherichia coli murF mutant. MurF1, expressed in Streptomyces lividans, can catalyze the addition of either D-Ala-D-Ala or D-Ala-D-Lac to the UDP-N-acetyl-muramyl-L-Ala-D-Glu-d-Lys. However, similarly expressed MurF2 shows a small enzymatic activity only with D-Ala-D-lactate. Introduction of a single copy of the entire set of van genes confers resistance to teicoplanin-type glycopeptides to S. coelicolor.

  8. Borrelidins C–E: New Antibacterial Macrolides from a Saltern-Derived Halophilic Nocardiopsis sp.

    Directory of Open Access Journals (Sweden)

    Jungwoo Kim

    2017-06-01

    Full Text Available Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C–E (1–3, along with a previously reported borrelidin (4. The planar structures of borrelidins C–E, which are new members of the rare borrelidin class of antibiotics, were elucidated by NMR, mass, IR, and UV spectroscopic analyses. The configurations of borrelidines C–E were determined by the interpretation of ROESY NMR spectra, J-based configuration analysis, a modified Mosher’s method, and CD spectroscopic analysis. Borrelidins C and D displayed inhibitory activity, particularly against the Gram-negative pathogen Salmonella enterica, and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines.

  9. Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

    Directory of Open Access Journals (Sweden)

    Naoya Oku

    2014-08-01

    Full Text Available Macroscopic gelatinous colonies of freshwater cyanobacterium Aphanothece sacrum, a luxury ingredient for Japanese cuisine, were found to contain a new oxylipin-derived macrolide, sacrolide A (1, as an antimicrobial component. The configuration of two chiral centers in 1 was determined by a combination of chiral anisotropy analysis and conformational analysis of different ring-opened derivatives. Compound 1 inhibited the growth of some species of Gram-positive bacteria, yeast Saccharomyces cerevisiae and fungus Penicillium chrysogenum, and was also cytotoxic to 3Y1 rat fibroblasts. Concern about potential food intoxication caused by accidental massive ingestion of A. sacrum was dispelled by the absence of 1 in commercial products. A manual procedure for degrading 1 in raw colonies was also developed, enabling a convenient on-site detoxification at restaurants or for personal consumption.

  10. Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum.

    Science.gov (United States)

    Oku, Naoya; Matsumoto, Miyako; Yonejima, Kohsuke; Tansei, Keijiroh; Igarashi, Yasuhiro

    2014-01-01

    Macroscopic gelatinous colonies of freshwater cyanobacterium Aphanothece sacrum, a luxury ingredient for Japanese cuisine, were found to contain a new oxylipin-derived macrolide, sacrolide A (1), as an antimicrobial component. The configuration of two chiral centers in 1 was determined by a combination of chiral anisotropy analysis and conformational analysis of different ring-opened derivatives. Compound 1 inhibited the growth of some species of Gram-positive bacteria, yeast Saccharomyces cerevisiae and fungus Penicillium chrysogenum, and was also cytotoxic to 3Y1 rat fibroblasts. Concern about potential food intoxication caused by accidental massive ingestion of A. sacrum was dispelled by the absence of 1 in commercial products. A manual procedure for degrading 1 in raw colonies was also developed, enabling a convenient on-site detoxification at restaurants or for personal consumption.

  11. Multidrug-resistant Mycoplasma genitalium infections in Europe.

    Science.gov (United States)

    Braam, J F; van Dommelen, L; Henquet, C J M; van de Bovenkamp, J H B; Kusters, J G

    2017-03-30

    In Japan and Australia, multidrug-resistant Mycoplasma genitalium infections are reported with increasing frequency. Although macrolide-resistant M. genitalium strains are common in Europe and North America, fluoroquinolone-resistant strains are still exceptional. However, an increase of multidrug-resistant M. genitalium in Europe and America is to be expected. The aim of this paper is to increase awareness on the rising number of multidrug-resistant M. genitalium strains. Here, one of the first cases of infection with a genetically proven multidrug-resistant M. genitalium strain in Europe is described. The patient was a native Dutch 47-year-old male patient with urethritis. Mycoplasma genitalium was detected, but treatment failed with azithromycin, doxycycline and moxifloxacin. A urogenital sample was used to determine the sequence of the 23S rRNA, gyrA, gyrB and parC genes. The sample contained an A2059G single nucleotide polymorphism (SNP) in the 23S rRNA gene and an SNP in the parC gene, resulting in an amino acid change of Ser83 → Ile, explaining both azithromycin and moxifloxacin treatment failure. The SNPs associated with resistance were probably generated de novo, as a link with high-prevalence areas was not established. It is, thus, predictable that there is going to be an increase of multidrug-resistant M. genitalium strains in Europe. As treatment options for multidrug-resistant M. genitalium are limited, the treatment of M. genitalium infections needs to be carefully considered in order to limit the rapid increase of resistance to macrolides and fluoroquinolones.

  12. Determination of metabolic resistance mechanisms in pyrethroid-resistant and fipronil-tolerant brown dog ticks.

    Science.gov (United States)

    Eiden, A L; Kaufman, P E; Oi, F M; Dark, M J; Bloomquist, J R; Miller, R J

    2017-09-01

    Rhipicephalus sanguineus (Latreille) (Ixodida: Ixodidae) is a three-host dog tick found worldwide that is able to complete its' entire lifecycle indoors. Options for the management of R. sanguineus are limited and its' control relies largely on only a few acaricidal active ingredients. Previous studies have confirmed permethrin resistance and fipronil tolerance in R. sanguineus populations, commonly conferred by metabolic detoxification or target site mutations. Herein, five strains of permethrin-resistant and three strains of fipronil-tolerant ticks were evaluated for metabolic resistance using synergists to block metabolic enzymes. Synergist studies were completed with triphenyl phosphate (TPP) for esterase inhibition, piperonyl butoxide (PBO) for cytochrome P450 inhibition, and diethyl maleate (DEM) for glutathione-S-transferase inhibition. Additionally, increased esterase activity was confirmed using gel electrophoresis. The most important metabolic detoxification mechanism in permethrin-resistant ticks was increased esterase activity, followed by increased cytochrome P450 activity. The inhibition of metabolic enzymes did not have a marked impact on fipronil-tolerant tick strains. © 2017 The Royal Entomological Society.

  13. Fluoroquinolone resistance in atypical pneumococci and oral streptococci: evidence of horizontal gene transfer of fluoroquinolone resistance determinants from Streptococcus pneumoniae.

    Science.gov (United States)

    Ip, Margaret; Chau, Shirley S L; Chi, Fang; Tang, Julian; Chan, Paul K

    2007-08-01

    Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of > or =4.0 microg/ml and unique sequence variations within the quinolone resistance-determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison with the Streptococcus pneumoniae R6 strain, were examined. These strains were reidentified using phenotypic methods, including detection of optochin susceptibility, bile solubility, and agglutination by serotype-specific antisera, and genotypic methods, including detection of pneumolysin and autolysin genes by PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis based on concatenated sequences of the six MLST loci distinguished the "atypical" strains from pneumococci, and these strains clustered closely with S. mitis. However, all these strains and five of nine strains from the viridans streptococcal group possessed one to three gyrA, gyrB, parC, and parE genes whose QRDR sequences clustered with those of S. pneumoniae, providing evidence of horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from pneumococci into viridans streptococci. These genes also conferred fluoroquinolone resistance to viridans streptococci. In addition, the fluoroquinolone resistance determinants of 32 well-characterized Streptococcus mitis and Streptococcus oralis strains from bacteremic patients were also compared. These strains have unique amino acid substitutions in GyrA and ParC that were distinguishable from those in fluoroquinolone-resistant pneumococci and the "atypical" isolates. Both recombinational events and de novo mutations play an important role in the development of fluoroquinolone resistance.

  14. Arsenic efflux governed by the arsenic resistance determinant of Staphylococcus aureus plasmid pI258.

    OpenAIRE

    Bröer, S; Ji, G.; Bröer, A; Silver, S

    1993-01-01

    The arsenic resistance operon of Staphylococcus aureus plasmid pI258 determined lowered net cellular uptake of 73As by an active efflux mechanism. Arsenite was exported from the cells; intracellular arsenate was first reduced to arsenite and then transported out of the cells. Resistant cells showed lower accumulation of 73As originating from both arsenate and arsenite. Active efflux from cells loaded with arsenite required the presence of the plasmid-determined arsB gene. Efflux of arsenic or...

  15. Determination of Ampicillin Resistant Enterococci (ARE Isolated From Canine and Feline Rectal Swabs

    Directory of Open Access Journals (Sweden)

    Baran CELIK

    2017-01-01

    Full Text Available Enterococci species, which are normal inhabitants of the gut flora of healthy animals and human, began to be recognized as an important pathogen in both human and veterinary medicine due to the acquired resistance profiles. The aim of the study is to examine the diversity of ampicillin resistance enterococci (ARE species in cats and dogs, their antimicrobial susceptibility profiles and to determine some of the virulence related genes; ace, gelE, efaA, agg and esp. For this purpose, rectal swabs from companion animals were collected and processed for ampicillin resistant enterococci isolation. One hundred fifty seven swab samples (86 canine and 71 feline were examined. ARE were isolated from 18 canine and 18 feline samples. All isolates identified as E. faecium by PCR. Antimicrobial susceptibilities of the isolates were determined by disk diffusion method. The isolates were resistant to ampicillin, penicillin, tetracycline (100%, followed by rifampicin and erythromycin (97%, streptomycin (92%, gentamicin (81%, ciprofloxacin (61%, nitrofurantoin (19%. Only two of E. faecium isolates were resistant to vancomycin and one to chloramphenicol. Multidrug resistance (resistance ≥4 antimicrobials observed in all isolates. Virulence genes ace, agg and esp were not detected in any of the tested isolates. The efaA and gelE genes detection rates were, 13.8% and 11.1% respectively. The ARE isolation rate among pet animals was 22.9%. Screening of antimicrobial resistant enterococci among companion animals would be useful to detect any emerging antimicrobial resistance problem related with public health.

  16. Resistance of determinant tomato varieties to the causal agents of bacterial wilt disease

    Directory of Open Access Journals (Sweden)

    Jana Víchová

    2011-01-01

    Full Text Available Resistance of determinant tomato varieties to pathogens causing bacterial wilt disease – Clavibacter michiganensis subsp. michiganensis (Cmm and Ralstonia solanacearum (Rs – was tested under greenhouse conditions. In tests to Cmm resistance, two inoculation methods were compared (inoculation “to the cut off top” of a plant and inoculation by three punctures into a stalk. The inoculation method “into a stalk” appeared to be most suitable. In both cases of inoculation, the highest level of resistance was found in Minigold variety. The rather high level of resistance was also found in varieties Aneta and Orange. In tests to Rs resistance, the most resistant varieties were Minigold, Aneta and Orange, which are recommended for direct consumption.

  17. The effect of milk on plasmatic and tissue levels of macrolides: in vivo study in rats

    Directory of Open Access Journals (Sweden)

    F. C. Groppo

    2009-01-01

    Full Text Available

    The ingestion of milk with drugs, particularly some antibiotics, is frequently recommended in order to decrease possible gastrointestinal discomfort. The objective of this study was to assess the interference of milk in the absorption and tissue levels of macrolide antibiotics (erythromycin, clarithromycin, roxithromycin and azithromycin. Forty female rats received surgicallyimplanted PVC sponges on their backs. One week later, granulomatous tissue was observed and the animals were divided into eight groups, which received erythromycin, clarithromycin, roxithromycin and azithromycin with and without milk. One hour after administration of antibiotic, the animals were sacrificed. The serum and tissue samples were submitted to microbiological assay with Micrococcus luteus ATCC 9341, in order to determine drug concentration. Milk did not cause any reduction in the serum and tissue levels of azithromycin and clarithromycin (p>0.05,t-test. However, ingestion of milk reduced by approximately 28.7% the roxithromycin (p<0.0001, t-test and by 34.1% the erythromycin (p<0.0001, t test serum concentrations. Similar effects were observed on tissue levels. Milk ingestion caused a reduction of approximately 20.8% in the roxithromycin (p<0.0001, t-test and 40% in the erythromycin (p<0.0001, t-test tissue levels. We concluded that erythromycin and roxithromycin should be not administered with milk. Keywords: Pharmacokinetics, macrolides, milk, serum concentration

  18. Susceptibility of streptococcus pneumoniae to fluoroquinolones and macrolides in upper respiratory tract infections.

    Science.gov (United States)

    Mykhalko, Yaroslav O; Duhovych, Tetyana V; Kish, Pavlo P

    Streptococcal species are known as the most common cause of bacterial upper respiratory tract infections (URTI). Once bacterial infection is diagnosed it demands empirical antibiotic prescription. On the other hand antimicrobial resistance is a global burden in today's medicine. For that reason, knowing of antimicrobial susceptibility patterns in population is an important background for successful treatment of bacterial caused URTI. The aim of this study was to analyze S. pneumoniae resistance and susceptibility patterns to fluoroquinolones and macrolides in URTI. The results of microbiological examination of 2,055 pharyngeal swabs taken from patients with bacterial caused tonsillitis, pharyngitis and laryngitis were analyzed. Antimicrobial susceptibility testing for levofloxacin, ofloxacin, gatifloxacin, erythromycin, clarithromycin, azithromycin was performed with the disk-diffusion method. The incidence of S. pneumoniae in the etiological structure of bacterial caused URTI was increasing from 22.47% of cases in 2011 to 36.48% in 2015. The susceptibility of this microorganism to ofloxacin, gatifloxacin and levofloxacin decreased from 96.25%, 100% and 95.00% in 2011 to 44.22%, 65.99% and 62.59% in 2015 respectively. The susceptibility of S. pneumoniae to erythromycin, azithromycin and clarithromycin also decreased from 30.00%, 63.75% and 41.25% in 2011 to 6.80%, 26.53%, 27.21 in 2015. Among investigated antibiotics levofloxacin can be recommended for empiric therapy of URTI because of high pneumococci susceptibility to this drug.

  19. Prevalence of plasmid-mediated multidrug resistance determinants in fluoroquinolone-resistant bacteria isolated from sewage and surface water.

    Science.gov (United States)

    Osińska, Adriana; Harnisz, Monika; Korzeniewska, Ewa

    2016-06-01

    Fluoroquinolones (FQs) are fully synthetic broad-spectrum antibacterial agents that are becoming increasingly popular in the treatment of clinical and veterinary infections. Being excreted during treatment, mostly as active compounds, their biological action is not limited to the therapeutic site, but it is moved further as resistance selection pressure into the environment. Water environment is an ideal medium for the aggregation and dissemination of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic resistance genes (ARGs), which can pose a serious threat to human health. Because of this, the aim of this study was to determine the number of fluoroquinolone-resistant bacteria (FQRB) and their share in total heterotrophic plate counts (HPC) in treated wastewater (TWW), and upstream and downstream river water (URW, DRW) samples where TWW is discharged. The spread of plasmid-mediated quinolone resistance (PMQR) determinants and the presence/absence of resistance genes to other most popular antibiotic groups (against tetracyclines and beta-lactams) in selected 116 multiresistant isolates were investigated. The share of FQRB in total HPC in all samples was rather small and ranged from 0.7 % in URW samples to 7.5 % in TWW. Bacteria from Escherichia (25.0 %), Acinetobacter (25.0 %), and Aeromonas (6.9 %) genera were predominant in the FQRB group. Fluoroquinolone resistance was mostly caused by the presence of the gene aac(6')-1b-cr (91.4 %). More rarely reported was the occurrence of qnrS, qnrD, as well as oqxA, but qnrA, qnrB, qepA, and oqxB were extremely rarely or never noted in FQRB. The most prevalent bacterial genes connected with beta-lactams' resistance in FQRB were bla TEM, bla OXA, and bla CTX-M. The bla SHV was less common in the community of FQRB. The occurrence of bla genes was reported in almost 29.3 % of FQRB. The most abundant tet genes in FQRB were tet(A), tet(L), tet(K), and tet(S). The prevalence of tet genes was observed in 41.4

  20. Macrolides and lincomycin susceptibility of Mycoplasma hyorhinis and variable mutation of domain II and V in 23S ribosomal RNA.

    Science.gov (United States)

    Kobayashi, Hideki; Nakajima, Hiromi; Shimizu, Yuka; Eguchi, Masashi; Hata, Eiji; Yamamoto, Koshi

    2005-08-01

    A total of 151 strains of Mycoplasma hyorhinis isolated from porcine lung lesions (weaned pigs, n=71, and finishers, n=80) were investigated for their in vitro susceptibility to 10 antimicrobial agents. Thirty-one strains (28 from weaned pigs and 3 from finishers) showed resistance to 16-membered macrolide antibiotics and lincomycin. The prevalence of the 16-membered macrolide-resistant M. hyorhinis strain in weaned pigs from Japanese herds has approximately quadrupled in the past 10 years. Several of the 31 strains were examined for mutations in the 23S ribosomal RNA (rRNA). All field strains tested showed a transition of A to G at position 2059 of 23S rRNA-rendered Escherichia coli. On the other hand, individual tylosin- and lincomycin-resistant mutants of M. hyorhinis were selected in vitro from the susceptible type strain BTS7 by 3 to 9 serial passages in subinhibitory concentrations of each antibiotic. The 23S rRNA sequences of both tylosin and lincomycin-resistant mutants were compared with that of the radical BTS7 strain. The BTS7 mutant strain selected by tylosin showed the same transition as the field-isolated strains of A2059G. However, the transition selected in lincomycin showed mutations in domains II and V of 23S rRNA, G2597U, C2611U in domain V, and the addition of an adenine at the pentameric adenine loop in domain II. The strain selected by lincomycin showed an additional point mutation of A2062G selected by tylosin.

  1. Molecular epidemiology, antimicrobial susceptibilities and resistance mechanisms of Streptococcus pyogenes isolates resistant to erythromycin and tetracycline in Spain (1994-2006)

    National Research Council Canada - National Science Library

    Rubio-López, Virginia; Valdezate, Sylvia; Alvarez, David; Villalón, Pilar; Medina, María José; Salcedo, Celia; Sáez-Nieto, Juan-Antonio

    2012-01-01

    Group A Streptococcus (GAS) causes human diseases ranging in severity from uncomplicated pharyngitis to life-threatening necrotizing fasciitis and shows high rates of macrolide resistance in several countries...

  2. Differential epigenetic compatibility of qnr antibiotic resistance determinants with the chromosome of Escherichia coli.

    Directory of Open Access Journals (Sweden)

    María B Sánchez

    Full Text Available Environmental bacteria harbor a plethora of genes that, upon their horizontal transfer to new hosts, may confer resistance to antibiotics, although the number of such determinants actually acquired by pathogenic bacteria is very low. The founder effect, fitness costs and ecological connectivity all influence the chances of resistance transfer being successful. We examined the importance of these bottlenecks using the family of quinolone resistance determinants Qnr. The results indicate the epigenetic compatibility of a determinant with the host genome to be of great importance in the acquisition and spread of resistance. A plasmid carrying the widely distributed QnrA determinant was stable in Escherichia coli, whereas the SmQnr determinant was unstable despite both proteins having very similar tertiary structures. This indicates that the fitness costs associated with the acquisition of antibiotic resistance may not derive from a non-specific metabolic burden, but from the acquired gene causing specific changes in bacterial metabolic and regulatory networks. The observed stabilization of the plasmid encoding SmQnr by chromosomal mutations, including a mutant lacking the global regulator H-NS, reinforces this idea. Since quinolones are synthetic antibiotics, and since the origin of QnrA is the environmental bacterium Shewanella algae, the role of QnrA in this organism is unlikely to be that of conferring resistance. Its evolution toward this may have occurred through mutations or because of an environmental change (exaptation. The present results indicate that the chromosomally encoded Qnr determinants of S. algae can confer quinolone resistance upon their transfer to E. coli without the need of any further mutation. These results suggest that exaptation is important in the evolution of antibiotic resistance.

  3. 大环内酯类抗生素糖基的结构修饰%Modification on sugars of the macrolide antibiotics

    Institute of Scientific and Technical Information of China (English)

    郭强; 马淑涛

    2013-01-01

    大环内酯类抗生素是由链霉菌产生的一类弱碱性抗生素及通过其结构修饰得到的衍生物.为发现具有优良抗耐药活性和其他生物活性的化合物、解决当前日益泛滥的细菌耐药性,研究工作者对大环内脂酯类化合物进行了大量的结构修饰.本文在简要介绍大环内酯类抗生素的发展概况的基础上,重点对大环内酯类化合物结构中克拉定糖和去氧氨基糖的结构修饰及对生物活性的影响进行综述.%Macrolide antibiotics produced from Streptomyces and their derivatives obtained by structural modifications are a series of antibacterial agents. In order to overcome the issue of drug resistance and discover novel compounds with remarkable antibacterial activity and other biological effects, numerous semi-synthetic modifications have been conducted on macrolide. In this review, we give an account of the development of macrolide antibiotics, based on which the structural modifications on the cladinose sugar and desosamine sugar of macrolides are highlighted.

  4. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides.

    Science.gov (United States)

    Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf; Douthwaite, Stephen

    2012-11-01

    Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC(50)], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site.

  5. Determinants of Intravascular Resistance in Indian Diabetic Nephropathy Patients: A Hospital-Based Study

    Directory of Open Access Journals (Sweden)

    Anubhav Thukral

    2011-01-01

    Full Text Available Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.

  6. Using Resistivity Measurements to Determine Anisotropy in Soil and Weathered Rock

    Directory of Open Access Journals (Sweden)

    S. Soto-Caban

    2013-08-01

    Full Text Available This study uses electrical resistivity measurements of soils and weathered rock to perform a fast and reliable evaluation of field anisotropy. Two test sites at New Concord, Ohio were used for the study. These sites are characterized by different landform and slightly east dipping limestone and siltstone formations of Pennsylvanian age. The measured resistivity ranged from 19 Ω∙m to 100 ��∙m, and varied with depth, landform, and season. The anisotropy was determined by a comparison of resistance values along the directions of strike and the dip. Measurements showed that the orientation of electrical anisotropy in the shallow ground may vary due to fluid connection, which is determined by the pore geometry in soil and rock, as well as by the direction of fluid movement. Results from this study indicated that a portable electrical resistivity meter is sensitive and reliable enough to be used for shallow ground fluid monitoring.

  7. Determination of Antibiotic Resistance Pattern of Pseudomonas aeruginosa Strains Isolated from Patients with Burn Wounds

    Directory of Open Access Journals (Sweden)

    Maryam Adabi

    2015-04-01

    Full Text Available Background & objectives: Wound infection is a predominant cause of death in burned patients who are clearly at increased risk of nosocomial infections. Pseudomonas aeruginosa is the most common cause of burn infections and is difficult to treat because of having high level of resistance to antibiotics. The aim of this study was to perform isolation, identification and determination of antibiotics resistance pattern of P. aeruginosa strains isolated from wounds of hospitalized burn patient.   Methods: Biochemical and molecular tests were used for identification of the P. aeruginosa and antibacterial susceptibility test was performed using disk diffusion (Kirby- Bauer methods. Then, the minimum inhibitory concentration (MIC was performed for four representatives of different groups of antibiotics.   Results: Among 94 evaluated strains of P. aeruginosa, 83 isolates (88.3% were multi drugs resistant. Based on Kirby-Bauer method, the most resistance was seen to cefepime (89.5 % and among the antibiotics studied to determine the MIC, the most resistance was observed to ciprofloxacin (89 %. Conclusion: These results indicate high range of resistance to different antibiotics among strains of P. aeruginosa isolated from burn wounds of patients. So, the fast and accurate measurement and evaluation of antibiotic resistance for appropriate antibiotic therapy of burned patients is imperative.

  8. Tests for determining impact resistance and strength of glass used for nuclear waste disposal

    Energy Technology Data Exchange (ETDEWEB)

    Bunnell, L.R.

    1979-05-01

    Tests are described for determining the impact resistance (Section A) and static tensile strength (Section B) of glasses containing simulated or actual nuclear wastes. This report describes the development and use of these tests to rank different glasses, to assess effects of devitrification, and to examine the effect of impact energy on resulting surface area. For clarity this report is divided into two sections, Impact Resistance and Tensile Strength.

  9. Prevalence of plasmid-mediated quinolone resistance and aminoglycoside resistance determinants among carbapeneme non-susceptible Enterobacter cloacae.

    Directory of Open Access Journals (Sweden)

    Shifeng Huang

    Full Text Available BACKGROUND: Simultaneous resistance to aminoglycosides and fluoroquinolones in carbapeneme non-susceptible (CNS isolates will inevitably create problems. The present study was performed to characterize the prevalence of the plasmid-mediated quinolone resistance determinants (QRDs and aminoglycoside resistance determinants (ARDs among the CNS Enterobacter cloacae (E. cloacae isolates in a Chinese teaching hospital, and to acquire their molecular epidemiological characteristics. METHODS: The β-lactamases genes (including class A carbapenemase genes bla(KPC and bla(SME, metallo-β-lactamase genes (MBLs bla(IMP, bla(VIM and bla(NDM, and extended spectrum β-lactamases (ESBLs,bla(CTX-M, bla(TEM and bla(SHV, QRDs (including qnrA, qnrB, qnrS and aac(6'-Ib-cr and ARDs (including aac(6'-Ib, armA and rmtB of these 35 isolates were determined by PCR and sequenced bidirectionally. The clonal relatedness was investigated by pulsed-field gel electrophoresis (PFGE. RESULTS: Of the 35 isolates, 9 (25.7% harbored a carbapenemase gene; 23 (65.7% carried ESBLs; 24 (68.6% were QRD positive; and 27 (77.1% were ARD positive. Among the 5 bla(IMP-8 positive strains, 4 (80% contained both ESBL and QRD genes, and all the 5 (100% harbored ARD genes. Of the 23 ESBLs positive isolates, 6 (26.1% were carbapenemase positive, 14 (60.9% were QRD positive, and 18 (78.3% were ARD positive. PFGE revealed genetic diversity among the 35 isolates, indicating that the high prevalence of CNS E. cloacae isolates was not caused by clonal dissemination. CONCLUSION: QRD and ARD genes were highly prevalent among the CNS E. cloacae isolates. Multiple resistant genes were co-expressed in the same isolates. The CNS E. cloacae isolate co-expressing bla(NDM-1, bla(IMP-26, qnrA1 and qnrS1 was first reported.

  10. A novel Erm monomethyltransferase in antibiotic-resistant isolates of Mannheimia haemolytica and Pasteurella multocida.

    Science.gov (United States)

    Desmolaize, Benoit; Rose, Simon; Warrass, Ralf; Douthwaite, Stephen

    2011-04-01

    Mannheimia haemolytica and Pasteurella multocida are aetiological agents commonly associated with respiratory tract infections in cattle. Recent isolates of these pathogens have been shown to be resistant to macrolides and other ribosome-targeting antibiotics. Direct analysis of the 23S rRNAs by mass spectrometry revealed that nucleotide A2058 is monomethylated, consistent with a Type I erm phenotype conferring macrolide-lincosamide resistance. The erm resistance determinant was identified by full genome sequencing of isolates. The sequence of this resistance determinant, now termed erm(42), has diverged greatly from all previously characterized erm genes, explaining why it has remained undetected in PCR screening surveys. The sequence of erm(42) is, however, completely conserved in six independent M. haemolytica and P. multocida isolates, suggesting relatively recent gene transfer between these species. Furthermore, the composition of neighbouring chromosomal sequences indicates that erm(42) was acquired from other members of the Pasteurellaceae. Expression of recombinant erm(42) in Escherichia coli demonstrated that the enzyme retains its properties as a monomethyltransferase without any dimethyltransferase activity. Erm(42) is a novel addition to the Erm family: it is phylogenetically distant from the other Erm family members and it is unique in being a bona fide monomethyltransferase that is disseminated between bacterial pathogens.

  11. Conjugation between quinolone-susceptible bacteria can generate mutations in the quinolone resistance-determining region, inducing quinolone resistance.

    Science.gov (United States)

    Pitondo-Silva, André; Martins, Vinicius Vicente; Silva, Carolina Fávero da; Stehling, Eliana Guedes

    2015-02-01

    Quinolones are an important group of antibacterial agents that can inhibit DNA gyrase and topoisomerase IV activity. DNA gyrase is responsible for maintaining bacteria in a negatively supercoiled state, being composed of subunits A and B. Topoisomerase IV is a homologue of DNA gyrase and consists of two subunits codified by the parC and parE genes. Mutations in gyrA and gyrB of DNA gyrase may confer resistance to quinolones, and the majority of resistant strains show mutations between positions 67 and 106 of gyrA, a region denoted the quinolone resistance-determining region (QRDR). The most frequent substitutions occur at positions 83 and 87, but little is known about the mechanisms promoting appearance of mutations in the QRDR. The present study proposes that some mutations in the QRDR could be generated as a result of the natural mechanism of conjugation between bacteria in their natural habitat. This event was observed following conjugation in vitro of two different isolates of quinolone-susceptible Pseudomonas aeruginosa, which transferred plasmids of different molecular weights to a recipient strain of Escherichia coli (HB101), also quinolone-susceptible, generating two different transconjugants that presented mutations in DNA gyrase and acquisition of resistance to all quinolones tested.

  12. Determining resistance to mastitis in a bovine subject comprises detecting the presence or absence of a genetic marker that is linked to a trait indicative of mastitis resistance

    DEFF Research Database (Denmark)

    2007-01-01

    The invention relates to a method for determining mastitis resistance in bovine subjects, wherein mastitis resistance comprise resistance to both sub-clinical and clinical mastitis. In particular, the method of the invention involves identification of genetic markers and/or Quantitative Trait Loc...

  13. Translocation of integron-associated resistance in a natural system: Acquisition of resistance determinants by Inc P and Inc W Plasmids from Salmonella enterica Typhimurium DT104

    DEFF Research Database (Denmark)

    Sandvang, Dorthe; Diggle, M.; Platt, D.J.

    2002-01-01

    Salmonella enterica Typhimurium DT104, 961368, a veterinary field isolate that encodes a chromosomal cluster of resistance genes as well as two integrons, was used to study the mobility of resistance cassettes (aadA2 and pse-1) and nonintegron-associated resistance determinants (chloramphenicol...

  14. Conjugative transfer of resistance determinants among human and bovine Streptococcus agalactiae.

    Science.gov (United States)

    Pinto, Tatiana Castro Abreu; Costa, Natália Silva; Corrêa, Ana Beatriz de Almeida; de Oliveira, Ivi Cristina Menezes; de Mattos, Marcos Correa; Rosado, Alexandre Soares; Benchetrit, Leslie Claude

    2014-01-01

    Streptococcus agalactiae (GBS) is a major source of human perinatal diseases and bovine mastitis. Erythromycin (Ery) and tetracycline (Tet) are usually employed for preventing human and bovine infections although resistance to such agents has become common among GBS strains. Ery and Tet resistance genes are usually carried by conjugative transposons (CTns) belonging to the Tn916 family, but their presence and transferability among GBS strains have not been totally explored. Here we evaluated the presence of Tet resistance genes (tetM and tetO) and CTns among Ery-resistant (Ery-R) and Ery-susceptible (Ery-S) GBS strains isolated from human and bovine sources; and analyzed the ability for transferring resistance determinants between strains from both origins. Tet resistance and int-Tn genes were more common among Ery-R when compared to Ery-S isolates. Conjugative transfer of all resistance genes detected among the GBS strains included in this study (ermA, ermB, mef, tetM and tetO), in frequencies between 1.10(-7) and 9.10(-7), was possible from bovine donor strains to human recipient strain, but not the other way around. This is, to our knowledge, the first report of in vitro conjugation of Ery and Tet resistance genes among GBS strains recovered from different hosts.

  15. UVc-irradiation sublethal stress does not alter antibiotic susceptibility of staphylococci (MRSA, MSSA, and coagulase-negative staphylococci) to β-lactam, macrolide, and fluoroquinolone antibiotic agents.

    Science.gov (United States)

    Maeda, Yasunori; Goldsmith, Colin E; Coulter, Wilson A; Millar, B Cherie; Dooley, James S G; Lowery, Colm J; Loughrey, Anne; Rooney, Paul J; McDowell, David A; Matsuda, Motoo; Moore, John E

    2012-01-01

    Skin tanning, either by exposure to natural sunlight or through use of UV sunbeds, has become a popular practice in the US, where it is estimated that approximately 1 million times per day someone in the US uses UV radiation for skin tanning, equating to 30 million Americans (circa 10% of the US population) who use a tanning bed. As well as exposing the host to periods of UV radiation, such practices also expose commensal skin bacteria, including Staphylococcus aureus, to such UV radiation. Previous work has indicated that environmental stresses on bacteria may lead to an upregulation of stress responses, in an attempt for the organism to combat the applied stress and remain viable. UV light may act as an environmental stress on bacteria, and so it was the aim of this study to examine the effect of UVc light on the antibiotic susceptibility of commensal skin bacteria, to determine if UV radiation would increase the antibiotic resistance of such skin flora and thus lead to a potential skin flora with increased antibiotic resistance. Previously, it has been shown that UVc light has a greater mutational effect on bacteria compared to lower-energy UV forms, including UVa and UVb light. Therefore, we decided to employ UVc light in our study to amplify the potential for mutational events occurring in skin staphylococci organisms (n=8) including methicillin-sensitive Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (n=4), and coagulase-negative staphylococci (Staphylococcus haemolyticus) (n=2) were exposed to varying degrees of sublethal radiation via UVc light, and their minimum inhibitory concentration (MIC) susceptibility was determined by broth dilution assay against three classes of commonly used antibiotics, namely β-lactams (penicillin), macrolides (erythromycin), and fluoroquinolones (ciprofloxacin). There was no significant difference between antibiotic susceptibility before UVc exposure and until maximum sublethal stress, prior to cell

  16. Determination of Stress-Rupture Parameters for Four Heat-Resisting Alloys

    Science.gov (United States)

    Lidman, William G.

    1947-01-01

    Stress-rupture data for four heat-resisting alloys are analyzed according to equations of the theory of rate processes. A method for determining the four parameters of structure and composition is demonstrated and the four parameters are determined for each of the alloys: forged S816, cast S816, cast S590, and cast Vitallium. It is concluded that parameters can be determined for an alloy provided sufficient reliable experimental data are available.

  17. Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?

    LENUS (Irish Health Repository)

    Murphy, D M

    2010-03-01

    The macrolides are a class of antibiotics widely prescribed in infectious disease. More recently, there has been considerable interest in potential indications for these agents, in addition to their simple antibacterial indications, in a number of lung pathophysiologies.

  18. Determining resistance to mastitis in a bovine subject comprises detecting the presence or absence of a genetic marker that is linked to a trait indicative of mastitis resistance

    DEFF Research Database (Denmark)

    2007-01-01

    The invention relates to a method for determining mastitis resistance in bovine subjects, wherein mastitis resistance comprise resistance to both sub-clinical and clinical mastitis. In particular, the method of the invention involves identification of genetic markers and/or Quantitative Trait Locus...... (QTL) for the determination of mastitis resistance in a bovine subject. The determination of mastitis resistance involves resolution of the specific microsatellite status. Furthermore, the invention relates to a diagnostic kit for detection of genetic marker(s) associated with mastitis resistance....... The method and kit of the present invention can be applied for selection of bovine subjects for breeding purposes. Thus, the invention provides a method of genetically selecting bovine subjects with mastitis resistance, thereby yielding cows less prone to mastitis...

  19. Mini-Mu insertions in the tetracycline resistance determinant from Proteus mirabilis

    Directory of Open Access Journals (Sweden)

    Magalhães V.D.

    1997-01-01

    Full Text Available The inducible tetracycline resistance determinant isolated from Proteus mirabilis cloned into the plasmid pACYC177 was mutagenized by insertion of a mini-Mu-lac phage in order to define the regions in the cloned sequences encoding the structural and regulatory proteins. Three different types of mutants were obtained: one lost the resistance phenotype and became Lac+; another expressed the resistance at lower levels and constitutively; the third was still dependent on induction but showed a lower minimal inhibitory concentration. The mutant phenotypes and the locations of the insertions indicate that the determinant is composed of a repressor gene and a structural gene which are not transcribed divergently as are other known tetracycline determinants isolated from Gram-negative bacteria

  20. Determination of Screw and Nail Withdrawal Resistance of Some Important Wood Species

    Directory of Open Access Journals (Sweden)

    Alper Aytekin

    2008-04-01

    Full Text Available In this study, screw and nail withdrawal resistance of fir (Abies nordmanniana, oak (Quercus robur L. black pine (Pinus nigra Arnold and Stone pine (Pinus pinea L. wood were determined and compared. The data represent the testing of withdrawal resistance of three types of screws as smart, serrated and conventional and common nails. The specimens were prepared according to TS 6094 standards. The dimensions of the specimens were 5x5x15cm and for all of the directions. Moreover, the specimens were conditioned at ambient room temperature and 65±2% relative humidity. The screws and nails were installed according to ASTM-D 1761 standards. Nail dimensions were 2.5mm diameter and 50 mm length, conventional screws were 4x50mm, serrated screws were 4x45mm and smart screws were 4x50mm. Results show that the maximum screw withdrawal resistance value was found in Stone pine for the serrated screw. There were no significant differences between Stone pine and oak regarding screw withdrawal resistance values. Conventional screw yielded the maximum screw withdrawal resistance value in oak, followed by Stone pine, black pine and fir. Oak wood showed the maximum screw withdrawal resistance value for the smart screw, followed by Stone pine, black pine, and fir. Oak wood showed higher nail withdrawal resistances than softwood species. It was also determined that oak shows the maximum nail withdrawal resistance in all types. The nail withdrawal resistances at the longitudinal direction are lower with respect to radial and tangential directions.

  1. EFFECT OF MACROLIDE ANTIBIOTICS ON VARIOUS CELL CULTURES IN VITRO: 1. CELL MORPHOLOGY

    Directory of Open Access Journals (Sweden)

    Renáta Kováčová

    2012-08-01

    Full Text Available The aim of our study was to evaluate the cytotoxicity of macrolide antibiotics (tilmicosin, tylosin and spiramycin of various concentrations on different cell cultures in vitro. Cellular lines from animal tissues (VERO cells - kidney cells of Macacus rhesus, FE cells - feline embryonal cells, BHK 21 cellular line from young hamster kidneys were used. Tilmicosin effect: BHK cells are most sensitive, significant decrease in vital cells occurs already at the concentration of 50 μg.ml-1. VERO cells were most resistant, significant decrease of vital cells was observed only at the concentration of 300 μg.ml-1. Tylosin effect: BHK cells can be considered most sensitive, since at concentrations higher than 500 μg.ml-1, no vital cells were observed. At the concentration of 1000 μg.ml-1 were 3.13% of vital and 70.52% of subvital FE cells. In Vero cells, we observed a significant decrease at the concentration of 750 μg.ml-1. Spiramycin effect: Significant decrease of vital BHK cells was observed at the concentration of 150 μg.ml-1, at the concentration of 300 μg.ml-1, no vital cells and only 7.53% of subvital cells were observed. At the concentration of 500 μg.ml-1 reported 10.34% of vital FE cells. At the concentration of 500 μg.ml-1 22.48% of vital and 71.16% of subvital VERO cells were recorded.

  2. Inhibition of Protein Synthesis on the Ribosome by Tildipirosin Compared with Other Veterinary Macrolides

    OpenAIRE

    Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf; Douthwaite, Stephen

    2012-01-01

    Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC50], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleo...

  3. Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice

    Directory of Open Access Journals (Sweden)

    Hajime Terao

    2003-01-01

    Full Text Available Background and aim: Low-dose and long-term administration of macrolide antibiotics into patients with chronic airway inflammatory diseases could favorably modify their clinical conditions. However, the therapeutic mode of action of macrolides is not well understood. Free oxygen radicals, including nitric oxide (NO, are well recognized as the important final effector molecules in the development and the maintenance of inflammatory diseases.

  4. Genome-wide identification of ampicillin resistance determinants in Enterococcus faecium.

    Directory of Open Access Journals (Sweden)

    Xinglin Zhang

    2012-06-01

    Full Text Available Enterococcus faecium has become a nosocomial pathogen of major importance, causing infections that are difficult to treat owing to its multi-drug resistance. In particular, resistance to the β-lactam antibiotic ampicillin has become ubiquitous among clinical isolates. Mutations in the low-affinity penicillin binding protein PBP5 have previously been shown to be important for ampicillin resistance in E. faecium, but the existence of additional resistance determinants has been suggested. Here, we constructed a high-density transposon mutant library in E. faecium and developed a transposon mutant tracking approach termed Microarray-based Transposon Mapping (M-TraM, leading to the identification of a compendium of E. faecium genes that contribute to ampicillin resistance. These genes are part of the core genome of E. faecium, indicating a high potential for E. faecium to evolve towards β-lactam resistance. To validate the M-TraM results, we adapted a Cre-lox recombination system to construct targeted, markerless mutants in E. faecium. We confirmed the role of four genes in ampicillin resistance by the generation of targeted mutants and further characterized these mutants regarding their resistance to lysozyme. The results revealed that ddcP, a gene predicted to encode a low-molecular-weight penicillin binding protein with D-alanyl-D-alanine carboxypeptidase activity, was essential for high-level ampicillin resistance. Furthermore, deletion of ddcP sensitized E. faecium to lysozyme and abolished membrane-associated D,D-carboxypeptidase activity. This study has led to the development of a broadly applicable platform for functional genomic-based studies in E. faecium, and it provides a new perspective on the genetic basis of ampicillin resistance in this organism.

  5. Whole Genome Sequencing for Surveillance of Antimicrobial Resistance in Actinobacillus pleuropneumoniae

    Science.gov (United States)

    Bossé, Janine T.; Li, Yanwen; Rogers, Jon; Fernandez Crespo, Roberto; Li, Yinghui; Chaudhuri, Roy R.; Holden, Matthew T. G.; Maskell, Duncan J.; Tucker, Alexander W.; Wren, Brendan W.; Rycroft, Andrew N.; Langford, Paul R.

    2017-01-01

    The aim of this study was to evaluate the correlation between antimicrobial resistance (AMR) profiles of 96 clinical isolates of Actinobacillus pleuropneumoniae, an important porcine respiratory pathogen, and the identification of AMR genes in whole genome sequence (wgs) data. Susceptibility of the isolates to nine antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, sulfisoxazole, tetracycline, tilmicosin, trimethoprim, and tylosin) was determined by agar dilution susceptibility test. Except for the macrolides tested, elevated MICs were highly correlated to the presence of AMR genes identified in wgs data using ResFinder or BLASTn. Of the isolates tested, 57% were resistant to tetracycline [MIC ≥ 4 mg/L; 94.8% with either tet(B) or tet(H)]; 48% to sulfisoxazole (MIC ≥ 256 mg/L or DD = 6; 100% with sul2), 20% to ampicillin (MIC ≥ 4 mg/L; 100% with blaROB-1), 17% to trimethoprim (MIC ≥ 32 mg/L; 100% with dfrA14), and 6% to enrofloxacin (MIC ≥ 0.25 mg/L; 100% with GyrAS83F). Only 33% of the isolates did not have detectable AMR genes, and were sensitive by MICs for the antimicrobial agents tested. Although 23 isolates had MIC ≥ 32 mg/L for tylosin, all isolates had MIC ≤ 16 mg/L for both erythromycin and tilmicosin, and no macrolide resistance genes or known point mutations were detected. Other than the GyrAS83F mutation, the AMR genes detected were mapped to potential plasmids. In addition to presence on plasmid(s), the tet(B) gene was also found chromosomally either as part of a 56 kb integrative conjugative element (ICEApl1) in 21, or as part of a Tn7 insertion in 15 isolates. Our results indicate that, with the exception of macrolides, wgs data can be used to accurately predict resistance of A. pleuropneumoniae to the tested antimicrobial agents and provides added value for routine surveillance.

  6. Comparison of Several Methods for Determining the Internal Resistance of Lithium Ion Cells

    Directory of Open Access Journals (Sweden)

    Hans-Georg Schweiger

    2010-06-01

    Full Text Available The internal resistance is the key parameter for determining power, energy efficiency and lost heat of a lithium ion cell. Precise knowledge of this value is vital for designing battery systems for automotive applications. Internal resistance of a cell was determined by current step methods, AC (alternating current methods, electrochemical impedance spectroscopy and thermal loss methods. The outcomes of these measurements have been compared with each other. If charge or discharge of the cell is limited, current step methods provide the same results as energy loss methods.

  7. Characterization of integrons and tetracycline resistance determinants in Aeromonas spp. isolated from South African aquaculture systems.

    Science.gov (United States)

    Jacobs, Liezl; Chenia, Hafizah Y

    2007-03-20

    An increasing incidence of multidrug resistance amongst Aeromonas spp. isolates, which are both fish pathogens and emerging opportunistic human pathogens, has been observed worldwide. This can be attributed to the horizontal transfer of mobile genetic elements, viz.: plasmids and class 1 integrons. The antimicrobial susceptibilities of 37 Aeromonas spp. isolates, from tilapia, trout and koi aquaculture systems, were determined by disc-diffusion testing. The plasmid content of each isolate was examined using the alkaline lysis protocol. Tet determinant type was determined by amplification using two degenerate primer sets and subsequent HaeIII restriction. The presence of integrons was determined by PCR amplification of three integrase genes, as well as gene cassettes, and the qacEDelta1-sulI region. Thirty-seven Aeromonas spp. isolates were differentiated into six species by aroA PCR-RFLP, i.e., A. veronii biovar sobria, A. hydrophila, A. encheleia, A. ichtiosoma, A. salmonicida, and A. media. High levels of resistance to tetracycline (78.3%), amoxicillin (89.2%), and augmentin (86.5%) were observed. Decreased susceptibility to erythromycin was observed for 67.6% of isolates. Although 45.9% of isolates displayed nalidixic acid resistance, majority of isolates were susceptible to the fluoroquinolones. The MAR index ranged from 0.12 to 0.59, with majority of isolates indicating high-risk contamination originating from humans or animals where antibiotics are often used. Plasmids were detected in 21 isolates, with 14 of the isolates displaying multiple plasmid profiles. Single and multiple class A family Tet determinants were observed in 27% and 48.7% of isolates, respectively, with Tet A being the most prevalent Tet determinant type. Class 1 integron and related structures were amplified and carried different combinations of the antibiotic resistance gene cassettes ant(3'')Ia, aac(6')Ia, dhfr1, oxa2a and/or pse1. Class 2 integrons were also amplified, but the

  8. Comparison of Several Methods for Determining the Internal Resistance of Lithium Ion Cells

    Science.gov (United States)

    Schweiger, Hans-Georg; Obeidi, Ossama; Komesker, Oliver; Raschke, André; Schiemann, Michael; Zehner, Christian; Gehnen, Markus; Keller, Michael; Birke, Peter

    2010-01-01

    The internal resistance is the key parameter for determining power, energy efficiency and lost heat of a lithium ion cell. Precise knowledge of this value is vital for designing battery systems for automotive applications. Internal resistance of a cell was determined by current step methods, AC (alternating current) methods, electrochemical impedance spectroscopy and thermal loss methods. The outcomes of these measurements have been compared with each other. If charge or discharge of the cell is limited, current step methods provide the same results as energy loss methods. PMID:22219678

  9. Antimicrobial resistance, virulence determinants and genetic profiles of clinical and nonclinical Enterococcus cecorum from poultry.

    Science.gov (United States)

    Jackson, C R; Kariyawasam, S; Borst, L B; Frye, J G; Barrett, J B; Hiott, L M; Woodley, T A

    2015-02-01

    Enterococcus cecorum has been implicated as a possible cause of disease in poultry. However, the characteristics that contribute to pathogenesis of Ent. cecorum in poultry have not been defined. In this study, Ent. cecorum from carcass rinsates (n = 75) and diseased broilers and broiler breeders (n = 30) were compared based upon antimicrobial resistance phenotype, the presence of virulence determinants and genetic relatedness using pulsed-field gel electrophoresis (PFGE). Of the 16 antimicrobials tested, Ent. cecorum from carcass rinsates and clinical cases were resistant to ten and six of the antimicrobials, respectively. The majority of Ent. cecorum from carcass rinsates was resistant to lincomycin (54/75; 72%) and tetracycline (46/75; 61.3%) while the highest level of resistance among clinical Ent. cecorum was to tetracycline (22/30; 73.3%) and erythromycin (11/30; 36.7%). Multidrug resistance (resistance to ≥2 antimicrobials) was identified in Ent. cecorum from carcass rinsates (53/75; 70.7%) and diseased poultry (18/30; 60%). Of the virulence determinants tested, efaAfm was present in almost all of the isolates (104/105; 99%). Using PFGE, the majority of clinical isolates clustered together; however, a few clinical isolates grouped with Ent. cecorum from carcass rinsates. These data suggest that distinguishing the two groups of isolates is difficult based upon the characterization criteria used.

  10. Nickel-resistance determinants in Acidiphilium sp. PM identified by genome-wide functional screening.

    Directory of Open Access Journals (Sweden)

    Patxi San Martin-Uriz

    Full Text Available Acidiphilium spp. are conspicuous dwellers of acidic, metal-rich environments. Indeed, they are among the most metal-resistant organisms; yet little is known about the mechanisms behind the metal tolerance in this genus. Acidiphilium sp. PM is an environmental isolate from Rio Tinto, an acidic, metal-laden river located in southwestern Spain. The characterization of its metal resistance revealed a remarkable ability to tolerate high Ni concentrations. Here we report the screening of a genomic library of Acidiphilium sp. PM to identify genes involved in Ni resistance. This approach revealed seven different genes conferring Ni resistance to E. coli, two of which form an operon encoding the ATP-dependent protease HslVU (ClpQY. This protease was found to enhance resistance to both Ni and Co in E. coli, a function not previously reported. Other Ni-resistance determinants include genes involved in lipopolysaccharide biosynthesis and the synthesis of branched amino acids. The diversity of molecular functions of the genes recovered in the screening suggests that Ni resistance in Acidiphilium sp. PM probably relies on different molecular mechanisms.

  11. Antibacterial activity of fosmidomycin on chromosomic and plasmid-determined fosfomycin-resistant strains.

    Science.gov (United States)

    Mendez, F J; Alvarez, A A; Mendoza, M C; Hardisson, C

    1985-04-01

    The antibacterial activity of fosmidomycin (Fm) on chromosomic and plasmid-determined fosfomycin-resistant (For) strains of Gram-negative bacteria was studied. Presence of For-plasmids did not protect host bacteria from the antibiotic effect of Fm. In clinical isolates Fm was more active than Fo in 67% of the strains whereas Fo was more active for only 2%; 76% of the strains showed cross resistance to both antibiotics. The Fmr character was not transferred by conjugation. For mutants selected in the hospital environment as well as in the laboratory did not always show cross resistance with Fm, and the alterations in the transport systems of both antibiotics were not the only mechanism of cross resistance.

  12. Activities of two novel macrolides, GW 773546 and GW 708408, compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin against Haemophilus influenzae.

    Science.gov (United States)

    Kosowska, Klaudia; Credito, Kim; Pankuch, Glenn A; Hoellman, Dianne; Lin, Gengrong; Clark, Catherine; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

    2004-11-01

    The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW 773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x 10(-9) to 2.2 x 10(-6) with

  13. Standard test method for determination of resistance to stable crack extension under low-constraint conditions

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2006-01-01

    1.1 This standard covers the determination of the resistance to stable crack extension in metallic materials in terms of the critical crack-tip-opening angle (CTOAc), ψc and/or the crack-opening displacement (COD), δ5 resistance curve (1). This method applies specifically to fatigue pre-cracked specimens that exhibit low constraint (crack-length-to-thickness and un-cracked ligament-to-thickness ratios greater than or equal to 4) and that are tested under slowly increasing remote applied displacement. The recommended specimens are the compact-tension, C(T), and middle-crack-tension, M(T), specimens. The fracture resistance determined in accordance with this standard is measured as ψc (critical CTOA value) and/or δ5 (critical COD resistance curve) as a function of crack extension. Both fracture resistance parameters are characterized using either a single-specimen or multiple-specimen procedures. These fracture quantities are determined under the opening mode (Mode I) of loading. Influences of environment a...

  14. Socioeconomic Determinants of Ciprofloxacin-Resistant Shigella Infections in Bangladeshi Children

    Directory of Open Access Journals (Sweden)

    Randon J. Gruninger

    2017-03-01

    Full Text Available Background: Shigella species (spp. are a leading cause of moderate to severe diarrhea in children worldwide. The recent emergence of quinolone-resistant Shigella spp. gives cause for concern, and South Asia has been identified as a reservoir for global spread. The influence of socioeconomic status on antimicrobial resistance in developing countries, such as those in South Asia, remains unknown. Methods: We used data collected from 2009 to 2014 from a hospital specializing in the treatment of diarrhea in Dhaka, Bangladesh, to determine the relationship between ciprofloxacin-resistant Shigella spp. isolates and measures of socioeconomic status in Bangladeshi children less than 5 years of age. Results: We found 2.7% (230/8, 672 of children who presented with diarrhea had Shigella spp. isolated from their stool, and 50% (115/230 had resistance to ciprofloxacin. Using multivariable logistic regression analysis, we found that children from families where the father’s income was in the highest quintile had significantly higher odds of having ciprofloxacin-resistant Shigella spp. compared to children in the lowest quintile (OR = 6.1, CI 1.9-19. Factors protective against the development of resistance included access to improved sanitation (OR = 0.27, CI 0.11-0.7, and improved water sources (OR = 0.48, CI 0.25-0.92. We did not find a relationship between ciprofloxacin resistance and other proxies for socioeconomic status, including the presence of animals in the home, nutritional status, paternal education level, and the number of family members in the home. Conclusions: Although the associations between wealth and antimicrobial resistance are not fully understood, possible explanations include increased access and use of antibiotics, greater access to healthcare facilities and thus resistant pathogens, or greater consumption of commercially produced foods prepared with antibiotics.

  15. MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells.

    Science.gov (United States)

    Fessler, Shawn P; Wotkowicz, Mark T; Mahanta, Sanjeev K; Bamdad, Cynthia

    2009-11-01

    In the United States, 211,000 women are diagnosed each year with breast cancer. Of the 42,000 breast cancer patients who overexpress the HER2 growth factor receptor, Herceptin). Despite those statistics, women diagnosed with breast cancer are now tested to determine how much of this important growth factor receptor is present in their tumor because patients whose treatment includes trastuzumab are three-times more likely to survive for at least 5 years and are two-times more likely to survive without a cancer recurrence. Unfortunately, even among the group whose cancers originally respond to trastuzumab, 25% of the metastatic breast cancer patients acquire resistance to trastuzumab within the first year of treatment. Follow-on "salvage" therapies have prolonged life for this group but have not been curative. Thus, it is critically important to understand the mechanisms of trastuzumab resistance and develop therapies that reverse or prevent it. Here, we report that molecular analysis of a cancer cell line that was induced to acquire trastuzumab resistance showed a dramatic increase in the amount of the cleaved form of the MUC1 protein, called MUC1*. We recently reported that MUC1* functions as a growth factor receptor on cancer cells and on embryonic stem cells. Here, we show that treating trastuzumab-resistant cancer cells with a combination of MUC1* antagonists and trastuzumab, reverses the drug resistance. Further, HER2-positive cancer cells that are intrinsically resistant to trastuzumab became trastuzumab-sensitive when treated with MUC1* antagonists and trastuzumab. Additionally, we found that tumor cells that had acquired Herceptin resistance had also acquired resistance to standard chemotherapy agents like Taxol, Doxorubicin, and Cyclophosphamide. Acquired resistance to these standard chemotherapy drugs was also reversed by combined treatment with the original drug plus a MUC1* inhibitor.

  16. QTL analysis of the genetic architecture determining resistance to fire blight in an apple progeny

    NARCIS (Netherlands)

    Calenge, F.; Drouet, D.; Weg, van de W.E.; Brisset, M.N.; Paulin, J.P.; Durel, C.E.

    2004-01-01

    Fire blight, caused by the bacterial pathogen Erwinia amylovora, is one of the most destructive diseases of apple (Malus x domestica). In order to analyse the genetic determinism of resistance to fire blight in apple, a quantitative trait analysis (QTL) approach was used. A F1 progeny of 164

  17. A Bioassay for Determining Resistance Levels in Tarnished Plant Bug Populations to Neonicotinoid Insecticides

    Science.gov (United States)

    A laboratory bioassay was developed and used to test field populations of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), for resistance development to the neonicitinoid insecticides imidacloprid (Trimax®) and thiamethoxam (Centric®). The bioassay determined LC50 values by feeding...

  18. QTL analysis of the genetic architecture determining resistance to fire blight in an apple progeny

    NARCIS (Netherlands)

    Calenge, F.; Drouet, D.; Weg, van de W.E.; Brisset, M.N.; Paulin, J.P.; Durel, C.E.

    2004-01-01

    Fire blight, caused by the bacterial pathogen Erwinia amylovora, is one of the most destructive diseases of apple (Malus x domestica). In order to analyse the genetic determinism of resistance to fire blight in apple, a quantitative trait analysis (QTL) approach was used. A F1 progeny of 164 individ

  19. Coagulase-negative staphylococci (CoNS) isolated from ready-to-eat food of animal origin--phenotypic and genotypic antibiotic resistance.

    Science.gov (United States)

    Chajęcka-Wierzchowska, Wioleta; Zadernowska, Anna; Nalepa, Beata; Sierpińska, Magda; Łaniewska-Trokenheim, Łucja

    2015-04-01

    The aim of this work was to study the pheno- and genotypical antimicrobial resistance profile of coagulase negative staphylococci (CoNS) isolated from 146 ready-to-eat food of animal origin (cheeses, cured meats, sausages, smoked fishes). 58 strains were isolated, they were classified as Staphylococcus xylosus (n = 29), Staphylococcus epidermidis (n = 16); Staphylococcus lentus (n = 7); Staphylococcus saprophyticus (n = 4); Staphylococcus hyicus (n = 1) and Staphylococcus simulans (n = 1) by phenotypic and genotypic methods. Isolates were tested for resistance to erythromycin, clindamycin, gentamicin, cefoxitin, norfloxacin, ciprofloxacin, tetracycline, tigecycline, rifampicin, nitrofurantoin, linezolid, trimetoprim, sulphamethoxazole/trimethoprim, chloramphenicol, quinupristin/dalfopristin by the disk diffusion method. PCR was used for the detection of antibiotic resistance genes encoding: methicillin resistance--mecA; macrolide resistance--erm(A), erm(B), erm(C), mrs(A/B); efflux proteins tet(K) and tet(L) and ribosomal protection proteins tet(M). For all the tet(M)-positive isolates the presence of conjugative transposons of the Tn916-Tn1545 family was determined. Most of the isolates were resistant to cefoxitin (41.3%) followed by clindamycin (36.2%), tigecycline (24.1%), rifampicin (17.2%) and erythromycin (13.8%). 32.2% staphylococcal isolates were multidrug resistant (MDR). All methicillin resistant staphylococci harboured mecA gene. Isolates, phenotypic resistant to tetracycline, harboured at least one tetracycline resistance determinant on which tet(M) was most frequent. All of the isolates positive for tet(M) genes were positive for the Tn916-Tn1545 -like integrase family gene. In the erythromycin-resistant isolates, the macrolide resistance genes erm(C) or msr(A/B) were present. Although coagulase-negative staphylococci are not classical food poisoning bacteria, its presence in food could be of public health significance due to the possible spread of

  20. Phenotypes, genotypes, serotypes and molecular epidemiology of erythromycin-resistant Streptococcus agalactiae in Italy.

    Science.gov (United States)

    De Francesco, M A; Caracciolo, S; Gargiulo, F; Manca, N

    2012-08-01

    The purpose of this investigation was to analyse Streptococcus agalactiae (group B Streptococcus, GBS) isolates collected in Italy from vaginal and urine samples in respect to their clonality, distribution of virulence factors and antimicrobial resistance determinants. Three hundred and eighty-eight GBS were recovered from clinical samples. They were analysed for antibiotic resistance profiling. Erythromycin-resistant strains were further characterised by multilocus sequence typing (MLST), serotyping and the detection of alp genes of the alpha-like protein (Alp) family. GBS isolates represented 40 different sequence types (STs), grouped in five clonal complexes (CCs) and belonged to seven serotypes. Most serotype V strains (81%) possessed alp2-3; serotype Ia carried mainly epsilon, while the serotype III mainly rib. All isolates were susceptible to penicillin, whereas resistance to erythromycin was detected in 15% of isolates. Most erythromycin-resistant GBS strains were of serotype V (56.8%) and belonged to the CC-1 group (50%). Macrolide resistance phenotypes were the cMLS(B) (46.5%) and the M phenotypes (46.5%) due to the presence of ermB and mefA/E genes, respectively. These results provide data which establish a baseline for monitoring erythromycin resistance in this region and also provide an insight into the correlation among clonal types, serotypes, surface protein and resistance genes. The increased prevalence of strains that displayed the M phenotype strengthens the importance of the epidemiological surveillance of macrolide resistance in GBS, which may also represent an important reservoir of resistance genes for other species.

  1. Acinetobacter baumannii Isolated from Lebanese Patients: Phenotypes and Genotypes of Resistance, Clonality, and Determinants of Pathogenicity

    Science.gov (United States)

    Dahdouh, Elias; Hajjar, Micheline; Suarez, Monica; Daoud, Ziad

    2016-01-01

    Introduction: Acinetobacter baumannii is a nosocomial pathogen that usually affects critically ill patients. High mortality rates have been associated with MDR A. baumannii infections. Carbapenem resistance among these isolates is increasing worldwide and is associated with certain International Clones (ICs) and oxacillinases (OXAs). Moreover, this organism possesses a wide range of virulence factors, whose expression is not yet fully understood. In this study, clinical A. baumannii isolates are characterized in terms of antibiotic resistance, mechanisms of carbapenem resistance, clonality, and virulence. Materials and Methods: A. baumannii clinical isolates (n = 90) where obtained from a tertiary care center in Beirut, Lebanon. API 20NE strips in addition to the amplification of blaOXA−51−like were used for identification. Antibiotic susceptibility testing by disk diffusion was then performed in addition to PCRs for the detection of the most commonly disseminated carbapenemases. Clonality was determined by tri-locus PCR typing and doubling times were determined for isolates with varying susceptibility profiles. Biofilm formation, hemolysis, siderophore production, proteolytic activity, and surface motility was then determined for all the isolates. Statistical analysis was then performed for the determination of associations. Results and Discussion: 81 (90%) of the isolates were resistant to carbapenems. These high rates are similar to other multi-center studies in the country suggesting the need of intervention on a national level. 74 (91.3%) of the carbapenem resistant isolates harbored blaOXA−23−like including two that also harbored blaOXA−24−like. 88.9% of the A. baumannii isolates pertained to ICII and three other international clones were detected, showing the wide dissemination of clones into geographically distinct locations. Virulence profiles were highly diverse and no specific pattern was observed. Nevertheless, an association between

  2. Antibiotic Resistance Determinant-Focused Acinetobacter baumannii Vaccine Designed Using Reverse Vaccinology

    Directory of Open Access Journals (Sweden)

    Zhaohui Ni

    2017-02-01

    Full Text Available As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices. These 35 antigens include 11 TonB dependent receptors, 8 porins, 7 efflux pump proteins, and 2 fimbrial proteins (FilF and CAM87009.1. CAM86003.1 was predicted to be an adhesin outer membrane protein absent from 3 antibiotic-sensitive strains and conserved in 21 antibiotic-resistant strains. Feasible anti-resistance vaccine candidates also include one extracellular protein (QnrA, 3 RND type outer membrane efflux pump proteins, and 3 CTX-M type β-lactamases. Among 39 β-lactamases, A. baumannii CTX-M-2, -5, and -43 enzymes are predicted as adhesins and better vaccine candidates than other β-lactamases to induce preventive immunity and enhance antibiotic treatments. This report represents the first reverse vaccinology study to systematically predict vaccine antigen candidates against antibiotic resistance for a microbial pathogen.

  3. Antibiotic Resistance Determinant-Focused Acinetobacter baumannii Vaccine Designed Using Reverse Vaccinology

    Science.gov (United States)

    Ni, Zhaohui; Chen, Yan; Ong, Edison; He, Yongqun

    2017-01-01

    As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices. These 35 antigens include 11 TonB dependent receptors, 8 porins, 7 efflux pump proteins, and 2 fimbrial proteins (FilF and CAM87009.1). CAM86003.1 was predicted to be an adhesin outer membrane protein absent from 3 antibiotic-sensitive strains and conserved in 21 antibiotic-resistant strains. Feasible anti-resistance vaccine candidates also include one extracellular protein (QnrA), 3 RND type outer membrane efflux pump proteins, and 3 CTX-M type β-lactamases. Among 39 β-lactamases, A. baumannii CTX-M-2, -5, and -43 enzymes are predicted as adhesins and better vaccine candidates than other β-lactamases to induce preventive immunity and enhance antibiotic treatments. This report represents the first reverse vaccinology study to systematically predict vaccine antigen candidates against antibiotic resistance for a microbial pathogen. PMID:28230771

  4. Antibiotic Resistance Determinant-Focused Acinetobacter baumannii Vaccine Designed Using Reverse Vaccinology.

    Science.gov (United States)

    Ni, Zhaohui; Chen, Yan; Ong, Edison; He, Yongqun

    2017-02-21

    As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices. These 35 antigens include 11 TonB dependent receptors, 8 porins, 7 efflux pump proteins, and 2 fimbrial proteins (FilF and CAM87009.1). CAM86003.1 was predicted to be an adhesin outer membrane protein absent from 3 antibiotic-sensitive strains and conserved in 21 antibiotic-resistant strains. Feasible anti-resistance vaccine candidates also include one extracellular protein (QnrA), 3 RND type outer membrane efflux pump proteins, and 3 CTX-M type β-lactamases. Among 39 β-lactamases, A. baumannii CTX-M-2, -5, and -43 enzymes are predicted as adhesins and better vaccine candidates than other β-lactamases to induce preventive immunity and enhance antibiotic treatments. This report represents the first reverse vaccinology study to systematically predict vaccine antigen candidates against antibiotic resistance for a microbial pathogen.

  5. Determination of Drug Resistance Pattern of Prevalent Bacteria Isolated from Patients with UTI

    Directory of Open Access Journals (Sweden)

    H Zandi

    2007-06-01

    Full Text Available Background: Urinary tract infections are the most prevalent bacterial infections in the world and using empiric antibiotic therapy may increase the drug resistance. This cross- sectional study accomplished to determine the prevalence of UTI and related antibiotic resistance pattern. Methods: UTI suspected patients referred to Yazd central laboratory studied. The urine samples cultured colonies with colony count of > 105 cfu/ml identified, and antibiotic resistance patterns determined by the standard disk diffusion method (Kirby-Bauer. Results: Out of 17353 samples 1623 (9.35% were positive culture. The most prevalent microorganisms were as follows: E.coli (47.07%. Enterobacter (12.07%. S. aureus (10.96%, Klebsiella pneumoniae (9.85%, CNS (8.37%, group B streptococci (4.86%. Enterococci (2.09%. Pseudomonas aeruginosa (1.54%. Proteus (1.17%. Nonhemolytic streptococci (0.86%, Citrobacter and α hemolytic Streptococci (0.55%. The antibiogram results showed that isolated strains had the most drug resistance as follows: to ampicillin (80%, SXT (53.66%, tetracycline (50.33%, cephalexin (22.92%, nalidixic acid (19.4%, nitrofruntain (17.12%, ceftizoxime (8.5% and ciprofloxacin (8%. Gram (+ cocci strains were 100% sensitive to vancomycin. Conclusion: selection of proper antibiotic against isolated species though susceptibility testing decreases the dissemination of resistant strains.

  6. Paths and determinants for Penicillium janthinellum to resist low and high copper.

    Science.gov (United States)

    Xu, Jian; Chen, Guo-Li; Sun, Xue-Zhe; Fan, Xian-Wei; You-Zhi, Li

    2015-08-12

    Copper (Cu) tolerance was well understood in fungi yeasts but not in filamentous fungi. Filamentous fungi are eukaryotes but unlike eukaryotic fungi yeasts, which are a collection of various fungi that are maybe classified into different taxa but all characterized by growth as filamentous hyphae cells and with a complex morphology. The current knowledge of Cu resistance of filamentous fungi is still fragmental and therefore needs to be bridged. In this study, we characterized Cu resistance of Penicillium janthinellum strain GXCR and its Cu-resistance-decreasing mutants (EC-6 and UC-8), and conducted sequencing of a total of 6 transcriptomes from wild-type GXCR and mutant EC-6 grown under control and external Cu. Taken all the results together, Cu effects on the basal metabolism were directed to solute transport by two superfamilies of solute carrier and major facilitator, the buffering free CoA and Acyl-CoA pool in the peroxisome, F-type H(+)-transporting ATPases-based ATP production, V-type H(+)-transporting ATPases-based transmembrane transport, protein degradation, and alternative splicing of pre-mRNAs. Roles of enzymatic and non-enzymatic antioxidants in resistance to low and high Cu were defined. The backbone paths, signaling systems, and determinants that involve resistance of filamentous fungi to high Cu were determined, discussed and outlined in a model.

  7. [Studies on cold resistance of hazel determined and analyzed by atomic absorption spectrometry].

    Science.gov (United States)

    Li, Xiu-Xia; Liu, Cheng-Cai; Zhang, Wei-Dong; Shao, Hong; Wu, Heng-Mei; Wang, Zhong; Yang, Yong-Nian; Li, Ji-Lin

    2010-06-01

    Using annual branch of hazel as the experimental materials, the K(+)-leakage and relative electric conductivity of three hazel species (six hazel clones) which had been treated with different low temperature were determined by electro-conductivity gauge and atomic absorption spectrometry. Regression models were established for low temperature to the K(+)-leakage or the relative electric conductivity of six hazel clones. The results showed that there was the same result of cold resistance for all clones using the two methods of comprehensive evaluation, and the indicator of K(+)-leakage rate determined by atomic absorption spectrometry can be used as a means of early identification of cold resistance of hazel clones. There were obvious differences among the clones in the ability of cold resistance. The order of the ability of cold resistance for the six hazel clones was C7R7 > Z-9-40 > C6R1 > CS2R1 > Z-9-22 > Z-9-30, and the order of the ability of cold resistance for the three hazel species was C. heterophylla > C. heterophyllax X (C. heterophylla X C. avellana) > C. heterophylla X C. avellana. The median lethal temperature of tissue for all clones is -26(-)-40 degrees "C.

  8. [Bacteriostatic and bactericidal activities of cyclines, macrolides and fluoroquinolones against Chlamydia trachomatis].

    Science.gov (United States)

    Dailloux, M; Villemain, P

    1992-05-01

    The in vitro activity of minocycline, doxycycline, erythromycin, roxithromycin, spiramycin, pefloxacin, and ofloxacin against ten C. trachomatis strains recovered from human genital tract specimens was evaluated. Mac Coy cell monolayers in 24-microwell plates were used. The C. trachomatis inoculum was 10(4) IFU/well. Appropriate dilutions of antibiotic were added and inclusions were detected by immunofluorescence using monoclonal antibodies. MICs were determined after 48 hours of exposure to each antimicrobial. The MIC90 for cyclines was 0.2 mg/l. Among tested macrolides, roxithromycin had a lower MIC than erythromycin (0.2 versus 0.4 mg/l) whereas spiramycin inhibited growth only in a concentration of 2 mg/l. Ofloxacin showed better activity than pefloxacin. Bactericidal activity was evaluated by determining two parameters: MBC1 (without transfer to new cells) measured the ability of a C. trachomatis particle to persist in a latent form within cells exposed to an antibiotic and to grow again following removal of the antibiotic, whereas MBC2 (with transfer to new cells) reflected infectivity of the bacteria after 48 hours exposure to the antimicrobial. None of the tested antibiotics was bactericidal according to both parameters. The ability of C. trachomatis to remain within antibiotic-exposed cells in a latent form was clearly demonstrated by the high MBC1 values. This feature may explain why recurrences are common in clinical practice.

  9. Prevalence of plasmid-mediated quinolone resistance determinants in Enterobacteriaceae strains isolated in North-East Italy.

    Science.gov (United States)

    Kocsis, B; Mazzariol, A; Kocsis, E; Koncan, R; Fontana, R; Cornaglia, G

    2013-02-01

    We investigated the prevalence of plasmid-mediated quinolone resistance genes in 756 clinical isolates of Enterobacteriaceae originating from Microbiology Diagnostic Laboratories of North-East Italy. Five point zero two percent of isolates carried a qnr determinant while the aac(6')-Ib-cr determinant was detected in 9·25% of isolates. We also investigated the association between the plasmid-mediated quinolone resistance and the beta-lactamase genes, and characterized the plasmids carrying these determinants of resistance.

  10. An assay for determining minimal concentrations of antibiotics that drive horizontal transfer of resistance.

    Science.gov (United States)

    Jutkina, Jekaterina; Rutgersson, Carolin; Flach, Carl-Fredrik; Larsson, D G Joakim

    2016-04-01

    Ability to understand the factors driving horizontal transfer of antibiotic resistance from unknown, harmless bacteria to pathogens is crucial in order to tackle the growing resistance problem. However, current methods to measure effects of stressors on horizontal gene transfer have limitations and often fall short, as the estimated endpoints can be a mix of both the number of transfer events and clonal growth of transconjugants. Our aim was therefore to achieve a proper strategy for assessing the minimal concentration of a stressor (exemplified by tetracycline) that drives horizontal transfer of antibiotic resistance from a complex community to a model pathogen. Conditions were optimized to improve a culture-based approach using the bacterial community of treated sewage effluent as donor, and fluorescent, traceable Escherichia coli as recipient. Reduced level of background resistance, differentiation of isolates as well as decreased risk for measuring effects of selection were achieved through the use of chromogenic medium, optimization of conjugation time as well as applying a different antibiotic for isolation of transconjugants than the one tested for its ability to drive transfer. Using this assay, we showed that a very low concentration of tetracycline, 10μg/L i.e. 150 times below the minimal inhibitory concentration of the recipient, promoted horizontal transfer of multiple antibiotic-resistance determinants. Higher concentrations favoured selection of a tetracycline-resistance phenotype along with a decline in the number of detectable transfer events. The described method can be used to evaluate different environmental conditions and factors that trigger horizontal dissemination of mobile resistance elements, eventually resulting in the formation of drug-resistant pathogens.

  11. Inhibitory effects of the macrolide antimicrobial tylosin on anaerobic treatment.

    Science.gov (United States)

    Shimada, Toshio; Zilles, Julie L; Morgenroth, Eberhard; Raskin, Lutgarde

    2008-09-01

    A laboratory-scale anaerobic sequencing batch reactor (ASBR) was operated using a glucose-based synthetic wastewater to study the effects of tylosin, a macrolide antimicrobial commonly used in swine production, on treatment performance. The experimental period was divided into three consecutive phases with different influent tylosin concentrations (0, 1.67, and 167 mg/L). The addition of 1.67 mg/L tylosin to the reactor had negligible effects on the overall treatment performance, that is, total methane production and effluent chemical oxygen demand did not change significantly (P tylosin was added. The addition of 167 mg/L tylosin to the reactor resulted in a gradual decrease in methane production and the accumulation of propionate and acetate. Subsequent inhibition of methanogenesis was attributed to a decrease in the pH of the reactor. After the addition of 167 mg/L tylosin to the reactor, an initial decrease in the rate of glucose uptake during the ASBR cycle followed by a gradual recovery was observed. In batch tests, the specific biogas production with the substrate butyrate was completely inhibited in the presence of tylosin. This study indicated that tylosin inhibited propionate- and butyrate-oxidizing syntrophic bacteria and fermenting bacteria resulting in unfavorable effects on methanogenesis.

  12. Antibiotic resistance, efflux pump genes and virulence determinants in Enterococcus spp. from surface water systems.

    Science.gov (United States)

    Molale, L G; Bezuidenhout, Cornelius Carlos

    2016-11-01

    The aim of this study was to report on antibiotic susceptibility patterns as well as highlight the presence of efflux pump genes and virulence genetic determinants in Enterococcus spp. isolated from South African surface water systems. One hundred and twenty-four Enterococcus isolates consisting of seven species were identified. Antimicrobial susceptibility testing revealed a high percentage of isolates was resistant to β-lactams and vancomycin. Many were also resistant to other antibiotic groups. These isolates were screened by PCR, for the presence of four efflux pump genes (mefA, tetK, tetL and msrC). Efflux genes mefA and tetK were not detected in any of the Enterococcus spp. However, tetL and msrC were detected in 17 % of the Enterococcus spp. The presence of virulence factors in the Enterococcus spp. harbouring efflux pump genes was determined. Virulence determinants were detected in 86 % of the Enterococcus spp. harbouring efflux pump genes. Four (asa1, cylA, gel and hyl) of the five virulence factors were detected. The findings of this study have demonstrated that Enterococcus from South African surface water systems are resistant to multiple antibiotics, some of which are frequently used for therapy. Furthermore, these isolates harbour efflux pump genes coding for resistance to antibiotics and virulence factors which enhance their pathogenic potential.

  13. Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing.

    Science.gov (United States)

    Abdolrasouli, Alireza; Rhodes, Johanna; Beale, Mathew A; Hagen, Ferry; Rogers, Thomas R; Chowdhary, Anuradha; Meis, Jacques F; Armstrong-James, Darius; Fisher, Matthew C

    2015-06-02

    . Over the last decade, an increasing number of A. fumigatus isolates from the clinic and from nature have been found to show resistance to azoles, suggesting that resistance is emerging through selection by the widespread usage of agricultural azole antifungal compounds. Aspergillosis is an emerging clinical problem, with high rates of treatment failures necessitating the development of new techniques for surveillance and for determining the genome-wide basis of azole resistance in A. fumigatus. Copyright © 2015 Abdolrasouli et al.

  14. Analysis of phenotype, genotype and serotype distribution in erythromycin-resistant group B streptococci isolated from vaginal flora in Southern Ireland.

    LENUS (Irish Health Repository)

    Kiely, R A

    2010-02-01

    The screening of 2000 women of childbearing age in Cork between 2004 and 2006 produced 37 erythromycin-resistant group B streptococcus (GBS) isolates. PCR analysis was performed to determine the basis for erythromycin resistance. The ermTR gene was most frequently expressed (n = 19), followed by the ermB gene (n = 8). Four isolates harboured the mefA gene. Six isolates yielded no PCR products. Some phenotype-genotype correlation was observed. All isolates expressing the mefA gene displayed the M phenotype whilst all those expressing ermB displayed the constitutive macrolide resistance (cMLS(B)) phenotype. Of 19 isolates that expressed the ermTR gene, 16 displayed the inducible macrolide resistance (iMLS(B)) phenotype. Serotype analysis revealed that serotypes III and V predominated in these isolates. The identification of two erythromycin-resistant serotype VIII isolates among this collection represents the first reported finding of erythromycin resistance in this serotype. A single isolate was non-typable using two latex agglutination serotyping kits.

  15. Aciclovir resistance among indian strains of Herpes simplex virus as determined using a dye uptake assay

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    Abraham A

    2007-01-01

    Full Text Available Resistance to aciclovir (ACV among Herpes simplex virus (HSV isolates is increasingly being reported in the literature particularly in immunocompromised patients. However, there is only limited data available from India despite widespread use of ACV in our hospital. A cross-sectional study was hence conducted to determine the aciclovir (ACV susceptibility of HSV 1 and 2 isolates using a dye uptake (DU assay. This study showed a 3.0% prevalence of ACV resistance among HSV-1 strains (2/66, median IC 50 0.098 µg/mL while in HSV-2 strains, it was 7.8% (5/64, median IC 50 0.195 µg/mL. The IC 50 for the HSV-1 and HSV-2 strains resistant to ACV was greater than or equal to 6.25 µg/mL.

  16. Determination of the EOS maragingsteel MS1 material resistance at low temperatures

    Directory of Open Access Journals (Sweden)

    J. Dobránsky

    2016-07-01

    Full Text Available This article deals with determination of the EOS MaragingSteel MS1 material resistance at different low temperatures. Material resistance was evaluated in two types of standardized specimens. The impact energy at the specimens tested at 10 °C, values for the specimens with no notch were compared to the V - notch specimens, higher by approximately one - third. When the temperature dropped to 0 °C, the values of the impact energy slightly decreased as well. It therefore follows that lower temperatures result in decrease in the values of the impact strength. This experiment provided us with the opportunity to find out whether the decrease in temperature impacts the resistance of the tested material.

  17. Bioactive 7-Oxabicyclic[6.3.0]lactam and 12-Membered Macrolides from a Gorgonian-Derived Cladosporium sp. Fungus

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    Fei Cao

    2015-07-01

    Full Text Available One new bicyclic lactam, cladosporilactam A (1, and six known 12-membered macrolides (2–7 were isolated from a gorgonian-derived Cladosporium sp. fungus collected from the South China Sea. Their complete structural assignments were elucidated by comprehensive spectroscopic investigation. Quantum chemistry calculations were used in support of the structural determination of 1. The absolute configuration of 1 was determined by calculation of its optical rotation. Cladosporilactam A (1 was the first example of 7-oxabicyclic[6.3.0]lactam obtained from a natural source. Compound 1 exhibited promising cytotoxic activity against cervical cancer HeLa cell line with an IC50 value of 0.76 μM.

  18. Effect of in-feed administration of tylosin phosphate on antibiotic resistance in enterococci isolated from feedlot steers

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    Alicia G Beukers

    2015-05-01

    Full Text Available Tylosin phosphate is a macrolide commonly administered to cattle in North America for the control of liver abscesses. This study investigated the effect of in-feed administration of tylosin phosphate to cattle at subtherapeutic levels and its subsequent withdrawal on macrolide resistance using enterococci as an indicator bacterium. Faecal samples were collected from steers that received no antibiotics and steers administered tylosin phosphate (11 ppm in-feed for 197 d and withdrawn 28 d before slaughter. Enterococcus species isolated from faecal samples were identified through sequencing the groES-EL intergenic spacer region and subject to antimicrobial susceptibility testing, identification of resistance determinants and pulsed-field gel electrophoresis profiling. Tylosin increased (P 0.05 between treatments on d 225. This suggests that antibiotic withdrawal prior to slaughter contributes to a reduction in the proportion of macrolide resistant enterococci entering the food chain. Among the 504 enterococci isolates characterised, E. hirae was found to predominate (n=431, followed by E. villorum (n=32, E. faecium (n=21, E. durans (n=7, E. casseliflavus (n=4, E. mundtii (n=4, E. gallinarum (n=3, E. faecalis (n=1, and E. thailandicus (n=1. The diversity of enterococci was greater in steers at arrival than at exit from the feedlot. Erythromycin resistant isolates harboured the erm(B and/or msrC gene. Similar PFGE profiles of eryR E. hirae n pre- and post-antibiotic treatment suggests the increased abundance of eryR enterococci after administration of tylosin phosphate reflects selection for strains that were within the bovine gastrointestinal tract of cattle at arrival.

  19. Prevalence and resistance pattern of Moraxella catarrhalis in community-acquired lower respiratory tract infections

    Directory of Open Access Journals (Sweden)

    Shaikh SBU

    2015-07-01

    Full Text Available Safia Bader Uddin Shaikh, Zafar Ahmed, Syed Ali Arsalan, Sana Shafiq Department of Pulmonology, Liaquat National Hospital, Karachi, Pakistan Introduction: Moraxella catarrhalis previously considered as commensal of upper respiratory tract has gained importance as a pathogen responsible for respiratory tract infections. Its beta-lactamase-producing ability draws even more attention toward its varying patterns of resistance. Methods: This was an observational study conducted to evaluate the prevalence and resistance pattern of M. catarrhalis. Patients aged 20–80 years admitted in the Department of Chest Medicine of Liaquat National Hospital from March 2012 to December 2012 were included in the study. Respiratory samples of sputum, tracheal secretions, and bronchoalveolar lavage were included, and their cultures were followed. Results: Out of 110 respiratory samples, 22 showed positive cultures for M. catarrhalis in which 14 were males and eight were females. Ten samples out of 22 showed resistance to clarithromycin, and 13 samples out of 22 displayed resistance to erythromycin, whereas 13 showed resistance to levofloxacin. Hence, 45% of the cultures showed resistance to macrolides so far and 59% showed resistance to quinolones. Conclusion: Our study shows that in our environment, M. catarrhalis may be resistant to macrolides and quinolones; hence, these should not be recommended as an alternative treatment in community-acquired lower respiratory tract infections caused by M. catarrhalis. However, a study of larger sample size should be conducted to determine if the recommendations are required to be changed. Keywords: community-acquired lower respiratory tract infections or pneumonia, M. catarrhalis, antibiotic resistance, gram-negative diplococcic, Pakistan

  20. Comparative Analysis of Three Methods for Determination of Imipenem Resistance in Pseudomonas aeruginosa

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    Tanaz Zabihi

    2016-02-01

    Full Text Available "> Background: These days, the antibiotic resistance of Pseudomonas aeruginosa isolates toimipenem has significantly increased. Therefore the study of resistance to imipenem in thisorganism to imipenem in determining the appropriate treatment is crucial and necessary. The goalof this study is to compare three phenotypic methods of E-test, disk diffusion and micro brothdilution in the study of resistance to imipenem in clinical isolates of P. aeruginosa.Methods: Within a 6-month interval, 120 clinical specimens were collected and evaluated. Allisolates were identified as P. aeruginosa by standard biochemical tests and amplification of 16SrRNA gene. Three phenotypic methods of E-test, disk diffusion, and micro broth dilution wereused to determine imipenem resistance in P. aeruginosa isolates.Results: Of the 96 P. aeruginosa isolates studied for their resistance to imipenem by the use ofE-test, disk diffusion and micro broth dilution methods, 38.5% of the strains in micro broth dilutionmethod and 33.3% in the two methods of E-test and disk diffusion were resistant to imipenem. Therate of sensitivity and specificity of disk diffusion and E-test methods were 100%, 90.1%, and theywere 100% and 83.1% for micro broth dilution, respectively.Conclusions: With regard to the results obtained from the comparison of the three methods100% agreement were observed among the antimicrobial susceptibility results obtained by the Etest and disk diffusion methods (P ≥ 0.05. Therefore, the use of disk diffusion method can bean appropriate replacement for E-test method with regard to its being easy and cost-effective.

  1. Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

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    Ana Teresa P. Carvalho

    2014-01-01

    Full Text Available OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047. A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009, whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094. In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010. However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut

  2. Factors determining sensitivity and resistance of tumor cells to arsenic trioxide.

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    Serkan Sertel

    Full Text Available Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC(50 values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis. Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways significantly predicted cellular response to arsenic trioxide. Then, we analyzed whether classical drug resistance factors may also play a role for arsenic trioxide. Cell lines transfected with cDNAs for catalase, thioredoxin, or the anti-apoptotic bcl-2 gene were more resistant to arsenic trioxide than mock vector transfected cells. Multidrug-resistant cells overexpressing the MDR1, MRP1 or BCRP genes were not cross-resistant to arsenic trioxide. Our approach revealed that response of tumor cells towards arsenic trioxide is multi-factorial.

  3. Phenotypic methods for determination of methicillin resistance in Staphylococcus spp. from health care workers

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    Marcelle Aquino Rabelo

    2013-04-01

    Full Text Available INTRODUCTION: Staphylococcus spp. is an important healthcare-associated pathogen and the identification of methicillin-resistant strains in samples of colonization may provide data to assist in the antimicrobial therapy success. OBJECTIVES: To determine the occurrence of colonization by methicillin-resistant Staphylococcus spp. (MRS, through the detection of the mecA gene and to evaluate different phenotypic methods for the presumptive detection of methicillin resistance in samples of the anterior nasal cavity and hands of the health care personnel of a university hospital in the state of Pernambuco, Brazil. METHODS: We selected the 28 isolates of Staphylococcus spp., which showed an intermediate or resistant phenotypic profile for oxacillin, detected by the Kirby Bauer technique. The methods used were disk-diffusion tests for cefoxitin, minimal inhibitory concentration by E-test for oxacillin, screening for oxacillin resistance and mecA gene detection by polymerase chain reaction (PCR. RESULTS: About the phenotypic methods utilized, only the E-test of oxacillin did not show a statistically significant difference in relation to PCR for the mecA gene detection, considered the gold standard. CONCLUSION: The E-test of oxacillin was the best of the phenotypic methods utilized. It is necessary to correctly detect MRS in healthy individuals, because they can act as carriers and can therefore be a potential source of microorganisms involved in hospital infections.

  4. Functional characterization of CYP107W1 from Streptomyces avermitilis and biosynthesis of macrolide oligomycin A.

    Science.gov (United States)

    Han, Songhee; Pham, Tan-Viet; Kim, Joo-Hwan; Lim, Young-Ran; Park, Hyoung-Goo; Cha, Gun-Su; Yun, Chul-Ho; Chun, Young-Jin; Kang, Lin-Woo; Kim, Donghak

    2015-06-01

    Streptomyces avermitilis contains 33 cytochrome P450 genes in its genome, many of which play important roles in the biosynthesis process of antimicrobial agents. Here, we characterized the biochemical function and structure of CYP107W1 from S. avermitilis, which is responsible for the 12-hydroxylation reaction of oligomycin C. CYP107W1 was expressed and purified from Escherichia coli. Purified proteins exhibited the typical CO-binding spectrum of P450. Interaction of oligomycin C and oligomycin A (12-hydroxylated oligomycin C) with purified CYP107W1 resulted in a type I binding with Kd values of 14.4 ± 0.7 μM and 2.0 ± 0.1 μM, respectively. LC-mass spectrometry analysis showed that CYP107W1 produced oligomycin A by regioselectively hydroxylating C12 of oligomycin C. Steady-state kinetic analysis yielded a kcat value of 0.2 min(-1) and a Km value of 18 μM. The crystal structure of CYP107W1 was determined at 2.1 Å resolution. The overall P450 folding conformations are well conserved, and the open access binding pocket for the large macrolide oligomycin C was observed above the distal side of heme. This study of CYP107W1 can help a better understanding of clinically important P450 enzymes as well as their optimization and engineering for synthesizing novel antibacterial agents and other pharmaceutically important compounds.

  5. Effects of Combined Treatment with Sansanmycin and Macrolides on Pseudomonas aeruginosa and Formation of Biofilm

    Institute of Scientific and Technical Information of China (English)

    YUE LI; YUN-YING XIE; RU-XIAN CHEN; HONG-ZHANG XU; GUO-JI ZHANG; JIN-ZHE LI; XIAO-MIAN LI

    2009-01-01

    Objective To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm. Methods Micro-dilution method was used to determine the minimal inhibitory concentrations (MICs) of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PA1 and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PA1 and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin. Results The MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PA1 and PA27853 strains through biofilms. PA1 and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin. Conclusion Sub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.

  6. August 2014 Phoenix pulmonary journal club: the use of macrolide antibiotics in chronic respiratory disease

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    Robbins RA

    2014-08-01

    Full Text Available No abstract available. Article truncated after 150 words. This month's journal club reviewed the role of macrolide antibiotics in chronic respiratory disease. Macrolide usage was suggested from observational studies in Japan in diffuse panbroncholitis, a disorder associated with chronic respiratory infection, usually Pseudomonas aeruginosa (1. Clinical improvement was noted despite doses of antibiotics well below the minimal inhibitory concentration (MIC of the antibiotic. This suggested the antibiotic was likely working by an anti-inflammatory effect. These observations were extended to cystic fibrosis (CF where prophylactic macrolide therapy in CF patients infected with Pseudomonas has become standard therapy (2. More recently, low dose macrolide therapy has been applied to non-CF lung diseases such as chronic obstructive pulmonary disease (COPD, bronchiectasis and asthma. Time did not permit a review of all studies so a representative sample was discussed. In patients with COPD, the four randomized, placebo-controlled trials reviewed all suggested that chronic therapy with macrolide antibiotics reduced COPD exacerbations (3-5. This ...

  7. Microcontroller based Stator Winding Resistance Determination of Induction Motor Drive on Temperature Variations

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    Siraj Ahmed T

    2014-05-01

    Full Text Available In this paper an experiment has been conducted to determine the online stator winding resistance of an induction motor, in industries as well as domestic purpose induction motors is largely utilized, as it has both applications of variable and constant torque operation nature. The major requirement of an electric drive system is its independent control of torque and speed; this is achieved in DC motor Drive but has more disadvantages. With the help of fast acting switching devices it is possible to independently control an induction motor. To control an induction motor drive various methods are available, direct torque control of induction motor is one of the best method of control compared to other, the only disadvantage is the torque ripple. Stator resistance is one of the parameter for the cause; hence its determination is essential. An experiment is conducted at various loads on an induction motor and then the temperature in the stator winding is noted at different instants using microcontroller, from the tabulated readings stator winding resistance is calculated and compared with the direct measurement by Volt-Ampere method. Further it is suggested that by implementing the actual online value of stator resistance of an induction motor dive torque ripple can be minimized.

  8. Antibiotic multiresistance plasmid pRSB101 isolated from a wastewater treatment plant is related to plasmids residing in phytopathogenic bacteria and carries eight different resistance determinants including a multidrug transport system.

    Science.gov (United States)

    Szczepanowski, Rafael; Krahn, Irene; Linke, Burkhard; Goesmann, Alexander; Pühler, Alfred; Schlüter, Andreas

    2004-11-01

    Ten different antibiotic resistance plasmids conferring high-level erythromycin resistance were isolated from an activated sludge bacterial community of a wastewater treatment plant by applying a transformation-based approach. One of these plasmids, designated pRSB101, mediates resistance to tetracycline, erythromycin, roxythromycin, sulfonamides, cephalosporins, spectinomycin, streptomycin, trimethoprim, nalidixic acid and low concentrations of norfloxacin. Plasmid pRSB101 was completely sequenced and annotated. Its size is 47 829 bp. Conserved synteny exists between the pRSB101 replication/partition (rep/par) module and the pXAC33-replicon from the phytopathogen Xanthomonas axonopodis pv. citri. The second pRSB101 backbone module encodes a three-Mob-protein type mobilization (mob) system with homology to that of IncQ-like plasmids. Plasmid pRSB101 is mobilizable with the help of the IncP-1alpha plasmid RP4 providing transfer functions in trans. A 20 kb resistance region on pRSB101 is located within an integron-containing Tn402-like transposon. The variable region of the class 1 integron carries the genes dhfr1 for a dihydrofolate reductase, aadA2 for a spectinomycin/streptomycin adenylyltransferase and bla(TLA-2) for a so far unknown Ambler class A extended spectrum beta-lactamase. The integron-specific 3'-segment (qacEDelta1-sul1-orf5Delta) is connected to a macrolide resistance operon consisting of the genes mph(A) (macrolide 2'-phosphotransferase I), mrx (hydrophobic protein of unknown function) and mphR(A) (regulatory protein). Finally, a putative mobile element with the tetracycline resistance genes tetA (tetracycline efflux pump) and tetR was identified upstream of the Tn402-specific transposase gene tniA. The second 'genetic load' region on pRSB101 harbours four distinct mobile genetic elements, another integron belonging to a new class and footprints of two more transposable elements. A tripartite multidrug (MDR) transporter consisting of an ATP

  9. DETERMINING DRIVING RESISTANCE WITH REBOUND OF PILE-TOP DURING PILE DRIVING

    Institute of Scientific and Technical Information of China (English)

    陈仁朋; 胡亚元; 陈云敏

    2001-01-01

    This paper presents a method to determine driving resistance with rebound of pile-top during pile driving. The soil around the pile shaft is assumed to be rigid-plastic, while that under the pile-tip is assumed to be ideally elastoplastic. The driving force acting on the pile-top is simplified to a triangular impact force. The kinematic equation of the pile-tip is established. From the one-dimensional wave equation, the movements of the pile-tip and pile-top are determined. The rebound at the pile-top can be written in a very concise form. It is shown that the shaft resistance makes the rebound at the pile-top decrease. In particular, when the pile is very long or the soil around the pile is very stiff, the decrease is very obvious.

  10. System and method for determining stator winding resistance in an AC motor using motor drives

    Science.gov (United States)

    Lu, Bin; Habetler, Thomas G; Zhang, Pinjia

    2013-02-26

    A system and method for determining the stator winding resistance of AC motors is provided. The system includes an AC motor drive having an input connectable to an AC source and an output connectable to an input terminal of an AC motor, a pulse width modulation (PWM) converter having switches therein to control current flow and terminal voltages in the AC motor, and a control system connected to the PWM converter. The control system generates a command signal to cause the PWM converter to control an output of the AC motor drive corresponding to an input to the AC motor, selectively generates a modified command signal to cause the PWM converter to inject a DC signal into the output of the AC motor drive, and determines a stator winding resistance of the AC motor based on the DC signal of at least one of the voltage and current.

  11. System and method for determining stator winding resistance in an AC motor

    Science.gov (United States)

    Lu, Bin; Habetler, Thomas G.; Zhang, Pinjia; Theisen, Peter J.

    2011-05-31

    A system and method for determining stator winding resistance in an AC motor is disclosed. The system includes a circuit having an input connectable to an AC source and an output connectable to an input terminal of an AC motor. The circuit includes at least one contactor and at least one switch to control current flow and terminal voltages in the AC motor. The system also includes a controller connected to the circuit and configured to modify a switching time of the at least one switch to create a DC component in an output of the system corresponding to an input to the AC motor and determine a stator winding resistance of the AC motor based on the injected DC component of the voltage and current.

  12. Aquatic toxicity of the macrolide antibiotic clarithromycin and its metabolites.

    Science.gov (United States)

    Baumann, Michaela; Weiss, Klaus; Maletzki, Dirk; Schüssler, Walter; Schudoma, Dieter; Kopf, Willi; Kühnen, Ute

    2015-02-01

    The human macrolide antibiotic clarithromycin is widespread in surface waters. Our study shows that its major metabolite 14-hydroxy(R)-clarithromycin is found in surface waters in comparable amounts. This metabolite is known to be pharmacologically active. Additionally, clarithromycin is partly metabolised to N-desmethyl-clarithromycin, which has no antimicrobial activity. For clarithromycin, some ecotoxicological studies on aquatic organisms have been published. However, many of them are not conform with the scientific principles as given in the "Technical guidance for deriving environmental quality standards" (TGD-EQS), because numerous studies were poorly documented and the methods did not contain analytical measurements confirming that the exposure concentrations were in the range of ± 20% of the nominal concentrations. Ecotoxicological effects of clarithromycin and its two metabolites on the zebrafish Danio rerio (embryo test), the microcrustacean Daphnia magna, the aquatic monocotyledonous macrophyte Lemna minor, the freshwater green alga Desmodesmus subspicatus (Chlorophyta) and the cyanobacterium Anabaena flosaquae were investigated in compliance with the TGD-EQS. Environmental risk assessment was performed using ErC10 values of Anabaena, the species most sensitive to clarithromycin and 14-hydroxy(R)-clarithromycin in our testing. Based oncomparable toxicity and similar concentrations of clarithromycin and its active metabolite 14-hydroxy(R)-clarithromycin in surface waters, an additional multiplication factor of 2 to the assessment factor of 10 on the ErC10 of clarithromycin should be used. Consequently, a freshwater quality standard of 0.130 μg L(-1) is proposed for clarithromycin as the "lead substance". Taking this additional multiplication factor of 2 into account, single monitoring of clarithromycin may be sufficient, in order to reduce the number of substances listed for routine monitoring programs.

  13. Determination of antimicrobial activity and resistance to oxidation of moringa peregrina seed oil.

    Science.gov (United States)

    Lalas, Stavros; Gortzi, Olga; Athanasiadis, Vasilios; Tsaknis, John; Chinou, Ioanna

    2012-02-24

    The antimicrobial activity of the oil extracted with n-hexane from the seeds of Moringa peregrina was tested against Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Candida albicans, C. tropicalis and C. glabrata. The oil proved effective against all of the tested microorganisms. Standard antibiotics (netilmycin, 5-flucytocine, intraconazole and 7-amino-4-methylcoumarin-3-acetic acid) were used for comparison. The resistance to oxidation of the extracted seed oil was also determined.

  14. Determination of Antimicrobial Activity and Resistance to Oxidation of Moringa peregrina Seed Oil

    Directory of Open Access Journals (Sweden)

    Ioanna Chinou

    2012-02-01

    Full Text Available The antimicrobial activity of the oil extracted with n-hexane from the seeds of Moringa peregrina was tested against Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Candida albicans, C. tropicalis and C. glabrata. The oil proved effective against all of the tested microorganisms. Standard antibiotics (netilmycin, 5-flucytocine, intraconazole and 7-amino-4-methylcoumarin-3-acetic acid were used for comparison. The resistance to oxidation of the extracted seed oil was also determined.

  15. Efficiency determination of resistive plate chambers for fast quasi-monoenergetic neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Roeder, M.; Cowan, T.E.; Kempe, M.; Yakorev, D. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Universitaet Dresden, Dresden (Germany); Elekes, Z. [MTA ATOMKI, Debrecen (Hungary); Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Aumann, T.; Caesar, C. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Technische Universitaet Darmstadt, Darmstadt (Germany); Bemmerer, D.; Sobiella, M.; Stach, D.; Wagner, A. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Boretzky, K.; Hehner, J.; Heil, M. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Maroussov, V. [Universitaet zu Koeln, Koeln (Germany); GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Nusair, O. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Al-Balqa Applied University, Salt (Jordan); Prokofiev, A.V. [Uppsala University, The Svedberg Laboratory, Uppsala (Sweden); Reifarth, R. [Johann Wolfgang Goethe - Universitaet, Frankfurt am Main (Germany); Zilges, A. [Universitaet zu Koeln, Koeln (Germany); Zuber, K. [Technische Universitaet Dresden, Dresden (Germany); Collaboration: R3B Collaboration

    2014-07-15

    Composite detectors made of stainless-steel converters and multigap resistive plate chambers have been irradiated with quasi-monoenergetic neutrons with a peak energy of 175 MeV. The neutron detection efficiency has been determined using two different methods. The data are in agreement with the output of Monte Carlo simulations. The simulations are then extended to study the response of a hypothetical array made of these detectors to energetic neutrons from a radioactive ion beam experiment. (orig.)

  16. Determination of viscous pressure losssand resistance upstream from the choke point from breathing gases of different physical properties

    DEFF Research Database (Denmark)

    Pedersen, O.F.

    2007-01-01

      Determination of viscous pressure loss and resistance upstream from the choke point from breathing gases of different physical properties Ole F. Pedersen, Institute of Public Health, University of Aarhus, Denmark. AIM. To determine viscous pressure losses and resistances  upstream to CP...

  17. Incidence, distribution, and spread of tetracycline resistance determinants and integron-associated antibiotic resistance genes among motile aeromonads from a fish farming environment

    DEFF Research Database (Denmark)

    Schmidt, Anja S.; Bruun, Morten Sichlau; Dalsgaard, Inger;

    2001-01-01

    cotransferred along with the tetracycline resistance determinants in 15 matings. Transconjugants were predominantly tetA positive (10 of 17) and contained class I integrons with two or more inserted antibiotic resistance genes. While there appeared to be a positive correlation between conjugative R...... in the dissemination of antibiotic resistance among environmental motile aeromonads.......A collection of 313 motile aeromonads isolated at Danish rainbow trout farms was analyzed to identify some of the genes involved in high levels of antimicrobial resistance found in a previous field trial (A. S. Schmidt, M. S. Bruun, I. Dalsgaard, K. Pedersen, and J. L. Larsen, Appl. Environ...

  18. Antibiotic resistance determinants and genetic analysis of Salmonella enterica isolated from food in Morocco.

    Science.gov (United States)

    Murgia, Manuela; Bouchrif, Brahim; Timinouni, Mohammed; Al-Qahtani, Ahmed; Al-Ahdal, Mohammed N; Cappuccinelli, Pietro; Rubino, Salvatore; Paglietti, Bianca

    2015-12-23

    Antimicrobial-resistant non-typhoidal Salmonella (NTS) are an important cause of infection in Africa, but there is a lack of information on their molecular mechanisms of resistance and epidemiology. This study contributes to fill this gap through the characterization by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), plasmid profiling and analysis of antibiotic-resistance determinants of 94 Salmonella enterica strains isolated from food in Morocco. PFGE revealed considerable heterogeneity among the strains, showing 32 pulsotypes. MLST of strains representative of the different serovars evidenced 13 sequence types (STs), three of which were newly identified (ST1694, ST1768 and ST1818) and nine not previously reported in Morocco. Thirty-four strains harbored from one to four plasmids, of IncI1 group in S. Mbandaka, IncFIIA in S. Typhimurium, IncL/M in S. Hadar and S. Blockley. For the first time in Morocco an intact Salmonella Genomic Island 1 (SGI1) carrying the resistance genes aadA2, floR, tetG, blaPSE-1 and sul1 was detected in S. Typhimurium DT104. In serovar Hadar resistance to ampicillin, tetracycline and streptomycin was associated to blaTEM-1, tetA and strA genes respectively, whereas one mutation in gyrA (Asp87Asn) and one in parC (Thr54Ser) genes conferred resistance to nalidixic acid. These findings improve the information on foodborne Salmonella in Morocco, evidencing the presence of MDR strains potentially dangerous to humans, and provide useful data for future studies.

  19. Genome-wide identification of antimicrobial intrinsic resistance determinants in Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Martin Vestergaard

    2016-12-01

    Full Text Available The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired resistance has received considerable attention, relatively little is known of intrinsic resistance that allows bacteria to naturally withstand antimicrobials. Gene products that confer intrinsic resistance to antimicrobial agents may be explored for alternative antimicrobial therapies, by potentiating the efficacy of existing antimicrobials. In this study, we identified the intrinsic resistome to a broad spectrum of antimicrobials in the human pathogen, Staphylococcus aureus. We screened the Nebraska Transposon Mutant Library of 1920 single-gene inactivations in S. aureus strain JE2, for increased susceptibility to the anti-staphylococcal antimicrobials (ciprofloxacin, oxacillin, linezolid, fosfomycin, daptomycin, mupirocin, vancomycin and gentamicin. 68 mutants were confirmed by E-test to display at least two-fold increased susceptibility to one or more antimicrobial agents. The majority of the identified genes have not previously been associated with antimicrobial susceptibility in S. aureus. For example, inactivation of genes encoding for subunits of the ATP synthase, atpA, atpB, atpG and atpH, reduced the minimum inhibitory concentration (MIC of gentamicin 16-fold. To elucidate the potential of the screen, we examined treatment efficacy in the Galleria mellonella infection model. Gentamicin efficacy was significantly improved, when treating larvae infected with the atpA mutant compared to wild type cells with gentamicin at a clinically relevant concentration. Our results demonstrate that many gene products contribute to the intrinsic antimicrobial resistance of S. aureus. Knowledge of these intrinsic resistance determinants provides alternative targets for compounds that may potentiate the efficacy of existing antimicrobial agents against this important pathogen.

  20. Isolation and Determination of Antibiotic Resistance Patterns in Nontyphoid Salmonella spp isolated from chicken

    Directory of Open Access Journals (Sweden)

    Seyyedeh Hoorieh Fallah

    2013-01-01

    Full Text Available Background: Salmonellosis is one of the most common food borne diseases in industrial and developing countries. In recent years, an increase in antimicrobial drug resistance, among non-typhoid Salmonella spp has been observed. Objectives: The aim of this study was to isolate and determine antibiotic resistance pattern in non-typhoid Salmonella spp. Materials and Methods: This descriptive study was done on 100 samples of chickens collected from 196 retail markets and was examined for the presence of Salmonella using standard bacteriological procedures and stereotyping kit. Antimicrobial susceptibility testing was performed by disk diffusion methods according to the National Committee for Clinical Laboratory Standards (CLSI. The data were analyzed by using the SPSS software version 18. Result: Forty- four percent of samples were contaminated with Salmonella infection and 56% didn’t have any contamination. The stereotyping results showed that 34 of 44 isolates of Salmonella belonged to Salmonella infantis (79.5 %, one strain (2.3% of group C and 8 strain (18.2% of group D. However, all these strains were sensitive to Cefotaxime and Ciprofloxacin, and 100% were resistant to Nalidixic acid, Tetracyclin and Sterptomycin. The most common resistance pattern (34.1% was towards six antibiotics, and 6.8% of strains were resistant to at least three antibiotics. Conclusion: High levels of resistance to antibiotics that are used commonly for human and poultry can be a warning for our community health and this information must be used to form important strategies for improvement of infection control.

  1. A Genetic Algorithm for Simultaneous Determination of Thin Films Thermal Transport Properties and Contact Resistance

    Institute of Scientific and Technical Information of China (English)

    Zhengxing HUANG; Zhen'an TANG; Ziqiang XU; Haitao DING; Yuqin GU

    2006-01-01

    A genetic algorithm (GA) was studied to simultaneously determine the thermal transport properties and the contact resistance of thin films deposited on a thick substrate. A pulsed photothermal reflectance (PPR) system was employed for the measurements. The GA was used to extract the thermal properties. Measurements were performed on SiO2 thin films of different thicknesses on silicon substrate. The results show that the GA accompanied with the PPR system is useful for the simultaneous determination of thermal properties of thin films on a substrate.

  2. Macrolide and fluoroquinolone mediated cardiac arrhythmias: clinical considerations and comprehensive review.

    Science.gov (United States)

    Cornett, Elyse; Novitch, Matthew B; Kaye, Alan D; Pann, Chris A; Bangalore, Harish Siddaiah; Allred, Gregory; Bral, Matthew; Jhita, Preya K; Kaye, Adam M

    2017-09-01

    While there is evidence for cardiac arrhythmias associated with macrolide and fluoroquinolone antibiotics, there is still debate among health care providers as to whether this risk of arrhythmia is overstated. A joint panel of the US Food and Drug Administration suggested that macrolide and fluoroquinolone labels need much stronger warnings regarding the possible serious adverse cardiac effects associated with these antibiotics, especially since they are so widely prescribed. And while health care providers may differ on the pertinence of the cardiac risks associated with antibiotic use, they can undoubtedly minimize the cardiac effects that are associated with these antibiotics by paying attention to the cardiac risk factors and drug history associated with the patient. Relevant studies for our review were identified from a PubMed search using keywords and combined word searches involving macrolides, fluoroquinolones, and cardiac arrhythmias. We attempted to include as many recent (>2015) articles as possible. We included case reports, randomized, controlled trials, observational studies, case-control studies, systematic reviews, and retrospective studies. Underlying cardiac issues can predispose patients to harmful cardiac side effects that can be exacerbated in the presence of antibiotics. The health care provider should rule out any risk factor associated with antibiotic-induced cardiac arrhythmia in the event that a patient does need a macrolide or fluoroquinolone antibiotic. Rigorous patient evaluation and a detailed patient history, including short and long term medication use, is the likely key to reducing any risk of cardiac arrhythmias associated with macrolides and fluoroquinolones. Clinicians should be cautious when prescribing macrolide and fluoroquinolone medications to patients with risk factors that may lead to antibiotic-induced cardiac arrhythmias, including a slow heart rate and those that are taking medications to treat arrhythmias.

  3. Metagenomic profiling of microbial composition and antibiotic resistance determinants in Puget Sound.

    Directory of Open Access Journals (Sweden)

    Jesse A Port

    Full Text Available Human-health relevant impacts on marine ecosystems are increasing on both spatial and temporal scales. Traditional indicators for environmental health monitoring and microbial risk assessment have relied primarily on single species analyses and have provided only limited spatial and temporal information. More high-throughput, broad-scale approaches to evaluate these impacts are therefore needed to provide a platform for informing public health. This study uses shotgun metagenomics to survey the taxonomic composition and antibiotic resistance determinant content of surface water bacterial communities in the Puget Sound estuary. Metagenomic DNA was collected at six sites in Puget Sound in addition to one wastewater treatment plant (WWTP that discharges into the Sound and pyrosequenced. A total of ~550 Mbp (1.4 million reads were obtained, 22 Mbp of which could be assembled into contigs. While the taxonomic and resistance determinant profiles across the open Sound samples were similar, unique signatures were identified when comparing these profiles across the open Sound, a nearshore marina and WWTP effluent. The open Sound was dominated by α-Proteobacteria (in particular Rhodobacterales sp., γ-Proteobacteria and Bacteroidetes while the marina and effluent had increased abundances of Actinobacteria, β-Proteobacteria and Firmicutes. There was a significant increase in the antibiotic resistance gene signal from the open Sound to marina to WWTP effluent, suggestive of a potential link to human impacts. Mobile genetic elements associated with environmental and pathogenic bacteria were also differentially abundant across the samples. This study is the first comparative metagenomic survey of Puget Sound and provides baseline data for further assessments of community composition and antibiotic resistance determinants in the environment using next generation sequencing technologies. In addition, these genomic signals of potential human impact can be used

  4. Diversity of mercury resistance determinants among Bacillus strains isolated from sediment of Minamata Bay.

    Science.gov (United States)

    Narita, Masaru; Chiba, Kazuyuki; Nishizawa, Hiroshi; Ishii, Hidenori; Huang, Chieh-Chen; Kawabata, Zen'ichiro; Silver, Simon; Endo, Ginro

    2003-06-06

    Thirty mercury-resistant (Hg R) Bacillus strains were isolated from mercury-polluted sediment of Minamata Bay, Japan. Mercury resistance phenotypes were classified into broad-spectrum (resistant to inorganic Hg(2+) and organomercurials) and narrow-spectrum (resistant to inorganic Hg(2+) and sensitive to organomercurials) groups. Polymerase chain reaction (PCR) product sizes and the restriction nuclease site maps of mer operon regions from all broad-spectrum Hg R Bacillus were identical to that of Bacillus megaterium MB1. On the other hand, the PCR products of the targeted merP (extracellular mercury-binding protein gene) and merA (intracellular mercury reductase protein gene) regions from the narrow-spectrum Hg R Bacillus were generally smaller than those of the B. megaterium MB1 mer determinant. Diversity of gene structure configurations was also observed by restriction fragment length polymorphism (RFLP) profiles of the merA PCR products from the narrow-spectrum Hg R Bacillus. The genetic diversity of narrow-spectrum mer operons was greater than that of broad-spectrum ones.

  5. Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.

    LENUS (Irish Health Repository)

    Fang, Fang

    2009-09-01

    Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.

  6. Qualitative and Quantitative Determination and Resistance Patterns of Salmonella from Poultry Carcasses.

    Science.gov (United States)

    Yamatogi, R S; Oliveira, H C; Possebon, F S; Pantoja, J C F; Joaquim, J G F; Pinto, J P A N; Araújo, J P

    2016-06-01

    Poultry products are important in the transmission of zoonotic pathogens, mainly Salmonella. This genus causes millions of foodborne diseases worldwide every year. Cross-contamination by food sources in human cases of salmonellosis and the increase in resistant strains have become important issues. A qualitative and quantitative Salmonella detection method was utilized in a poultry slaughterhouse in São Paulo State, Brazil. We collected 33 samples from different batches of carcasses. Each sample was analyzed at three process points: postbleeding, postdefeathering, and postchilling. A fourth point, retail simulation, was added to simulate retail market storage at 5°C for 72 h. The qualitative methods revealed 100% (33 samples) contamination at postbleeding, 39% (13 samples) contamination at postdefeathering, 58% (19 samples) contamination at postchilling, and 30% (10 samples) contamination at the retail simulation. The quantitative results, determined by the most-probable-number (MPN) technique, ranged from 2,400 MPN/g. We identified 23 Salmonella serovars; the most prevalent were Mbandaka, Senftenberg, and Enteritidis. Resistance to nalidixic acid was significantly more common (P < 0.05) than resistance to other antimicrobial agents. Five multidrug-resistant strains were identified. This study contributes important epidemiological data and demonstrates the need to improve sanitary conditions in slaughterhouses.

  7. Determination and optimization of joint torques and joint reaction forces in therapeutic exercises with elastic resistance.

    Science.gov (United States)

    Biscarini, Andrea

    2012-01-01

    A model has been developed to definitively characterize the resistance properties and the joint loading (i.e., shear and compressive components of the joint reaction force) in single-joint exercises with ideal elastic bands. The model accounts for the relevant geometric and elastic properties of the band, the band pre-stretching, and the relative positioning among the joint center of rotation and the fixation points of the band. All the possible elastic torque profiles of ascending-descending, descending, or ascending type were disclosed in relation to the different ranges of joint angles. From these results the elastic resistance setting that best reproduces the average-user's knee extensor torque in maximal isometric/isokinetic efforts was determined. In this optimized setting, the shear tibiofemoral reaction force corresponding to an anterior (posterior) tibial displacement was 65% smaller than (nearly the same as) that obtained in a cam-equipped leg-extension equipment for equal values of resistance torque peak, whereas the compressive tibiofemoral reaction force was 22% higher. Compared to a weight-stack leg-extension equipment, an elastic resistance optimized setting has the potential to give a more effective quadriceps activation across the range of motion, and greatly reduces the anterior cruciate ligament strain force, which represents the main drawback of existing open kinetic-chain knee-extension exercises.

  8. Comparative study of bactericidal activities, postantibiotic effects, and effects of bacterial virulence of penicillin G and six macrolides against Streptococcus pneumoniae.

    Science.gov (United States)

    Fuursted, K; Knudsen, J D; Petersen, M B; Poulsen, R L; Rehm, D

    1997-04-01

    In this report, we present MIC, bactericidal activity, postantibiotic effect (PAE), and in vivo infectivity data for postantibiotic-phase pneumococci. We compared and evaluated penicillin G and six macrolides, erythromycin, azithromycin, clarithromycin, dirithromycin, roxithromycin, and spiramycin, against 10 strains of pneumococci with various levels of susceptibility to penicillin. All of the agents, except azithromycin, exhibited a bactericidal effect (a > or = 3 log10 decrease in the number of CFU per milliliter) after 4 h of exposure to a concentration equal to 10 times the MIC, displaying the following hierarchy: spiramycin = penicillin G = erythromycin = dirithromycin = clarithromycin = roxithromycin > azithromycin. The bactericidal rate of penicillin G was significantly lower for resistant strains (MIC, > or = 2 microg/ml), while bactericidal rates of macrolides were unaffected by penicillin susceptibility. A PAE was induced in all of the strains by all of the antibiotics after exposure for 1 h to a concentration equivalent to 10 times the MIC. The mean duration of PAEs varied between 2.3 and 3.9 h, showing the following hierarchy: spiramycin = dirithromycin = clarithromycin = erythromycin = roxithromycin > azithromycin > penicillin G. Virulence studies were performed with immunocompetent mice by intraperitoneal inoculation of virulent, penicillin-susceptible serotype 3 pneumococci which had been pre-exposed to penicillin G or a macrolide for 1 h. A significant decrease in the virulence of postantibiotic-phase pneumococci was induced only by erythromycin, azithromycin, dirithromycin, and spiramycin, displaying 5.9-, 7.1-, 4.2-, and 3.6-fold increases in the 50% lethal dose (LD50) compared to a control suspension, respectively. No significant correlation could be demonstrated between the LD50 and the MIC, bactericidal activity, or PAE duration. These results suggest that antimicrobial interaction with host defenses in terms of virulence might be a

  9. COMPARATIVE STUDY OF ANTI-INFLAMMATORY ACTIVITY OF NEWER MACROLIDES WITH ETORICOXIB

    Directory of Open Access Journals (Sweden)

    Gajendra Naidu

    2014-03-01

    Full Text Available The present study was designed to investigate the anti-inflammatory activity of macrolides and to compare with standard non- steroidal anti-inflammatory drug (NSAID etoricoxib. This study was conducted in male wistar albino rats by inducing edema with 1% carrageenan. Animals were divided into 5 groups with 6 in each and paw edema volume was measured by digital plethysmograph before and 3hrs after 1% carrageenan administration. Percentage of inhibition of paw edema was calculated. Results showed macrolides having significant anti-inflammatory activity & the anti-inflammatory activity of roxithromycin was almost equally comparable with etoricoxib

  10. Discovery of the butenyl-spinosyn insecticides: novel macrolides from the new bacterial strain Saccharopolyspora pogona.

    Science.gov (United States)

    Lewer, Paul; Hahn, Donald R; Karr, Laura L; Duebelbeis, Dennis O; Gilbert, Jeffrey R; Crouse, Gary D; Worden, Thomas; Sparks, Thomas C; Edwards, Pat McKamey Rex; Graupner, Paul R

    2009-06-15

    A new bacterium, Saccharopolyspora pogona (NRRL30141) was discovered which produced a series of very potent insecticidal compounds structurally related to the 'classical' (i.e., C-21-ethyl) spinosyns. A series of fermentations gave sufficient extract to allow the isolation and characterization of a total of 31 new metabolites. The majority of these compounds contained a but-1-enyl group at C-21 of the macrolide in place of the ethyl group in the 'classical' spinosyn series, corresponding to an additional acetate group incorporated during their biosynthesis. Additionally a variety of other new functionality was seen including hydroxylations, several novel forosamine sugar replacements, and a novel 14-membered macrolide ring analog.

  11. Molecular characterization of genes encoding the quinolone resistance determining regions of Malaysian Streptococcus pneumoniae strains

    Directory of Open Access Journals (Sweden)

    Kumari N

    2008-01-01

    Full Text Available Genes encoding the quinolones resistance determining regions (QRDRs in Streptococcus pneumoniae were detected by PCR and the sequence analysis was carried out to identify point mutations within these regions. The study was carried out to observe mutation patterns among S. pneumoniae strains in Malaysia. Antimicrobial susceptibility testing of 100 isolates was determined against various antibiotics, out of which 56 strains were categorised to have reduced susceptibility to ciprofloxacin (≥2 μg/mL. These strains were subjected to PCR amplification for presence of the gyrA, parC , gyrB and parE genes. Eight representative strains with various susceptibilities to fluoroquinolones were sequenced. Two out of the eight isolates that were sequenced were shown to have a point mutation in the gyrA gene at position Ser81. The detection of mutation at codon Ser81 of the gyrA gene suggested the potential of developing fluoroquinolone resistance among S. pneumoniae isolates in Malaysia. However, further experimental work is required to confirm the involvement of this mutation in the development of fluoroquinolone resistance in Malaysia.

  12. Helicobacter pylori antibiotic resistance in Iran

    Institute of Scientific and Technical Information of China (English)

    Marjan Mohammadi; Delaram Doroud; Nazanin Mohajerani; Sadegh Massarrat

    2005-01-01

    AIM: To examine the frequency of antibiotic resistance in Iranian Helicobacter pylori(H pylori) strains isolated from two major hospitals in Tehran.METHODS: Examination of antibiotic resistance was performed on 120 strains by modified disc diffusion test and PCR-RFLP methods. In addition, in order to identify the possible causes of the therapeutic failure in Iran, we also determined the resistance of these strains to the most commonly used antibiotics (metronidazole, amoxicillin,and tetracycline) by modified disc diffusion test.RESULTS: According to modified disc diffusion test, 1.6% of the studied strains were resistant to amoxicillin, 16.7% to clarithromycin, 57.5% to metronidazole, and there was no resistance to tetracycline. Of the clarithromycin resistant strains, 73.68% had the A2143G mutation in the 23S rRNA gene, 21.05% A2142C, and 5.26% A2142G.None of the sensitive strains were positive for any of the three point mutations. Of the metronidazole resistant strains, deletion in rdxA gene was studied and detected in only 6 (5%) of the antibiogram-based resistant strains.None of the metronidazole sensitive strains possessed rdxA gene deletion.CONCLUSION: These data show that despite the fact that clarithromycin has not yet been introduced to the Iranian drug market as a generic drug, nearly 20% rate of resistance alerts toward the frequency of macrolide resistance strains, which may be due to the widespread prescription of erythromycin in Iran. rdxA gene inactivation,if present in Iranian H pylori strains, may be due to other genetic defects rather than gene deletion.

  13. Determinants of Pseudomonas putida WCS358 involved in inducing systemic resistance in plants.

    Science.gov (United States)

    Meziane, Hamid; VAN DER Sluis, Ientse; VAN Loon, Leendert C; Höfte, Monica; Bakker, Peter A H M

    2005-03-01

    SUMMARY Pseudomonas putida WCS358 is a plant growth-promoting rhizobacterium originally isolated from the rhizosphere of potato. It can suppress soil-borne plant diseases by siderophore-mediated competition for iron, but it has also been reported to result in induced systemic resistance (ISR) in Arabidopsis thaliana. Bacterial determinants of this strain involved in inducing systemic resistance in Arabidopsis were investigated using a Tn5 transposon mutant defective in biosynthesis of the fluorescent siderophore pseudobactin, a non-motile Tn5 mutant lacking flagella, and a spontaneous phage-resistant mutant lacking the O-antigenic side chain of the lipopolysaccharides (LPS). When using Pseudomonas syringae pv. tomato as the challenging pathogen, purified pseudobactin, flagella and LPS all triggered ISR. However, the mutants were all as effective as the parental strain, suggesting redundancy in ISR-triggering traits in WCS358. The Botrytis cinerea-tomato, B. cinerea-bean and Colletotrichum lindemuthianum-bean model systems were used to test further the potential of P. putida WCS358 to induce ISR. Strain WCS358 significantly reduced disease development in all three systems, indicating that also on tomato and bean WCS358 can trigger ISR. In both tomato and bean, the LPS mutant had lost the ability to induce resistance, whereas the flagella mutant was still effective. In bean, the pseudobactin mutant was still effective, whereas this mutant has lost its effectivity in tomato. In both bean and tomato, flagella isolated from the parental strain were not effective, whereas LPS or pseudobactin did induce systemic resistance.

  14. Antimicrobial resistance determinants in Staphylococcus spp. recovered from birds of prey in Portugal.

    Science.gov (United States)

    Sousa, Margarida; Silva, Nuno; Igrejas, Gilberto; Silva, Filipe; Sargo, Roberto; Alegria, Nuno; Benito, Daniel; Gómez, Paula; Lozano, Carmen; Gómez-Sanz, Elena; Torres, Carmen; Caniça, Manuela; Poeta, Patrícia

    2014-07-16

    Antibiotic resistance among wild animals represent an emerging public health concern. The objective of this study was to analyze the staphylococcal nasal microbiota in birds of prey and their content in antimicrobial resistance determinants. Nasal samples from 16 birds of prey were collected, swabs were dipped and incubated into BHI broth [6.5% NaCl] and later seeded on manitol salt agar and oxacillin-resistance screening agar base media. Staphylococcal colonies were isolated from both media and were identified by biochemical and molecular methods. Susceptibility testing to 18 antimicrobial agents was performed by disk-diffusion method. Six of the 16 tested animals carried staphylococci (37.5%) and 7 isolates of the following species were recovered: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus sciuri rodentium, Staphylococcus cohnii urealitycum, and Staphylococcus gallinarum. The S. aureus isolate was penicillin-resistant (with blaZ gene) but methicillin-susceptible and was ascribed to spa-type t012, sequence-type ST30 and agr-type III. The S. epidermidis isolate carried blaZ, mecA, mrs(A/B), mphC, tet(K), drfA, and fusC genes, ica operon, and was typed as ST35. The genes ant6'-Ia, tet(K), tet(L), dfrG, cat221, cat194, and cat223 were detected in S. saprophyticus or S. gallinarum isolates. Birds of prey seem to be a natural reservoir of S. aureus and coagulase-negative staphylococci resistant to multiple antibiotics. Due to the convergence between habitats, the contact between wildlife, other animals and humans is now more common and this involves an increased possibility of interchange of these microorganisms in the different ecosystems.

  15. Determination of resistance to salt crystallization on natural stone measured with ultrasonic wave

    DEFF Research Database (Denmark)

    Alm, D.; Brix, S.; Kjærgaard, H. Howe;

    2008-01-01

    The use of panels as facade cladding has increased substantially during the last few decades. However, during recent years reports of facade problems have increased dramatically. Facade cladding has, in some cases, suffered from problems with durability such as exfoliation, disintegration of macr...... porosity while Perlatino has 1.1 % in open porosity. By means of ultrasonic measurements it is possible to detect damage in stones exposed to salt crystallization cycles. The results show a tendency to less resistance of salt crystallization for more porous materials....... and after salt exposure. Four different stones are investigated: the limestone Bateig Azul, the sandstone Oberkirchener, the limestone Perlatino, and the limestone Travertine. The procedure for the salt crystallization test is EN 12370 standard “Natural stone test methods – Determination of resistance...

  16. Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei

    Science.gov (United States)

    Munday, Jane C.; Settimo, Luca; de Koning, Harry P.

    2015-01-01

    Drug resistance in pathogenic protozoa is very often caused by changes to the ‘transportome’ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (DA; Berenil®), cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (melarsoprol/pentamidine cross resistance, MPXR) is the result of loss of a separate high affinity pentamidine transporter (HAPT1). A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the “selectivity region” of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a

  17. Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori.

    Science.gov (United States)

    Luo, Xiao-Feng; Jiao, Jian-Hua; Zhang, Wen-Yue; Pu, Han-Ming; Qu, Bao-Jin; Yang, Bing-Ya; Hou, Min; Ji, Min-Jun

    2016-07-07

    To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR). The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion. The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin. The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and

  18. A portable wheel tester for tyre-road friction and rolling resistance determination

    Science.gov (United States)

    Pytka, J.; Budzyński, P.; Tarkowski, P.; Piaskowski, M.

    2016-09-01

    The paper describes theory of operation, design and construction as well as results from primarily experiments with a portable wheel tester that has been developed by the authors as a device for on-site determination of tyre-road braking/driving friction and rolling resistance. The paper includes schematics, drawings, descriptions as well as graphical results form early tests with the presented device. It is expected that the tester can be useful in road accident reconstruction applications as well as in vehicle dynamics research.

  19. Roof structure theory and support resistance determination of longwall face in shallow seam

    Institute of Scientific and Technical Information of China (English)

    HUANG Qing-xiang(黄庆享)

    2003-01-01

    This paper presents the structure models founded in shallow seam, the roof asymmetry arch with three articulations in roof first weighting and the step voussoir beam in roof periodic weighting. These structure models are differ from classic theory, it establishes the new roof control theory of instability structure roof, especially in shallow seam. Based on the new roof structure theory, the support working state of "given sliding load" is put forward, and the factor of load transmitting is introduced to determine the load on roof structure. Therefore, the proper and accurate calculating methods of support resistance are established. Based on this, the dynamic structure theory in shallow seam could be predicted.

  20. Antimicrobial resistance among Campylobacter jejuni isolated from raw poultry meat at retail level in Denmark

    DEFF Research Database (Denmark)

    Andersen, S. R.; Saadbye, P.; Shukri, Naseer Mahmoud

    2006-01-01

    of resistance among C. jejuni were observed for tetracycline, nalidixic acid and ciprofloxacin, whereas macrolide resistance was rarely detected. C. jejuni originating from other poultry meat (mainly duck and turkey meat) exhibited the highest occurrences of antimicrobial resistance monitored; approximately one...... for chloramphenicol, nalidixic acid and ciprofloxacin (P

  1. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance$

    Institute of Scientific and Technical Information of China (English)

    Nishant A. Dafale n; Uttam P. Semwal; Rupak K. Rajput; G.N. Singh

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Re-sistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the potency of antibiotics. HPLC method is commonly used for the quantification of potency of antibiotics, but unable to determine the bioactivity; whereas microbiological assay estimates both potency and bioactivity of antibiotics. Additionally, bioassay is used to estimate the effective dose against antibiotic resistant microbes. Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutation prevention concentration (MPC) and critical concentration (Ccr) which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

  2. A new macrolide and glycosides from the stem of Sargentodoxa cuneata

    Institute of Scientific and Technical Information of China (English)

    Zhi Xian Chen; Dai Lin Liu; Wen Yuan Gao; Tie Jun Zhang

    2009-01-01

    A new macrolide glycoside, cuneataside F was isolated from the n-butanol extract of the stem of Sargentodoxa cuneata. The structure was elucidated on the basis of extensive ID and 2D NMR as well as HRESI-MS spectroscopic analysis.

  3. Enantioselective synthesis in carbohydrate-based drug discovery: imino sugars, alkaloids and macrolide antibiotics.

    Science.gov (United States)

    Xavier, Nuno M; Rauter, Amélia P

    2014-01-01

    This review is dedicated to enantioselective methods for the generation of carbohydrate-based lead compounds for drug research. Selected examples encompassing imino sugars, bicyclic imino sugar-type alkaloids such as castanospermine, swainsonine, or alexine, as well as macrolide glycosides are covered and discussed.

  4. Amphidinolides B4 and B5, Potent Cytotoxic 26-Membered Macrolides from Dinoflagellate Amphidinium Species

    Directory of Open Access Journals (Sweden)

    Jun’ichi Kobayashi

    2005-03-01

    Full Text Available Abstract: Two new cytotoxic 26-membered macrolides, amphidinolides B4 (1 and B5 (2, have been isolated from a marine dinoflagellate Amphidinium sp. (strain Y-100, and the structures were elucidated on the basis of detailed analyses of 2D NMR data including 13C−13C correlations.

  5. Fate and Ecotoxicology of Veterinary Macrolide and Sulfonamide Antibiotics in Surface Water

    Science.gov (United States)

    Antibiotics are carried from manured lands and production sites in runoff to surface waters. Our objectives were to assess the environmental fate and ecotoxicology of two macrolide antibiotics (tylosin and erythromycin) and sulfamethazine. Experiments were designed to simulate Midwestern farm pond c...

  6. Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Jane Claire Munday

    2015-03-01

    Full Text Available Drug resistance in pathogenic protozoa is very often caused by changes to the ‘transportome’ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (Berenil®, cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (MPXR is the result of loss of a separate High Affinity Pentamidine Transporter (HAPT1. A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the selectivity region of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a possible structural rationale for this

  7. Distribution of resistance genetic determinants among Vibrio cholerae isolates of 2012 and 2013 outbreaks in IR Iran.

    Science.gov (United States)

    Rezaie, Niloofar; Bakhshi, Bita; Najar-Peerayeh, Shahin

    2017-03-01

    The objective of this study was to characterize antimicrobial resistance determinants in relation to antimicrobial susceptibility and genotyping profile in 20 clinical isolates of Vibrio cholerae. All of the isolates were resistant to streptomycin. The second most prevalent resistance was observed to trimethoprim (75%), co-trimoxazole (60%), tetracycline (50%), and minocycline (45%). About 50% of the isolates fulfilled the criteria of Multi Drug Resistance (MDR) phenotype. None of the isolates carried tet A, B, C, and, D determinants. This finding shows that tetracycline resistance determinants recognized so far, does not satisfactorily describe the 50% tetracycline resistance phenotype in this study, suggesting the possible contribution of other not yet characterized resistance mechanisms involved. Class 1 integron, widely distributed among enteric bacteria, was not detected among V. cholerae strains under study. Conversely, 100% of the isolates harbored SXT constin(int), among which 70% were positive for dfrA1, strA, and strB genes. The sul1gene was present in 60% of the isolates while none of them contained floR gene. All the isolates uniformly appeared to be identical in fingerprinting profiles expected from outbreak strains. In conclusion, SXT element with its mosaic structure was the exclusive antimicrobial resistance determinant of clonal V. cholerae isolates taken from outbreaks of 2012 and 2013 in Iran. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Resistance determinant erm(X) is borne by transposon Tn5432 in Bifidobacterium thermophilum and Bifidobacterium animals subsp. lactis

    NARCIS (Netherlands)

    Hoek, van A.H.A.M.; Mayrhofer, S.; Domig, K.J.; Aarts, H.J.M.

    2008-01-01

    The erm(X) gene from erythromycin- and clindamycin-resistant Bifidobacterium strains was characterised by polymerase chain reaction and sequence analysis, including flanking regions. Results suggest that the resistance determinant was part of transposon Tn5432 that has been described in several oppo

  9. Molecular epidemiology and distribution of serotypes, genotypes, and antibiotic resistance genes of Streptococcus agalactiae clinical isolates from Guelma, Algeria and Marseille, France.

    Science.gov (United States)

    Bergal, A; Loucif, L; Benouareth, D E; Bentorki, A A; Abat, C; Rolain, J-M

    2015-12-01

    This study describes, for the first time, the genetic and phenotypic diversity among 93 Streptococcus agalactiae (group B Streptococcus, GBS) isolates collected from Guelma, Algeria and Marseille, France. All strains were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The molecular support of antibiotic resistance and serotyping were investigated by polymerase chain reaction (PCR). The phylogenetic lineage of each GBS isolate was determined by multilocus sequence typing (MLST) and grouped into clonal complexes (CCs) using eBURST. The isolates represented 37 sequence types (STs), 16 of which were novel, grouped into five CCs, and belonging to seven serotypes. Serotype V was the most prevalent serotype in our collection (44.1%). GBS isolates of each serotype were distributed among multiple CCs, including cps III/CC19, cps V/CC1, cps Ia/CC23, cps II/CC10, and cps III/CC17. All isolates presented susceptibility to penicillin, whereas resistance to erythromycin was detected in 40% and tetracycline in 82.2% of isolates. Of the 37 erythromycin-resistant isolates, 75.7% showed the macrolide-lincosamide-streptogramin B (MLSB)-resistant phenotype and 24.3% exhibited the macrolide (M)-resistant phenotype. Constitutive MLSB resistance (46%) mediated by the ermB gene was significantly associated with the Guelma isolates, whereas the M resistance phenotype (24.3%) mediated by the mefA/E gene dominated among the Marseille isolates and belonged to ST-23. Tetracycline resistance was predominantly due to tetM, which was detected alone (95.1%) or associated with tetO (3.7%). These results provide epidemiological data in these regions that establish a basis for monitoring increased resistance to erythromycin and also provide insight into correlations among clones, serotypes, and resistance genes.

  10. Can Soil Penetration Resistance and Bulk Density Be Determined in a Single Undisturbed Sample?

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    Carolina Fernandes

    2015-06-01

    Full Text Available Soil quality indicators such as penetration resistance (PR and bulk density (BD are traditionally determined in a single undisturbed soil sample. The aim of this study was to assess the effect of PR measurements of undisturbed samples on the determination of BD in the same sample of two soils differing in clay contents. To this end, samples were collected from the 0.00-0.10 and 0.10-0.20 m layers of two soils of clayey and very clayey texture. Volumetric rings were used to collect a total of 120 undisturbed soil samples from each soil layer that were divided into two subsets containing 60 units each. One sample set, designated “perforated samples”, was used to determine PR and BD in the same undisturbed sample; the other, named “intact samples”, was used to determine BD only. Bulk density values for perforated and intact samples were compared by analysis of variance, using a completely randomized experimental design. Means were compared by the t-test at 5 %. The BD values for the clayey soil were similar in perforated and intact samples from the two layers. However, BD of the very clayey soil was lower in the perforated than in the intact samples at both depths. Therefore, PR and BD in clayey soils can be accurately determined in the same undisturbed sample whereas in very clayey soils, different samples are required for this purpose.

  11. Detection of tetracycline resistance determinant tetA gene and antimicrobial resistance pattern in Escherichia coli isolates recovered from healthy layer chickens

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    A. Balasubramaniam

    2014-09-01

    Full Text Available Aim: The aim was to study the occurrence of tetracycline resistance determinant tetA gene, and antibacterial resistance pattern in commensal Escherichia coli recovered from healthy non-clinical layer chickens. Materials and Methods: Twenty-four cloacal swabs were obtained from 15 flocks in five different layer farms located at around Namakkal, which is a place of high-intensity layer chicken rearing in south India. Identification of E. coli was carried out by performing cultural and biochemical tests. Antimicrobial resistance test was carried out using disc diffusion method. The polymerase chain reaction employing tetAC forward and tetAC reverse primers were carried out to detect tetA gene conferring resistance to tetracycline. Result: All the collected cloacal swabs yielded E. coli. Twenty-one isolates (88% were resistant to tetracycline antibiotic in disc diffusion method. All the isolates showed resistance to more than six antibiotics, which implied existence of multidrug resistant microbiota in intestine of poultry. Only seven (29% isolates showed the presence of tetA gene indicating the involvement of either other one or more efflux gene(s, namely tetB, tetC and tetD or ribosomal protection encoded by tetM, tetO, tetQ and tetS genes than tetA gene. Conclusion: Based on the presence of tetA gene among tetracycline-resistant bacteria in healthy non-clinical food-producing animals such as layer chickens, it can be significant in human medicine as tetA gene could easily be spread to other bacteria. This kind of phenomenon can be extrapolated in transfer of resistance for other antibacterial essential for treating bacterial infections in human. We conclude that preventing the spread of antimicrobial resistance through direct or indirect contact, consumed food/feed and through the environment is empirical in reduction of failures while treating bacterial infections.

  12. Detection of plasmid-mediated IMP-1 metallo-β-lactamase and quinolone resistance determinants in an ertapenem-resistant Enterobacter cloacae isolate

    Institute of Scientific and Technical Information of China (English)

    Li-rong CHEN; Hong-wei ZHOU; Jia-chang CAI; Rong ZHANG; Gong-xiang CHEN

    2009-01-01

    Objective: To investigate the mechanism of carbapenem resistance and the occurrence of plasmid-mediated quinolone resistance determinants qnr and aac(6')-Ib-cr in a clinical isolate of Enterobacter cloacae. Methods: An ertapenem-resistant E. cloacae ZY106, which was isolated from liquor puris of a female gastric cancer patient in a Chinese hospital, was investigated. Antibiotic susceptibilities were determined by agar dilution method. Conjugation experiments, isoelectric focusing, polymerase chain reaction (PCR), and DNA sequence analyses of plasmid-mediated carbapenemases and quinolone resistance determinants were preformed to confirm the genotype. Outer membrane proteins (OMPs) were examined by urea-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Urea-SDS-PAGE). Results: Minimum inhibitory concentrations (MCs) of imipenem, mer-openem, and ertapenem for ZY106 were 2,4, and 16 ug/ml, respectively. Conjugation studies with Escherichia coli resulted in the transfer of significantly reduced carbapenem susceptibility. ZY106 produced IMP-1 metallo-p-lactamase and CTX-M-3 extended-spectrum P-lactamase, and E. coli transconjugant produced IMP-1. Plasmid-mediated quinolone resistance determinant qnrSI was detected in ZY106. Transfer of the qnrSI-encoding-plasmid into E. coli by conjugation resulted in intermediate resistance to ciprofloxacin in E. coli transconjugant. Urea-SDS-PAGE analysis of OMPs showed that ZY106 lacked an OMP of approximately 38 KDa. Conclusion: It is the first IMP-1-producing Enterobacteriaceae in China and the first report of a clinical isolate that harbors both blaIMP and qnrS genes as well. The blaIMP-1, blaCTX-M-3, and qnrSl are encoded at three different plasmids. IMP-1 combined with the loss of an OMP possibly resulted in ertapenem resistance and reduced imipenem and mero-penem susceptibility in E. cloacae.

  13. Azithromycin 1.5g Over 5 Days Compared to 1g Single Dose in Urethral Mycoplasma genitalium: Impact on Treatment Outcome and Resistance.

    Science.gov (United States)

    Read, Tim R H; Fairley, Christopher K; Tabrizi, Sepehr N; Bissessor, Melanie; Vodstrcil, Lenka; Chow, Eric P F; Grant, Mieken; Danielewski, Jennifer; Garland, Suzanne M; Hocking, Jane S; Chen, Marcus Y; Bradshaw, Catriona S

    2017-02-01

    We evaluated the impact of extended azithromycin (1.5g over 5 days) on selection of macrolide resistance and microbiological cure in men with Mycoplasma genitalium urethritis during 2013-2015 and compared this to cases treated with azithromycin 1g in 2012-2013. Microbiological cure was determined for men with M. genitalium urethritis treated with azithromycin 1.5g using quantitative polymerase chain reaction specific for M. genitalium DNA on samples 14-100 days post-treatment. Pre- and post-treatment macrolide resistance mutations were detected by sequencing the 23 S gene. There was no difference in proportions with microbiological cure between azithromycin 1.5g and 1g: 62/106 (58%; 95% confidence interval [CI], 49%, 68%) and 56/107 (52%; 95%CI 42-62%), P = .34, respectively. Also, there was no difference in the proportion of wild-type 23 S rRNA (presumed macrolide sensitive) infections cured after 1.5g and azithromycin 1g: 28/34 (82%; 95%CI 65-92%) and 49/60 (82%; 95%CI 70-90%), P=1.0, respectively. There was no difference between 1.5g and 1g in the proportions of wild-type infections with post-treatment resistance mutations: 4/34 (12%; 95%CI 3-27%) and 11/60 (18%; 95%CI 10-30%), respectively, P = .40. Pre-treatment resistance was present in 51/98 (52%; 95%CI 42-62%) cases in 2013-2015 compared to 47/107 (44%; 95%CI 34-54%) in 2012-2013, P = .25. Extended azithromycin 1.5g was no more effective than a single 1g dose at achieving cure of M. genitalium urethritis and importantly did not reduce the selection of macrolide resistance. Nonmacrolide and new approaches for the treatment of M. genitalium urethritis are required. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  14. DETERMINATION THE PERMISSIBLE FORCES IN ASSESSING THE LIFT RESISTANT FACTOR OF FREIGHT CARS IN TRAINS

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    A. O. Shvets

    2016-02-01

    Full Text Available Purpose. In the analytical research are considered: 1 relationships between the longitudinal force acting on the car in the train; 2 lateral and vertical forces of interaction in the contact zone «wheel – rail»; 3 dynamic indicators of cars with the magnitude of the car lift resistance factor; 4 obtaining of the dependencies between them. Methodology. The study was conducted by an analytical method assessing the sustainability of the freight car when driving at different speeds on the straight and curved track sections. Findings. In the process of studying the motion of the train, in the investigation of transport events, as well as during the training on the simulator operator, to assess the actions of the driver, the values of the longitudinal forces in the inter car connections are used. To calculate the longitudinal compressive forces, acting on the car, in which car lift resistance factor will be equal to the allowable value (critical force. To assess the impact on the value of the longitudinal force speed, coefficients of the vertical and horizontal dynamics, as well as the wind load on the side surface of the car body are the results of calculations of motion of the empty gondola car, model № 12-532 curve radius of 250 m with a rise of 150 mm and a transverse run of body of car frame relative to the track axis of the guide section 50 mm. Originality. In this study, the technique of determining the longitudinal compressive force was shown, that is somewhat different from the standard. So, as well as assessing the impact on it the speed of rolling coefficients of vertical and horizontal dynamics and wind load on the side surface of the car body. Practical value. The authors developed proposals on the enhancement of existing methods for determining the value of the longitudinal compressive forces acting on the car in which the safety value of the car lift resistance factor will be equal to the allowable value. It will evaluate the

  15. Streptococcus peumoniae in an Egyptian urban community:incidence of erythromycin-resistance determinants and antibiotic susceptibility profile

    Institute of Scientific and Technical Information of China (English)

    Fatma Abdelaziz Amer; Eman Mohamed Elbehedy; Mohamed Elahmady

    2008-01-01

    Objectives:To determine the incidence of resistance of Streptococcus (Strep).pneumoniae isolated in our lo-cality to erythromycin,to screen for the two resistance determinants erm(B)and mef(A)genes,and to identi-fy the susceptibility profile to commonly used antibiotics.Methods:Samples were collected from patients at-tending the Outpatient Department of Zagazig University Hospital,Zagazig,Egypt,between February 2006 and March 2007.Strep.pneumoniae was identified by conventional procedures.Susceptibilities to erythromycin and 15 antibiotics were identified by disc diffusion method,as outlined by CLSI.E-test was used for MIC de-termination of erythromycin.erm(B)and mef(A)genes were detected by PCR.Results:Eighty-one Strep. pneumoniae strains were identified.Fifty-one of them (63 %)were erythromycin-resistant,and mef(A)gene was the predominant resistance determinant.Vancomycin,imipenem and gatifloxacin had the best activity a-gainst the isolates,whereas tetracycline had the least.Forty-two (51.85%)out of the 81 Strep.pneumoniae strains were multidrug-resistant.Conclusions:High incidence of resistance to erythromycin and multiple anti-microbials existed.mef(A)was the principal erythromycin-resistance gene.

  16. Determination of J-resistance curves of nuclear structure materials by iteration method

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Thak Sang; Lee, Bong Sang; Yoon, Ji Hyun; Kuk, Il Hiun; Hong, Jun Hwa [KAERI, Taejon (Korea, Republic of)

    1998-05-01

    An iteration method has been developed for determining crack growth and fracture resistance curve (J-R curve) from the load versus load-line displacement record only. In this method, the hardening curve, the load versus displacement curve at a given crack length, is assumed to be a power-law function, where the exponent varies with the crack length. The exponent is determined by an interative calculation method with the assumption that the exponent varies linearly with the load-line displacement. The proposed method was applied to the static J-R tests using compact tension (CT) specimens, a three-point bend (TPB) specimen, and a cracked round bar (CRB) specimen as well as it was applied to the quasi-dynamic J-R tests using CT specimens. The J-R curves determined by the proposed method were compared with those obtained by the conventional testing methodologies. The results showed that the J-R curves could be determined directly by the proposed iteration method with sufficient accuracy in the specimens from SA508, SA533, and SA516 pressure vessel steels and SA312 Type 347 stainless steel.

  17. Transfer of penicillin resistance from Streptococcus oralis to Streptococcus pneumoniae identifies murE as resistance determinant.

    Science.gov (United States)

    Todorova, Katya; Maurer, Patrick; Rieger, Martin; Becker, Tina; Bui, Nhat Khai; Gray, Joe; Vollmer, Waldemar; Hakenbeck, Regine

    2015-09-01

    Beta-lactam resistant clinical isolates of Streptococcus pneumoniae contain altered penicillin-binding protein (PBP) genes and occasionally an altered murM, presumably products of interspecies gene transfer. MurM and MurN are responsible for the synthesis of branched lipid II, substrate for the PBP catalyzed transpeptidation reaction. Here we used the high-level beta-lactam resistant S. oralis Uo5 as donor in transformation experiments with the sensitive laboratory strain S. pneumoniae R6 as recipient. Surprisingly, piperacillin-resistant transformants contained no alterations in PBP genes but carried murEUo5 encoding the UDP-N-acetylmuramyl tripeptide synthetase. Codons 83-183 of murEUo5 were sufficient to confer the resistance phenotype. Moreover, the promoter of murEUo5 , which drives a twofold higher expression compared to that of S. pneumoniae R6, could also confer increased resistance. Multiple independent transformations produced S. pneumoniae R6 derivatives containing murEUo5 , pbp2xUo5 , pbp1aUo5 and pbp2bUo5 , but not murMUo5 sequences; however, the resistance level of the donor strain could not be reached. S. oralis Uo5 harbors an unusual murM, and murN is absent. Accordingly, the peptidoglycan of S. oralis Uo5 contained interpeptide bridges with one L-Ala residue only. The data suggest that resistance in S. oralis Uo5 is based on a complex interplay of distinct PBPs and other enzymes involved in peptidoglycan biosynthesis.

  18. Comparison of multi-drug resistant environmental methicillin-resistant Staphylococcus aureus [MRSA] isolated from recreational beaches and high touch surfaces in built environments

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    Marilyn C Roberts

    2013-04-01

    Full Text Available Over the last decade community-acquired methicillin-resistant Staphylococcus aureus [MRSA] has emerged as a major cause of disease in the general population with no health care exposure or known classical risk factors for MRSA infections. The potential community reservoirs have not been well defined though certain strains such as ST398 and USA300 have been well studied in some settings. MRSA has been isolated from recreational beaches, high-touch surfaces in homes, universities and other community environmental surfaces. However, in most cases the strains were not characterized to determine if they are related to community-acquired or hospital-acquired clinical strains. We compared 55 environmental MRSA from 805 samples including sand, fresh and marine water samples from local marine and fresh water recreational beaches (n=296, high touch surfaces on the University of Washington campus (n=294, surfaces in UW undergraduate housing (n=85, and the local community (n=130. Eleven USA300, representing 20% of the isolates, were found on the UW campus surfaces, student housing surfaces and on the community surfaces but not in the recreational beach samples from the Northwest USA. Similarly, the predominant animal ST133 was found in the recreational beach samples but not in the high touch surface samples. All USA300 isolates were multi-drug resistant carrying 2-6 different antibiotic resistance genes coding for kanamycin, macrolides and/or macrolides-lincosamides-streptogramin B and tetracycline, with the majority [72%] carrying 4-6 different antibiotic resistance genes. A surprising 98% of the 55 MRSA isolates were resistant to other classes of antibiotics and most likely represent reservoirs for these genes in the environment.

  19. The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

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    Jyh-Ming Liou

    Full Text Available The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.The defined daily dose (DDD of antibiotics was analyzed using the Taiwan National Health Insurance (NHI research database. H. pylori strains isolated from treatment naïve (N=1395 and failure from prior eradication therapies (N=360 from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001. The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001, which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

  20. High basal defense gene expression determines sorghum resistance to the whorl-feeding insect southwestern corn borer.

    Science.gov (United States)

    Cheng, Wei-Ning; Lei, Jia-Xin; Rooney, William L; Liu, Tong-Xian; Zhu-Salzman, Keyan

    2013-06-01

    Southwestern corn borer (SWCB, Diatraea grandiosella) and fall armyworm (FAW, Spodoptera frugiperda) are major pests of sorghum in the southern United States. Host plant resistance is a desirable means for reducing plant damage and yield losses from both insects. In this study, we evaluated 12 sorghum lines for whorl-stage resistance to leaf-feeding SWCB and FAW in greenhouse and laboratory bioassays. Differential plant responses were detected against the two insects. Among 12 lines tested, CM1821, Della and PI196583 were resistant to both insects, while BTx2752 was largely susceptible. Line R.09110 was resistant to SWCB, but susceptible to FAW, whereas Redbine-60 was susceptible to SWCB, but not to FAW. In addition, we quantified various chemical components in the plants and determined their association with insect resistance. Tannin and chlorophyll in leaves did not show any significant correlation with resistance to either insects, but contents of soluble protein in general were negatively correlated with resistance to both insects. Endogenous soluble sugar and dhurrin were only positively correlated with resistance to SWCB, but not with FAW resistance. To gain some molecular insight into resistance mechanism of sorghum to SWCB, we performed qPCR reactions for key genes encoding enzymes involved in dhurrin and jasmonic acid (JA) biosynthesis on selected resistant or susceptible lines. Although these genes were rapidly and strongly induced by insect feeding in all lines, the observed resistance is likely explained by higher constitutive dhurrin contents in some resistant lines and higher basal JA biosynthesis in others. Our results suggest that sorghum utilizes multiple strategies to defend itself against SWCB.

  1. High basal defense gene expression determines sorghum resistance to the whorl-feeding insect southwestern corn borer

    Institute of Scientific and Technical Information of China (English)

    Wei-Ning Cheng; Jia-Xin Lei; William L.Rooney; Tong-Xian Liu; Keyan Zhu-Salzman

    2013-01-01

    Southwestern corn borer (SWCB,Diatraea grandiosella) and fall armyworm (FAW,Spodoptera frugiperda) are major pests of sorghum in the southern United States.Host plant resistance is a desirable means for reducing plant damage and yield losses from both insects.In this study,we evaluated 12 sorghum lines for whorl-stage resistance to leaf-feeding SWCB and FAW in greenhouse and laboratory bioassays.Differential plant responses were detected against the two insects.Among 12 lines tested,CM1821,Della and PI196583 were resistant to both insects,while BTx2752 was largely susceptible.Line R.09110 was resistant to SWCB,but susceptible to FAW,whereas Redbine-60 was susceptible to SWCB,but not to FAW.In addition,we quantified various chemical components in the plants and determined their association with insect resistance.Tannin and chlorophyll in leaves did not show any significant correlation with resistance to either insects,but contents of soluble protein in general were negatively correlated with resistance to both insects.Endogenous soluble sugar and dhurrin were only positively correlated with resistance to SWCB,but not with FAW resistance.To gain some molecular insight into resistance mechanism of sorghum to SWCB,we performed qPCR reactions for key genes encoding enzymes involved in dhurrin and jasmonic acid (JA) biosynthesis on selected resistant or susceptible lines.Although these genes were rapidly and strongly induced by insect feeding in all lines,the observed resistance is likely explained by higher constitutive dhurrin contents in some resistant lines and higher basal JA biosynthesis in others.Our results suggest that sorghum utilizes multiple strategies to defend itself against SWCB.

  2. Extensively Drug-Resistant Klebsiella pneumoniae Causing Nosocomial Bloodstream Infections in China: Molecular Investigation of Antibiotic Resistance Determinants, Informing Therapy, and Clinical Outcomes

    Directory of Open Access Journals (Sweden)

    Wenzi Bi

    2017-06-01

    Full Text Available The rise in diversity of antimicrobial resistance phenotypes seen in Klebsiella pneumoniae is becoming a serious antibiotic management problem. We sought to investigate the molecular characteristics and clinical implications of extensively drug-resistant (XDR K. pneumoniae isolated from different nosocomial bloodstream infections (BSIs patients from July 2013 to November 2015. Even in combination treatment, meropenem did not protect against mortality of BSIs patients (P = 0.015. In contrast, tigecycline in combination with other antimicrobial agents significantly protected against mortality (P = 0.016. Antimicrobial susceptibility tests, molecular detection of antibiotic resistance determinants, conjugation experiments, multilocus sequence typing (MLST, S1-PFGE, Southern blot, SDS-PAGE, immunoblot analysis, and pulsed-field gel electrophoresis (PFGE were used to characterize these isolates. These XDR K. pneumoniae strains were resistant to conventional antimicrobials except tigecycline and polymyxin B and co-harbored diverse resistance determinants. rmtB, blaKPC−2 as well as blaCTX−M−9 were located on a transferable plasmid of ~54.2 kb and the most predominant replicon type was IncF. 23 of the 35 isolates belonging the predominant clone were found to incorporate the globally-disseminated sequence type ST11, but others including a unique, previously undiscovered lineage ST2281 (allelic profile: 4-1-1-22-7-4-35 were also found and characterized. The porins OmpK35 and OmpK36 were deficient in two carbapenemase-negative carbapenem-resistant strains, suggesting decreased drug uptake as a mechanism for carbapenem resistance. This study highlights the importance of tracking hospital acquired infections, monitoring modes of antibiotic resistance to improve health outcomes of BSIs patients and to highlight the problems of XDR K. pneumoniae dissemination in healthcare settings.

  3. Genotypes and antibiotic resistance of canine Campylobacter jejuni isolates.

    Science.gov (United States)

    Amar, Chantal; Kittl, Sonja; Spreng, David; Thomann, Andreas; Korczak, Bożena M; Burnens, André P; Kuhnert, Peter

    2014-01-10

    Campylobacter jejuni is the most important cause of bacterial gastroenteritis in humans. It is a commensal in many wild and domestic animals, including dogs. Whereas genotypes of human and chicken C. jejuni isolates have been described in some detail, only little information on canine C. jejuni genotypes is available. To gain more information on genotypes of canine C. jejuni and their zoonotic potential, isolates from routine diagnostics of diarrheic dogs as well as isolates of a prevalence study in non-diarrheic dogs were analyzed. Prevalence of thermophilic Campylobacter among non-diarrheic dogs was 6.3% for C. jejuni, 5.9% for Campylobacter upsaliensis and 0.7% for Campylobacter coli. The C. jejuni isolates were genotyped by multi locus sequence typing (MLST) and flaB typing. Resistance to macrolides and quinolones was genetically determined in parallel. Within the 134 genotyped C. jejuni isolates 57 different sequence types (ST) were found. Five STs were previously unrecognized. The most common STs were ST-48 (11.2%), ST-45 (10.5%) and ST-21 (6.0%). Whereas no macrolide resistance was found, 28 isolates (20.9%) were resistant to quinolones. ST-45 was significantly more prevalent in diarrheic than in non-diarrheic dogs. Within the common time frame of isolation 94% of the canine isolates had a ST that was also found in human clinical isolates. In conclusion, prevalence of C. jejuni in Swiss dogs is low but there is a large genetic overlap between dog and human isolates. Given the close contact between human and dogs, the latter should not be ignored as a potential source of human campylobacteriosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Advances in pneumococcal antibiotic resistance.

    Science.gov (United States)

    Song, Jae-Hoon

    2013-10-01

    Antimicrobial resistance and serotypes in Streptococcus pneumoniae have been evolving with the widespread use of antibiotics and the introduction of pneumococcal conjugate vaccines (PCV). Particularly, among various types of antimicrobial resistance, macrolide resistance has most remarkably increased in many parts of the world, which has been reported to be >70% among clinical isolates from Asian countries. Penicillin resistance has dramatically decreased among nonmeningeal isolates due to the changes in resistance breakpoints, although resistance to other β-lactams such as cefuroxime has increased. Multidrug resistance became a serious concern in the treatment of invasive pneumococcal diseases, especially in Asian countries. After PCV7 vaccination, serotype 19A has emerged as an important cause of invasive pneumococcal diseases which was also associated with increasing prevalence of multidrug resistance in pneumococci. Widespread use of PCV13, which covers additional serotypes 3, 6A and 19A, may contribute to reduce the clonal spread of drug-resistant 19A pneumococci.

  5. Determination of resistance to salt crystallization on natural stone measured with ultrasonic wave

    DEFF Research Database (Denmark)

    Alm, D.; Brix, S.; Kjærgaard, H. Howe

    2008-01-01

    The use of panels as facade cladding has increased substantially during the last few decades. However, during recent years reports of facade problems have increased dramatically. Facade cladding has, in some cases, suffered from problems with durability such as exfoliation, disintegration of macr...... porosity while Perlatino has 1.1 % in open porosity. By means of ultrasonic measurements it is possible to detect damage in stones exposed to salt crystallization cycles. The results show a tendency to less resistance of salt crystallization for more porous materials....... of macrostructure and loss of strength. The damage may to some extent be accelerated by salt crystallization. This is an investigation of the durability of stones exposed to salt crystallization, by means of ultrasonic velocity measurements, compressive strength measurements and analysis of thin sections before...... and after salt exposure. Four different stones are investigated: the limestone Bateig Azul, the sandstone Oberkirchener, the limestone Perlatino, and the limestone Travertine. The procedure for the salt crystallization test is EN 12370 standard “Natural stone test methods – Determination of resistance...

  6. Diversity of Antimicrobial Resistance and Virulence Determinants in Pseudomonas aeruginosa Associated with Fresh Vegetables

    Directory of Open Access Journals (Sweden)

    Kashina Allydice-Francis

    2012-01-01

    Full Text Available With the increased focus on healthy eating and consuming raw vegetables, this study assessed the extent of contamination of fresh vegetables by Pseudomonas aeruginosa in Jamaica and examined the antibiotic susceptibility profiles and the presence of various virulence associated determinants of P. aeruginosa. Analyses indicated that vegetables from retail markets and supermarkets were widely contaminated by P. aeruginosa; produce from markets were more frequently contaminated, but the difference was not significant. Lettuce and carrots were the most frequently contaminated vegetables, while tomatoes were the least. Pigment production (Pyoverdine, pyocyanin, pyomelanin and pyorubin, fluorescein and alginate were common in these isolates. Imipenem, gentamicin and ciprofloxacin were the most inhibitory antimicrobial agents. However, isolates were resistant or showed reduced susceptibility to ampicillin, chloramphenicol, sulphamethoxazole/trimethoprim and aztreonam, and up to 35% of the isolates were resistant to four antimicrobial agents. As many as 30% of the isolates were positive for the fpv1 gene, and 13% had multiple genes. Sixty-four percent of the isolates harboured an exoenzyme gene (exoS, exoT, exoU or exoY, and multiple exo genes were common. We conclude that P. aeruginosa is a major contaminant of fresh vegetables, which might be a source of infection for susceptible persons within the community.

  7. Automated systems in the identification and determination of methicillin resistance among coagulase negative staphylococci

    Directory of Open Access Journals (Sweden)

    Juliana Caierão

    2006-05-01

    Full Text Available Coagulase-negative staphylococci (CoNS are an important cause of nosocomial bacteremia, specially in patients with indwelling devices or those submitted to invasive medical procedures. The identification of species and the accurate and rapid detection of methicillin resistance are directly dependent on the quality of the identification and susceptibility tests used, either manual or automated. The objective of this study was to evaluate the accuracy of two automated systems MicroScan and Vitek - in the identification of CoNS species and determination of susceptibility to methicillin, considering as gold standard the biochemical tests and the characterization of the mecA gene by polymerase chain reaction, respectively. MicroScan presented better results in the identification of CoNS species (accuracy of 96.8 vs 78.8%, respectively; isolates from the following species had no precise identification: Staphylococcus haemolyticus, S. simulans, and S. capitis. Both systems were similar in the characterization of methicillin resistance. The higher discrepancies for gene mec detection were observed among species other than S. epidermidis (S. hominis, S. saprophyticus, S. sciuri, S. haemolyticus, S. warneri, S. cohnii, and those with borderline MICs.

  8. Characterization of Multidrug Resistant E. faecalis Strains from Pigs of Local Origin by ADSRRS-Fingerprinting and MALDI -TOF MS; Evaluation of the Compatibility of Methods Employed for Multidrug Resistance Analysis

    Science.gov (United States)

    Nowakiewicz, Aneta; Ziółkowska, Grażyna; Zięba, Przemysław; Gnat, Sebastian; Trościańczyk, Aleksandra; Adaszek, Łukasz

    2017-01-01

    The aim of this study was to characterize multidrug resistant E. faecalis strains from pigs of local origin and to analyse the relationship between resistance and genotypic and proteomic profiles by amplification of DNA fragments surrounding rare restriction sites (ADSRRS-fingerprinting) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI -TOF MS). From the total pool of Enterococcus spp. isolated from 90 pigs, we selected 36 multidrug resistant E. faecalis strains, which represented three different phenotypic resistance profiles. Phenotypic resistance to tetracycline, macrolides, phenicols, and lincomycin and high-level resistance to aminoglycosides were confirmed by the occurrence of at least one corresponding resistance gene in each strain. Based on the analysis of the genotypic and phenotypic resistance of the strains tested, five distinct resistance profiles were generated. As a complement of this analysis, profiles of virulence genes were determined and these profiles corresponded to the phenotypic resistance profiles. The demonstration of resistance to a wide panel of antimicrobials by the strains tested in this study indicates the need of typing to determine the spread of resistance also at the local level. It seems that in the case of E. faecalis, type and scope of resistance strongly determines the genotypic pattern obtained with the ADSRRS-fingerprinting method. The ADSRRS-fingerprinting analysis showed consistency of the genetic profiles with the resistance profiles, while analysis of data with the use of the MALDI- TOF MS method did not demonstrate direct reproduction of the clustering pattern obtained with this method. Our observations were confirmed by statistical analysis (Simpson’s index of diversity, Rand and Wallace coefficients). Even though the MALDI -TOF MS method showed slightly higher discrimination power than ADSRRS-fingerprinting, only the latter method allowed reproduction of the clustering pattern of

  9. Experimental determination of vertical uprooting resistance for grass species used in flume experiments

    Science.gov (United States)

    Edmaier, K.; Crouzy, B.; Ennos, R.; Burlando, P.; Perona, P.

    2012-12-01

    Vegetation affects river morphodynamics by contributing to the stabilization of alluvial sediment via the root system. The survival and establishment of riparian pioneer vegetation on river bars and islands is determined by timescales of vegetation growth and flood interarrival times. Several laboratory experiments have investigated the role of vegetation in river morphodynamics but none of those has quantied the forces involved to produce uprooting of growing plants. Thus, parallel analyses on root resistance to uprooting are needed. In this work we investigate the uprooting resistance of young vegetation in laboratory experiments, where we vertically uprooted seedlings of Avena sativa and Medicago sativa. Uprooting force and work were related to the root structure (root length, number of roots, root tortuosity) and environmental conditions (grain size, saturation). We found the uprooting work of both species to follow a power law relation with the total root length which was found to be the main driving factor of the process. In addition, the number of roots was found to increase uprooting work. For similar total root length, the multi-root system of Avena sativa shows greater uprooting resistance in terms of work than the single-root system of Medicago sativa. Less sediment saturation produces higher uprooting forces and favors root breaking. Smaller sediment sizes lead to a higher uprooting resistance than bigger ones. Nevertheless, both saturation and grain size showed minor influence on the uprooting process compared to root characteristics. From measured uprooting forces of Avena sativa grown on sediment with a grain size distribution similar to that used in the flume experiments of Perona et al. (2012) we computed the ensemble probability of Avena sativa being uprooted by a particular drag force at certain growth stages, allowing us to compute a probability distribution of being uprooted in dependence of the root length and thus experimentally assess the

  10. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology.

    Science.gov (United States)

    Gibson, Molly K; Forsberg, Kevin J; Dantas, Gautam

    2015-01-01

    Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.

  11. Genetic dissection of sex determinism, inflorescence morphology and downy mildew resistance in grapevine.

    Science.gov (United States)

    Marguerit, Elisa; Boury, Christophe; Manicki, Aurélie; Donnart, Martine; Butterlin, Gisèle; Némorin, Alice; Wiedemann-Merdinoglu, Sabine; Merdinoglu, Didier; Ollat, Nathalie; Decroocq, Stéphane

    2009-05-01

    A genetic linkage map of grapevine was constructed using a pseudo-testcross strategy based upon 138 individuals derived from a cross of Vitis vinifera Cabernet Sauvignon x Vitis riparia Gloire de Montpellier. A total of 212 DNA markers including 199 single sequence repeats (SSRs), 11 single strand conformation polymorphisms (SSCPs) and two morphological markers were mapped onto 19 linkage groups (LG) which covered 1,249 cM with an average of 6.7 cM between markers. The position of SSR loci in the maps presented here is consistent with the genome sequence. Quantitative traits loci (QTLs) for several traits of inflorescence and flower morphology, and downy mildew resistance were investigated. Two novel QTLs for downy mildew resistance were mapped on linkage groups 9 and 12, they explain 26.0-34.4 and 28.9-31.5% of total variance, respectively. QTLs for inflorescence morphology with a large effect (14-70% of total variance explained) were detected close to the Sex locus on LG 2. The gene of the enzyme 1-aminocyclopropane-1-carboxylic acid synthase, involved in melon male organ development and located in the confidence interval of all QTLs detected on the LG 2, could be considered as a putative candidate gene for the control of sexual traits in grapevine. Co-localisations were found between four QTLs, detected on linkage groups 1, 14, 17 and 18, and the position of the floral organ development genes GIBBERELLIN INSENSITIVE1, FRUITFULL, LEAFY and AGAMOUS. Our results demonstrate that the sex determinism locus also determines both flower and inflorescence morphological traits.

  12. Antibiotic Resistance among Clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013.

    Science.gov (United States)

    Beeton, Michael L; Chalker, Victoria J; Jones, Lucy C; Maxwell, Nicola C; Spiller, O Brad

    2015-10-12

    Ureaplasma spp. are associated with numerous clinical sequelae with treatment options being limited due to patient and pathogen factors. This report examines the prevalence and mechanisms of antibiotic resistance among clinical strains isolated from 95 neonates, 32 women attending a sexual health clinic, and 3 patients under investigation for immunological disorders, between 2007 and 2013 in England and Wales. MICs were determined by using broth microdilution assays, and a subset of isolates were compared using the broth microdilution method and the Mycoplasma IST2 assay. The underlying molecular mechanisms for resistance were determined for all resistant isolates. Three isolates carried the tet(M) tetracycline resistance gene (2.3%; confidence interval [CI], 0.49 to 6.86%); two isolates were ciprofloxacin resistant (1.5%; CI, 0.07 to 5.79%) but sensitive to levofloxacin and moxifloxacin, while no resistance was seen to any macrolides tested. The MIC values for chloramphenicol were universally low (2 μg/ml), while inherently high-level MIC values for gentamicin were seen (44 to 66 μg/ml). The Mycoplasma IST2 assay identified a number of false positives for ciprofloxacin resistance, as the method does not conform to international testing guidelines. While antibiotic resistance among Ureaplasma isolates remains low, continued surveillance is essential to monitor trends and threats from importation of resistant clones.

  13. Biomonitoring marine habitats in reference to antibiotic resistant bacteria and ampicillin resistance determinants from oviductal fluid of the nesting green sea turtle, Chelonia mydas.

    Science.gov (United States)

    Al-Bahry, S N; Al-Zadjali, M A; Mahmoud, I Y; Elshafie, A E

    2012-06-01

    During the egg-laying process, oviductal fluid was collected using a non-invasive procedure from the cloacal vent of the green turtles. Forty-two independent isolates of antibiotic-resistant bacteria from 11 genera were obtained from 20 turtles during nesting. The dominant isolate was Citrobacter (52.4%), followed by Pseudomonas, Proteus, Enterobacter, Salmonella, Escherichia coli, Shigella, Edwardsiella, Morganella, Providencia and Arcomobacter. Most of the isolates were resistant to ampicillin. Ampicillin-resistant isolates showed variations in their resistance for the following classes of β-lactamases: extended-spectrum β-lactamases (EBSLs), AmpC type β-lactamases C (AmpC), and screen-positive β-lactamase. None of the isolates produced metallo β-lactamase. Some ampicillin-resistant genes were detected by multiplex polymerase chain reaction (PCR) only. Inhibitor based test (IBT) categorized some isolates as AmpC β-lactamase producers. β-Lactamase genes were detected from a few strains. The sequencing of those genes revealed the presence of cephamycinase (CMY) and AmpC β-lactamases. The oviductal fluid was used in this study as a source of bacterial antibiotic-resistant determinants for biomonitoring marine turtles exposed to contaminated effluents. This data can be of value in understanding the decline of this endangered species as a result of exposure to marine pollution which is threatening their survival.

  14. Multi-class determination and confirmation of antibiotic residues in honey using LC-MS/MS

    Science.gov (United States)

    A multi-class method was developed for the determination and confirmation in honey of tetracyclines (chlortetracycline, doxycycline, oxytetracycline, and tetracycline), fluoroquinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, and sarafloxacin), macrolides (tylosin), lincosamides (lin...

  15. Identification of Tet 39, a novel class of tetracycline resistance determinant in Acinetobacter spp. of environmental and clinical origin

    DEFF Research Database (Denmark)

    Agersø, Yvonne; Guardabassi, L.

    2005-01-01

    A novel tetracycline resistance determinant named Tet 39 was found in unrelated Acinetobacter strains isolated from freshwater trout farms (n=4) and sewage (n=6) in Denmark, and from a clinical specimen in the Netherlands (n=1). The determinant was located on transferable plasmids and consisted o...

  16. How should we be determining background and baseline antibiotic resistance levels in agroecosystem research?

    Science.gov (United States)

    Although historically antibiotic resistance has occurred naturally in environmental bacteria, many questions remain regarding the specifics of how humans and animals contribute to the development and spread of antibiotic resistance in agroecosystems. Additional research is necessary to completely u...

  17. Genetically Determined Insulin Resistance is Characterized by Down-Regulation of Mitochondrial Oxidative Metabolism in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas M; Skov, Vibe; Wojtaszewski, Jørgen

    2010-01-01

    Transcriptional profiling of skeletal muscle from patients with type 2 diabetes and high-risk individuals have demonstrated a co-ordinated down-regulation of oxidative phosphorylation (OxPhos) genes, suggesting a link between insulin resistance and mitochondrial dysfunction. However, whether...... mitochondrial dysfunction is a cause or consequence of insulin resistance remains to be clarified. In the present study, we tested the hypothesis that mitochondrial oxidative metabolism was down-regulated in skeletal muscle of patients with genetically determined insulin resistance. Skeletal muscle biopsies.......02), and complex V (ATP5B; p=0.005). Our data demonstrate that genetically determined insulin resistance is associated with a co-ordinated down-regulation of OxPhos components both at the transcriptional and translational level. These findings suggest that an impaired biological response to insulin in skeletal...

  18. Nucleotide sequence of the aacC2 gene, a gentamicin resistance determinant involved in a hospital epidemic of multiply resistant members of the family Enterobacteriaceae.

    OpenAIRE

    Vliegenthart, J S; Ketelaar-van Gaalen, P A; Van de Klundert, J A

    1989-01-01

    A gentamicin resistance determinant of a conjugative plasmid from Enterobacter cloacae was cloned on a 3.2-kilobase fragment in the PstI site of pBR322. Substrate profiles for eight aminoglycosides at three concentrations showed that the resistance was due to aminoglycoside-(3)-N-acetyltransferase isoenzyme II. Insertion mapping by the gamma-delta transposon revealed that the size of the gene was approximately 1 kilobase. Nucleotide sequencing of the aacC2 gene identified an open reading fram...

  19. Airborne allergic contact dermatitis from tylosin in pharmacy compounders and cross-sensitization to macrolide antibiotics.

    Science.gov (United States)

    Malaiyandi, Viba; Houle, Marie Claude; Skotnicki-Grant, Sandy

    2012-01-01

    Tylosin is a broad-spectrum macrolide antibiotic that is restricted to veterinary use. Allergic contact dermatitis (ACD) caused by tylosin has been reported in the literature from the farming industry and veterinary medicine. It is also reported as the most common antibiotic to cause ACD in the previously mentioned occupational settings. We present 2 cases of airborne ACD from tylosin among veterinary pharmaceutical compounding technicians. To our knowledge, only one other case of patch test-confirmed tylosin ACD has been reported in the manufacturing setting. Based on our results, cross-sensitization to other clinically relevant macrolides does not appear to be a concern. Our cases highlight the importance of patch testing among pharmaceutical compounders where the incidence of an airborne contact may be greater, given that the exposure is to the powdered form of potential allergens.

  20. [In vitro comparative activity of five macrolides against 190 Branhamella catarrhalis strains].

    Science.gov (United States)

    Chardon, H; Bellon, O; Bourgeois, F; Lagier, E

    1989-05-01

    We compared the in vitro activity of 5 macrolides against 190 strains of Branhamella catarrhalis; 48 strains were isolated at Centre Hospitalier, Aix-en-Provence, the 142 others were isolated during 1987, in 15 different Centres-Hospitaliers-Généraux in France. 153 strains were betalactamase producing strains; no difference in susceptibility to erythromycin was observed on betalactamase producing and non producing strains. Three active macrolides against 100% of strains were: erythromycin (MIC 50 = 0.25 mg/l - MIC 90 = 0.50 mg/l), roxithromycin (MIC 50 = 0.50 mg/l - MIC 90 = 0.50 mg/l) and josamycin (MIC 50 = 0.50 mg/l - MIC 90 = 1 mg/l); A lower activity was noted on midecamycin (mic 50 = 2 mg/l - MIC 90 = 2 mg/l) and spiramycin (MIC 50 = 4 mg/l - MIC 90 = 8 mg/l).

  1. Prevalence of quinolone resistance determinants in non-typhoidal Salmonella isolates from human origin in Extremadura, Spain.

    Science.gov (United States)

    Campos, Maria Jorge; Palomo, Gonzalo; Hormeño, Lorena; Herrera-León, Silvia; Domínguez, Lucas; Vadillo, Santiago; Píriz, Segundo; Quesada, Alberto

    2014-05-01

    Resistance to the quinolones nalidixic acid (NAL) and ciprofloxacin (CIP) and the occurrence of quinolone resistance determinants have been investigated in 300 non-typhoidal Salmonella from human origin, isolated in the years between 2004 and 2008, in 6 hospitals within Extremadura (Spain). Salmonella Enteritidis was the major serotype found among quinolone-resistant isolates, most of which were clustered by clonal analysis to a single clone, which presented D87 or S83 substitutions in GyrA. Eleven isolates presented the non-classical quinolone resistance phenotype (resistance to CIP and susceptibility to NAL), lacking mutations in the quinolone resistance determinant region of topoisomerase genes. Among them, one Salmonella Typhimurium isolate carried a qnrS1 gene in a low-molecular-weight plasmid, pQnrS1-HLR25, identical to plasmids previously found in the UK, Taiwan, and USA. The occurrence of this genetic element could represent a risk for the horizontal transmission of quinolone resistance among Enterobacteriaceae in the Iberian Peninsula.

  2. Rapid determination of β-lactam antimicrobial resistance in bacteria by a liquid chromatography-mass spectrometry-based method.

    Science.gov (United States)

    Kang, JeongWoo; Hossain, Md Akil; Park, Hae-Chul; Jang, Yangho; Kim, Seonhwa; Song, Jae Young; Lee, Kwang-Jick; Kim, Tae-Wan

    2016-11-01

    Conventional antimicrobial susceptibility tests (ASTs) are very time consuming and insufficiently precise to promptly select a proper antimicrobial treatment. This difficulty disrupts the management of infections and exacerbates the development of antimicrobial resistance. Generally, antimicrobial resistance involves the chemical modification of an antimicrobial compound to an inactive form by an enzyme released by bacteria. This modification causes a structural change and is followed by a characteristic mass shift of the antimicrobials. Using this mechanism, we developed a new liquid chromatography-mass spectrometry method to rapidly determine the degree of resistance of Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium), Escherichia coli, and Staphylococcus aureus to amoxicillin, ampicillin, and penicillin G, respectively. This method was successfully applied to 20 bacterial isolates from Korean slaughterhouses and farms. There were 18-Da mass shifts in resistant strains compared with susceptible strains of Salmonella Typhimurium, E. coli, and S. aureus, and the intensities of the hydrolyzed penicillin mass spectra were much higher in resistant strains than those in susceptible strains, which together indicate the reliability of this method. A comparison of the mass spectrometry-derived results with that from conventional ASTs revealed an identical classification of the tested bacteria according to sensitivity and resistance. Notably, this assay method requires only 2 h for determining the susceptibility status of a strain. This newly developed method is able to determine the extent of antimicrobial resistance qualitatively and quantitatively within a very short time and could be used to replace conventional AST methods. Graphical abstract Rapid determination of β-lactam antimicrobial resistance in bacteria by LC-MS/MS.

  3. Ethylmethanesulfonate Saturation Mutagenesis in Arabidopsis to Determine Frequency of Herbicide Resistance

    Science.gov (United States)

    Plant resistance to glyphosate has been reported far less frequently than resistance to sulfonylurea and imidazolinone herbicides. However, these studies tend to be anecdotal, without side by side comparisons for a single species or natural isolate. In this study, we tested the frequencies of resist...

  4. The evidence for clonal spreading of quinolone resistance with a particular clonal complex of Campylobacter jejuni.

    Science.gov (United States)

    Kovač, J; Cadež, N; Lušicky, M; Nielsen, E Møller; Ocepek, M; Raspor, P; Možina, S Smole

    2014-12-01

    Campylobacter is the most prevalent cause of bacterial gastroenteritis worldwide and it represents a significant public health risk of increasing severity due to its escalating resistance to clinically important quinolone and macrolide antibiotics. As a zoonotic pathogen Campylobacter is transmitted along the food chain and naturally cycles from environmental waters, feedstuff, animals and food to humans. We determined antibiotic resistance profiles, as well as multilocus sequence types and flaA-SVR types for 52 C. jejuni isolated in Slovenia from human, animal, raw and cured chicken meat and water samples. Twenty-eight different sequence types, arranged in ten clonal complexes, three new allele types and five new sequence types were identified, indicating the relatively high diversity in a small group of strains. The assignment of strains from different sources to the same clonal complexes indicates their transmission along the food supply chain. The most prevalent clonal complex was CC21, which was also the genetic group with 95% of quinolone-resistant strains. Based on the genetic relatedness of these quinolone-resistant strains identified by polymerase chain reaction with a mismatch amplification mutation assay and sequencing of the quinolone resistance-determining region of the gyrA gene, we conclude that the high resistance prevalence observed indicates the local clonal spread of quinolone resistance with CC21.

  5. Determination of enterotoxigenic and methicillin resistant Staphylococcus aureus in ice cream.

    Science.gov (United States)

    Gücükoğlu, Ali; Çadirci, Özgür; Terzi, Göknur; Kevenk, T Onur; Alişarli, Mustafa

    2013-05-01

    The aim of this study was to determine the prevalence of enterotoxigenic and methicillin-resistant Staphylococcus aureus in ice creams. After culture-based identification of isolates, the presence of 16S rRNA and nuc was confirmed by mPCR. S. aureus was identified in 18 of 56 fruity (32.1%), 4 of 32 vanilla (12.5%), and 1 of 12 chocolate (8.3%) ice creams. S. aureus was identified as 38 isolates in 23 ice cream samples by culture-based techniques, but only 35 isolates were confirmed by PCR as S. aureus. To determine the enterotoxigenic properties of PCR-confirmed S. aureus isolates, a toxin detection kit was used (SET RPLA®). Of the 12 enterotoxigenic S. aureus isolates, 9 SEB (75%), 1 SED (8.3%), 1 SEB+SED (8.3%), and 1 SEA+SEB+SED (8.3%) expressing isolates were found. The presence of enterotoxin genes (sea, seb, sed) was identified in 13 (37.1%) out of 35 isolates by the mPCR technique. In the ice cream isolates, the sea, seb, and sed genes were detected: 1 sea (7.6%), 9 seb (69.2%), 1 sed (7.6%), 1 seb+sed (7.6%), and 1 sea+seb+sed (7.6%), respectively. The sec gene was not detected in any of these isolates. One of the 35 (2.8%) S. aureus strain was mecA positive.

  6. Trace analysis of trimethoprim and sulfonamide, macrolide, quinolone, and tetracycline antibiotics in chlorinated drinking water using liquid chromatography electrospray tandem mass spectrometry

    Science.gov (United States)

    Ye, Z.; Weinberg, H.S.; Meyer, M.T.

    2007-01-01

    A multirun analytical method has been developed and validated for trace determination of 24 antibiotics including 7 sulfonamides, 3 macrolides, 7 quinolones, 6 tetracyclines, and trimethoprim in chlorine-disinfected drinking water using a single solid-phase extraction method coupled to liquid chromatography with positive electrospray tandem mass spectrometry detection. The analytes were extracted by a hydrophilic-lipophilic balanced resin and eluted with acidified methanol (0.1% formic acid), resulting in analyte recoveries generally above 90%. The limits of quantitation were mostly below 10 ng/L in drinking water. Since the concentrated sample matrix typically caused ion suppression during electrospray ionization, the method of standard addition was used for quantitation. Chlorine residuals in drinking water can react with some antibiotics, but ascorbic acid was found to be an effective chlorine quenching agent without affecting the analysis and stability of the antibiotics in water. A preliminary occurrence study using this method revealed the presence of some antibiotics in drinking waters, including sulfamethoxazole (3.0-3.4 ng/L), macrolides (1.4-4.9 ng/L), and quinolones (1.2-4.0 ng/L). ?? 2007 American Chemical Society.

  7. A seventeen-year observation of the antimicrobial susceptibility of clinical Campylobacter jejuni and the molecular mechanisms of erythromycin-resistant isolates in Beijing, China.

    Science.gov (United States)

    Zhou, Jiyuan; Zhang, Maojun; Yang, Wanna; Fang, Yuqing; Wang, Guiqiang; Hou, Fengqin

    2016-01-01

    To investigate the dynamic development of the antimicrobial resistance of Campylobacter jejuni isolated from human diarrhea in Beijing, China, between 1994 and 2010, and to further analyze the molecular mechanisms of erythromycin-resistant strains. Susceptibility tests were performed on 203 non-duplicate clinical C. jejuni strains against eight common antibiotics using the standard agar dilution method. The molecular determinants were further studied in the erythromycin (ERY) non-susceptible strains. The analysis focused on the 23S rRNA gene, the rplD and rplV ribosomal genes, the ermB gene, and the regulatory region of the CmeABC efflux pump. The rates of resistance of C. jejuni to ciprofloxacin (CIP), nalidixic acid (NAL), doxycycline (DOX), tetracycline (TET), florfenicol (FFC), and chloramphenicol (CHL) increased significantly over the period studied (all pjejuni strains were ERY non-susceptible. The A2075G mutation in the 23S rRNA was found in all of the resistant strains except cj8091, which harbored the ermB gene. Interestingly, the ermB gene was also detected in intermediately resistant isolates, and the earliest ermB-positive strain cj94473 was derived in 1994. Moreover, none of the ribosomal rplD or rplV genes harbored mutations that have been described to confer resistance to macrolides. Different mutations affecting the regulatory region of the CmeABC efflux pump were also found. This is the first comprehensive study on the recent trend in antimicrobial resistance and the molecular mechanisms of macrolide resistance in clinical C. jejuni strains isolated in China. More stringent monitoring and regulation of human and animal antimicrobial use are warranted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. HIV-1 resistance to neutralizing antibodies: Determination of antibody concentrations leading to escape mutant evolution.

    Science.gov (United States)

    Magnus, Carsten; Reh, Lucia; Trkola, Alexandra

    2016-06-15

    Broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) are considered vital components of novel therapeutics and blueprints for vaccine research. Yet escape to even the most potent of these antibodies is imminent in natural infection. Measures to define antibody efficacy and prevent mutant selection are thus urgently needed. Here, we derive a mathematical framework to predict the concentration ranges for which antibody escape variants can outcompete their viral ancestors, referred to as mutant selection window (MSW). When determining the MSW, we focus on the differential efficacy of neutralizing antibodies against HIV-1 in two canonical infection routes, free-virus infection and cell-cell transmission. The latter has proven highly effective in vitro suggesting its importance for both in vivo spread as well as for escaping targeted intervention strategies. We observed a range of MSW patterns that highlight the potential of mutants to arise in both transmission pathways and over wide concentration ranges. Most importantly, we found that only when the arising mutant has both, residual sensitivity to the neutralizing antibody and reduced infectivity compared to the parental virus, antibody dosing outside of the MSW to restrict mutant selection is possible. Emergence of mutants that provide complete escape and have no considerable fitness loss cannot be prevented by adjusting antibody doses. The latter may in part explain the ubiquitous resistance to neutralizing antibodies observed in natural infection and antibody treatment. Based on our findings, combinations of antibodies targeting different epitopes should be favored for antibody-based interventions as this may render complete resistance less likely to occur and also increase chances that multiple escapes result in severe fitness loss of the virus making longer-term antibody treatment more feasible. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  9. The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides.

    Science.gov (United States)

    Zhi, Duo; Feng, Pan-Feng; Sun, Jia-Liang; Guo, Fengfeng; Zhang, Rui; Zhao, Xin; Li, Bao-Xin

    2015-08-30

    As is well-known, hERG plays an essential role in phase III repolarization of cardiac action potentials. Blocking of hERG channels can lead to LQTS. Inhibition of the metabolism of CYPs activities may elevate plasma levels, to further increase accumulation of drug on cardiac. The elevated serum levels may however elicit unexpected toxicities. Therefore, the inhibition tests of hERG and CYP are central to the preclinical studies because they may lead to severe cardiac toxicity. Berberine is widely used as an antibacterial agent and often combined with macrolides to treat gastropathy. Our objective was to assess cardiac toxicity during the combined use of Berberine with macrolides. (1) Azithromycin reduced hERG currents by accelerated channel inactivation. (2) The combination of Berberine with Azithromycin reduced hERG currents, producing an inhibitive effect stronger than use of a single drug alone, due to the high binding affinity for the onset of inactivation. (3) When cells were perfused concomitantly with Berberine and Clarithromycin, they showed a stronger inhibitive effect on hERG currents by decreasing the time constant for the onset of inactivation. (4) The combined administration of Berberine with Clarithromycin had a powerful inhibitive effect on CYP3A activities than use of a single drug alone. Collectively, these results demonstrated that concomitant use of Berberine with macrolides may require close monitoring because of potential drug toxicities, especially cardiac toxicity.

  10. Microbiological assay for the analysis of certain macrolides in pharmaceutical dosage forms.

    Science.gov (United States)

    Mahmoudi, A; Fourar, R E-A; Boukhechem, M S; Zarkout, S

    2015-08-01

    Clarithromycin (CLA) and roxithromycin (ROX) are macrolide antibiotics with an expanded spectrum of activity that are commercially available as tablets. A microbiological assay, applying the cylinder-plate method and using a strain of Micrococcus luteus ATCC 9341 as test organism, has been used and validated for the quantification of two macrolide drugs; CLA and ROX in pure and pharmaceutical formulations. The validation of the proposed method was carried out for linearity, precision, accuracy and specificity. The linear dynamic ranges were from 0.1 to 0.5μg/mL for both compounds. Logarithmic calibration curve was obtained for each macrolide (r>0.989) with statistically equal slopes varying from 3.275 to 4.038, and a percentage relative standard deviation in the range of 0.24-0.92%. Moreover, the method was applied successfully for the assay of the studied drugs in pharmaceutical tablet dosage forms. Recovery from standard addition experiments in commercial products was 94.71-96.91% regarding clarithromycin and 93.94-98.12% regarding roxithromycin, with a precision (%RSD) 1.32-2.11%. Accordingly, this microbiological assay can be used for routine quality control analysis of titled drugs in tablet formulations.

  11. Antimicrobial Resistance of Staphylococcal Strains Isolated from Various Pathological Products

    Directory of Open Access Journals (Sweden)

    Laura-Mihaela SIMON

    2010-12-01

    Full Text Available Background: The optimal choice of antimicrobial therapy is an important problem in hospital environment in which the selection of resistant and virulent strains easy occurs. S. aureus and especially MRSA(methicillin-resistant S. aureus creates difficulties in both treatment and prevention of nosocomial infections. Aim: The purpose of this study is to determine the sensitivity and the resistance to chemotherapy of staphylococci strains isolated from various pathological products. Material and Method: We identified Staphylococccus species after morphological appearance, culture properties, the production of coagulase, hemolisines and the enzyme activity. The susceptibility tests were performed on Mueller-Hinton medium according to CLSI (Clinical and Laboratory Standards Institute. Results: The strains were: MSSA (methicillin-susceptible S. aureus (74%, MRSA (8%, MLS B (macrolides, lincosamides and type B streptogramines resistance (12% and MRSA and MLS B (6%. MRSA strains were more frequently isolated from sputum. MRSA associated with the MLS B strains were more frequently isolated from pus. MLS B strains were more frequently isolated from sputum and throat secretions. All S. aureus strains were susceptible to vancomycin and teicoplanin. Conclusions: All staphylococcal infections require resistance testing before treatment. MLS B shows a high prevalence among strains of S. aureus. The association between MLS B and MRSA remains a major problem in Romania.

  12. Determination of sex and scrapie resistance genotype in preimplantation ovine embryos.

    Science.gov (United States)

    Guignot, Florence; Baril, Gerard; Dupont, Francis; Cognie, Yves; Folch, Jose; Alabart, Jose Luis; Poulin, Naty; Beckers, Jean-Francois; Bed'hom, Bertrand; Babilliot, Jean-Marc; Mermillod, Pascal

    2009-02-01

    The aim of this study was to test the accuracy of genotype diagnosis after pre-amplification of DNA extracted from biopsies obtained by microblade cutting of ovine embryos and to evaluate the viability of biopsied embryos after vitrification/warming and transfer to recipients. Sex and PrP genotypes were determined. Sex diagnosis was done by PCR amplification of ZFX/ZFY and SRY sequences after PEP-PCR while PrP genotype determination was performed after specific pre-amplification of specific target including codons 136, 154 and 171. Embryos were collected at Day 7 after oestrus. Blastocysts and expanded blastocysts were biopsied immediately after collection whereas compacted morulae were biopsied after 24 hr of in vitro culture. Eighty-nine biopsied embryos were frozen by vitrification. Fresh and vitrified whole embryos were kept as control. DNA of biopsies was extracted and pre-amplified. Sex diagnosis was efficient for 96.6% of biopsies and PrP genotyping was determined in 95.8% of codons. After embryo transfer, no significant difference was observed in lambing rate between biopsied, vitrified control and fresh embryos (54.5%, 60% and 66.6%, respectively). Embryo survival rate was not different between biopsied and whole vitrified embryos (P = 0.38). At birth, 96.7% of diagnosed sex and 95.4% of predetermined codons were correct. Lamb PrP profiles were in agreement with parental genotype. PEP-PCR coupled with sex diagnosis and nested PCR coupled with PrP genotype predetermination are very accurate techniques to genotype ovine embryo before transfer. These original results allow planning of selection of resistant genotype to scrapie and sex of offspring before transfer of cryopreserved embryo.

  13. Using a local-interaction model to determine the resistance to penetration of projectiles into sandy soil

    Science.gov (United States)

    Kotov, V. L.; Balandin, V. V.; Bragov, A. M.; Linnik, E. Yu.; Balandin, V. V.

    2013-07-01

    A local-interaction model describing the penetration of axisymmetric projectiles into sandy soil at a constant velocity is studied experimentally and theoretically. Two approaches to the determination of the parameters of the quadratic local-interaction model are considered. The first approach is based on the use of the solution of the problem of spherical-cavity expansion taking into account the dynamic compressibility and shear resistance of soil. In the second approach, model parameters are determined based on the experimental dependence of the resistance to penetration of conical projectiles into a sandy soil on the impact velocity. Good agreement was obtained between the results of experiments, two-dimensional numerical calculations, and calculations for the local interaction model based on the solution of the spherical-cavity expansion problem and used to determine the maximum resistance to penetration of conical and spherical projectiles.

  14. Analysis of methods for determining cutting resistance of tools on the shearer drum of a shearer loader

    Energy Technology Data Exchange (ETDEWEB)

    Krauze, K. (Akademia Gorniczo-Hutnicza, Cracow (Poland). Instytut Maszyn Gorniczych, Przerobczych i Automatyki)

    1989-01-01

    Comparatively evaluates methods for determining resistance of coal cut by a single radial or tangential tool on the shearer of a shearer loader. Methods developed by Bieron, Ewans, Nishimatsu and Merchants as well as empirical methods used in Poland are analyzed. Evaluations show that none of the methods is a universal method. The method of empirical formulae should be used for optimization of shearer loader drive systems. Ewans' method should be used for determining cutting resistance of brittle rocks when tangential tools are used. Bieron's and Nishimatsu's methods are used for radial tools and firm coal with plastic properties. Merchants' and Bieron's methods for determining coal resistance to cutting by tangential tools produce inaccurate results. 14 refs.

  15. Study on Drug Resistance and Relative Mechanisms of Chlamydia Trachomatis

    Institute of Scientific and Technical Information of China (English)

    侯淑萍; 刘全忠

    2004-01-01

    Abstract: Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use of antibiotics an increasing number of drug-resistant Chlamydia trachomatis cases have been reported. This review summarizes the resistant conditions and the possible resistance mechanisms of C.T..

  16. In vitro capability of faropenem to select for resistant mutants of Streptococcus pneumoniae and Haemophilus influenzae.

    Science.gov (United States)

    Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; Dewasse, Bonifacio; Beachel, Linda; Ednie, Lois; Appelbaum, Peter C

    2008-02-01

    When tested against nine strains of pneumococci and six of Haemophilus influenzae of various resistotypes, faropenem failed to select for resistant mutants after 50 days of consecutive subculture in subinhibitory concentrations. Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones.

  17. Characterization of the quinolone resistant determining regions in clinical isolates of pneumococci collected in Canada

    Directory of Open Access Journals (Sweden)

    Melano Roberto

    2010-01-01

    Full Text Available Abstract Background The objective of this study was to examine Streptococcus pneumoniae isolates collected from a longitudinal surveillance program in order to determine their susceptibility to currently used fluoroquinolones and of the frequency and type of mutations in the quinolone-resistant determining regions (QRDRs of their parC and gyrA genes. Methods The Canadian Bacterial Surveillance Network has been collecting clinical isolates of S. pneumoniae from across Canada since 1988. Broth microdilution susceptibility testing was carried out according to the Clinical and Laboratory Standards Institute guidelines. The QRDRs of the parC and gyrA genes were sequenced for all isolates with ciprofloxacin MIC ≥ 4 mg/L, and a large representative sample of isolates (N = 4,243 with MIC ≤ 2 mg/L. Results A total of 4,798 out of 30,111 isolates collected from 1988, and 1993 to 2007 were studied. Of those isolates that were successfully sequenced, 184 out of 1,032 with mutations in parC only, 11 out of 30 with mutations in gyrA only, and 292 out of 298 with mutations in parC and gyrA were considered resistant to ciprofloxacin (MIC ≥ 4 mg/L. The most common substitutions in the parC were at positions 137 (n = 722, 79 (n = 209, and 83 (n = 56, of which substitutions at positions 79 and 83 were associated with 4-fold increase in MIC to ciprofloxacin, whereas substitutions at position 137 had minimal effect on the ciprofloxacin MIC. A total of 400 out of 622 isolates with Lys-137 parC mutation belonged to serotypes 1, 12, 31, 7A, 9V, 9N and 9L, whereas only 49 out of 3064 isolates with no mutations belonged to these serotypes. Twenty-one out of 30 isolates with substitutions at position 81 of the gyrA gene had an increased MIC to ciprofloxacin. Finally, we found that isolates with mutations in both parC and gyrA were significantly associated with increased MIC to fluoroquinolones. Conclusions Not all mutations, most frequently Lys-137, found in the

  18. Indirect resistance to several classes of antibiotics in cocultures with resistant bacteria expressing antibiotic-modifying or -degrading enzymes.

    Science.gov (United States)

    Nicoloff, Hervé; Andersson, Dan I

    2016-01-01

    Indirect resistance (IR), the ability of an antibiotic-resistant population of bacteria to protect a susceptible population, has been previously observed for β-lactamase-producing bacteria and associated with antimicrobial treatment failures. Here, we determined whether other resistance determinants could cause IR in the presence of five other classes of antibiotics. A test was designed to detect IR and 14 antibiotic resistance genes were tested in the presence of 13 antibiotics from six classes. A bioassay was used to measure the ability of resistance-causing enzymes to decrease the concentration of active antibiotics in the medium. We confirmed IR in the presence of β-lactam antibiotics (ampicillin and mecillinam) when TEM-1A was expressed. We found that bacteria expressing antibiotic-modifying or -degrading enzymes Ere(A), Tet(X2) or CatA1 caused IR in the presence of macrolides (erythromycin and clarithromycin), tetracyclines (tetracycline and tigecycline) and chloramphenicol, respectively. IR was not observed with resistance determinants that did not modify or destroy antibiotics or with enzymes modifying aminoglycosides or degrading fosfomycin. IR was dependent on the resistance enzymes decreasing the concentration of active antibiotics in the medium, hence allowing nearby susceptible bacteria to resume growth once the antibiotic concentration fell below their MIC. IR was not limited to β-lactamase-producing bacteria, but was also caused by resistant bacteria carrying cytoplasmic antibiotic-modifying or -degrading enzymes that catalyse energy-consuming reactions requiring complex cellular cofactors. Our results suggest that IR is common and further emphasizes that coinfecting agents and the human microflora can have a negative impact during antimicrobial therapy. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Antibiotic Resistance of Campylobacter jejuni and C. coli Isolated from Children with Diarrhea in Thailand and Japan.

    Science.gov (United States)

    Pham, Ngan Thi Kim; Thongprachum, Aksara; Tran, Dinh Nguyen; Nishimura, Shuichi; Shimizu-Onda, Yuko; Trinh, Quang Duy; Khamrin, Pattara; Ukarapol, Nuthapong; Kongsricharoern, Tipachan; Komine-Aizawa, Shihoko; Okitsu, Shoko; Maneekarn, Niwat; Hayakawa, Satoshi; Ushijima, Hiroshi

    2016-01-01

    A total of 29 Campylobacter jejuni and C. coli strains were isolated from Thai and Japanese children with diarrhea using the Loop-mediated Isothermal Amplification method. The samples were evaluated for mutations in gyrA and 23S rRNA in order to assess resistance against fluoroquinolones and macrolides, respectively. Among the isolated strains, 9 (8 C. jejuni and 1 C. coli) were from Thai children, and the other 20 (C. jejuni) were isolated from Japanese children. High fluoroquinolone resistance rates were observed in Thai (66.7%) and Japanese (90%) children. Macrolide resistance was not observed in Japanese children but was observed at a considerable rate of 12.5% of C. jejuni isolated in the Thai cohort. The results indicate that continuous monitoring of resistance of Campylobacter strains to fluoroquinolones and macrolides is definitely necessary.

  20. Streptococcus pneumoniae R6 interspecies transformation: genetic analysis of penicillin resistance determinants and genome-wide recombination events.

    Science.gov (United States)

    Sauerbier, Julia; Maurer, Patrick; Rieger, Martin; Hakenbeck, Regine

    2012-11-01

    Interspecies gene transfer has been implicated as the major driving force for the evolution of penicillin resistance in Streptococcus pneumoniae. Genomic alterations of S. pneumoniae R6 introduced during four successive transformations with DNA of the high-level penicillin-resistant Streptococcus mitis B6 with beta-lactam selection have now been determined and the contribution of genes to high resistance levels was analysed genetically. Essential for high level resistance to penicillins of the transformant CCCB was the combination of murM(B) (6) and the 3' region of pbp2b(B) (6) . Sequences of both genes were detected in clinical isolates of S. pneumoniae, confirming the participation of S. mitis in the global gene pool of beta-lactam resistance determinants. The S. mitis PBP1b gene which contains an authentic stop codon within the transpeptidase domain is now shown to contribute only marginal to resistance, but it is possible that the presence of its transglycosylase domain is important in the context of cognate PBPs. The genome sequence of CCCB revealed 36 recombination events, including deletion and acquisition of genes and repeat elements. A total of 78 genes were affected representing 67 kb or 3.3% of the genome, documenting extensive alterations scattered throughout the genome.

  1. The ratio of Mcl-1 and Noxa determines ABT737 resistance in squamous cell carcinoma of the skin.

    Science.gov (United States)

    Geserick, P; Wang, J; Feoktistova, M; Leverkus, M

    2014-09-11

    Tumour progression and therapy resistance in squamous cell carcinoma of the skin (SCC) is strongly associated with resistance to intrinsic mitochondrial apoptosis. We thus investigated the role of various anti-apoptotic Bcl-2 proteins for apoptosis protection in SCC using the BH3 agonist ABT737 that can overcome multidomain Bcl-2 protein protection. Sensitive SCC cells underwent rapid loss of mitochondrial membrane potential (MMP), subsequent apoptosis concomitant with caspase-3 activation and an early release of mitochondria-derived cytochrome c and smac/DIABLO. In contrast, ABT737 resistance in subsets of SCC cells was not explained by XIAP, important for protection from DR-induced apoptosis in SCC. Of note, ABT737 did not prime SCC cells to DR-induced apoptosis. Interestingly, the ratio of Mcl-1 and Noxa determined sensitivity to ABT737: loss of Mcl-1 rendered resistant cells sensitive to ABT737, whereas loss of Noxa promoted resistance in sensitive cells. In line, suppression of Mcl-1 by the pan-Bcl-2 inhibitor Obatoclax or overexpression of Noxa rendered resistant SCC cells sensitive to BH3 mimetics. Our data indicate that targeting of the Mcl-1/Noxa axis is important to overcome resistance to mitochondrial apoptosis in SCC. Therefore, combination treatment of ABT737 or derivatives with Mcl-1 inhibitors, or inducers of Noxa, may represent a novel option of targeted therapy in metastatic SCC of the skin.

  2. Determinants of antimicrobial resistance in Escherichia coli strains isolated from faeces and urine of women with recurrent urinary tract infections.

    Directory of Open Access Journals (Sweden)

    Casper D J den Heijer

    Full Text Available For women with recurrent urinary tract infections (rUTI, the contribution of antibiotic use versus patient-related factors in determining the presence of antimicrobial resistance in faecal and urinary Escherichia coli, obtained from the same patient population, has not been assessed yet. Within the context of the 'Non-antibiotic prophylaxis for recurrent urinary tract infections' (NAPRUTI study, the present study assessed determinants of antimicrobial resistance in E. coli isolated from urinary and faecal samples of women with rUTIs collected at baseline. Potential determinants of resistance were retrieved from self-administered questionnaires. From 434 asymptomatic women, 433 urinary and 424 faecal samples were obtained. E. coli was isolated from 146 (34% urinary samples and from 336 (79% faecal samples, and subsequently tested for antimicrobial susceptibility. Multivariable analysis showed trimethoprim/sulfamethoxazole (SXT use three months prior to inclusion to be associated with urine E. coli resistance to amoxicillin (OR 3.6, 95% confidence interval: 1.3-9.9, amoxicillin-clavulanic acid (OR 4.4, 1.5-13.3, trimethoprim (OR 3.9, 1.4-10.5 and SXT (OR 3.2, 1.2-8.5, and with faecal E. coli resistance to trimethoprim (OR 2.0, 1.0-3.7. The number of UTIs in the preceding year was correlated with urine E. coli resistance to amoxicillin-clavulanic acid (OR 1.11, 1.01-1.22, trimethoprim (OR 1.13, 1.03-1.23 and SXT (OR 1.10, 1.01-1.19. Age was predictive for faecal E. coli resistance to amoxicillin (OR 1.02, 1.00-1.03, norfloxacin and ciprofloxacin (both OR 1.03, 1.01-1.06. In conclusion, in women with rUTI different determinants were found for urinary and faecal E. coli resistance. Previous antibiotic use and UTI history were associated with urine E. coli resistance and age was a predictor of faecal E. coli resistance. These associations could best be explained by cumulative antibiotic use.

  3. Application of bioassay technique to determine onduty herbicide resistance in soil

    Science.gov (United States)

    Bakar, F. A. A.; Ismail, B. S.; Bajrai, F. S. M.

    2016-11-01

    A study was conducted to determine the resistance of OnDuty herbicide in paddy soil with different concentrations by using a broadleaf plant, Brassica juncea. The herbicide was used in the Clearfield® Production System that was adopted in Malaysia to overcome problems mainly caused by weedy rice. Evaluation of herbicide half-life was based on bioassay technique with different concentrations, i.e 0% (control), 50% (half dose), 100% (recommended dose) and 200% (double dose). The study was done in three replicates and followed the Complete Randomized Block Design (CRBD). Results showed that there was a correlation between the amount of herbicide doses and degradation period. The highest half-life value was shown by root inhibition in the double dose concentration of 33 days half-life, followed by the recommended dose with 23 days half-life. Meanwhile, the half dose treatment indicated a half-life value of 17 days for root and 11 days for shoot. Therefore, application of herbicides should follow the recommended dose as the degradation period will not be too long, hence providing maximum effectiveness of the herbicide to overcome weed infestation problems.

  4. Detection of Genes that Determine Maize Grain Quality Characteristics and Resistance to Stress Factors

    Directory of Open Access Journals (Sweden)

    Markovskyi, O.V.

    2014-01-01

    Full Text Available 200 experimental maize samples (Maize Company were examined for the presence of genes that determine the quality characteristics of grain (wx and fl-2 genes, herbicide (bar (pat, epsps genes and insect (cry-genes resistance. The total DNA was extracted from maize living plant tissue. Primers to detect wx, fl-2, bar (pat, mepsps, CP4 epsps, cry1A(b, cry1F, cry1A.105, mcry3A, cry2Ab2, cry3Bb1, cry34Ab1, cry35Ab1 genes were designed and selected. Multiplex and Touchdown PCR were worked out. PCR amplification of certain sequences was carried out. No transgenes (bar (pat, mepsps, CP4 epsps, cry1A(b, cry1F, cry1A.105, mcry3A, cry2Ab2, cry3Bb1, cry34Ab1, cry35Ab1 were found among 200 analyzed experimental maize samples. At the same time, fl-2 gene was found in 41 samples, wx gene was found in 192 analyzed samples.

  5. In situ determination of the static inductance and resistance of a plasma focus capacitor bank.

    Science.gov (United States)

    Saw, S H; Lee, S; Roy, F; Chong, P L; Vengadeswaran, V; Sidik, A S M; Leong, Y W; Singh, A

    2010-05-01

    The static (unloaded) electrical parameters of a capacitor bank are of utmost importance for the purpose of modeling the system as a whole when the capacitor bank is discharged into its dynamic electromagnetic load. Using a physical short circuit across the electromagnetic load is usually technically difficult and is unnecessary. The discharge can be operated at the highest pressure permissible in order to minimize current sheet motion, thus simulating zero dynamic load, to enable bank parameters, static inductance L(0), and resistance r(0) to be obtained using lightly damped sinusoid equations given the bank capacitance C(0). However, for a plasma focus, even at the highest permissible pressure it is found that there is significant residual motion, so that the assumption of a zero dynamic load introduces unacceptable errors into the determination of the circuit parameters. To overcome this problem, the Lee model code is used to fit the computed current trace to the measured current waveform. Hence the dynamics is incorporated into the solution and the capacitor bank parameters are computed using the Lee model code, and more accurate static bank parameters are obtained.

  6. Reproducible extracellular vesicle size and concentration determination with tunable resistive pulse sensing

    Directory of Open Access Journals (Sweden)

    Frank A. W. Coumans

    2014-12-01

    Full Text Available Introduction: The size of extracellular vesicles (EVs can be determined with a tunable resistive pulse sensor (TRPS. Because the sensing pore diameter varies from pore to pore, the minimum detectable diameter also varies. The aim of this study is to determine and improve the reproducibility of TRPS measurements. Methods: Experiments were performed with the qNano system (Izon using beads and a standard urine vesicle sample. With a combination of voltage and stretch that yields a high blockade height, we investigate whether the minimum detected diameter is more reproducible when we configure the instrument targeting (a fixed stretch and voltage, or (b fixed blockade height. Results: Daily measurements with a fixed stretch and voltage (n=102 on a standard urine sample show a minimum detected vesicle diameter of 128±19 nm [mean±standard deviation; coefficient of variation (CV 14.8%]. The vesicle concentration was 2.4·109±3.8·109 vesicles/mL (range 1.4·108–1.8·1010. When we compared setting a fixed stretch and voltage to setting a fixed blockade height on 3 different pores, we found a minimum detected vesicle diameter of 118 nm (CV 15.5%, stretch, and 123 nm (CV 4.5%, blockade height. The detected vesicle concentration was 3.2–8.2·108 vesicles/mL with fixed stretch and 6.4–7.8·108 vesicles/mL with fixed blockade height. Summary/conclusion: Pore-to-pore variability is the cause of the variation in minimum detected size when setting a fixed stretch and voltage. The reproducibility of the minimum detectable diameter is much improved by setting a fixed blockade height.

  7. Aspirin resistance in patients with acute coronary events: risk factors and prevalence as determined by whole blood multiple electrode aggregometry.

    Science.gov (United States)

    Ibrahim, O; Maskon, O; Darinah, Noor; Raymond, A A; Rahman, M M

    2013-11-01

    To determine the prevalence of aspirin resistance and associated risk factors based on biochemical parameters using whole blood multiple electrode aggregometry. The study was conducted at the outpatients cardiology clinic of the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from August 2011 to February 2012. Subjects on aspirin therapy were divided into two groups; first-ever coronary event and recurrent coronary event. Aspirin resistance was measured by a Multiplate(®) platelet analyser. A total of 74 patients (63 male, 11 female), with a mean age of 57.93 ± 74.1years were enrolled in the study. The patients were divided into two groups -first-ever coronary event group (n=52) and recurrent coronary event group (n=22). Aspirin resistance was observed in 12 out of 74 (16%) of the study patients, which consisted of 11 patients from the first-ever coronary event group and one patient from the recurrent coronary event group. There were significant correlations between aspirin resistance and age (r = -0.627; p = 0.029), total cholesterol (r = 0.608; p = 0.036) and LDL (r = 0.694; p = 0.012). LDL was the main predictor for area under the curve (AUC) for aspirin resistance. However, there was no association between aspirin resistance and cardiovascular events in both groups in this study. Aspirin resistance was observed in 16% of the study population. LDL was the major predictor of aspirin resistance. No association was found in the study between aspirin resistance with recurrent coronary events.

  8. Determination of viscous pressure losssand resistance upstream from the choke point from breathing gases of different physical properties

    DEFF Research Database (Denmark)

    Pedersen, O.F.

    2007-01-01

      Determination of viscous pressure loss and resistance upstream from the choke point from breathing gases of different physical properties Ole F. Pedersen, Institute of Public Health, University of Aarhus, Denmark. AIM. To determine viscous pressure losses and resistances  upstream to CP...... flows after breathing air,  20% oxygen in He and 20% oxygen in SF6 . For construction of MFSR-curves. Lung elastic recoil pressures were estimated  from ECCS reference values (Bull. europ. Physiopath. resp. 1983, 19  (suppl 5),28-31). The model described in the figure was used. The extrapolated flow FY...... 1, but certainly different from1.5, indicating predominant laminar flow upstream to CP. The upstream resistance is low, and lower than directly measured (JAP 83:1721-32,1997). This is a possibility if CP is more peripheral than assumed in that study.  ...

  9. Contribution of topoisomerase IV mutation to quinolone resistance in Mycoplasma genitalium.

    Science.gov (United States)

    Yamaguchi, Yuko; Takei, Masaya; Kishii, Ryuta; Yasuda, Mitsuru; Deguchi, Takashi

    2013-04-01

    The mechanism of quinolone resistance in Mycoplasma genitalium remains poorly understood due to difficulties with in vitro culture, especially of clinical isolates. In this study, to confirm the association between mutations in topoisomerases and antimicrobial susceptibilities to quinolones, ciprofloxacin-resistant mutant strains were selected using the cultivable type strain ATCC 33530. Sequence analysis revealed that the mutant strains harbored mutations in topoisomerase IV: Gly81Cys in ParC, Pro261Thr in ParC, or Asn466Lys in ParE. The MICs of all quinolones tested against the mutant strains were 2- to 16-fold higher than those against the wild-type strain. No cross-resistance was observed with macrolides or tetracyclines. We determined the inhibitory activities of quinolones against DNA gyrase and topoisomerase IV in order to investigate the correlation between antimicrobial susceptibility and inhibitory activity against the target enzymes, considered the primary targets of quinolones. Furthermore, using enzymatic analysis, we confirmed that Gly81Cys in the ParC quinolone resistance-determining region (QRDR) contributed to quinolone resistance. This is the first study to isolate quinolone-resistant mutant strains of M. genitalium harboring substitutions in the parC or parE gene in vitro and to measure the inhibitory activities against the purified topoisomerases of M. genitalium.

  10. Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing

    NARCIS (Netherlands)

    Abdolrasouli, A.; Rhodes, J.; Beale, M.A.; Hagen, F.; Rogers, T.R.; Chowdhary, A.; Meis, J.F.G.M.; Armstrong-James, D.; Fisher, M.C.

    2015-01-01

    A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole

  11. Interrogating the plasmidome to determine antibiotic resistance gene mobility within the swine fecal microbiota

    Science.gov (United States)

    The use of antibiotics in animal production has been highlighted as a key contributor to the increasing prevalence of antibiotic resistance in agroecosystems. Gram negative bacteria, such as the Enterobacteriaceae, are important facilitators for resistance gene dissemination in the environment and i...

  12. Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing

    NARCIS (Netherlands)

    Abdolrasouli, A.; Rhodes, J.; Beale, M.A.; Hagen, F.; Rogers, T.R.; Chowdhary, A.; Meis, J.F.G.M.; Armstrong-James, D.; Fisher, M.C.

    2015-01-01

    A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole anti

  13. Autosomal male determination in a spinosad-resistant housefly strain from Denmark

    DEFF Research Database (Denmark)

    Højland, Dorte H; Scott, Jeffrey G; Vagn Jensen, Karl-Martin

    2014-01-01

    BACKGROUND The housefly, Musca domestica L., is a global pest and has developed resistance to most insecticides applied for its control. The insecticide spinosad plays an important role in housefly control. Females of the Danish housefly strain 791spin are threefold more resistant to spinosad tha...

  14. Determination of resistance to Fusarium oxysporum f. sp. lycopersici via molecular markers in tomato lines

    Directory of Open Access Journals (Sweden)

    Hasan PINAR

    2013-06-01

    Full Text Available Fusarium oxysporum f. sp. lycopersici (FOL is common in tomato production areas where intensive production causes huge losses. Other plant species as well as biological and chemical control is insufficient to fight with the disease. The most effective solution to this problem is the use of resistant varieties. Fusarium oxysporum f. sp. lycopersici resistance has been transferred to most of the commercial varieties via classical and molecular marker-assisted selection (MAS. The use of molecular markers in the development of new varieties resistant to this disease, but not allelic race-specific resistance genes allows pyramiding to these genes at one cultivar. Markers which linked to resistance genes for FOL races (0, 1, 2 were improved and routinely used in tomato breeding programs. In this study, 450 pure tomato lines from the gene pool of tomato to the fore in terms of yield and some quality characteristics in Alata Horticultural Research Station Directorate were screened for Fusarium oxysporum f. sp. lycopersici (FOL resistance via developed SCAR and CAPS markers linked to I-1 and I-2. The 88 tomato lines had I-1 gene and 74 of tomato lines yielded band of homozygote resistance allele for I-2. Obtained results in this study show that developed molecular markers for Fusarium oxysporum f. sp. resistance can use easily for the developing of new cultivars.

  15. Novel homologs of the multiple resistance regulator marA in antibiotic-contaminated environments.

    Science.gov (United States)

    Castiglioni, Sara; Pomati, Francesco; Miller, Kristin; Burns, Brendan P; Zuccato, Ettore; Calamari, Davide; Neilan, Brett A

    2008-10-01

    Antibiotics are commonly detected in the environment as contaminants. Exposure to antibiotics may induce antimicrobial-resistance, as well as the horizontal transfer of resistance genes in bacterial populations. We selected the resistance gene marA, mediating resistance to multiple antibiotics, and explored its distribution in sediment and water samples from surface and sewage treatment waters. Ciprofloxacin and ofloxacin (fluoroquinolones), sulphamethoxazole (sulphonamide), erythromycin, clarythromycin, and spiramycin (macrolides), lincomycin (lincosamide), and oxytetracycline (tetracycline) were measured in the same samples to determine antibiotic contamination. Bacterial populations from environmental samples were challenged with antibiotics to identify resistant isolates. The gene marA was found in almost all environmental samples and was confirmed by PCR amplification in antibiotic-resistant colonies. 16S rDNA sequencing revealed that the majority of resistant isolates belonged to the Gram-positive genus Bacillus, not previously known to possess the regulator marA. We assayed the incidence of marA in environmental bacterial populations of Escherichia coli and Bacillus by quantitative real-time PCR in correlation with the levels of antibiotics. Phylogenetic analysis indicated the possible lateral acquisition of marA by Bacillus from Gram-negative Enterobacteriaceae revealing a novel marA homolog in Bacillus. Quantitative PCR assays indicate that the frequency of this gene in antropised environments seems to be related to bacterial exposure to water-borne antibiotics.

  16. Determinants of between-country differences in ambulatory antibiotic use and antibiotic resistance in Europe: a longitudinal observational study.

    Science.gov (United States)

    Blommaert, A; Marais, C; Hens, N; Coenen, S; Muller, A; Goossens, H; Beutels, P

    2014-02-01

    To identify key determinants explaining country-year variations in antibiotic use and resistance. Ambulatory antibiotic use data [in defined daily doses per 1000 inhabitants per day (DIDs)] for 19 European countries from 1999 to 2007 were collected, along with 181 variables describing countries in terms of their agriculture, culture, demography, disease burden, education, healthcare organization and socioeconomics. After assessing data availability, overlap and relevance, multiple imputation generalized estimating equations were applied with a stepwise selection procedure to select significant determinants of global antibiotic use (expressed in DIDs), relative use of subgroups (amoxicillin and co-amoxiclav) and resistance of Escherichia coli and Streptococcus pneumoniae. Relative humidity, healthcare expenditure proportional to gross domestic product, feelings of distrust, proportion of population aged >65 years and availability of treatment guidelines were associated with higher total antibiotic use expressed in DIDs. Restrictions on marketing activities towards prescribers, population density, number of antibiotics, educational attainment and degree of atheism were associated with a lower number of total DIDs used. Relative prescribing of amoxicillin and co-amoxiclav was mainly determined by healthcare system choices [e.g. general practitioner (GP) registration and restricted marketing]. Specific antibiotic use was found to be a significant determinant of resistance for some but not all drug/organism combinations. Incentives to stimulate GP gatekeeping were associated with lower levels of resistance, and life expectancy at age 65+ and atheism were associated with more resistance. Myriad factors influence antibiotic use and resistance at the country level and an important part of these can be modified by policy choices.

  17. Method of determination of temperature and heat resistance of the points on the integrated circuit crystal surface

    Directory of Open Access Journals (Sweden)

    Popov V. M.

    2011-12-01

    Full Text Available Method for visualization of integrated circuit (IC surface temperature by means of the liquid crystal film deposited from solution on its surface is proposed. The boundaries of local regions represent isotherms with corresponding phase transitions. On the base of isotherms positions and consumed by IC power thermal resistances between crystal and environment are determined.

  18. DETERMINATION OF THE SPECTRUM OF ANTIBIOTIC RESISTANCE GENES HAVE PHENOTYPIC RESISTANT STRAINS OF PARIETAL INTESTINAL MICROBIOTA IN RATS BY RT-PCR

    Directory of Open Access Journals (Sweden)

    Bukina Y.V.

    2016-06-01

    Full Text Available Introduction. The problem of formation of bacterial resistance to glycopeptides and beta-lactam antibiotics (cephalosporins and carbapenems are used worldwide for the treatment of severe community acquired and nosocomial infections, especially caused by polymicrobial flora has become global and is a major factor limiting the effectiveness of antibiotic therapy. In this regard, the study of genetic microbial resistance determinants allows not only to carry out an effective antibiotic therapy, but also to identify two main processes leading to the development of epidemiologically significant events: the introduction of the agent in the risk population from the outside and in situ pathogen (spontaneous genetic drift targeted restructuring of the population. Therefore, the aim of our study was to investigate the resistance genes to carbapenems, cephalosporins, glycopeptides have clinically important phenotype of resistant strains of microorganisms families Enterobacteriaceae, Pseudomonadaceae, Bacteroidaceae, Enterococcaceae, Peptostreptococcaceae. Materials and methods. As a material for PCR studies 712 phenotypically resistant strains of microorganisms isolated from 80 rats "Wistar" line in microbiological study microflora of the wall were used. During the investigation 474 isolates of bacteria of the family Enterobacteriaceae, 39 - Pseudomonadaceae, 71 - Bacteroidaceae, 96 - Enterococcaceae, 32 - Peptostreptococcaceae were studied. Isolation of DNA from bacteria in the study was performed using reagents "DNA-Express" ("Litekh", Russia. For the detection of resistance genes by PCR in real time (RT-PCR reagent kits "FLUOROPOL-RV" ("Litekh", Russia were used. During the experiment, the VIM genes, OXA-48, NDM, KPC, responsible for the resistance of microorganisms to carbapenems, CTX-M - resistance to cephalosporins, as well as genes Van A and van B, the development of resistance to glycopeptides (vancomycin and teicoplanin were determined. Analysis

  19. [Comparative study of intramacrophagic penetration and action on phagocytosis of a macrolide (spiramycin) and a fluoroquinolone (pefloxacin)].

    Science.gov (United States)

    Desnottes, J F; Diallo, N

    1990-04-01

    Antibiotic-phagocyte interaction is an important parameter involved in the elimination process of intracellular bacteria. The aim of the present study was to compare, using the same model, the phagocytic uptake and the intracellular activity of a macrolide and a quinolone. Accumulation of spiramycin and pefloxacin by guinea pig peritoneal macrophages (GPpM) was studied by means of a velocity-gradient centrifugation technique and expression of the ratio of the cellular concentration of antibiotic to the extracellular concentration (IC-EC). Three aspects of Staphylococcus aureus (209-P) phagocytosis were studied: 1) the phagocytic capacity (PC), mean number of ingested cocci by GpPM; 2) the phagocytic activity (PA), percentage of phagocyting GpPM with at least one bacterium; 3) the number of intracellular viable bacteria (IVB). Phagocytic capacity and phagocytic activity were determined by fluorescence microscopy using S. aureus stained with acridine orange. Intracellular viable bacteria were quantified by standard colony counts (CFU). The ratios of intracellular to extracellular concentration of pefloxacin and spiramycin are respectively 9 and 23. Pretreatment of guinea-pig peritoneal macrophages with 10 mg/l of each antibiotic does not modify phagocytic capacity and phagocytic activity, but lead to a decrease of intracellular viable bacteria. S. aureus pretreatment with 1/4 the MIC of each antibiotic increased phagocytic capacity and phagocytic activity and decrease intracellular viable bacteria (especially spiramycin).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Clinical Application of Development of Nonantibiotic Macrolides That Correct Inflammation-Driven Immune Dysfunction in Inflammatory Skin Diseases

    Directory of Open Access Journals (Sweden)

    Carmen Rodriguez-Cerdeira

    2012-01-01

    Full Text Available Background. Inflammation-driven immune dysfunction supports the development of several chronic human disorders including skin diseases. Nonantibiotic macrolides have anti-inflammatory and/or immunomodulatory activity that suggests the exploitation of these in the treatment of skin diseases characterized by inflammatory disorders. Materials and Methods. We performed an extensive review of the nonantibiotic macrolide literature published between 2005 and 2012, including cross-references of any retrieved articles. We also included some data from our own experience. Results. Calcineurin antagonists such as tacrolimus and ascomycins (e.g., pimecrolimus act by inhibiting the activation of the nuclear factor for activated T cells (NFAT. There are new applications for these macrolides that have been available for several years and have been applied to skin and hair disorders such as atopic dermatitis, oral lichen planus, vitiligo, chronic autoimmune urticaria, rosacea, alopecia areata, pyoderma gangrenosum, Behcet’s disease, neutrophilic dermatosis, and lupus erythematosus. We also reviewed new macrolides, like rapamycin, everolimus, and temsirolimus. In addition to the literature review, we report a novel class of nonantibiotic 14-member macrocycle with anti-inflammatory and immunomodulatory effects. Conclusions. This paper summarizes the most important clinical studies and case reports dealing with the potential benefits of nonantibiotic macrolides which have opened new avenues in the development of anti-inflammatory strategies in the treatment of cutaneous disorders.

  1. Antimicrobial Resistance Mechanisms among Campylobacter

    Science.gov (United States)

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  2. Antimicrobial resistance mechanisms among Campylobacter.

    Science.gov (United States)

    Wieczorek, Kinga; Osek, Jacek

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

  3. Determinants of quinolone resistance in Escherichia coli causing community-acquired urinary tract infection in Bejaia, Algeria.

    Science.gov (United States)

    Betitra, Yanat; Teresa, Vinuesa; Miguel, Viñas; Abdelaziz, Touati

    2014-06-01

    To investigate the mechanisms of quinolone resistance and the association with other resistance markers among Esherichia coli (E. coli) strains isolated from outpatient with urinary tract infection in north of Algeria. A total of 30 nalidixic acid-resistant E. coli isolates from outpatient with urinary tract infections from January 2010 to April 2011 in north of Algeria (Bejaia) were studied. Antimicrobial susceptibility was determined by disc diffusion assay, minimal inhibitory concentrations (MIC) of quinolone were determined by microdilution. Mutations in the Quinolone Resistance-Determining Region (QRDR) of gyrA and parC genes and screening for qnr (A, B and S) and bla genes were done by PCR and DNA sequencing. Most of the E. coli isolates (56.66%) were shown to carry mutations in gyrA and parC (gyrA: Ser83Leu + Asp87Asn and parC:Ser80Ile). While, 16.66% had only an alteration in gyrA: Ser83Leu. One isolate produced qnrB-like and two qnrS-like. Four isolates were CTX-M-15 producers associated with TEM-1 producing in one case. Co-expression of blaCTX-M-15 and qnrB was determined in one E. coli isolate. Our findings suggested the community emergence of gyrA and parC alterations and Qnr determinants that contributed to the development and spread of fluoroquinolone resistance in Algerian E. coli isolates. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  4. A multicopy suppressor screening approach as a means to identify antibiotic resistance determinant candidates in Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Moy Richard L

    2008-07-01

    Full Text Available Abstract Background Yersinia pestis is the causative agent of plague and a potential agent of bioterrorism and biowarfare. The plague biothreat and the emergence of multidrug-resistant plague underscore the need to increase our understanding of the intrinsic potential of Y. pestis for developing antimicrobial resistance and to anticipate the mechanisms of resistance that may emerge in Y. pestis. Identification of Y. pestis genes that, when overexpressed, are capable of reducing antibiotic susceptibility is a useful strategy to expose genes that this pathogen may rely upon to evolve antibiotic resistance via a vertical modality. In this study, we explored the use of a multicopy suppressor, Escherichia coli host-based screening approach as a means to expose antibiotic resistance determinant candidates in Y. pestis. Results We constructed a multicopy plasmid-based, Y. pestis genome-wide expression library of nearly 16,000 clones in E. coli and screened the library for suppressors of the antimicrobial activity of ofloxacin, a fluoroquinolone antibiotic. The screen permitted the identification of a transcriptional regulator-encoding gene (robAYp that increased the MIC99 of ofloxacin by 23-fold when overexpressed from a multicopy plasmid in Y. pestis. Additionally, we found that robAYp overexpression in Y. pestis conferred low-level resistance to many other antibiotics and increased organic solvent tolerance. Overexpression of robAYp also upregulated the expression of several efflux pumps in Y. pestis. Conclusion Our study provides proof of principle for the use of multicopy suppressor screening based on the tractable and easy-to-manipulate E. coli host as a means to identify antibiotic resistance determinant candidates of Y. pestis.

  5. Genome-Wide Identification of Antimicrobial Intrinsic Resistance Determinants in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Leng, Bingfeng; Haaber, Jakob

    2016-01-01

    The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired resistance has received considerable attention, relatively little is known of intrinsic resistance that allows bacteria to naturally withstand antimicrobials. Gene products......, atpA, atpB, atpG and atpH, reduced the minimum inhibitory concentration (MIC) of gentamicin 16-fold. To elucidate the potential of the screen, we examined treatment efficacy in the Galleria mellonella infection model. Gentamicin efficacy was significantly improved, when treating larvae infected...

  6. Resistance to infection with Eimeria vermiformis in mouse radiation chimeras is determined by donor bone-marrow cells

    Energy Technology Data Exchange (ETDEWEB)

    Joysey, H.S.; Wakelin, D.; Rose, M.E.

    1988-05-01

    The course of infection with Eimeria vermiformis was determined in BALB/b, BALB/c, and C57BL/10ScSn (B10) mice and in radiation chimeras prepared from the H-2-compatible BALB/b and B10 mice. The BALB strains, irrespective of H-2 haplotype, were resistant, the B10 mice were susceptible, and in the chimeras infection was characterized by the genotype of the donated bone-marrow cells and not by the phenotype of the recipient. Thus, the genetic control of relative resistance or susceptibility to infection with this parasite is expressed through bone-marrow-derived cells.

  7. Automated ribotyping and antibiotic resistance determining of Bacillus spp from conjunctiva of diabetic patients

    Directory of Open Access Journals (Sweden)

    Sertaç Argun Kıvanç

    2014-02-01

    Conclusion: Diabetic patients seem to be more prone to B. cereus infections than healthy individuals. It would be greatly beneficial to understand and recognize the prevalence of microorganisms and their resistance patterns for better outcome in ocular surgeries.

  8. Eradication of carriage with methicillin-resistant Staphylococcus aureus: determinants of treatment failure

    NARCIS (Netherlands)

    H.S.M. Ammerlaan; J.A.J.W. Kluytmans; H. Berkhout; A. Buiting; E.I.G.B. de Brauwer; P.J. van den Broek; P. van Gelderen; S.C.A.P. Leenders; A. Ott; C.J.J. Richter; L. Spanjaard; I.J.B. Spijkerman; F.H. van Tiel; G.P. Voorn; M.W.H. Wulf; J. van Zeijl; A. Troelstra; M.J.M. Bonten

    2011-01-01

    Background: Using data from an observational study in which the effectiveness of a guideline for eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage was evaluated, we identified variables that were associated with treatment failure. Methods: A multivariate logistic regression

  9. Screening of antibiotic resistance determinants in Gram-negative bacteria isolated from environmental reservoirs

    OpenAIRE

    Carvalho, Sofia Rêgo de, 1988-

    2011-01-01

    Tese de mestrado. Biologia (Microbiologia Aplicada). Universidade de Lisboa, Faculdade de Ciências, 2011 Antibiotics are one of the most successful forms of chemotherapy and saved million of lives placing most bacterial infectious diseases under control. However, this success has been compromised the continuous selective pressure exerted by antibiotics use has resulted in multi-resistance bacteria bearing resistance mechanisms to several antibiotics. Nowadays, there is an increased recogni...

  10. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance

    OpenAIRE

    Nishant A. Dafale; Uttam P. Semwal; Rupak K. Rajput; Singh, G. N.

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Resistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the pote...

  11. Determination of resistance to Fusarium oxysporum f. sp. lycopersici via molecular markers in tomato lines

    OpenAIRE

    PINAR, Hasan; ATA, Atilla; Keleş, Davut; Mutlu,Nedim; DENLİ, Nihal; ÜNLÜ, Mustafa

    2013-01-01

    Fusarium oxysporum f. sp. lycopersici (FOL) is common in tomato production areas where intensive production causes huge losses. Other plant species as well as biological and chemical control is insufficient to fight with the disease. The most effective solution to this problem is the use of resistant varieties. Fusarium oxysporum f. sp. lycopersici resistance has been transferred to most of the commercial varieties via classical and molecular marker-assisted selection (MAS). The use of molecu...

  12. The composition and compression of biofilms developed on ultrafiltration membranes determine hydraulic biofilm resistance.

    Science.gov (United States)

    Derlon, Nicolas; Grütter, Alexander; Brandenberger, Fabienne; Sutter, Anja; Kuhlicke, Ute; Neu, Thomas R; Morgenroth, Eberhard

    2016-10-01

    This study aimed at identifying how to improve the level of permeate flux stabilisation during gravity-driven membrane filtration without control of biofilm formation. The focus was therefore on understanding (i) how the different fractions of the biofilms (inorganics particles, bacterial cells, EPS matrix) influence its hydraulic resistance and (ii) how the compression of biofilms impacts its hydraulic resistance, i.e., can water head be increased to increase the level of permeate flux stabilisation. Biofilms were developed on ultrafiltration membranes at 88 and 284 cm water heads with dead-end filtration for around 50 days. A larger water head resulted in a smaller biofilm permeability (150 and 50 L m(-2) h(-1) bar(-1) for biofilms grown at 88 cm and 284 cm water head, respectively). Biofilms were mainly composed of EPS (>90% in volume). The comparison of the hydraulic resistances of biofilms to model fouling layers indicated that most of the hydraulic resistance is due to the EPS matrix. The compressibility of the biofilm was also evaluated by subjecting the biofilms to short-term (few minutes) and long-term variations of transmembrane pressures (TMP). A sudden change of TMP resulted in an instantaneous and reversible change of biofilm hydraulic resistance. A long-term change of TMP induced a slow change in the biofilm hydraulic resistance. Our results demonstrate that the response of biofilms to a TMP change has two components: an immediate variation of resistance (due to compression/relaxation) and a long-term response (linked to biofilm adaptation/growth). Our results provide relevant information about the relationship between the operating conditions in terms of TMP, the biofilm structure and composition and the resulting biofilm hydraulic resistance. These findings have practical implications for a broad range of membrane systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Distribution of putative virulence genes and antimicrobial drug resistance in Vibrio harveyi

    Digital Repository Service at National Institute of Oceanography (India)

    Parvathi, A.; Mendez, D.; Anto, C.

    . monodon hatchery and grow out systems, where they can infect post larvae causing large scale mortalities [3, 4]. Infection with biofilm forming V. harveyi resistant to multiple antibiotics has been previously reported from India [5]. The pathogenic... resistant to neomycin. Since kanamycin, streptomycin and neomycin belong to aminoglycoside group of antibiotics, the resistance to multiple antibiotics of the same class is expected. Similarly, resistance to macrolids erythromycin and azithromycin, β...

  14. Emergence of a Streptococcus pneumoniae clinical isolate highly resistant to telithromycin and fluoroquinolones.

    Science.gov (United States)

    Faccone, Diego; Andres, Patricia; Galas, Marcelo; Tokumoto, Marta; Rosato, Adriana; Corso, Alejandra

    2005-11-01

    Streptococcus pneumoniae is a major pathogen causing community-acquired pneumonia and acute bronchitis. Macrolides, fluoroquinolones (FQs), and, recently, telithromycin (TEL) constitute primary therapeutic options, and rare cases of resistance have been reported. In this report, we describe the emergence of an S. pneumoniae clinical isolate with high-level TEL resistance (MIC, 256 microg/ml) and simultaneous resistance to FQs. Ongoing studies are oriented to elucidate the precise mechanism of resistance to TEL.

  15. Enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical isolates of Shigella due to synergism between efflux pump expression & mutations in quinolone resistance determining region

    Directory of Open Access Journals (Sweden)

    Neelam Taneja

    2015-01-01

    Full Text Available Background & objectives: There is a worldwide emergence of fluoroquinolone resistance in Shigella species. To understand the molecular mechanisms associated with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant strains and laboratory-induced spontaneous mutants of Shigella spp. were used and the relative contributions of acrAB-tolC efflux pumps, gyrase and topoisomerase target gene mutations towards fluoroquinolone resistance were determined. Methods: Eight Shigella flexneri and six S. dysenteriae clinical isolates were studied. Three consecutive mutants resistant to ciprofloxacin for S. flexneri SFM1 (≥0.25 µg/ml, SFM2 (≥4 µg/ml and SFM3 (≥32 µg/ml were selected in 15 steps from susceptible isolates by serial exposure to increasing concentrations of nalidixic acid and ciprofloxacin. Similarly, two mutants for S. dysenteriae SDM1 (≥0.25 µg/ml and SDM2 (≥4 µg/ml were selected in eight steps. After PCR amplification sequence analyses of gyrase and topoisomerase target genes were performed. Expression of efflux genes acrA, acrB, acrR and tolC was measured using real-time PCR. Results: Mutations were observed in gyrA Ser [83]→Leu, Asp [87]→Asn/Gly, Val [196]→Ala and in parC Phe [93]→Val, Ser [80]→Ile, Asp [101]→Glu and Asp [110]→Glu. Overall, acrA and acrB overexpression was associated with fluoroquinolone resistance ( p0 <0.05; while tolC and acrR expression levels did not. Interpretation & conclusions: Fluoroquinolone resistance in Shigella spp. is the end product of either a single or a combination of mutations in QRDRs and/ or efflux activity. Novel polymorphisms were observed at Val [196]→Ala in gyrA in clinical isolates and Phe [93]→Val, Asp [101]→Glu, Asp [110]→Glu and in parC in majority of laboratory-grown mutants.

  16. 13-Deoxytedanolide, a marine sponge-derived antitumor macrolide, binds to the 60S large ribosomal subunit.

    Science.gov (United States)

    Nishimura, Shinichi; Matsunaga, Shigeki; Yoshida, Minoru; Hirota, Hiroshi; Yokoyama, Shigeyuki; Fusetani, Nobuhiro

    2005-01-17

    13-Deoxytedanolide is a potent antitumor macrolide isolated from the marine sponge Mycale adhaerens. In spite of its remarkable activity, the mode of action of 13-deoxytedanolide has not been elucidated. [11-3H]-(11S)-13-Deoxydihydrotedanolide derived from the macrolide was used for identifying the target molecule from the yeast cell lysate. Fractionation of the binding protein revealed that the labeled 13-deoxytedanolide derivative strongly bound to the 80S ribosome as well as to the 60S large subunit, but not to the 40S small subunit. In agreement with this observation, 13-deoxytedanolide efficiently inhibited the polypeptide elongation. Interestingly, competition studies demonstrated that 13-deoxytedanolide shared the binding site on the 60S large subunit with pederin and its marine-derived analogues. These results indicate that 13-deoxytedanolide is a potent protein synthesis inhibitor and is the first macrolide to inhibit the eukaryotic ribosome.

  17. CONFLEX/MM3 search/minimization study of the conformations of the macrolide antibiotic tylosin

    Science.gov (United States)

    Ivanov, Petko M.

    2002-03-01

    The conformations of the 16-membered macrolide antibiotic tylosin were studied with the MM3 force field. The CONFLEX conformational search procedure was used for finding low-energy conformations. The computed data are indicative for the existence of several conformations in equilibrium. The intramolecular hydrogen bonds play an important role for the preferred geometry of the macroring and the conformations of the side chains. The present results provide further insight into the most probable conformations of tylosin and compliment an earlier analysis based on NMR techniques.

  18. Synthesis of Key Fragments of Amphidinolide Q — A Cytotoxic 12-membered Macrolide

    Directory of Open Access Journals (Sweden)

    Kohei Kawa

    2011-06-01

    Full Text Available b-Hydroxy aldehyde and alkyl ketone moieties were effectively synthesized as key intermediates of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp.. The asymmetric center of the former derivative was produced by Sharpless asymmetric epoxidation, followed by E-selective 1,4-addition to give the sp2 methyl group. Derivatization of the L-ascorbic acid derivative by Evans asymmetric alkylation and Peterson olefination provided the latter intermediate. The coupling reaction of the segments was examined.

  19. In Vitro Capability of Faropenem To Select for Resistant Mutants of Streptococcus pneumoniae and Haemophilus influenzae▿ †

    Science.gov (United States)

    Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; Dewasse, Bonifacio; Beachel, Linda; Ednie, Lois; Appelbaum, Peter C.

    2008-01-01

    When tested against nine strains of pneumococci and six of Haemophilus influenzae of various resistotypes, faropenem failed to select for resistant mutants after 50 days of consecutive subculture in subinhibitory concentrations. Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones. PMID:18086853

  20. A method to rapidly determine the sintering process parameters of powder metallurgy by real-time resistivity monitoring

    Science.gov (United States)

    Xiao, Zhen; Liu, Huanchao; Geng, Haoran; Leng, Jinfeng

    2016-10-01

    A new method, which is called the resistivity method, is applied in this paper to explore the optimum sintering parameters of powder metallurgy (PM) since general methods are always labor-intensive and time-consuming. This method can probe the resistivity of the powder metallurgy samples in real-time during the sintering process, to quickly estimate the change of the relative density, which consequently determine the properties of the sintered item. As an example, in this paper, copper/tungsten carbide (Cu/WC) composites and pure aluminum (Al) powder compacts are experimentally considered. As a result, for the Cu/WC composites, the highest value of relative density appeared at the holding time of 50 min where the sample has the lowest resistivity. For the Al compacts, the optimum sintering temperature is 450 °C, and the longer the holding time the better.

  1. Recognition determinants for proteins and antibiotics within 23S rRNA

    DEFF Research Database (Denmark)

    Douthwaite, Stephen Roger; Voldborg, Bjørn Gunnar Rude; Hansen, Lykke Haastrup

    1995-01-01

    Ribosomal RNAs fold into phylogenetically conserved secondary and tertiary structures that determine their function in protein synthesis. We have investigated Escherichia coli 23S rRNA to identify structural elements that interact with antibiotic and protein ligands. Using a combination of molecu......Ribosomal RNAs fold into phylogenetically conserved secondary and tertiary structures that determine their function in protein synthesis. We have investigated Escherichia coli 23S rRNA to identify structural elements that interact with antibiotic and protein ligands. Using a combination......-proteins L10.(L12)4 and L11 and is inhibited by interaction with the antibiotic thiostrepton. The peptidyltransferase center within domain V is inhibited by macrolide, lincosamide, and streptogramin B antibiotics, which interact with the rRNA around nucleotide A2058. Drug resistance is conferred by mutations...

  2. Experimental determination of the electrical resistivity of iron at Earth’s core conditions

    Science.gov (United States)

    Ohta, Kenji; Kuwayama, Yasuhiro; Hirose, Kei; Shimizu, Katsuya; Ohishi, Yasuo

    2016-06-01

    Earth continuously generates a dipole magnetic field in its convecting liquid outer core by a self-sustained dynamo action. Metallic iron is a dominant component of the outer core, so its electrical and thermal conductivity controls the dynamics and thermal evolution of Earth’s core. However, in spite of extensive research, the transport properties of iron under core conditions are still controversial. Since free electrons are a primary carrier of both electric current and heat, the electron scattering mechanism in iron under high pressure and temperature holds the key to understanding the transport properties of planetary cores. Here we measure the electrical resistivity (the reciprocal of electrical conductivity) of iron at the high temperatures (up to 4,500 kelvin) and pressures (megabars) of Earth’s core in a laser-heated diamond-anvil cell. The value measured for the resistivity of iron is even lower than the value extrapolated from high-pressure, low-temperature data using the Bloch-Grüneisen law, which considers only the electron-phonon scattering. This shows that the iron resistivity is strongly suppressed by the resistivity saturation effect at high temperatures. The low electrical resistivity of iron indicates the high thermal conductivity of Earth’s core, suggesting rapid core cooling and a young inner core less than 0.7 billion years old. Therefore, an abrupt increase in palaeomagnetic field intensity around 1.3 billion years ago may not be related to the birth of the inner core.

  3. Heat resistance of viable but non-culturable Escherichia coli cells determined by differential scanning calorimetry.

    Science.gov (United States)

    Castro-Rosas, Javier; Gómez-Aldapa, Carlos Alberto; Villagómez Ibarra, José Roberto; Santos-López, Eva María; Rangel-Vargas, Esmeralda

    2017-10-16

    Several reports have suggested that the viable but non-culturable (VBNC) state is a resistant form of bacterial cells that allows them to remain in a dormant form in the environment. Nevertheless, studies on the resistance of VBNC bacterial cells to ecological factors are limited, mainly because techniques that allow this type of evaluation are lacking. Differential scanning calorimetry (DSC) has been used to study the thermal resistance of culturable bacteria but has never been used to study VBNC cells. In this work, the heat resistance of Escherichia coli cells in the VBNC state was studied using the DSC technique. The VBNC state was induced in E. coli ATCC 25922 by suspending bacterial cells in artificial sea water, followed by storage at 3 ± 2°C for 110 days. Periodically, the behaviour of E. coli cells was monitored by plate counts, direct viable counts and DSC. The entire bacterial population entered the VBNC state after 110 days of storage. The results obtained with DSC suggest that the VBNC state does not confer thermal resistance to E. coli cells in the temperature range analysed here. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Antibiotic resistance analysis of fecal coliforms to determine fecal pollution sources in a mixed-use watershed.

    Science.gov (United States)

    Burnes, Brian S

    2003-06-01

    Antibiotic resistance analysis was performed on fecal coliform (FC) bacteria from a mixed-use watershed to determine the source, human or nonhuman, of fecal coliform contamination. The study consisted of discriminant analysis of antibiotic resistance patterns generated by exposure to four concentrations of six antibiotics (ampicillin, gentamicin sulfate, kanamycin, spectinomycin dihydrochloride, streptomycin sulfate, and tetracycline hydrochloride). A reference database was constructed from 1125 fecal coliform isolates from the following sources: humans, domestic animals (cats and dogs), agricultural animals (chickens, cattle, and horses), and wild animals. Based on similar antibiotic resistance patterns, cat and dog isolates were grouped as domestic animals and horse and cattle isolates were grouped as livestock. The resulting average rate of correct classification (ARCC) for human and nonhuman isolates was 94%. A total of 800 FC isolates taken from the watershed during either a dry event or a wet event were classified according to source. Human sources contribute a majority (> 50%) of the baseflow FC isolates found in the watershed in urbanized areas. Chicken and livestock sources are responsible for the majority of the baseflow FC isolates found in the rural reaches of the watershed. Stormwater introduces FC isolates from domestic (approximately 16%) and wild (approximately 21%) sources throughout the watershed and varying amounts (up to 60%) from chicken and livestock sources. These results suggest that antibiotic resistance patterns of FC may be used to determine sources of fecal contamination and aid in the direction of water quality improvement.

  5. Distribution of virulence determinants among antimicrobial-resistant and antimicrobial-susceptible Escherichia coli implicated in urinary tract infections

    Directory of Open Access Journals (Sweden)

    SAM Stephenson

    2016-01-01

    Full Text Available Introduction: Uropathogenic Escherichia coli (UPEC rely on the correlation of virulence expression with antimicrobial resistance to persist and cause severe urinary tract infections (UTIs. Objectives: We assessed the virulence pattern and prevalence among UPEC strains susceptible and resistant to multiple antimicrobial classes. Methods: A total of 174 non-duplicate UPEC strains from patients with clinically significant UTIs were analysed for susceptibility to aminoglycoside, antifolate, cephalosporin, nitrofuran and quinolone antibiotics for the production of extended-spectrum β-lactamases and for the presence of six virulence determinants encoding adhesins (afimbrial, Type 1 fimbriae, P and S-fimbriae and toxins (cytotoxic necrotising factor and haemolysin. Results: Relatively high resistance rates to nalidixic acid, ciprofloxacin, cephalothin and trimethoprim-sulfamethoxazole (82%, 78%, 62% and 59%, respectively were observed. Fourteen distinct patterns were identified for the virulence determinants such as afaBC, cnfI, fimH, hylA, papEF and sfaDE. The toxin gene, cnfI (75.3%, was the second most prevalent marker to the adhesin, fimH (97.1%. The significant association of sfaDE/hylA (P < 0.01 among antimicrobial resistant and susceptible strains was also observed notwithstanding an overall greater occurrence of virulence factors among the latter. Conclusions: This study provides a snapshot of UPEC complexity in Jamaica and highlights the significant clonal heterogeneity among strains. Such outcomes emphasise the need for evidence-based strategies in the effective management and control of UTIs.

  6. Determination of renal vascular resistance in dogs with diabetes mellitus and hyperadrenocorticism.

    Science.gov (United States)

    Novellas, R; de Gopegui, R Ruiz; Espada, Y

    2008-11-15

    In dogs, diabetes mellitus and hyperadrenocorticism are causes of hypertension associated with increases in vascular peripheral resistance. In human patients, the renal resistive index (ri) and pulsatility index (pi) are related to hypertension and diabetes and are used as indicators of disease severity. In this study the renal vascular resistance was measured in 12 dogs with hyperadrenocorticism, three with diabetes mellitus and four with both conditions, and the possible relationships between the two indices, blood pressure and biochemical parameters were investigated. Hypertension, defined as a systolic blood pressure more than 150 mmHg, was recorded in two of the dogs with hyperadrenocorticism and three of the dogs with hyperadrenocorticism and diabetes. The overall mean values for ri, pi and systolic blood pressure were higher in the diseased group of dogs than in 27 healthy dogs, and both indices were correlated with blood glucose concentration.

  7. Virulence determinants, drug resistance and mobile genetic elements of Laribacter hongkongensis: a genome-wide analysis

    Directory of Open Access Journals (Sweden)

    Lau Susanna KP

    2011-04-01

    Full Text Available Abstract Background Laribacter hongkongensis is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes in its genome related to the various steps in the infective process, drug resistance and mobile genetic elements. Results For acid and bile resistance, L. hongkongensis possessed a urease gene cassette, two arc gene clusters and bile salt efflux systems. For intestinal colonization, it possessed a putative adhesin of the autotransporter family homologous to those of diffusely adherent Escherichia coli (E. coli and enterotoxigenic E. coli. To evade from host defense, it possessed superoxide dismutase and catalases. For lipopolysaccharide biosynthesis, it possessed the same set of genes that encode enzymes for synthesizing lipid A, two Kdo units and heptose units as E. coli, but different genes for its symmetrical acylation pattern, and nine genes for polysaccharide side chains biosynthesis. It contained a number of CDSs that encode putative cell surface acting (RTX toxin and hemolysins and intracellular cytotoxins (patatin-like proteins and enzymes for invasion (outer membrane phospholipase A. It contained a broad variety of antibiotic resistance-related genes, including genes related to β-lactam (n = 10 and multidrug efflux (n = 54. It also contained eight prophages, 17 other phage-related CDSs and 26 CDSs for transposases. Conclusions The L. hongkongensis genome possessed genes for acid and bile resistance, intestinal mucosa colonization, evasion of host defense and cytotoxicity and invasion. A broad variety of antibiotic resistance or multidrug resistance genes, a high number of prophages, other phage-related CDSs and CDSs for transposases, were also identified.

  8. Effects of in-feed copper and tylosin supplementations on copper and antimicrobial resistance in faecal enterococci of feedlot cattle.

    Science.gov (United States)

    Amachawadi, R G; Scott, H M; Aperce, C; Vinasco, J; Drouillard, J S; Nagaraja, T G

    2015-06-01

    The objective was to investigate whether in-feed supplementation of copper, at elevated level, co-selects for macrolide resistance in faecal enterococci. The study was conducted in cattle (n = 80) with a 2 × 2 factorial design of copper (10 or 100 mg kg(-1) of feed) and tylosin (0 or 10 mg kg(-1) of feed). Thirty-seven isolates (4·6%; 37/800) of faecal enterococci were positive for the tcrB and all were Enterococcus faecium. The prevalence was higher among cattle fed diets with copper and tylosin (8·5%) compared to control (2·0%), copper (4·5%) and tylosin (3·5%) alone. All tcrB-positive isolates were positive for erm(B) and tet(M) genes. Median copper minimum inhibitory concentrations (MICs) for tcrB-positive and tcrB-negative enterococci were 20 and 4 mmol l(-1) , respectively. Feeding of elevated dietary copper and tylosin alone or in combination resulted in an increased prevalence of tcrB and erm(B)-mediated copper and tylosin-resistant faecal enterococci in feedlot cattle. In-feed supplementation of elevated dietary copper has the potential to co-select for macrolide resistance. Further studies are warranted to investigate the factors involved in maintenance and dissemination of the resistance determinants and their co-selection mechanism in relation to feed-grade antimicrobials' usage in feedlot cattle. © 2015 The Society for Applied Microbiology.

  9. Características de la resistencia antimicrobiana de una colección clínica de Strptococcus pyogenes Antimicrobial resistance of Streptococcus pyogenes clinical strains

    Directory of Open Access Journals (Sweden)

    Romeo S. Rodríguez

    2000-06-01

    Full Text Available OBJETIVO: Determinar la susceptibilidad antimicrobiana de Streptococcus pyogenes con el fin de estimar la prevalencia de los fenotipos de resistencia a los macrólidos. MATERIAL Y MÉTODOS: Se realizó un estudio de tipo transversal, en 1999, en el que se evaluaron 100 cepas de S. pyogenes, aislados en el Hospital Infantil de México Federico Gómez, en el lapso comprendido entre 1992 y 1998, procedentes de niños con faringoamigdalitis, conservadas en congelación en el laboratorio de bacteriología hasta su procesamiento. Se determinó la susceptibilidad antimicrobiana a algunos beta-lactámicos, macrólidos y clindamicina. La resistencia a eritromicina se probó por medio de la prueba de difusión de doble disco. Se calcularon medidas de tendencia central. RESULTADOS: Todas las cepas fueron sensibles a los beta-lactámicos y clindamicina; 16% fueron resistentes a los macrólidos, y todas correspondieron al fenotipo M. CONCLUSIONES: Es conveniente realizar periódicamente pruebas de escrutinio para conocer los posibles cambios en los patrones de sensibilidad estreptocócica.OBJECTIVE: To determine the antibiotic susceptibility of recent isolates of Streptococcus pyogenes and to evaluate the prevalence of macrolide-resistant phenotypes. MATERIAL AND METHODS: In 1999, we conducted a cross-sectional study at Mexico Children's Hospital "Federico Gomez",