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Sample records for fluoroquinolone resistance genes

  1. 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.

  2. Occurrence of fluoroquinolones and fluoroquinolone-resistance genes in the aquatic environment.

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    Adachi, Fumie; Yamamoto, Atsushi; Takakura, Koh-Ichi; Kawahara, Ryuji

    2013-02-01

    Fluoroquinolones (FQs) have been detected in aquatic environments in several countries. Long-term exposure to low levels of antimicrobial agents provides selective pressure, which might alter the sensitivity of bacteria to antimicrobial agents in the environment. Here, we examined FQ levels and the resistance of Escherichia coli (E. coli) to FQs by phenotyping and genotyping. In the aquatic environment in Osaka, Japan, ciprofloxacin, enoxacin, enfloxacin, lomefloxacin, norfloxacin, and ofloxacin were detected in concentrations ranging from 0.1 to 570 ng L(-1). FQ-resistant E. coli were also found. Although no obvious correlation was detected between the concentration of FQs and the presence of FQ-resistant E. coli, FQ-resistant E. coli were detected in samples along with FQs, particularly ciprofloxacin and ofloxacin. Most FQ-resistant E. coli carried mutations in gyrA, parC, and parE in quinolone resistance-determining regions. No mutations in gyrB were detected in any isolates. Amino acid changes in these isolates were quite similar to those in clinical isolates. Six strains carried the plasmid-mediated quinolone resistance determinant qnrS1 and expressed low susceptibility to ciprofloxacin and nalidixic acid: the minimum inhibitory concentrations ranged from 0.25 μg mL(-1) for ciprofloxacin, and from 8 to 16 μg mL(-1) for nalidixic acid. This finding confirmed that plasmids containing qnr genes themselves did not confer full resistance to quinolones. Because plasmids are responsible for much of the horizontal gene transfer, these genes may transfer and spread in the environment. To our knowledge, this is the first report of plasmid-mediated quinolone resistance determinant qnrS1 in the aquatic environment, and this investigation provides baseline data on antimicrobial resistance profiles in the Osaka area.

  3. Fluoroquinolone-induced gene transfer in multidrug-resistant Salmonella

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    Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity. Bacterial exposure to fluoroquinolones can cause DNA damage and induce a bacterial SOS response to stimulate repair of damaged DNA. Certain prophages (integrated in bacterial chromosomes) ...

  4. Fluoroquinolone resistance in Campylobacter

    Science.gov (United States)

    Fluoroquinolone-resistant Campylobacter jejuni and C. coli are common in animals because of the use of fluoroquinolones as therapeutic agents in animal husbandry, particularly in chickens and other poultry. Campylobacter is a commensal in poultry, and therefore, poultry and poultry products are the...

  5. Characterization of a mutation in the parE gene that confers fluoroquinolone resistance in Streptococcus pneumoniae.

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    Perichon, B; Tankovic, J; Courvalin, P

    1997-01-01

    We report a mutation in the parE genes of two in vitro mutants of Streptococcus pneumoniae responsible for low-level resistance to fluoroquinolones. Sequential acquisition of mutations in parE and gyrA leads to higher levels of resistance. This confirms that topoisomerase IV is the primary target of fluoroquinolones in S. pneumoniae.

  6. Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella.

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    Bearson, Bradley L; Brunelle, Brian W

    2015-08-01

    Fluoroquinolones are broad-spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity, which can cause DNA damage and result in bacterial cell death. In response to DNA damage, bacteria induce an SOS response to stimulate DNA repair. However, the SOS response may also induce prophage with production of infectious virions. Salmonella strains typically contain multiple prophages, and certain strains including phage types DT120 and DT104 contain prophage that upon induction are capable of generalised transduction. In this study, strains of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium DT120 and DT104 were exposed to fluoroquinolones important for use in human and veterinary disease therapy to determine whether prophage(s) are induced that could facilitate phage-mediated gene transfer. Cultures of MDR S. Typhimurium DT120 and DT104 containing a kanamycin resistance plasmid were lysed after exposure to fluoroquinolones (ciprofloxacin, enrofloxacin and danofloxacin). Bacterial cell lysates were able to transfer the plasmid to a recipient kanamycin-susceptible Salmonella strain by generalised transduction. In addition, exposure of DT120 to ciprofloxacin induced the recA gene of the bacterial SOS response and genes encoded in a P22-like generalised transducing prophage. This research indicates that fluoroquinolone exposure of MDR Salmonella can facilitate horizontal gene transfer, suggesting that fluoroquinolone usage in human and veterinary medicine may have unintended consequences, including the induction of phage-mediated gene transfer from MDR Salmonella. Stimulation of gene transfer following bacterial exposure to fluoroquinolones should be considered an adverse effect, and clinical decisions regarding antibiotic selection for infectious disease therapy should include this potential risk. Published by Elsevier B.V.

  7. Cloning and Sequence Analysis of gyrB Gene of Fluoroquinolones-resistant Salmonella Isolated from Chickens

    Institute of Scientific and Technical Information of China (English)

    LIU Fang-ping; TONG Heng-min; LI Chang-wen

    2005-01-01

    Nine strains resistant to five fluoroquinolones (Ciprofloxacin, Ofloxacin, Enrofloxacin, Danofloxacin,Sarafloxacin) were isolated from clinical samples and extracted the chromosomal DNA of these strains. Designed primers to amplify the Quinolone-resistance-determining region (QRDR) of gyrB gene, then the PCR products were cloned and the sequence was analyzed. In comparison with the standarded strain NCTC5776, no mutation was found in the QRDR of gyrB gene of all resistant strains. The result indicated that the QRDR of gyrB has little relationship with fluoroquinolone resistance to salmonella.

  8. Mutation in grlA and norA genes in Fluoroquinolone resistant strains of S. aureus

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    Leila Asadpour

    2017-03-01

    Full Text Available Background and Aim. Fluoroquinolones are one of the most commonly used broad spectrum classes of antibiotics with increasingly drug resistance. The present study was aimed to investigate mutation in grlA and norA genes in fluoroquinolone resistant strains of   S. aureus. Materials and methods: In this cross-sectional study, 85 strains of S. aureus was isolated from different clinical samples by biochemical and molecular tests. Susceptibility to fluoroquinolones in the isolates was tested by the disc diffusion method and broth macrodilution method was used to investigate ciprofloxacin minimum inhibitory concentration. Mutations in the quinolone resistance-determining regions (QRDR in chromosomal grlA gene and norA gen mutations was investigated in quinolone-resistant S. aureus isolates, by PCR amplification of grlA and norA genes and sequencing.   Results. Out of 85 tested bacteria, 17 (20% isolates recognized as fluoroquinolones resistant. Minimum inhibitory concentration of ciprofluxacin for resistant isolates ranged between 32 to 512 µg/ml. Two single point mutations S80F and P144S and one double mutation S80F + P144S were determined in grlA gene of Fluoroquinolone resistant strains of S. aureus  but none of resistant strains showed mutation in norA gene. Conclusion. The obtained results demonstrated that grlA gene mutation is one of the most important mechanisms of resistance to ciprofloxacin in clinical isolates of S. aureus in Rasht and most of resistant isolates acquired common mutation in codon 80. Key Words: Fluoroquinolone, S. aureus, grlA , norA

  9. The co-selection of fluoroquinolone resistance genes in the gut flora of Vietnamese children.

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    Le Thi Minh Vien

    Full Text Available Antimicrobial consumption is one of the major contributing factors facilitating the development and maintenance of bacteria exhibiting antimicrobial resistance. Plasmid-mediated quinolone resistance (PMQR genes, such as the qnr family, can be horizontally transferred and contribute to reduced susceptibility to fluoroquinolones. We performed an observational study, investigating the copy number of PMQR after antimicrobial therapy. We enrolled 300 children resident in Ho Chi Minh City receiving antimicrobial therapy for acute respiratory tract infections (ARIs. Rectal swabs were taken on enrollment and seven days subsequently, counts for Enterobacteriaceae were performed and qnrA, qnrB and qnrS were quantified by using real-time PCR on metagenomic stool DNA. On enrollment, we found no association between age, gender or location of the participants and the prevalence of qnrA, qnrB or qnrS. Yet, all three loci demonstrated a proportional increase in the number of samples testing positive between day 0 and day 7. Furthermore, qnrB demonstrated a significant increase in copy number between paired samples (p<0.001; Wilcoxon rank-sum, associated with non-fluoroquinolone combination antimicrobial therapy. To our knowledge, this is the first study describing an association between the use of non-fluoroquinolone antimicrobials and the increasing relative prevalence and quantity of qnr genes. Our work outlines a potential mechanism for the selection and maintenance of PMQR genes and predicts a strong effect of co-selection of these resistance determinants through the use of unrelated and potentially unnecessary antimicrobial regimes.

  10. Charcterization of Type Ⅱ Topoisomerase Gene Mutations in Clinical Isolates of Mycoplasma Hominis Resistant to Fluoroquinolones

    Institute of Scientific and Technical Information of China (English)

    吴移谋; 张文波; 姚艳冰

    2002-01-01

    Objective: To analyze type Ⅱ topoisomerase genes inclinical isolates of fluoroquinolone-resistant Mycoplasmahominis. Methods: Eight isolates of M.hominis cross resistant to 6fluoroquinolones were selected from 103 clinical strains ofM.hominis using a broth microdilution method. Type IItopoisomerase genes were amplified by PCR and directlysequenced. Nucleotide sequences were compared to sequencesfrom a susceptible strain (M.hominis PG2I). Results: MICs of resistant Mh isolates were 4- to 512-fold higher than MICs from the susceptible reference strain.Sequence comparison revealed a C to T change at 113nt ingyrA QRDR led to the substitution of Ser83 by Leucine and noamino acid change in gyrB. A change of G to T at 134nt inparC QRDR led to the substitution of Ser80 by Isoleucine anda G to A change at 70nt in parE QRDR led to the substitutionof Aspartic acid by Asparagine. Conclusion: These results suggest that a C to T change atll3nt in gyrA, a G to T change at 134nt in parC and a G to Achange at 70nt in patrE are associated with fluoroquinoloneresistance of M.hominis.

  11. A novel method to discover fluoroquinolone antibiotic resistance (qnr genes in fragmented nucleotide sequences

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    Boulund Fredrik

    2012-12-01

    Full Text Available Abstract Background Broad-spectrum fluoroquinolone antibiotics are central in modern health care and are used to treat and prevent a wide range of bacterial infections. The recently discovered qnr genes provide a mechanism of resistance with the potential to rapidly spread between bacteria using horizontal gene transfer. As for many antibiotic resistance genes present in pathogens today, qnr genes are hypothesized to originate from environmental bacteria. The vast amount of data generated by shotgun metagenomics can therefore be used to explore the diversity of qnr genes in more detail. Results In this paper we describe a new method to identify qnr genes in nucleotide sequence data. We show, using cross-validation, that the method has a high statistical power of correctly classifying sequences from novel classes of qnr genes, even for fragments as short as 100 nucleotides. Based on sequences from public repositories, the method was able to identify all previously reported plasmid-mediated qnr genes. In addition, several fragments from novel putative qnr genes were identified in metagenomes. The method was also able to annotate 39 chromosomal variants of which 11 have previously not been reported in literature. Conclusions The method described in this paper significantly improves the sensitivity and specificity of identification and annotation of qnr genes in nucleotide sequence data. The predicted novel putative qnr genes in the metagenomic data support the hypothesis of a large and uncharacterized diversity within this family of resistance genes in environmental bacterial communities. An implementation of the method is freely available at http://bioinformatics.math.chalmers.se/qnr/.

  12. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains

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    Alefiya Neemuchwala

    2016-01-01

    Full Text Available Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12% among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen.

  13. Rapid evolution of fluoroquinolone-resistant Escherichia coli in Nigeria is temporally associated with fluoroquinolone use

    Science.gov (United States)

    2011-01-01

    Background Antibiotic resistance has necessitated fluoroquinolone use but little is known about the selective forces and resistance trajectory in malaria-endemic settings, where selection from the antimalarial chloroquine for fluoroquinolone-resistant bacteria has been proposed. Methods Antimicrobial resistance was studied in fecal Escherichia coli isolates in a Nigerian community. Quinolone-resistance determining regions of gyrA and parC were sequenced in nalidixic acid resistant strains and horizontally-transmitted quinolone-resistance genes were sought by PCR. Antimicrobial prescription practices were compared with antimicrobial resistance rates over a period spanning three decades. Results Before 2005, quinolone resistance was limited to low-level nalixidic acid resistance in fewer than 4% of E. coli isolates. In 2005, the proportion of isolates demonstrating low-level quinolone resistance due to elevated efflux increased and high-level quinolone resistance and resistance to the fluoroquinolones appeared. Fluoroquinolone resistance was attributable to single nucleotide polymorphisms in quinolone target genes gyrA and/or parC. By 2009, 35 (34.5%) of isolates were quinolone non-susceptible with nine carrying gyrA and parC SNPs and six bearing identical qnrS1 alleles. The antimalarial chloroquine was heavily used throughout the entire period but E. coli with quinolone-specific resistance mechanisms were only detected in the final half decade, immediately following the introduction of the fluoroquinolone antibacterial ciprofloxacin. Conclusions Fluoroquinolones, and not chloroquine, appear to be the selective force for fluoroquinolone-resistant fecal E. coli in this setting. Rapid evolution to resistance following fluoroquinolone introduction points the need to implement resistant containment strategies when new antibacterials are introduced into resource-poor settings with high infectious disease burdens. PMID:22060770

  14. Genome-wide transcriptome analysis of fluoroquinolone resistance in clinical isolates of Escherichia coli.

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    Yamane, Takashi; Enokida, Hideki; Hayami, Hiroshi; Kawahara, Motoshi; Nakagawa, Masayuki

    2012-04-01

    Coincident with their worldwide use, resistance to fluoroquinolones in Escherichia coli has increased. To identify the gene expression profiles underlying fluoroquinolone resistance, we carried out genome-wide transcriptome analysis of fluoroquinolone-sensitive E. coli. Four fluoroquinolone-sensitive E. coli and five fluoroquinolone-resistant E. coli clinical isolates were subjected to complementary deoxyribonucleic acid microarray analysis. Some upregulated genes' expression was verified by real-time polymerase chain reaction using 104 E. coli clinical isolates, and minimum inhibitory concentration tests were carried out by using their transformants. A total of 40 genes were significantly upregulated in fluoroquinolone-resistant E. coli isolates (P fluoroquinolone-resistant E. coli. One of the phage shock protein operons, pspC, was significantly upregulated in 50 fluoroquinolone-resistant E. coli isolates (P fluoroquinolone-resistant E. coli. Deoxyribonucleic acid adenine methyltransferase (dam), which represses type I fimbriae genes, was significantly upregulated in the clinical fluoroquinolone-resistant E. coli isolates (P = 0.007). We established pspC- and dam-expressing E. coli transformants from fluoroquinolone-sensitive E. coli, and the minimum inhibitory concentration tests showed that the transformants acquired fluoroquinolone resistance, suggesting that upregulation of these genes contributes to acquiring fluoroquinolone resistance. Upregulation of psp operones and dam underlying pilus operons downregulation might be associated with fluoroquinolone resistance in E. coli. © 2011 The Japanese Urological Association.

  15. Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5α.

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    Yassien, M A M; Elfaky, M A

    2015-11-01

    A spontaneous fluoroquinolone-resistant mutant (STM1) was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi) clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5α and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A) conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5α, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5α, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5α.

  16. Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5α

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    M.A.M. Yassien

    2015-11-01

    Full Text Available A spontaneous fluoroquinolone-resistant mutant (STM1 was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5α and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5α, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5α, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5α.

  17. A novel gene amplification causes upregulation of the PatAB ABC transporter and fluoroquinolone resistance in Streptococcus pneumoniae.

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    Baylay, Alison J; Ivens, Alasdair; Piddock, Laura J V

    2015-01-01

    Overexpression of the ABC transporter genes patA and patB confers efflux-mediated fluoroquinolone resistance in Streptococcus pneumoniae and is also linked to pneumococcal stress responses. Although upregulation of patAB has been observed in many laboratory mutants and clinical isolates, the regulatory mechanisms controlling expression of these genes are unknown. In this study, we aimed to identify the cause of high-level constitutive overexpression of patAB in M184, a multidrug-resistant mutant of S. pneumoniae R6. Using a whole-genome transformation and sequencing approach, we identified a novel duplication of a 9.2-kb region of the M184 genome which included the patAB genes. This duplication did not affect growth and was semistable with a low segregation rate. The expression levels of patAB in M184 were much higher than those that could be fully explained by doubling of the gene dosage alone, and inactivation of the first copy of patA had no effect on multidrug resistance. Using a green fluorescent protein reporter system, increased patAB expression was ascribed to transcriptional read-through from a tRNA gene upstream of the second copy of patAB. This is the first report of a large genomic duplication causing antibiotic resistance in S. pneumoniae and also of a genomic duplication causing antibiotic resistance by a promoter switching mechanism.

  18. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones.

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    Li, Qiming; Xie, Longxiang; Long, Quanxin; Mao, Jinxiao; Li, Hui; Zhou, Mingliang; Xie, Jianping

    2015-07-03

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics.

  19. Unexpected distribution of the fluoroquinolone-resistance gene qnrB in Escherichia coli isolates from different human and poultry origins in Ecuador.

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    Armas-Freire, Paulina I; Trueba, Gabriel; Proaño-Bolaños, Carolina; Levy, Karen; Zhang, Lixin; Marrs, Carl F; Cevallos, William; Eisenberg, Joseph N S

    2015-06-01

    Fluoroquinolone resistance can be conferred through chromosomal mutations or by the acquisition of plasmids carrying genes such as the quinolone resistance gene (qnr). In this study, 3,309 strains of commensal Escherichia coli were isolated in Ecuador from: (i) humans and chickens in a rural northern coastal area (n = 2368, 71.5%) and (ii) chickens from an industrial poultry operation (n = 827, 25%). In addition, 114 fluoroquinolone-resistant strains from patients with urinary tract infections who were treated at three urban hospitals in Quito, Ecuador were analyzed. All of the isolates were subjected to antibiotic susceptibility screening. Fluoroquinolone-resistant isolates (FRIs) were then screened for the presence of qnrB genes. A significantly higher phenotypic resistance to fluoroquinolones was determined in E. coli strains from chickens in both the rural area (22%) and the industrial operation (10%) than in strains isolated from humans in the rural communities (3%). However, the rates of qnrB genes in E. coli isolates from healthy humans in the rural communities (11 of 35 isolates, 31%) was higher than in chickens from either the industrial operations (3 of 81 isolates, 6%) or the rural communities (7 of 251 isolates, 2.8%). The occurrence of qnrB genes in human FRIs obtained from urban hospitals was low (1 of 114 isolates, 0.9%). These results suggested that the qnrB gene is more widely distributed in rural settings, where antibiotic usage is low, than in urban hospitals and industrial poultry operations. The role of qnrB in clinical resistance to fluoroquinolones is thus far unknown.

  20. Fluoroquinolone-Resistant Haemophilus parasuis Isolates Exhibit More Putative Virulence Factors than Their Susceptible Counterparts

    OpenAIRE

    Zhang, Qiang; Liu, Jiantao; Yan, Shuxian; Yang, Yujie; Zhang, Anding; Jin, Meilin

    2013-01-01

    The prevalence of 23 putative virulence factors among fluoroquinolone-susceptible and -resistant Haemophilus parasuis isolates was analyzed. Putative hemolysin precursor, fimbrial assembly chaperone, and type I site-specific restriction modification system R subunit genes were more prevalent among fluoroquinolone-resistant H. parasuis isolates than among fluoroquinolone-susceptible H. parasuis isolates. Fluoroquinolone resistance may be associated with an increase in the presence of some viru...

  1. Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella

    Science.gov (United States)

    Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity, which can cause damage DNA and result in bacterial cell death. In response to DNA damage, bacteria induce an SOS response to stimulate repair of damaged DNA. However, the SOS response may al...

  2. Development of Multiplex-Mismatch Amplification Mutation-PCR Assay for Simultaneous Detection of Campylobacter jejuni and Mutation in gyrA Gene Related to Fluoroquinolone Resistance.

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    Cui, Mingquan; Wu, Chenbin; Zhang, Peng; Wu, Congming

    2016-11-01

    Campylobacter jejuni, a foodborne pathogen, is the major cause of enteritis in humans worldwide, however, its increasing resistance to fluoroquinolones reported recently is of a major concern. In the present study, multiplex-mismatch amplification mutation assay-polymerase chain reaction (MMAMA-PCR) was developed for the first time with the aim to quickly identify C. jejuni and to detect the single nucleotide mutation (C-257 to T) frequently observed in gyrA gene, associated with the acquisition of resistance to fluoroquinolones. In this assay, mismatch amplification mutation primers for the detection of gyrA mutation in C. jejuni were coupled with primers for the hip gene encoding for hippuricase and 16S rRNA gene of C. jejuni, respectively, in the multiplex PCR assay. The specificity and accuracy of this method were analyzed by the use of 78 C. jejuni strains with previously confirmed resistance phenotypes and the mutation (C-257 to T) in gyrA gene, as well as 107 clinical isolates of various bacterial species, including 29 C. jejuni isolates. This study indicates that MMAMA-PCR is a promising assay for the rapid identification of C. jejuni with a specific mutation in gyrA gene, responsible for the resistance to fluoroquinolones.

  3. Fate of tetracycline, sulfonamide and fluoroquinolone resistance genes and the changes in bacterial diversity during composting of swine manure.

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    Selvam, Ammaiyappan; Xu, Delin; Zhao, Zhenyong; Wong, Jonathan W C

    2012-12-01

    This study monitored the abundance of antibiotic resistant genes (ARGs) and the bacterial diversity during composting of swine manure spiked with chlortetracycline, sulfadiazine and ciprofloxacin at two different levels and a control without antibiotics. Resistance genes of tetracycline (tetQ, tetW, tetC, tetG, tetZ and tetY), sulfonamide (sul1, sul2, dfrA1 and dfrA7) and fluoroquinolone (gyrA and parC) represented 0.02-1.91%, 0.67-10.28% and 0.00005-0.0002%, respectively, of the total 16S rDNA copies in the initial composting mass. After 28-42 days of composting, these ARGs, except parC, were undetectable in the composting mass indicating that composting is a potential method of manure management. Polymerase chain reaction-denaturing gradient gel electrophoresis analysis of bacterial 16S rDNA of the composting mass indicated that the addition of antibiotics up to 100, 20 and 20mg/kg of chlortetracycline, sulfadiazine and ciprofloxacin, respectively, elicited only a transient perturbation and the bacterial diversity was restored in due course of composting.

  4. Resistance surveillance studies: a multifaceted problem--the fluoroquinolone example.

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    Dalhoff, A

    2012-06-01

    flora colonizing the gut, nose, oropharynx, and skin, so that horizontal gene transfer between the commensal flora and the offending pathogen as well as inter- and intraspecies recombinations contribute to the emergence and spread of fluoroquinolone resistance among pathogenic streptococci. Although interspecies recombinations are not yet the major cause for the emergence of fluoroquinolone resistance, its existence indicates that a large reservoir of fluoroquinolone resistance exists. Thus, a scenario resembling that of a worldwide spread of β-lactam resistance in pneumococci is conceivable. However, many resistance surveillance studies suffer from inaccuracies like the sampling of a selected patient population, restricted geographical sampling, and undefined requirements of the user, so that the results are biased. The number of national centers is most often limited with one to two participating laboratories, so that such studies are point prevalence but not surveillance studies. Selected samples are analyzed predominantly as either hospitalized patients or patients at risk or those in whom therapy failed are sampled; however, fluoroquinolones are most frequently prescribed by the general practitioner. Selected sampling results in a significant over-estimation of fluoroquinolone resistance in outpatients. Furthermore, the requirements of the users are often not met; the prescribing physician, the microbiologist, the infection control specialist, public health and regulatory authorities, and the pharmaceutical industry have diverse interests, which, however, are not addressed by different designs of a surveillance study. Tools should be developed to provide customer-specific datasets. Consequently, most surveillance studies suffer from well recognized but uncorrected biases or inaccuracies. Nevertheless, they provide important information that allows the identification of trends in pathogen incidence and antimicrobial resistance.

  5. SOS response and its regulation on the fluoroquinolone resistance.

    Science.gov (United States)

    Qin, Ting-Ting; Kang, Hai-Quan; Ma, Ping; Li, Peng-Peng; Huang, Lin-Yan; Gu, Bing

    2015-12-01

    Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change-mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo.

  6. Mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Yujiao, Zhang; Xiaojing, Li; Kaixia, Mi

    2016-10-20

    Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.

  7. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics - Fluoroquinolones

    Science.gov (United States)

    Li, Qiming; Xie, Longxiang; Long, Quanxin; Mao, Jinxiao; Li, Hui; Zhou, Mingliang; Xie, Jianping

    2015-01-01

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics. PMID:26139381

  8. Fluoroquinolone prophylaxis against febrile neutropenia in areas with high fluoroquinolone resistance--an Asian perspective.

    Science.gov (United States)

    Ng, Esther Shu-Ting; Liew, Yixin; Koh, Liang Piu; Hsu, Li Yang

    2010-09-01

    Febrile neutropenia remains a major cause of morbidity and mortality in patients receiving chemotherapy. Major prophylactic strategies include granulocyte colony-stimulating factor and antibiotics, the most widely used of which are fluoroquinolones. While fluoroquinolone prophylaxis has been shown to be effective in areas where fluoroquinolone resistance is low, this same efficacy has not been proven in areas where resistance is high, such as in Asia. Given the increase in antimicrobial resistance with the use of prophylaxis, the risks and benefits of this strategy need to be carefully considered. This review presents the evidence for and against fluoroquinolone prophylaxis in areas of high fluoroquinolone resistance.

  9. Rapid evolution of fluoroquinolone-resistant Escherichia coli in Nigeria is temporally associated with fluoroquinolone use

    National Research Council Canada - National Science Library

    Lamikanra, Adebayo; Crowe, Jennifer L; Lijek, Rebeccah S; Odetoyin, Babatunde W; Wain, John; Aboderin, A Oladipo; Okeke, Iruka N

    2011-01-01

    Antibiotic resistance has necessitated fluoroquinolone use but little is known about the selective forces and resistance trajectory in malaria-endemic settings, where selection from the antimalarial...

  10. Detection of fluoroquinolone resistance by mutation in gyrA gene of Campylobacter spp. isolates from broiler and laying (Gallus gallus domesticus hens,from Rio de Janeiro State, Brazil

    Directory of Open Access Journals (Sweden)

    Beatriz da Silva Frasao

    2015-11-01

    Full Text Available Poultry are considered to be the main reservoir of Campylobacter spp. bacteria, an important pathogen for humans. Many studies have reported a rapid selection of fluoroquinolone-resistant strains following the widespread use of these antimicrobials in poultry production and human medicine. The main mechanism of fluoroquinolone resistance in Campylobacter is a mutation in the Quinolone Resistance Determinant Region (QRDR in the gyrA gene, which codes for the subunit of the enzyme DNA gyrase, the target for fluoroquinolone. The aim of this study was to investigate the mutation in QRDR in the gyrA gene of Campylobacter strains previously isolated from broiler carcasses and feces of laying hens. Thirty-eight strains of C. jejuni and 19 C. coli strains (n=57, previously characterized as resistant to ciprofloxacin and enrofloxacin by the disk diffusion method and minimum inhibitory concentration (MIC, were selected. For detection of the mutation, a fragment of 454pb QRDR in the gyrA gene was used for direct sequencing. All strains presented the QRDR mutation in the gyrA gene at codon 86 (Thr-86-Ile, which confers resistance to fluoroquinolones. Other known silent mutations were observed. This genotypic characterization of fluoroquinolone resistance in Campylobacter strains has confirmed the prior phenotypic detection of the resistance. The Thr-86-Ile mutation was observed in all samples confirming that this is the predominant mutation in enrofloxacin and ciprofloxacin resistant strains of C. jejuni and C. coli.

  11. Topical fluoroquinolone use as a risk factor for in vitro fluoroquinolone resistance in ocular cultures.

    Science.gov (United States)

    Fintelmann, Robert E; Hoskins, Eliza N; Lietman, Thomas M; Keenan, Jeremy D; Gaynor, Bruce D; Cevallos, Vicky; Acharya, Nisha R

    2011-04-01

    To determine whether recent use of topical fluoroquinolones is a risk factor for in vitro fluoroquinolone resistance in Staphylococcus aureus ocular isolates. Disk diffusion susceptibility testing for ciprofloxacin, moxifloxacin, and gatifloxacin was performed for all ocular isolates of S aureus at the Francis I. Proctor Foundation microbiology laboratory from January 1, 2005, to December 31, 2008. The medical records of patients with positive S aureus cultures were reviewed to determine topical or systemic fluoroquinolone use within the 3 months prior to culture. The Fisher exact test was used to compare the proportion of patients who used topical fluoroquinolones in the past 3 months among fluoroquinolone-sensitive and -resistant cases. Logistic regression was used to determine risk factors for fluoroquinolone resistance. Of 200 S aureus cultures, 41 were resistant to ciprofloxacin, moxifloxacin, and gatifloxacin (20.5%). Fluoroquinolone-resistant S aureus isolates were from older patients (mean [SD] age, 65.5 [25.0] years) compared with fluoroquinolone-susceptible isolates (mean [SD] patient age, 52.1 [22.1] years) (P = .003). Use of fluoroquinolones within the 3 months before testing was more frequent in resistant isolates (29%) than in susceptible isolates (11%) (P = .005), as was recent hospitalization (22% of resistant isolates, 0% of susceptible isolates) (P fluoroquinolone use within 3 months was a significant predictor of fluoroquinolone resistance (P = .046), along with age, systemic immunosuppression, and topical fluoroquinolone use between 3 and 6 months before testing. Recent topical fluoroquinolone use is significantly associated with fluoroquinolone resistance in S aureus isolates from ocular cultures.

  12. Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals

    Science.gov (United States)

    Kang, Min-Hee; Chae, Min-Joo; Yoon, Jang-Won; Lee, So-Young; Yoo, Jong-Hyun; Park, Hee-Myung

    2014-01-01

    Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern. PMID:24982521

  13. Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals.

    Science.gov (United States)

    Kang, Min-Hee; Chae, Min-Joo; Yoon, Jang-Won; Lee, So-Young; Yoo, Jong-Hyun; Park, Hee-Myung

    2014-07-01

    Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern.

  14. GyrA and ParC Gene Mutation of Clinically Isolated Fluoroquinolones-resistant Strain of Salmonella

    Institute of Scientific and Technical Information of China (English)

    LIU Fangping; TONG Hengmin

    2006-01-01

    Nine strains resistant to five fluoroquinolones (Ciprofloxacin, Ofloxacin, Enrofloxacin, Danofloxacin,Sarafloxacin) were isolated from clinical samples and extracted the chromosomal DNA of these strains. Designed primers to amplify the Quinolone-resistance-determining region (QRDR) of gyrA and parC, then the PCR products were sequenced and analyzed. In comparision with NCTC5776, a single mutation was found at base 371 in gyrA of strain 38which changed from C to T, and a single mutation was found at base 350 in gyrA of strain 60 which changed from A to C.No mutation was found in gyrA of the rest The mutation of strain 38 led to an amino acid substitution of Arg99Cys and the mutation of 60 led to an amino acid substitution of Met 92 Leu. No mutation was found in parC QRDR of all the isolates. These results indicats that the DNA gyrase will be the primary target to salmonella of fluoroquinolone.

  15. The incidence of fluoroquinolone resistant infections after prostate biopsy--are fluoroquinolones still effective prophylaxis?

    Science.gov (United States)

    Feliciano, Joseph; Teper, Ervin; Ferrandino, Michael; Macchia, Richard J; Blank, William; Grunberger, Ivan; Colon, Ivan

    2008-03-01

    Fluoroquinolones have been shown to decrease infective complications after prostate biopsy. However, fluoroquinolone resistance is emerging. We quantified contemporary rates of infective complications and the incidence of fluoroquinolone resistant infections after prostate biopsy under fluoroquinolone prophylaxis. We retrospectively evaluated the records of 1,273 patients who underwent prostate biopsy at New York Harbor Veterans Affairs Hospital from January 2004 to December 2006. Patients received levofloxacin or gatifloxacin. Using the Veterans Affairs computerized patient record system we reviewed all patient visits within 1 month after prostate biopsy. Visits were queried for infective symptoms. Positive cultures were evaluated for resistance patterns. The annual and overall incidence of infective complications and fluoroquinolone resistant infections was calculated. Of 1,273 patients 31 (2.4%) presented with infective symptoms after biopsy. The overall incidence of fluoroquinolone resistant infections was 1.2% (15 cases). When stratified by year, there were statistically significant increases in the incidence of infective complications and fluoroquinolone resistance from 2004 to 2006. Of the positive cultures those from 89% of patients yielded Escherichia coli and 90% were fluoroquinolone resistant. Fluoroquinolone resistant E. coli were also resistant to gentamicin in 22% of cases, trimethoprim/sulfamethoxazole in 44%, piperacillin in 72% and ampicillin in 94%. However, 100% sensitivity was demonstrated for amikacin, ceftazidime and ceftriaxone. Fluoroquinolones are still effective as antibiotic prophylaxis for prostate biopsies but there is an increase in infective complications and fluoroquinolone resistance. When patients present with post-prostate biopsy infective symptoms, almost 50% are associated with fluoroquinolone resistant pathogens. Empirical treatment with ceftriaxone, ceftazidime or amikacin should be initiated until culture specific therapy can

  16. 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.

  17. High-level fluoroquinolone resistant Salmonella enterica serovar Kentucky ST198 epidemic clone with IncA/C conjugative plasmid carrying bla(CTX-M-25) gene.

    Science.gov (United States)

    Wasyl, Dariusz; Kern-Zdanowicz, Izabela; Domańska-Blicharz, Katarzyna; Zając, Magdalena; Hoszowski, Andrzej

    2015-01-30

    Multidrug resistant Salmonella Kentucky strains have been isolated from turkeys in Poland since 2009. Multiple mutations within chromosomal genes gyrA and parC were responsible for high-level ciprofloxacin resistance. One of the isolates was extended spectrum β-lactamase- (ESBL) positive: the strain 1643/2010 carried a conjugative 167,779 bps plasmid of IncA/C family. The sequence analysis revealed that it carried a blaCTX-M-25 gene and an integron with another β-lactamase encoding gene-blaOXA-21. This is the first known report of a CTX-M-25 encoding gene both in Poland and in Salmonella Kentucky world-wide, as well as in the IncA/C plasmid. Analysis of the integron showed a novel arrangement of gene cassettes-aacA4, aacC-A1 and blaOXA-21 where the latter might result from an intergeneric gene transfer. The study confirmed Salmonella Kentucky population isolated in Poland belongs to global epidemics of high level fluoroquinolone resistant clone ST198 that can carry rare β-lactamase genes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Key role of Mfd in the development of fluoroquinolone resistance in Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Jing Han

    2008-06-01

    Full Text Available Campylobacter jejuni is a major food-borne pathogen and a common causative agent of human enterocolitis. Fluoroquinolones are a key class of antibiotics prescribed for clinical treatment of enteric infections including campylobacteriosis, but fluoroquinolone-resistant Campylobacter readily emerges under the antibiotic selection pressure. To understand the mechanisms involved in the development of fluoroquinolone-resistant Campylobacter, we compared the gene expression profiles of C. jejuni in the presence and absence of ciprofloxacin using DNA microarray. Our analysis revealed that multiple genes showed significant changes in expression in the presence of a suprainhibitory concentration of ciprofloxacin. Most importantly, ciprofloxacin induced the expression of mfd, which encodes a transcription-repair coupling factor involved in strand-specific DNA repair. Mutation of the mfd gene resulted in an approximately 100-fold reduction in the rate of spontaneous mutation to ciprofloxacin resistance, while overexpression of mfd elevated the mutation frequency. In addition, loss of mfd in C. jejuni significantly reduced the development of fluoroquinolone-resistant Campylobacter in culture media or chickens treated with fluoroquinolones. These findings indicate that Mfd is important for the development of fluoroquinolone resistance in Campylobacter, reveal a previously unrecognized function of Mfd in promoting mutation frequencies, and identify a potential molecular target for reducing the emergence of fluoroquinolone-resistant Campylobacter.

  19. Bacteriophages as a reservoir of extended-spectrum β-lactamase and fluoroquinolone resistance genes in the environment.

    Science.gov (United States)

    Marti, E; Variatza, E; Balcázar, J L

    2014-07-01

    Six antibiotic resistance genes (blaCTX-M , blaSHV , blaTEM , qnrA, qnrB and qnrS) were quantified by qPCR in both phage and bacterial DNA fractions of environmental water samples in order to determine the contribution of phages to the dissemination of antibiotic resistance genes (ARGs) in the environment. Although the highest copy numbers (p bacteriophages are a potential reservoir of resistance genes and may act as efficient vehicles for horizontal gene transfer. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  20. Fluoroquinolone resistance in Streptococcus pneumoniae from a university hospital, Thailand.

    Science.gov (United States)

    Srifuengfung, Somporn; Tribuddharat, Chanwit; Chokephaibulkit, Kulkanya; Comerungsee, Sopita

    2010-11-01

    The most frequent markers of fluoroquinolone resistance in S. pneumoniae are chromosomal mutations in the quinolone-resistance-determining regions of DNA gyrase and topoisomerase IV encoding for the gyrA, gyrB and parC, parE genes. In 2008, 6.5% of the Streptococcus pneumoniae isolates in a Bangkok university hospital were resistant to ofloxacin. Using PCR and DNA sequencing, we identified mutations in both the gyrA and parC genes of four ofloxacin- and ciprofloxacin-resistant S. pneumoniae isolates (minimum inhibitory concentrations > 32 microg/ml). Mutations were found in the gyrA gene at positions Ser81Phe, Glu85Gly, Glu85Lys and in the parC gene at position Ser79Tyr. Three isolates had mutations in both genes. Two of the isolates were serotype 6B and two were serotypes not contained in currently licensed pneumococcal vaccines. This is the first report of the mechanisms of fluoroquinolone resistance in S. pneumoniae in Thailand.

  1. Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Farhat, Maha R; Jacobson, Karen R; Franke, Molly F; Kaur, Devinder; Sloutsky, Alex; Mitnick, Carole D; Murray, Megan

    2016-03-01

    Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the gyr genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of gyr mutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full gyrA and gyrB open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that gyrB mutations contribute to fluoroquinolone resistance both individually and through interactions with gyrA mutations. These effects were statistically significant. In these clinical isolates, several gyrA and gyrB mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of gyr mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of gyr mutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use

    Directory of Open Access Journals (Sweden)

    Axel Dalhoff

    2012-01-01

    Full Text Available This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except S. pneumoniae and H. influenzae, causing community-acquired respiratory tract infections. However, 10 to 30% of these isolates harbored first-step mutations conferring low level fluoroquinolone resistance. Fluoroquinolone resistance increased in Enterobacteriaceae causing community acquired or healthcare associated urinary tract infections and intraabdominal infections, exceeding 50% in some parts of the world, particularly in Asia. One to two-thirds of Enterobacteriaceae producing extended spectrum -lactamases were fluoroquinolone resistant too. Furthermore, fluoroquinolones select for methicillin resistance in Staphylococci. Neisseria gonorrhoeae acquired fluoroquinolone resistance rapidly; actual resistance rates are highly variable and can be as high as almost 100%, particularly in Asia, whereas resistance rates in Europe and North America range from 30% in established sexual networks. In general, the continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some guidelines, for example, treatment of urinary tract, intra-abdominal, skin and skin structure infections, and traveller’s diarrhea, or even precludes the use in indications like sexually transmitted diseases and enteric fever.

  3. Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use

    Science.gov (United States)

    Dalhoff, Axel

    2012-01-01

    This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except S. pneumoniae and H. influenzae, causing community-acquired respiratory tract infections. However, 10 to 30% of these isolates harbored first-step mutations conferring low level fluoroquinolone resistance. Fluoroquinolone resistance increased in Enterobacteriaceae causing community acquired or healthcare associated urinary tract infections and intraabdominal infections, exceeding 50% in some parts of the world, particularly in Asia. One to two-thirds of Enterobacteriaceae producing extended spectrum β-lactamases were fluoroquinolone resistant too. Furthermore, fluoroquinolones select for methicillin resistance in Staphylococci. Neisseria gonorrhoeae acquired fluoroquinolone resistance rapidly; actual resistance rates are highly variable and can be as high as almost 100%, particularly in Asia, whereas resistance rates in Europe and North America range from 30% in established sexual networks. In general, the continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some guidelines, for example, treatment of urinary tract, intra-abdominal, skin and skin structure infections, and traveller's diarrhea, or even precludes the use in indications like sexually transmitted diseases and enteric fever. PMID:23097666

  4. Prevalence and characteristics of extended-spectrum β-lactamase and plasmid-mediated fluoroquinolone resistance genes in Escherichia coli isolated from chickens in Anhui province, China.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available The aim of this study was to characterize the prevalence of extended-spectrum β-lactamase (ESBL genes and plasmid-mediated fluoroquinolone resistance (PMQR determinants in 202 Escherichia coli isolates from chickens in Anhui Province, China, and to determine whether ESBL and PMQR genes co-localized in the isolates. Antimicrobial susceptibility for 12 antimicrobials was determined by broth microdilution. Polymerase chain reactions (PCRs, DNA sequencing, and pulsed field gel electrophoresis (PFGE were employed to characterize the molecular basis for β-lactam and fluoroquinolone resistance. High rates of antimicrobial resistance were observed, 147 out of the 202 (72.8% isolates were resistant to at least 6 antimicrobial agents and 28 (13.9% of the isolates were resistant to at least 10 antimicrobials. The prevalence of blaCTX-M, blaTEM-1 and blaTEM-206 genes was 19.8%, 24.3% and 11.9%, respectively. Seventy-five out of the 202 (37.1% isolates possessed a plasmid-mediated quinolone resistance determinant in the form of qnrS (n = 21; this determinant occurred occasionally in combination with aac(6'-1b-cr (n = 65. Coexistence of ESBL and/or PMQR genes was identified in 31 of the isolates. Two E. coli isolates carried blaTEM-1, blaCTX-M and qnrS, while two others carried blaCTX-M, qnrS and aac(6'-1b-cr. In addition, blaTEM-1, qnrS and aac(6'-1b-cr were co-located in two other E. coli isolates. PFGE analysis showed that these isolates were not clonally related and were genetically diverse. To the best of our knowledge, this study is the first to describe detection of TEM-206-producing E. coli in farmed chickens, and the presence of blaTEM-206, qnrS and aac(6'-1b-cr in one of the isolates.

  5. Risk factors for fluoroquinolone resistance in ocular cultures.

    Science.gov (United States)

    Lee, Junsung; Choi, Sangkyung

    2015-02-01

    To identify the risk factors associated with fluoroquinolone resistance in patients undergoing cataract surgery. A total of 1,125 patients (1,125 eyes) who underwent cataract surgery at Veterans Health Service Medical Center from May 2011 to July 2012 were enrolled in this study. Conjunctival cultures were obtained from the patients on the day of surgery before instillation of any ophthalmic solutions. The medical records of patients with positive coagulase negative staphylococcus (CNS) and Staphylococcus aureus (S. aureus) cultures were reviewed to determine factors associated with fluoroquinolone resistance. Of 734 CNS and S. aureus cultures, 175 (23.8%) were resistant to ciprofloxacin, levofloxacin, gatifloxacin, or moxifloxacin. Use of fluoroquinolone within 3 months and within 1 year before surgery, topical antibiotic use other than fluoroquinolone, systemic antibiotic use, recent hospitalization, ocular surgery, intravitreal injection and use of eyedrops containing benzalkonium chloride were significantly more frequent in resistant isolates than in susceptible isolates. In multivariable logistic regression analysis, ocular surgery (odds ratio [OR], 8.457), recent hospitalization (OR, 6.646) and use of fluoroquinolone within 3 months before surgery (OR, 4.918) were significant predictors of fluoroquinolone resistance, along with intravitreal injection (OR, 2.976), systemic antibiotic use (OR, 2.665), use of eyedrops containing benzalkonium chloride (OR, 2.323), use of fluoroquinolone within 1 year before surgery (OR, 1.943) and topical antibiotic use other than fluoroquinolone (OR, 1.673). Recent topical fluoroquinolone use, hospitalization and ocular surgery were significantly associated with fluoroquinolone resistance in CNS and S. aureus isolates from ocular culture.

  6. Correlation between virulence genotype and fluoroquinolone resistance in carbapenem-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Cho, Hye Hyun; Kwon, Kye Chul; Kim, Semi; Koo, Sun Hoe

    2014-07-01

    Pseudomonas aeruginosa is a clinically important pathogen that causes opportunistic infections and nosocomial outbreaks. Recently, the type III secretion system (TTSS) has been shown to play an important role in the virulence of P. aeruginosa. ExoU, in particular, has the greatest impact on disease severity. We examined the relationship among the TTSS effector genotype (exoS and exoU), fluoroquinolone resistance, and target site mutations in 66 carbapenem-resistant P. aeruginosa strains. Sixty-six carbapenem-resistant P. aeruginosa strains were collected from patients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Minimum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to determine the TTSS effector genotype and quinolone resistance-determining regions (QRDRs) of the respective target genes gyrA, gyrB, parC, and parE. A higher proportion of exoU+ strains were fluoroquinolone-resistant than exoS+ strains (93.2%, 41/44 vs. 45.0%, 9/20; P≤0.0001). Additionally, exoU+ strains were more likely to carry combined mutations than exoS+ strains (97.6%, 40/41 vs. 70%, 7/10; P=0.021), and MIC increased as the number of active mutations increased. The recent overuse of fluoroquinolone has led to both increased resistance and enhanced virulence of carbapenem-resistant P. aeruginosa. These data indicate a specific relationship among exoU genotype, fluoroquinolone resistance, and resistance-conferring mutations.

  7. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics - Fluoroquinolones

    OpenAIRE

    Qiming Li; Longxiang Xie; Quanxin Long; Jinxiao Mao; Hui Li; Mingliang Zhou; Jianping Xie

    2015-01-01

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoro...

  8. Relationship between ParE gene mutation and fluoroquinolones resistance in Mycoplasma hominis%人型支原体ParE基因突变与耐氟喹诺酮类药物的关系

    Institute of Scientific and Technical Information of China (English)

    罗永慧; 段颖卿; 甘雪华; 王旭菲; 舒向荣

    2014-01-01

    目的:探讨人型支原体对氟喹诺酮类药物的耐药机制。方法自临床分离的8株耐氟喹诺酮类药物的人型支原体(Mh),对其ParE基因PCR扩增后进行测序分析,与基因库中的野生型菌株MHPG21基因序列比对,分析ParE基因突变位点与菌株耐氟喹诺酮类药物的关系。结果与野生株MHPG21对比,6株检出ParE基因所编码的氨基酸残基发生D 426→N变异。结论 Mh临床分离株对氟喹诺酮类药物的耐药可能与ParE基因所编码的氨基酸残基D 426→N变异有关。%Objective To explore the fluoroquinolones resistance meachanisms of Mycoplasma hominis (Mh). Methods A total of 8 strains of Mh with different fluoroquinolones resistance phenotype were analyzed, the ParE gene was amplified and sequenced. The sequencing results of ParE gene were compared with that in the wild type strain PG21, then analyzed the relation between ParE gene mutation and fluoroquinolones resistance. Results Compared with wild strain PG21, ParE gene in 6 strains got a D426→N mutation. Conclusion The fluoroquinolones resistance of Mh might be associate with ParE gene D426→N mutation.

  9. Fluoroquinolone Resistance and Mutation Patterns in gyrA and parC Genes in Neisseria gonorrhoeae Isolates from Shanghai,China

    Institute of Scientific and Technical Information of China (English)

    Tiejun ZHANG; Xiaoming ZHOU; Yue CHEN; Weiming GU; Tao ZHANG; Qingwu JIANG

    2009-01-01

    In order to study the resistance of Neisseria (N.) gonorrhoeae to the fluoroquinolone and detect mutation patterns of quinolone resistance-determining regions (QRDRs) of clinical isolates in Shanghai,China,a total of 80 clinical isolates of N.gonorrhoeae were consecutively collected from Shanghai.The MIC of fluoroquinolone for the isolates was examined by using the agar dilution method and the mutation profiles of the QRDRs of gyrA and parC were analyzed by sequencing and restriction fragment length polymorphism (RFLP).Chi-square test was used for comparison of the mutation patterns.The results showed that:(1) High percentages of the 8 isolates were resistant to ciprofloxacin (95.0%),ofloxacin (95.0%) and lomefloxacin (97.5%),only one strain was susceptible to the ciprofloxacin.(2) Sensitive strains had a substitute of Asp95→Ala in the gyrA,and all isolates that were resistant or intermediated to the ciprofloxacin,had a double mutation in the gyrA (Set91,Ala 92 and Asp95).Some strains also had a mutation in the parC.(3) The MICs of these isolates were significantly associated with the mutation patterns in the gyrA and parC.A double mutation of gyrA combined with parC87 mutation was a predominant pattern in Shanghai and could mediate high level resistance to ciprofloxacin.It suggests that mutations in the QRDRs of gyrA and parC .may be re-sponsible for the fluoroquinolone resistance.And fluoroquinolone could not be used as the first line antibiotics for gonorrhea treatment any more in Shanghai,China.

  10. Resistance in Escherichia coli: variable contribution of efflux pumps with respect to different fluoroquinolones.

    Science.gov (United States)

    Huguet, A; Pensec, J; Soumet, C

    2013-05-01

    Resistance to fluoroquinolones is partially the result of a decrease in drug accumulation in Escherichia coli through different mechanisms. However, the variable contribution of these mechanisms with respect to different fluoroquinolones is poorly investigated. Therefore, the current study aimed to compare the contribution of resistance attributed to efflux-mediated mechanisms for different fluoroquinolones. Susceptibility of enrofloxacin, marbofloxacin and ciprofloxacin were compared after treatment with an efflux pump inhibitor in 17 ciprofloxacin-resistant E. coli isolates, and also the expression profile of the genes encoding the porins and efflux pumps involved in this resistance was evaluated. After treatment with the efflux pump inhibitor Phe-Arg-β-naphthylamide (PAβN), susceptibilities differed significantly between antimicrobial agents, the decrease for MIC being higher for enrofloxacin than for marbofloxacin or ciprofloxacin. AcrB expression level increased significantly (+26%) in ciprofloxacin-resistant E. coli isolates compared with ciprofloxacin-susceptible isolates, whereas the expression level decreased for ompF (-50%) and ompC (-30%). There was a higher contribution of resistance nodulation division (RND) efflux pumps to resistance to hydrophobic fluoroquinolones. Comparison between expression profile of efflux pumps and hydrophobicity of the antimicrobial agents could result in variable resistance for different fluoroquinolones. © 2013 The Society for Applied Microbiology.

  11. High Proportion of Fluoroquinolone-Resistant Mycobacterium tuberculosis Isolates with Novel Gyrase Polymorphisms and a gyrA Region Associated with Fluoroquinolone Susceptibility

    Science.gov (United States)

    Devasia, Rose; Blackman, Amondrea; Eden, Svetlana; Li, Haijing; Maruri, Fernanda; Shintani, Ayumi; Alexander, Charles; Kaiga, Anne; Stratton, Charles W.; Warkentin, Jon; Tang, Yi-Wei

    2012-01-01

    Fluoroquinolone resistance in Mycobacterium tuberculosis can be conferred by mutations in gyrA or gyrB. The prevalence of resistance mutations outside the quinolone resistance-determining region (QRDR) of gyrA or gyrB is unclear, since such regions are rarely sequenced. M. tuberculosis isolates from 1,111 patients with newly diagnosed culture-confirmed tuberculosis diagnosed in Tennessee from 2002 to 2009 were screened for phenotypic ofloxacin resistance (>2 μg/ml). For each resistant isolate, two ofloxacin-susceptible isolates were selected: one with antecedent fluoroquinolone exposure and one without. The complete gyrA and gyrB genes were sequenced and compared with M. tuberculosis H37Rv. Of 25 ofloxacin-resistant isolates, 11 (44%) did not have previously reported resistance mutations. Of these, 10 had novel polymorphisms: 3 in the QRDR of gyrA, 1 in the QRDR of gyrB, and 6 outside the QRDR of gyrA or gyrB; 1 did not have any gyrase polymorphisms. Polymorphisms in gyrA codons 1 to 73 were more common in fluoroquinolone-susceptible than in fluoroquinolone-resistant strains (20% versus 0%; P = 0.016). In summary, almost half of fluoroquinolone-resistant M. tuberculosis isolates did not have previously described resistance mutations, which has implications for genotypic diagnostic tests. PMID:22189117

  12. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates

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    Meng Dong-Ya

    2014-01-01

    Full Text Available To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs of DNA gyrase (gyrA and gyrB and topoisomerase IV (parC and parE in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX, intermediate resistant to Levofloxacin (LVX and Sparfloxacin (SFX, and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  13. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates.

    Science.gov (United States)

    Meng, Dong-Ya; Sun, Chang-Jian; Yu, Jing-Bo; Ma, Jun; Xue, Wen-Cheng

    2014-01-01

    To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  14. High proportion of heteroresistance in gyrA and gyrB in fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates.

    Science.gov (United States)

    Eilertson, Brandon; Maruri, Fernanda; Blackman, Amondrea; Herrera, Miguel; Samuels, David C; Sterling, Timothy R

    2014-06-01

    Heteroresistance is the coexistence of populations with differing nucleotides at a drug resistance locus within a sample of organisms. Although Sanger sequencing is the gold standard for sequencing, it may be less sensitive than deep sequencing for detecting fluoroquinolone heteroresistance in Mycobacterium tuberculosis. Twenty-seven fluoroquinolone monoresistant and 11 fluoroquinolone-susceptible M. tuberculosis isolates were analyzed by Sanger and Illumina deep sequencing. Individual sequencing reads were analyzed to detect heteroresistance in the gyrA and gyrB genes. Heteroresistance to fluoroquinolones was identified in 10/26 (38%) phenotypically fluoroquinolone-resistant samples and 0/11 (P = 0.02) fluoroquinolone-susceptible controls. One resistant sample was excluded because of contamination with the laboratory strain M. tuberculosis H37Rv. Sanger sequencing revealed resistance-conferring mutations in 15 isolates, while deep sequencing revealed mutations in 20 isolates. Isolates with fluoroquinolone resistance-conferring mutations by Sanger sequencing all had at least those same mutations identified by deep sequencing. By deep sequencing, 10 isolates had a single fixed (defined as >95% frequency) mutation, while 10 were heteroresistant, 5 of which had a single unfixed (defined as fluoroquinolone-resistant M. tuberculosis isolates with heteroresistance than did Sanger sequencing. The heteroresistant isolates frequently demonstrated multiple mutations, but resistant isolates with fixed mutations each had only a single mutation. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Fluoroquinolone resistance mechanisms of Shigella flexneri isolated in Bangladesh.

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    Ishrat J Azmi

    Full Text Available To investigate the prevalence and mechanisms of fluoroquinolone resistance in Shigella species isolated in Bangladesh and to compare with similar strains isolated in China.A total of 3789 Shigella isolates collected from Clinical Microbiology Laboratory of icddr,b, during 2004-2010 were analyzed for antibiotic susceptibility. Analysis of plasmids, plasmid-mediated quinolone-resistance genes, PFGE, and sequencing of genes of the quinolone-resistance-determining regions (QRDR were conducted in representative strains isolated in Bangladesh and compared with strains isolated in Zhengding, China. In addition, the role of efflux-pump was studied by using the efflux-pump inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP.Resistance to ciprofloxacin in Shigella species increased from 0% in 2004 to 44% in 2010 and S. flexneri was the predominant species. Of Shigella spp, ciprofloxacin resistant (CipR strains were mostly found among S. flexneri (8.3%, followed by S. sonnei (1.5%. Within S. flexneri (n = 2181, 14.5% were resistance to ciprofloxacin of which serotype 2a was predominant (96%. MIC of ciprofloxacin, norfloxacin, and ofloxacin were 6-32 mg/L, 8-32 mg/L, and 8-24 mg/L, respectively in S. flexneri 2a isolates. Sequencing of QRDR genes of resistant isolates showed double mutations in gyrA gene (Ser83Leu, Asp87Asn/Gly and single mutation in parC gene (Ser80Ile. A difference in amino acid substitution at position 87 was found between strains isolated in Bangladesh (Asp87Asn and China (Asp87Gly except for one. A novel mutation at position 211 (His→Tyr in gyrA gene was detected only in the Bangladeshi strains. Susceptibility to ciprofloxacin was increased by the presence of CCCP indicating the involvement of energy dependent active efflux pumps. A single PFGE type was found in isolates from Bangladesh and China suggesting their genetic relatedness.Emergence of fluoroquinolone resistance in Shigella undermines a major challenge in current

  16. Fluoroquinolone Resistance Mechanisms of Shigella flexneri Isolated in Bangladesh

    Science.gov (United States)

    Azmi, Ishrat J.; Khajanchi, Bijay K.; Akter, Fatema; Hasan, Trisheeta N.; Shahnaij, Mohammad; Akter, Mahmuda; Banik, Atanu; Sultana, Halima; Hossain, Mohammad A.; Ahmed, Mohammad K.; Faruque, Shah M.; Talukder, Kaisar A.

    2014-01-01

    Objective To investigate the prevalence and mechanisms of fluoroquinolone resistance in Shigella species isolated in Bangladesh and to compare with similar strains isolated in China. Methods A total of 3789 Shigella isolates collected from Clinical Microbiology Laboratory of icddr,b, during 2004–2010 were analyzed for antibiotic susceptibility. Analysis of plasmids, plasmid-mediated quinolone-resistance genes, PFGE, and sequencing of genes of the quinolone-resistance-determining regions (QRDR) were conducted in representative strains isolated in Bangladesh and compared with strains isolated in Zhengding, China. In addition, the role of efflux-pump was studied by using the efflux-pump inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP). Results Resistance to ciprofloxacin in Shigella species increased from 0% in 2004 to 44% in 2010 and S. flexneri was the predominant species. Of Shigella spp, ciprofloxacin resistant (CipR) strains were mostly found among S. flexneri (8.3%), followed by S. sonnei (1.5%). Within S. flexneri (n = 2181), 14.5% were resistance to ciprofloxacin of which serotype 2a was predominant (96%). MIC of ciprofloxacin, norfloxacin, and ofloxacin were 6–32 mg/L, 8–32 mg/L, and 8–24 mg/L, respectively in S. flexneri 2a isolates. Sequencing of QRDR genes of resistant isolates showed double mutations in gyrA gene (Ser83Leu, Asp87Asn/Gly) and single mutation in parC gene (Ser80Ile). A difference in amino acid substitution at position 87 was found between strains isolated in Bangladesh (Asp87Asn) and China (Asp87Gly) except for one. A novel mutation at position 211 (His→Tyr) in gyrA gene was detected only in the Bangladeshi strains. Susceptibility to ciprofloxacin was increased by the presence of CCCP indicating the involvement of energy dependent active efflux pumps. A single PFGE type was found in isolates from Bangladesh and China suggesting their genetic relatedness. Conclusions Emergence of fluoroquinolone resistance in Shigella

  17. Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

    Science.gov (United States)

    Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N; Harris, Anthony D; Smith, Catherine A; Maslow, Joel

    2008-04-01

    We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples.

  18. Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey.

    Science.gov (United States)

    Sanches, Bruno Squarcio; Martins, Gustavo Miranda; Lima, Karine; Cota, Bianca; Moretzsohn, Luciana Dias; Ribeiro, Laercio Tenorio; Breyer, Helenice P; Maguilnik, Ismael; Maia, Aline Bessa; Rezende-Filho, Joffre; Meira, Ana Carolina; Pinto, Henrique; Alves, Edson; Mascarenhas, Ramiro; Passos, Raissa; de Souza, Julia Duarte; Trindade, Osmar Reni; Coelho, Luiz Gonzaga

    2016-09-07

    To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods. The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization. Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. The H. pylori clarithromycin resistance rate in Brazil is at the

  19. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

    Science.gov (United States)

    2011-01-01

    Background Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones. Results Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds. Conclusions The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role

  20. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

    LENUS (Irish Health Repository)

    Costa, Sofia SANTOS

    2011-10-27

    Abstract Background Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones. Results Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds. Conclusions The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential

  1. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

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    Costa Sofia

    2011-10-01

    Full Text Available Abstract Background Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones. Results Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s of mutation(s found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds. Conclusions The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study

  2. Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India.

    Science.gov (United States)

    Banerjee, Tuhina; Anupurba, Shampa

    2016-10-01

    Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

  3. Fluoroquinolone resistance during 2000–2005 : An observational study

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    Sheehan Paul

    2008-05-01

    Full Text Available Abstract Background Moxifloxacin is a respiratory fluoroquinolone with a community acquired pneumonia indication. Unlike other fluoroquinolones used in our healthcare system, moxifloxacin's urinary excretion is low and thus we hypothesized that increased use of moxifloxacin is associated with an increase in fluoroquinolone resistance amongst gram negative uropathogens. Methods All antibiograms for Gram negative bacteria were obtained for 2000 to 2005. The defined daily dose (DDD for each fluoroquinolone was computed according to World Health Organization criteria. To account for fluctuation in patient volume, DDD/1000 bed days was computed for each year of study. Association between DDD/1000 bed days for each fluoroquinolone and the susceptibility of Gram negative bacteria to ciprofloxacin was assessed using Pearson's Correlation Coefficient, r. Results During the study period, there were 48,261 antibiograms, 347,931 DDD of fluoroquinolones, and 1,943,338 bed days. Use of fluoroquinolones among inpatients decreased from 237.2 DDD/1000 bed days in 2000 to 115.2 DDD/1000 bed days in 2005. With the exception of Enterobacter aerogenes, moxifloxacin use was negatively correlated with sensitivity among all 13 Gram negative species evaluated (r = -0.07 to -0.97. When the sensitivities of all Gram negative organisms were aggregated, all fluoroquinolones except moxifloxacin were associated with increased sensitivity (r = 0.486 to 1.000 while moxifloxacin was associated with decreased sensitivity (r = -0.464. Conclusion Moxifloxacin, while indicated for empiric treatment of community acquired pneumonia, may have important negative influence on local antibiotic sensitivities amongst Gram negative organisms. This effect was not shared by other commonly used members of the fluoroquinolone class.

  4. 猪链球菌对氟喹诺酮类药物的耐药性与靶位突变相关性%Relationship between Fluoroquinolone Resistance and Gene Mutation in streptococcus suis

    Institute of Scientific and Technical Information of China (English)

    芮萍; 马增军; 段玲欣; 刘谢荣; 倪静; 沈建忠

    2011-01-01

    To detect the relationship between fluoroquinolone resistance and gyrA and parC gene mutation in Streptococcus suis. The MIC of 34 strains of Streptococcus suis were determined by microdilution. The genes encoding the quinolone-resistance determining region (QRDRs) of parC and gyrA in fluoroquinolone-susceptible and -resistant Streptococcus suis clinical isolates were identified and sequenced. Ser to Phe and Arg to Leu mutation at position 79 and 87 of the parC gene was detected in fluoroquinolone resistance S. suis, and Arg to Ser, or Ser to Arg mutations at the position 66 or 81 of gyrA gene were detected in 4 highly resistance strains; no amino acid changes in gyrA or parC were detected for 9 fluoroquinolone-susceptible strains, the mutations in both genes was found in the strains with MIC of fluoroquinolone higher than 32μg · L-1. Mutations in parC gene result in low level resistance against fluoroquinolone, and high level resistance is resulted from the mutations in gyrA and parC both genes.%旨在了解猪链球菌对氟喹诺酮类药物耐药性与parC、gyrA基因突变的相关性,通过微量稀释法测定34株猪链球菌对4种氟喹诺酮类药物的MIC值,采用PCR方法扩增并测序分析了临床分离的猪链球菌对氟唪诺酮类约物10株耐药株和9株敏感株的parC和gyrA基因喹诺酮耐药决定区(QRDRs).在氟喹诺酮类药物耐药菌株parC基因QRDRs发生Ser79→Phe、Arg 87→Leu的氨基酸突变,在4株高度耐药菌株gyrA基因QRDRs发生Arg66→Ser,Ser81→Arg氨基酸突变;当菌株对氟喹诺酮类药物敏感时,parC和gyrA基因的QRDR区均未有突变;而当MIC≥32 μg·L-1 时,parC的氨基酸发生了 Ser79→Phe的突变,同时发生gyrA氨基酸Arg66→Ser,Set81→Arg突变.结果表明,猪链球菌对氟喹诺酮类药物低水平类耐药是由parC单一位点突变引起,而高水平耐药是由parC和gyrA双位点突变引起.

  5. Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients.

    Science.gov (United States)

    Ahmad, Nafees; Javaid, Arshad; Sulaiman, Syed Azhar Syed; Ming, Long Chiau; Ahmad, Izaz; Khan, Amer Hayat

    2016-01-01

    Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan. To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients. This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients' socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis. High degree of drug resistance (median 5 drugs, range 2-8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR=1.953, p=0.034) and public private mix (OR=2.824, p=0.046) sectors were predictors of ofloxacin resistance. The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public-private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  6. Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients

    Directory of Open Access Journals (Sweden)

    Nafees Ahmad

    Full Text Available Abstract Background Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan. Objective To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients. Methods This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients’ socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis. Results High degree of drug resistance (median 5 drugs, range 2–8 was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%, and more than half were resistant to second line drugs (55.1%. The majority of the patients were ofloxacin resistant (52.7%. Upon multivariate analysis previous tuberculosis treatment at private (OR = 1.953, p = 0.034 and public private mix (OR = 2.824, p = 0.046 sectors were predictors of ofloxacin resistance. Conclusion The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public–private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.

  7. Cotrimoxazole treats fluoroquinolone-resistant Salmonella typhi H58 infection.

    Science.gov (United States)

    Karki, Manan; Pandit, Sarbagya; Baker, Stephen; Basnyat, Buddha

    2016-10-26

    A woman aged 20 years presented with fever and no localising signs. She was treated with cotrimoxazole and the subsequent blood culture was positive for Salmonella typhi (S. typhi), which was resistant to fluoroquinolones but susceptible to cotrimoxazole. Genotyping identified an FQ-R subclade of H58 S. typhi Fever clearance time was 4 days after starting the antibiotics, and no relapses were noted on 2 months of follow-up. This inexpensive, well-known and easily available antimicrobial could be suitably redeployed for fluoroquinolone-resistant enteric fever in South Asia.

  8. Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story.

    Science.gov (United States)

    Nelson, Jennifer M; Chiller, Tom M; Powers, John H; Angulo, Frederick J

    2007-04-01

    Campylobacter species cause 1.4 million infections each year in the United States. Fluoroquinolones (e.g., ciprofloxacin) are commonly used in adults with Campylobacter infection and other infections. Fluoroquinolones (e.g., enrofloxacin) are also used in veterinary medicine. Human infections with fluoroquinolone-resistant Campylobacter species have become increasingly common and are associated with consumption of poultry. These findings, along with other data, prompted the US Food and Drug Administration to propose the withdrawal of fluoroquinolone use in poultry in 2000. A lengthy legal hearing concluded with an order to withdraw enrofloxacin from use in poultry (effective in September 2005). Clinicians are likely to continue to encounter patients with fluoroquinolone-resistant Campylobacter infection and other enteric infection because of the continued circulation of fluoroquinolone-resistant Campylobacter species in poultry flocks and in persons returning from foreign travel who have acquired a fluoroquinolone-resistant enteric infection while abroad. Judicious use of fluoroquinolones and other antimicrobial agents in human and veterinary medicine is essential to preserve the efficacy of these important chemotherapeutic agents.

  9. Fluoroquinolone resistance mechanisms in urinary tract pathogenic Escherichia coli isolated during rapidly increasing fluoroquinolone consumption in a low-use country

    DEFF Research Database (Denmark)

    Christiansen, Nina; Nielsen, Lene; Jakobsen, Lotte

    2011-01-01

    (6')-Ib-cr gene was detected on plasmids from five isolates showing ciprofloxacin MICs >512 mg/L. No overall clonal relationship among isolates was found according to PFGE. Target modification is the dominating fluoroquinolone resistance mechanism often found in combination with efflux and sometimes...

  10. In vitro selection of resistance in Escherichia coli and Klebsiella spp. at in vivo fluoroquinolone concentrations

    Science.gov (United States)

    2010-01-01

    Background Fluoroquinolones are potent antimicrobial agents used for the treatment of a wide variety of community- and nosocomial- infections. However, resistance to fluoroquinolones in Enterobacteriaceae is increasingly reported. Studies assessing the ability of fluoroquinolones to select for resistance have often used antimicrobial concentrations quite different from those actually acquired at the site of infection. The present study compared the ability to select for resistance of levofloxacin, ciprofloxacin and prulifloxacin at concentrations observed in vivo in twenty strains of Escherichia coli and Klebsiella spp. isolated from patients with respiratory and urinary infections. The frequencies of spontaneous single-step mutations at plasma peak and trough antibiotic concentrations were calculated. Multi-step selection of resistance was evaluated by performing 10 serial cultures on agar plates containing a linear gradient from trough to peak antimicrobial concentrations, followed by 10 subcultures on antibiotic-free agar. E. coli resistant strains selected after multi-step selection were characterized for DNA mutations by sequencing gyrA, gyrB, parC and parE genes. Results Frequencies of mutations for levofloxacin and ciprofloxacin were less than 10-11 at peak concentration, while for prulifloxacin they ranged from fluoroquinolones, levofloxacin was the most capable of limiting the occurrence of resistance. PMID:20409341

  11. 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.

  12. Low prevalence of fluoroquinolone resistant strains and resistance precursor strains in Streptococcus pneumoniae from patients with community-acquired pneumonia despite high fluoroquinolone usage.

    Science.gov (United States)

    Pletz, Mathias W; van der Linden, Mark; von Baum, Heike; Duesberg, Christoph B; Klugman, Keith P; Welte, Tobias

    2011-01-01

    We investigated the usage of fluoroquinolones and the prevalence of fluoroquinolone resistant pneumococci and their precursors (first step mutants and efflux expressing isolates) in patients with community-acquired pneumonia, who were enroled into the German CAPNETZ surveillance study from 2002 to 2006 before the introduction of the pneumococcal conjugate vaccine (n=5780). Thirty-eight percent of all outpatients received fluoroquinolones. Moxifloxacin accounted for 70%, levofloxacin for 19% and ciprofloxacin for 9% of all fluoroquinolone prescriptions. One hundred and sixty-three pneumococcal isolates from 556 patients with pneumococcal pneumonia were analyzed for fluoroquinolone resistance, efflux phenotype, prevalence of mutations within the quinolone-resistance determining regions and clonality. None of the isolates exhibited fluoroquinolone resistance, 1.2% of the isolates contained a first step mutation and 6.7% exhibited an efflux phenotype. There was no clonal relationship among these strains at increased risk for fluoroquinolone resistance. The absence of fluoroquinolone resistance in the context of high fluoroquinolone usage might be explained by the high proportion of third-generation fluoroquinolones with enhanced activity against pneumococci. Copyright © 2010 Elsevier GmbH. All rights reserved.

  13. Reduction of fluoroquinolone use is associated with a decrease in methicillin-resistant Staphylococcus aureus and fluoroquinolone-resistant Pseudomonas aeruginosa isolation rates: a 10 year study.

    Science.gov (United States)

    Lafaurie, Matthieu; Porcher, Raphael; Donay, Jean-Luc; Touratier, Sophie; Molina, Jean-Michel

    2012-04-01

    High rates of methicillin-resistant Staphylococcus aureus (MRSA) and fluoroquinolone-resistant Pseudomonas aeruginosa may be related, in part, to the overuse of fluoroquinolones. The objective was to analyse and correlate long-term surveillance data on MRSA and fluoroquinolone-resistant P. aeruginosa rates and antibiotic consumption after implementation of an institution-wide programme to reduce fluoroquinolone use. An interrupted time series/quasi-experimental study of monthly fluoroquinolone use and MRSA and fluoroquinolone-resistant P. aeruginosa isolation rates was carried out in a tertiary hospital during three periods: pre-intervention (January 2000-August 2005), intervention (September 2005-March 2006), and post-intervention (March 2006-March 2010). The effect of the intervention on the consumption of fluoroquinolones and bacterial resistance was assessed using segmented regression analyses. Mean monthly fluoroquinolone consumption dropped by 29.1 defined daily doses per 1000 patient-days (DDD/1000 PD) (95% CI 13.1-45.9; P = 0.0005) from a mean of 148.2 to 119.1 DDD/1000 PD during the intervention period. A sustained and significant decrease in fluoroquinolone consumption of -0.95 DDD/1000 PD/month was also observed during the post-intervention period (P = 0.0002). During the post-intervention period the rate of fluoroquinolone-resistant P. aeruginosa continuously decreased, from a mean of 42% to 26%, with a constant relative change rate of -13%/year (95% CI -19 to -5, P = 0.001). A decrease in the MRSA rate was observed during the intervention period, from a mean resistance rate of 27% to 21% (P fluoroquinolone control programme on the reduction of fluoroquinolone use with a significant decrease in fluoroquinolone-resistant P. aeruginosa and MRSA rates over 4 years.

  14. Molecular characterization of fluoroquinolone-resistant Aeromonas spp. isolated from imported shrimp.

    Science.gov (United States)

    Shakir, Zakiya; Khan, Saeed; Sung, Kidon; Khare, Sangeeta; Khan, Ashraf; Steele, Roger; Nawaz, Mohamed

    2012-11-01

    Sixty-three nalidixic acid-resistant Aeromonas sp. isolates were obtained from imported shrimp. Phylogenetic analysis of gyrB sequences indicated that 18 were A. enteropelogenes, 26 were A. caviae, and 19 were A. sobria. Double missense mutations in the quinolone resistance-determining region (QRDR) of gyrA at codon 83 (Ser→Val/Ile) and codon 92 (Leu→Met) coupled with a point mutation of parC at codon 80 (Ser→Ile/Phe) conferred high levels of quinolone resistance in the isolates. A majority of A. enteropelogenes and A. caviae strains harbored toxin genes, whereas only a few A. sobria strains harbored these genes. The fluoroquinolone-resistant Aeromonas spp. exhibited higher cytotoxicity than fluoroquinolone-sensitive, virulent Aeromonas spp. to rat epithelial cells.

  15. Quantitative Contributions of Target Alteration and Decreased Drug Accumulation to Pseudomonas aeruginosa Fluoroquinolone Resistance

    Science.gov (United States)

    Bruchmann, Sebastian; Dötsch, Andreas; Nouri, Bianka; Chaberny, Iris F.

    2013-01-01

    Quinolone antibiotics constitute a clinically successful and widely used class of broad-spectrum antibiotics; however, the emergence and spread of resistance increasingly limits the use of fluoroquinolones in the treatment and management of microbial disease. In this study, we evaluated the quantitative contributions of quinolone target alteration and efflux pump expression to fluoroquinolone resistance in Pseudomonas aeruginosa. We generated isogenic mutations in hot spots of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, and parC and inactivated the efflux regulator genes so as to overexpress the corresponding multidrug resistance (MDR) efflux pumps. We then introduced the respective mutations into the reference strain PA14 singly and in various combinations. Whereas the combined inactivation of two efflux regulator-encoding genes did not lead to resistance levels higher than those obtained by inactivation of only one efflux regulator-encoding gene, the combination of mutations leading to increased efflux and target alteration clearly exhibited an additive effect. This combination of target alteration and overexpression of efflux pumps was commonly observed in clinical P. aeruginosa isolates; however, these two mechanisms were frequently found not to be sufficient to explain the level of fluoroquinolone resistance. Our results suggest that there are additional mechanisms, independent of the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and/or MexXY-OprM efflux pump, that increase ciprofloxacin resistance in isolates with mutations in the QRDRs. PMID:23274661

  16. Introduction and establishment of fluoroquinolone-resistant Shigella sonnei into Bhutan

    Science.gov (United States)

    Chung The, Hao; Rabaa, Maia A.; Thanh, Duy Pham; Ruekit, Sirigade; Wangchuk, Sonam; Dorji, Tshering; Tshering, Kinzang Pem; Nguyen, To Nguyen Thi; Vinh, Phat Voong; Thanh, Tuyen Ha; Minh, Chau Nguyen Ngoc; Turner, Paul; Sar, Poda; Thwaites, Guy; Holt, Kathryn E.; Thomson, Nicholas R.; Bodhidatta, Ladaporn; Jeffries Mason, Carl; Baker, Stephen

    2015-01-01

    Shigella sonnei is a major contributor to the global burden of diarrhoeal disease, generally associated with dysenteric diarrhoea in developed countries but also emerging in developing countries. The reason for the recent success of S. sonnei is unknown, but is likely catalysed by its ability to acquire resistance against multiple antimicrobials. Between 2011 and 2013, S. sonnei exhibiting resistance to fluoroquinolones, the first-line treatment recommended for shigellosis, emerged in Bhutan. Aiming to reconstruct the introduction and establishment of fluoroquinolone-resistant S. sonnei populations in Bhutan, we performed whole-genome sequencing on 71 S. sonnei samples isolated in Bhutan between 2011 and 2013.We found that these strains represented an expansion of a clade within the previously described lineage III, found specifically in Central Asia. Temporal phylogenetic reconstruction demonstrated that all of the sequenced Bhutanese S. sonnei diverged from a single ancestor that was introduced into Bhutan around 2006. Our data additionally predicted that fluoroquinolone resistance, conferred by mutations in gyrA and parC, arose prior to the introduction of the founder strain into Bhutan. Once established in Bhutan, these S. sonnei had access to a broad gene pool, as indicated by the acquisition of extended-spectrum β-lactamase-encoding plasmids and genes encoding type IV pili. The data presented here outline a model for the introduction and maintenance of fluoroquinolone-resistant S. sonnei in a new setting. Given the current circulation of fluoroquinolone-resistant S. sonnei in Asia, we speculate that this pattern of introduction is being recapitulated across the region and beyond.

  17. Low rate of fluoroquinolone resistance in Mycobacterium tuberculosis isolates from northern Tanzania.

    Science.gov (United States)

    van den Boogaard, Jossy; Semvua, Hadija H; van Ingen, Jakko; Mwaigwisya, Solomon; van der Laan, Tridia; van Soolingen, Dick; Kibiki, Gibson S; Boeree, Martin J; Aarnoutse, Rob E

    2011-08-01

    Fluoroquinolones are used in second-line treatment of tuberculosis (TB) and have a potential role in shortening TB treatment duration. The wide use of fluoroquinolones in the treatment of other infections, including respiratory tract infections in patients with (undiagnosed) active TB, could result in fluoroquinolone-resistant Mycobacterium tuberculosis. We determined the rate of fluoroquinolone resistance in M. tuberculosis isolates obtained from Tanzanian patients and linked this to previous fluoroquinolone exposure and mycobacterial resistance to rifampicin and isoniazid. A total of 291 M. tuberculosis isolates were obtained between April 2009 and June 2010 from patients with smear-positive pulmonary TB and tested for susceptibility to ciprofloxacin, moxifloxacin, rifampicin and isoniazid. Information on previous fluoroquinolone use was obtained by interviewing patients and checking their medical files. Only 2 (0.7%) of the 291 M. tuberculosis isolates were resistant to ciprofloxacin; 1 of which was intermediately resistant to moxifloxacin as well. These two isolates were susceptible to rifampicin and isoniazid. Twenty-two (8%) of the 291 patients had a history of fluoroquinolone use (median: 7 days; interquartile range: 5-10 days). The patients from whom the fluoroquinolone-resistant M. tuberculosis isolates were obtained had no known history of previous fluoroquinolone use. Our findings indicate that the rate of fluoroquinolone-resistant M. tuberculosis in Tanzanian patients with TB is low and not related to previous, brief episodes of exposure to fluoroquinolones. The findings favour future application of fluoroquinolones in TB treatment regimens of shorter duration.

  18. Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes

    National Research Council Canada - National Science Library

    Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B; Sotgiu, Giovanni; Cox, Helen S; Holtz, Timothy H; Hollm-Delgado, Maria-Graciela; Keshavjee, Salmaan; DeRiemer, Kathryn; Centis, Rosella; D'Ambrosio, Lia; Lange, Christoph G; Bauer, Melissa; Menzies, Dick

    2013-01-01

    ...) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome...

  19. Characterization of recombinant fluoroquinolone-resistant pneumococcus-like isolates.

    Science.gov (United States)

    Balsalobre, Luz; Ortega, Montserrat; de la Campa, Adela G

    2013-01-01

    Fourteen fluoroquinolone-resistant streptococcal isolates with recombinant DNA topoisomerase genes, preliminarily identified as pneumococci, were further characterized using phenotypic and genotypic approaches. Phenotypic tests classified them as atypical pneumococci. Phylogenetic relationships were analyzed by using the sequences of seven housekeeping alleles from these isolates and from isolates of Streptococcus pneumoniae, Streptococcus mitis, Streptococcus oralis, and Streptococcus pseudopneumoniae. Four isolates grouped with S. pneumoniae, seven grouped with S. pseudopneumoniae, and three grouped with S. mitis. These results generally agreed with those obtained with an optochin susceptibility test and with the organization of the atp operon chromosomal region, encoding the F(o)F(1) H(+)-ATPase (the target of optochin). All seven isolates grouping with S. pseudopneumoniae share the same spr1368-atpC-atpA gene order; all four grouping with S. pneumoniae share the spr1368-IS1239-atpC-atpA order, and two out of the three grouping with S. mitis share the spr1284-atpC-atpA order. In addition, evidence for recombination within the seven housekeeping alleles of the S. pseudopneumoniae population was provided by several methods: the index of association (0.4598, P < 0.001), the pairwise homoplasy index, and the split-decomposition method. This study confirms the existence of pneumococci among the alpha-hemolytic streptococci with DNA topoisomerase genes showing a mosaic structure and reveals a close relationship between atypical pneumococci and S. pseudopneumoniae.

  20. Characterization of fluoroquinolone resistance and qnr diversity in Enterobacteriaceae from municipal biosolids.

    Directory of Open Access Journals (Sweden)

    Ella eKaplan

    2013-06-01

    Full Text Available Municipal biosolids produced during activated sludge treatment applied in waste water treatment plants, are significant reservoirs of antibiotic resistance, since they assemble both natural and fecal microbiota, as well as residual concentrations of antibiotic compounds. This raises major concerns regarding the environmental and epidemiological consequences of using them as fertilizers for crops. The second generation fluoroquinolone ciprofloxacin is probably the most abundant antibiotic compound detected in municipal biosolids due to its widespread use and sorption properties. Although fluoroquinolone resistance was originally thought to result from mutations in bacterial gyrase and topoisomerase IV genes, it is becoming apparent that it is also attributed to plasmid-associated resistance factors, which may propagate environmental antibiotic resistance. The objective of this study was to assess the impact of the activated sludge process on fluoroquinolone resistance. The scope of resistances and mobile genetic mechanisms associated with fluoroquinolone resistance were evaluated by screening large collections of ciprofloxacin-resistant Enterobacteriaceae strains from sludge (n=112 and from raw sewage (n=89. Plasmid-mediated quinolone resistance determinants (qnrA, B and S were readily detected in isolates from both environments, the most dominant being qnrS. Interestingly, all qnr variants were significantly more abundant in sludge isolates than in the isolates from raw sewage. Almost all of ciprofloxacin-resistant isolates were resistant to multiple antibiotic compounds. The sludge isolates were on the whole resistant to a broader range of antibiotic compounds than the raw sewage isolates; however this difference was not statistically significant. Collectively, this study indicates that the activated sludge selects for multiresistant bacterial strains, and that mobile quinolone-resistance elements may have a selective advantage in the activated

  1. In vitro activity of WQ-3810, a novel fluoroquinolone, against multidrug-resistant and fluoroquinolone-resistant pathogens.

    Science.gov (United States)

    Kazamori, Daichi; Aoi, Hiroshi; Sugimoto, Kaori; Ueshima, Taichi; Amano, Hirotaka; Itoh, Kenji; Kuramoto, Yasuhiro; Yazaki, Akira

    2014-11-01

    The aim of this study was to examine the in vitro antibacterial activity of WQ-3810, a new fluoroquinolone, against clinically relevant pathogens such as Acinetobacter baumannii, Escherichia coli and Streptococcus pneumoniae, including multidrug-resistant (MDR) and fluoroquinolone-resistant (FQR) isolates, compared with those of ciprofloxacin, levofloxacin, moxifloxacin and gemifloxacin. WQ-3810 demonstrated the most potent activity against the antimicrobial-resistant pathogens tested. Against A. baumannii, including MDR isolates, the potency of WQ-3810 [minimum inhibitory concentration for 90% of the organisms (MIC(90))=1 mg/L] was more than eight-fold higher than that of ciprofloxacin (64 mg/L) and levofloxacin (8 mg/L). Against E. coli and S. pneumoniae, including FQR isolates, WQ-3810 (MIC(90)=4 mg/L and 0.06 mg/L, respectively) was also more active than ciprofloxacin (64 mg/L and 2 mg/L) and levofloxacin (32 mg/L and 2 mg/L). Furthermore, WQ-3810 was the most potent among the fluoroquinolones tested against meticillin-resistant Staphylococcus aureus (MRSA) and Neisseria gonorrhoeae, including FQR isolates. In particular, WQ-3810 demonstrated highly potent activity against FQR isolates of A. baumannii, E. coli and S. pneumoniae with amino acid mutation(s) in the quinolone resistance-determining region of DNA gyrase and/or topoisomerase IV, which are the target enzymes of fluoroquinolones. An enzyme inhibition study performed using FQR E. coli DNA gyrase suggested that the potent antibacterial activity of WQ-3810 against drug-resistant isolates partly results from the strong inhibition of the target enzymes. In conclusion, this study demonstrated that WQ-3810 exhibits extremely potent antibacterial activity over the existing fluoroquinolones, particularly against MDR and FQR pathogens. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Association of fluoroquinolone resistance, virulence genes, and IncF plasmids with extended-spectrum-β-lactamase-producing Escherichia coli sequence type 131 (ST131) and ST405 clonal groups.

    Science.gov (United States)

    Matsumura, Yasufumi; Yamamoto, Masaki; Nagao, Miki; Ito, Yutaka; Takakura, Shunji; Ichiyama, Satoshi

    2013-10-01

    The global increase of extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli is associated with the specific clonal group sequence type 131 (ST131). In order to understand the successful spread of ESBL-producing E. coli clonal groups, we characterized fluoroquinolone resistance determinants, virulence genotypes, and plasmid replicons of ST131 and another global clonal group, ST405. We investigated 41 ST131-O25b, 26 ST131-O16, 41 ST405, and 41 other ST (OST) ESBL-producing isolates, which were collected at seven acute care hospitals in Japan. The detection of ESBL types, fluoroquinolone resistance-associated mutations (including quinolone resistance-determining regions [QRDRs]), virulence genotypes, plasmid replicon types, and IncF replicon sequence types was performed using PCR and sequencing. blaCTX-M, specifically blaCTX-M-14, was the most common ESBL gene type among the four groups. Ciprofloxacin resistance was found in 90% of ST131-O25b, 19% of ST131-O16, 100% of ST405, and 54% of OST isolates. Multidrug resistance was more common in the ST405 group than in the ST131-O25 group (56% versus 32%; P = 0.045). All ST131-O25b isolates except one had four characteristic mutations in QRDRs, but most of the isolates from the other three groups had three mutations in common. The ST131-O25b and ST405 groups had larger numbers of virulence genes than the OST group. All of the ST131-O25b and ST405 isolates and most of the ST131-O16 and OST isolates carried IncF replicons. The most prevalent IncF replicon sequence types differed between the four clonal groups. Both the ST131-O25b and ST405 clonal groups had a fluoroquinolone resistance mechanism in QRDRs, multidrug resistance, high virulence, and IncF plasmids, suggesting the potential for further global expansion and a need for measures against these clonal groups.

  3. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones

    National Research Council Canada - National Science Library

    Li, Qiming; Xie, Longxiang; Long, Quanxin; Mao, Jinxiao; Li, Hui; Zhou, Mingliang; Xie, Jianping

    2015-01-01

    .... Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics...

  4. Fluoroquinolones: is there a different mechanism of action and resistance against Streptococcus pneumoniae?

    Science.gov (United States)

    Harding, I; Simpson, I

    2000-10-01

    Starting in the 1950s, study and elucidation of the biochemical mechanisms of resistance to antibiotics led to the understanding of both the biology of bacteria and the mode of action of antibiotics. This holds true for the relationship between Streptococcus pneumoniae and the fluoroquinolones. A new feature in this approach is the availability of the nearly complete chromosome sequence of this major human pathogen. In S. pneumoniae, resistance appears to be mainly due to mutational alterations in the intracellular targets of the fluoroquinolones, the type II DNA topoisomerase gyrase and topoisomerase IV. Both enzymes appear to be the primary targets of the drugs in this species. Mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene or the parC gene, which encode the A subunits of DNA gyrase and topoisomerase IV respectively, confer resistance to single-step mutants. Mutations in gyrB and parE, which encode the B subunits of DNA gyrase and topo IV, respectively, have also been implicated in the fluoroquinolone resistance of certain mutants obtained in vitro. The antibiotics most affected by a single mutation are those for which the mutation occurs in their preferred target e.g. gyrase for sparfloxacin and gatifloxacin and topo IV for ciprofloxacin and levofloxacin. The activity of all fluoroquinolones is decreased further when two or more mutations are present. Because they possess similar targets of action, there is cross resistance, albeit at various degrees depending on the intrinsic activity of the molecule, among fluoroquinolones. This stresses, once more, the misleading concept of breakpoints for clinical categorization. A second mechanism of resistance, enhanced active efflux of hydrophilic quinolones such as norfioxacin and ciprofloxacin, is mediated by the membrane-associated protein, PmrA (pneumococcal multidrug resistance). This protein is a 12-transmembrane segment proton-dependent multidrug efflux pump of the major

  5. Fluoroquinolone-resistance mechanisms and phylogenetic background of clinical Escherichia coli strains isolated in south-east Poland.

    Science.gov (United States)

    Korona-Glowniak, Izabela; Skrzypek, Kinga; Siwiec, Radosław; Wrobel, Andrzej; Malm, Anna

    2016-07-01

    Fluorochinolones are a class of broad-spectrum antimicrobials in the treatment of several infections, including those caused by Escherichia coli. Due to the increasing resistance of bacteria to antimicrobials, an understanding of fluoroquinolone resistance is important for infection control. The aim of this study was to determine susceptibility of clinical E. coli strains to fluoroquinolones and characterize their mechanisms of quinolone resistance. Totally, 79 non-duplicate clinical E. coli isolates included in this study were mainly from skin lesion -36 (45.6%) isolates; 54 (68.4%) isolates were assigned to phylogenetic B2 group. Resistance to ciprofloxacin was found in 20 isolates. In the quinolone resistance-determining region (QRDR) region of gyrA and parC, 4 types of point mutations were detected. Mutations in parC gene were found in all strains with gyrA mutations. Predominance of double mutation in codon 83 and 87 of gyrA (90%) and in codon 80 of parC (90%) was found. Moreover, plasmid-mediated quinolone resistance (PMRQ) determinants (qnrA or qnrB and/or aac(6')-Ib-cr) were present in 5 (25%) out of 20 fluoroquinolone-resistant isolates. Resistance to fluoroquinolones in all of the tested clinical E. coli isolates correlated with point mutations in both gyrA and parC. The majority of fluoroquinolone-resistant strains belonged to D and B2 phylogenetic groups.

  6. Dose-related selection of fluoroquinolone-resistant Escherichia coli.

    Science.gov (United States)

    Olofsson, Sara K; Marcusson, Linda L; Strömbäck, Ann; Hughes, Diarmaid; Cars, Otto

    2007-10-01

    To investigate the effects of clinically used doses of norfloxacin, ciprofloxacin and moxifloxacin on survival and selection in Escherichia coli populations containing fluoroquinolone-resistant subpopulations and to measure the value of the pharmacodynamic index AUC/mutant prevention concentration (MPC) that prevents the growth of pre-existing resistant mutants. Mixed cultures of susceptible wild-type and isogenic single (gyrA S83L) or double (gyrA S83L, Delta marR) fluoroquinolone-resistant mutants were exposed to fluoroquinolones for 24 h in an in vitro kinetic model. Antibiotic concentrations modelled pharmacokinetics attained with clinical doses. All tested doses eradicated the susceptible wild-type strain. Norfloxacin 200 mg administered twice daily selected for both single and double mutants. Ciprofloxacin 250 mg administered twice daily eradicated the single mutant, but not the double mutant. For that, 750 mg administered twice daily was required. Moxifloxacin 400 mg once daily eliminated the single mutant, but did not completely remove the double mutant. The MPC of ciprofloxacin was determined and based on those dose simulations that eradicated mutant subpopulations, an AUC/MPC(wild-type) of 35 prevented selection of the single mutant, whereas an AUC/MPC(single mutant) of 14 (equivalent to an AUC/MPC(wild-type) of 105) prevented selection of the double mutant. All tested clinical dosing regimens were effective in eradicating susceptible bacteria, but ciprofloxacin 750 mg twice daily was the only dose that prevented the selection of single- and double-resistant E. coli mutants. Thus, among approved fluoroquinolone dosing regimens, some are significantly more effective than others in exceeding the mutant selection window and preventing the enrichment of resistant mutants.

  7. Occurrence of (fluoro)quinolones and (fluoro)quinolone resistance in soil receiving swine manure for 11 years.

    Science.gov (United States)

    Xu, Yonggang; Yu, Wantai; Ma, Qiang; Zhou, Hua

    2015-10-15

    Because of the widespread use of antibiotics in animal breeding, the agricultural application of animal manure can lead to the introduction of antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes to the soil and surrounding environment, which may pose a threat to public health. In this study, we investigated the status of (fluoro)quinolone (FQ) residues and FQ resistance levels in soil with and without receiving long-term swine manure. Six FQs (pipemidic acid, lomefloxacin, enrofloxacin, norfloxacin, ciprofloxacin, and ofloxacin) were only detected in manured soil, with individual concentrations ranging from below the detection limit to 27.2 μg kg(-1) and increasing with the increase in swine manure application rates. Higher load rates of swine manure yielded a higher number of ciprofloxacin-resistant (CIPr) bacteria after spreading. A total of 24 CIPr bacterial isolates were obtained from the tested soil, which belonged to four phyla (Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes) or were related to nine different genera. Only 18 isolates from manured soil were positive for five plasmid-mediated quinolone resistance (PMQR) genes (aac(6')-Ib-cr, qnrD, qepA, oqxA, and oqxB). To our knowledge, this study is the first to examine the occurrence of PMQR genes in FQ-resistant bacteria from the soil environment. A similar result was observed for the total DNA from soil, with the exception of aac(6')-Ib being detected in the control sample. The absolute and relative abundances of total PMQR genes also increased with fertilization quantity. Significant correlations were observed between FQ resistance levels and FQ concentrations. These results indicated that the agricultural application of swine manure led to FQ residues and enhanced FQ resistance. This investigation provides baseline data on FQ resistance profiles in soils receiving long-term swine manure. Copyright © 2015. Published by Elsevier B.V.

  8. Multiple Antimicrobial Resistance and Novel Point Mutation in Fluoroquinolone-Resistant Escherichia coli Isolates from Mangalore, India.

    Science.gov (United States)

    Kogaluru Shivakumaraswamy, Santhosh; Vijaya Kumar, Deekshit; Moleyuru Nagarajappa, Venugopal; Karunasagar, Iddya; Karunasagar, Indrani

    2017-04-26

    Fluoroquinolone resistance in bacteria is usually associated with mutations in the topoisomerase regions. We report a novel point mutation in fluoroquinolone-resistant Escherichia coli strains. E. coli isolated from the environment in and around Mangalore, India, were examined for their antimicrobial resistance profile to 12 antibiotics and for the antibiotic resistance genes by polymerase chain reaction. Of the 67 E. coli isolated, 24 (35.8%) were sensitive to all antibiotics and 43 (64.2%) showed resistance to at least one of the 12 antibiotics used in the study. One isolate (EC10) was resistant to nine of the 12 antibiotics used. Resistance to nalidixic acid was the most common (34.32%), followed by nitrofurantoin (26.86%), tetracycline (22.38%), ampicillin (20.89%), cotrimoxazole (13.43%), ciprofloxacin (11.94%), gentamicin (10.44%), piperacillin/tazobactam (7.46%), chloramphenicol (7.46%), and cefotaxime (4.47%). Least resistance was observed for meropenem (1.49%) and none of the isolates showed resistance to imipenem. All the isolates harbored resistance genes corresponding to their antimicrobial resistance. Few quinolone-resistant isolates carried single point mutation (ser83Leu) and some had double point mutation (Ser83Leu and Asp87Asn) in gyrA. A third novel point mutation was also observed at position 50 with the change in the amino acid from tyrosine to cysteine (Tyr50Cys) in gyrA region. The study throws light on a novel point mutation in fluoroquinolone-resistant isolates. While the study helps to understand the risk and occurrence of antibiotic resistance among gram-negative bacteria from the environment, the alarming rate of antibiotic-resistant bacteria is a cause of concern in addressing infections.

  9. New insights into fluoroquinolone resistance in Mycobacterium tuberculosis: functional genetic analysis of gyrA and gyrB mutations.

    Directory of Open Access Journals (Sweden)

    Seidu Malik

    Full Text Available Fluoroquinolone antibiotics are among the most potent second-line drugs used for treatment of multidrug-resistant tuberculosis (MDR TB, and resistance to this class of antibiotics is one criterion for defining extensively drug resistant tuberculosis (XDR TB. Fluoroquinolone resistance in Mycobacterium tuberculosis has been associated with modification of the quinolone resistance determining region (QRDR of gyrA. Recent studies suggest that amino acid substitutions in gyrB may also play a crucial role in resistance, but functional genetic studies of these mutations in M. tuberculosis are lacking. In this study, we examined twenty six mutations in gyrase genes gyrA (seven and gyrB (nineteen to determine the clinical relevance and role of these mutations in fluoroquinolone resistance. Transductants or clinical isolates harboring T80A, T80A+A90G, A90G, G247S and A384V gyrA mutations were susceptible to all fluoroquinolones tested. The A74S mutation conferred low-level resistance to moxifloxacin but susceptibility to ciprofloxacin, levofloxacin and ofloxacin, and the A74S+D94G double mutation conferred cross resistance to all the fluoroquinolones tested. Functional genetic analysis and structural modeling of gyrB suggest that M330I, V340L, R485C, D500A, D533A, A543T, A543V and T546M mutations are not sufficient to confer resistance as determined by agar proportion. Only three mutations, N538D, E540V and R485C+T539N, conferred resistance to all four fluoroquinolones in at least one genetic background. The D500H and D500N mutations conferred resistance only to levofloxacin and ofloxacin while N538K and E540D consistently conferred resistance to moxifloxacin only. Transductants and clinical isolates harboring T539N, T539P or N538T+T546M mutations exhibited low-level resistance to moxifloxacin only but not consistently. These findings indicate that certain mutations in gyrB confer fluoroquinolone resistance, but the level and pattern of resistance varies

  10. Accumulation of plasmid-mediated fluoroquinolone resistance genes, qepA and qnrS1, in Enterobacter aerogenes co-producing RmtB and class A beta-lactamase LAP-1.

    Science.gov (United States)

    Park, Yeon-Joon; Yu, Jin Kyung; Kim, Sang-Il; Lee, Kyungwon; Arakawa, Yoshichika

    2009-01-01

    A new plasmid-mediated fluoroquinolone efflux pump gene, qepA, is known to be associated with the rmtB gene, which confers high-level resistance to aminoglycosides. We investigated the qepA gene in 573 AmpC-producing Enterobacteriaceae including one Citrobacter freundii known to harbor rmtB. Of them, two clonally unrelated E. aerogenes harbored qepA. Both isolates co-harbored rmtB, qnrS1, qepA, and bla(LAP-1) on an IncFI type plasmid. The qepA was flanked by two copies of IS26 containing ISCR3C, tnpA, tnpR, bla(TEM), and rmtB. The qnrS1 and bla(LAP-1) were located upstream of qepA. All the resistance determinants (qepA, qnrS1, rmtB, and bla(LAP-1)) were co-transferred to E. coli J53 by filter mating from both isolates. Although the prevalence of qepA is currently low, considering the presence of ISCR3C and the possibility of co-selection and co-transferability of plasmids, more active surveillance for these multi-drug resistant bacteria and prudent use of antimicrobials are needed.

  11. Relationships among Ciprofloxacin, Gatifloxacin, Levofloxacin, and Norfloxacin MICs for Fluoroquinolone-Resistant Escherichia coli Clinical Isolates▿

    Science.gov (United States)

    Becnel Boyd, Lauren; Maynard, Merry J.; Morgan-Linnell, Sonia K.; Horton, Lori Banks; Sucgang, Richard; Hamill, Richard J.; Jimenez, Javier Rojo; Versalovic, James; Steffen, David; Zechiedrich, Lynn

    2009-01-01

    Fluoroquinolones are some of the most prescribed antibiotics in the United States. Previously, we and others showed that the fluoroquinolones exhibit a class effect with regard to the CLSI-established breakpoints for resistance, such that decreased susceptibility (i.e., an increased MIC) to one fluoroquinolone means a simultaneously decreased susceptibility to all. For defined strains, however, clear differences exist in the pharmacodynamic properties of each fluoroquinolone and the extent to which resistance-associated genotypes affect the MICs of each fluoroquinolone. In a pilot study of 920 clinical Escherichia coli isolates, we uncovered tremendous variation in norfloxacin MICs. The MICs for all of the fluoroquinolone-resistant isolates exceeded the resistance breakpoint, reaching 1,000 μg/ml. Approximately 25% of the isolates (n = 214), representing the full range of resistant norfloxacin MICs, were selected for the simultaneous determinations of ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs. We found that (i) great MIC variation existed for all four fluoroquinolones, (ii) the ciprofloxacin and levofloxacin MICs of >90% of the fluoroquinolone-resistant isolates were higher than the resistance breakpoints, (iii) ciprofloxacin and levofloxacin MICs were distributed into two distinct groups, (iv) the MICs of two drug pairs (ciprofloxacin and norfloxacin by Kendall's Tau-b test and gatifloxacin and levofloxacin by paired t test) were similar with statistical significance but were different from each other, and (v) ∼2% of isolates had unprecedented fluoroquinolone MIC relationships. Thus, although the fluoroquinolones can be considered equivalent with regard to clinical susceptibility or resistance, fluoroquinolone MICs differ dramatically for fluoroquinolone-resistant clinical isolates, likely because of differences in drug structure. PMID:18838594

  12. Emergence of fluoroquinolone-resistant Propionibacterium acnes caused by amino acid substitutions of DNA gyrase but not DNA topoisomerase IV.

    Science.gov (United States)

    Nakase, Keisuke; Sakuma, Yui; Nakaminami, Hidemasa; Noguchi, Norihisa

    2016-12-01

    With the aim of elucidating the mechanisms of fluoroquinolones resistance in Propionibacterium acnes, we determined the susceptibility of fluoroquinolones in 211 isolates from patients with acne vulgaris. We identified five isolates (2.4%) with reduced susceptibility to nadifloxacin (minimum inhibitory concentration ≥ 4 μg/ml). Determination of the sequences of the DNA gyrase (gyrA and gyrB) and DNA topoisomerase (parC and parE) genes showed the amino acid substitutions Ser101Leu and Asp105Gly of GyrA in four and one of the isolates, respectively. In vitro mutation experiments showed that low-level fluoroquinolone-resistant mutants with the Ser101Leu or Asp105Gly substitution in GyrA could be obtained from selection with ciprofloxacin and levofloxacin. The pattern of substitution (Ser101Trp in GyrA) caused by nadifloxacin selection was different from that induced by the other fluoroquinolones. In the isolation of further high-level resistant mutants, acquisition of another amino acid substitution of GyrB in addition to those of GyrA was detected, but there were no substitutions of ParC and ParE. In addition, the mutant prevention concentration and mutation frequency of nadifloxacin were lowest among the tested fluoroquinolones. The growth of the Ser101Trp mutant was lower than that of the other mutants. Our findings suggest that the Ser101Trp mutant of P. acnes emerges rarely and disappears immediately, and the risk for the prevalence of fluoroquinolones-resistant P. acnes differs according to the GyrA mutation type. To our knowledge, this study is the first to demonstrate the mechanisms of resistance to fluoroquinolones in P. acnes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. [Resistance to fluoroquinolones in 2013: what are the consequences in internal medicine?].

    Science.gov (United States)

    de Lastours, V; Fantin, B

    2014-09-01

    Because of their important qualities, fluoroquinolones are amongst the most prescribed antibiotics in the world. The corollary of this success is the rapid increase in resistance to fluoroquinolones, responsible for treatment failures. Moreover, fluoroquinolone-resistance is often accompanied by resistance to other classes of antibiotics. Currently, significant levels of resistance are found both in hospitals and in community settings, severely limiting possibilities for empirical use of fluoroquinolones. A major mechanism explaining the rapid emergence of resistance to fluoroquinolones is their specific impact on human microbiota and the selection of resistant strains in the microbiota, which seems to be an unavoidable ecological side effect. In order to preserve the efficiency of this important class of antibiotics, limiting their use and respecting good practice recommendations are essential. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system

    Science.gov (United States)

    Maruri, Fernanda; Sterling, Timothy R.; Kaiga, Anne W.; Blackman, Amondrea; van der Heijden, Yuri F.; Mayer, Claudine; Cambau, Emmanuelle; Aubry, Alexandra

    2012-01-01

    Fluoroquinolone resistance in Mycobacterium tuberculosis has become increasingly important. A review of mutations in DNA gyrase, the fluoroquinolone target, is needed to improve the molecular detection of resistance. We performed a systematic review of studies reporting mutations in DNA gyrase genes in clinical M. tuberculosis isolates. From 42 studies that met inclusion criteria, 1220 fluoroquinolone-resistant M. tuberculosis isolates underwent sequencing of the quinolone resistance-determining region (QRDR) of gyrA; 780 (64%) had mutations. The QRDR of gyrB was sequenced in 534 resistant isolates; 17 (3%) had mutations. Mutations at gyrA codons 90, 91 or 94 were present in 654/1220 (54%) resistant isolates. Four different GyrB numbering systems were reported, resulting in mutation location discrepancies. We propose a consensus numbering system. Most fluoroquinolone-resistant M. tuberculosis isolates had mutations in DNA gyrase, but a substantial proportion did not. The proposed consensus numbering system can improve molecular detection of resistance and identification of novel mutations. PMID:22279180

  15. Consumption patterns and in vitro resistance of Streptococcus pneumoniae to fluoroquinolones.

    Science.gov (United States)

    Simoens, Steven; Verhaegen, Jan; van Bleyenbergh, Pascal; Peetermans, Willy E; Decramer, Marc

    2011-06-01

    This article analyzes patterns of consumption of fluoroquinolones and documents the in vitro resistances of Streptococcus pneumoniae isolates to fluoroquinolones in the ambulatory care setting in Belgium over time. The volume of fluoroquinolone consumption has fallen consistently since 2003. Fluoroquinolones were used primarily for their registered indications (i.e., urinary tract infections and lower respiratory tract infections). The MIC distributions of moxifloxacin and levofloxacin in S. pneumoniae isolates remained stable during 2004 to 2009, and the level of resistance to moxifloxacin and levofloxacin was low (≤1%).

  16. Emergence and Acquisition of Fluoroquinolone-Resistant Gram-Negative Bacilli in the Intestinal Tracts of Mice Treated with Fluoroquinolone Antimicrobial Agents▿

    OpenAIRE

    Pultz, Michael J; Nerandzic, Michelle M.; Stiefel, Usha; Donskey, Curtis J.

    2008-01-01

    After mice received orogastric administration of a fluoroquinolone-resistant Klebsiella pneumoniae strain, subcutaneous treatment with ciprofloxacin, levofloxacin, and moxifloxacin promoted persistent low-density colonization in 10% to 40% of the mice, whereas treatment with clindamycin consistently promoted high-density colonization. No emergence of fluoroquinolone-resistant gram-negative bacilli was detected in the mice during or after treatment with the fluoroquinolone antimicrobial agents.

  17. Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131.

    Science.gov (United States)

    Ben Zakour, Nouri L; Alsheikh-Hussain, Areej S; Ashcroft, Melinda M; Khanh Nhu, Nguyen Thi; Roberts, Leah W; Stanton-Cook, Mitchell; Schembri, Mark A; Beatson, Scott A

    2016-04-26

    Escherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publically available genomes from different countries and used this data set to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986 and illustrate the impact of this pivotal event on the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131. Escherichia coli sequence type 131 (ST131) is a recently emerged and globally disseminated multidrug-resistant clone frequently associated with human urinary tract and bloodstream infections. In this study, we have used two large publically available genomic data sets to define a number of critical steps in the evolution of this important pathogen. We show that resistance to fluoroquinolones, a class of broad-spectrum antibiotic used extensively in human medicine and veterinary practice, developed in ST131 soon after the introduction of these antibiotics in the United States, most likely in North America. We also mapped the acquisition of several fitness and virulence determinants by ST131 and demonstrate these events occurred prior to the development of fluoroquinolone resistance. Thus, ST131 has

  18. ESBL Genotypes in Fluoroquinolone-Resistant and Fluoroquinolone-Susceptible ESBL-Producing Escherichia coli Urinary Isolates in Manitoba

    Directory of Open Access Journals (Sweden)

    Philippe RS Lagacé-Wiens

    2007-01-01

    Full Text Available OBJECTIVE: Extended-spectrum beta-lactamase (ESBL-producing Escherichia coli are increasingly common in nosocomial and community settings. Furthermore, fluoroquinolone (FQ and even multidrug resistance (MDR appear to be associated with certain ESBL genotypes. The purpose of the present study was to determine which ESBL genotypes are associated with FQ and MDR in E coli urinary isolates in Manitoba.

  19. The role of fluoroquinolones in the management of urinary tract infections in areas with high rates of fluoroquinolone-resistant uropathogens.

    Science.gov (United States)

    Chen, Y-H; Ko, W-C; Hsueh, P-R

    2012-08-01

    Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole-resistant uropathogens. However, because of the increased use of both oral and parenteral fluoroquinolones for other kinds of infections, increasing rates of resistance to fluoroquinolones among the most common uropathogens have challenged this recommendation, particularly in the Asia-Pacific region. The current interpretative criteria for the in vitro susceptibility of uropathogens to some fluoroquinolones, such as levofloxacin and ciprofloxacin, are set according to their therapeutic efficacy for bloodstream infections, and are not specific to UTIs. Fluoroquinolones exhibit concentration-dependent antibacterial activity, high renal excretion, and relatively early and prolonged urinary bactericidal titers. Whether or not current interpretative criteria for the in vitro susceptibility of uropathogens to fluoroquinolones predict clinical failure in treating UTIs is still controversial. The Clinical and Laboratory Standards Institute (CLSI) has established UTI-specific breakpoints for resistance to a few fluoroquinolones. However, the application of high-dose fluoroquinolone therapy for the treatment of mild to moderate UTIs caused by isolates with higher minimum inhibitory concentrations (MICs) of several fluoroquinolones needs to be re-validated based on more relevant clinical studies, prudent pharmacokinetic/pharmacodynamic (PK/PD) considerations, and thorough study of the mutant prevention concentration of fluoroquinolones in the treatment of UTI.

  20. Fluoroquinolone resistance in the rectal carriage of men in an active surveillance cohort: longitudinal analysis.

    Science.gov (United States)

    Cohen, Jason E; Landis, Patricia; Trock, Bruce J; Patel, Hiten D; Ball, Mark W; Auwaerter, Paul G; Schaeffer, Edward; Carter, H Ballentine

    2015-02-01

    Rectal swabs can identify men with fluoroquinolone resistant bacteria and decrease the infection rate after transrectal ultrasound guided prostate biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of fluoroquinolone resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance with time. We evaluated 416 men with prostate cancer on active surveillance who underwent rectal swabs to assess the rate of fluoroquinolone resistance compared to that in men undergoing diagnostic transrectal ultrasound guided prostate biopsy. The chi-square test and Student t-test were used to compare categorical and continuous variables, respectively. Poisson regression analysis was used for multivariate analysis. On the initial swab fluoroquinolone resistance was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221 (24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0% of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p fluoroquinolone. Resistance is significantly associated with diabetes but the number of prior biopsies is not. Men with fluoroquinolone resistant flora tend to remain resistant with time. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project.

    Science.gov (United States)

    Zignol, Matteo; Dean, Anna S; Alikhanova, Natavan; Andres, Sönke; Cabibbe, Andrea Maurizio; Cirillo, Daniela Maria; Dadu, Andrei; Dreyer, Andries; Driesen, Michèle; Gilpin, Christopher; Hasan, Rumina; Hasan, Zahra; Hoffner, Sven; Husain, Ashaque; Hussain, Alamdar; Ismail, Nazir; Kamal, Mostofa; Mansjö, Mikael; Mvusi, Lindiwe; Niemann, Stefan; Omar, Shaheed V; Qadeer, Ejaz; Rigouts, Leen; Ruesch-Gerdes, Sabine; Schito, Marco; Seyfaddinova, Mehriban; Skrahina, Alena; Tahseen, Sabira; Wells, William A; Mukadi, Ya Diul; Kimerling, Michael; Floyd, Katherine; Weyer, Karin; Raviglione, Mario C

    2016-10-01

    Pyrazinamide and fluoroquinolones are essential antituberculosis drugs in new rifampicin-sparing regimens. However, little information about the extent of resistance to these drugs at the population level is available. In a molecular epidemiology analysis, we used population-based surveys from Azerbaijan, Bangladesh, Belarus, Pakistan, and South Africa to investigate resistance to pyrazinamide and fluoroquinolones among patients with tuberculosis. Resistance to pyrazinamide was assessed by gene sequencing with the detection of resistance-conferring mutations in the pncA gene, and susceptibility testing to fluoroquinolones was conducted using the MGIT system. Pyrazinamide resistance was assessed in 4972 patients. Levels of resistance varied substantially in the surveyed settings (3·0-42·1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1·0-16·6% for ofloxacin, to 0·5-12·4% for levofloxacin, and 0·9-14·6% for moxifloxacin when tested at 0·5 μg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 μg/mL was low in all countries. Although pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 19-63% of patients with rifampicin-resistant tuberculosis. Even though the high level of resistance to ofloxacin found in Pakistan is worrisome because it might be the expression of extensive and unregulated use of fluoroquinolones in some parts of Asia, the negligible levels of resistance to fourth-generation fluoroquinolones documented in all survey sites is an encouraging finding. Rational use of this class of antibiotics should therefore be ensured to preserve its effectiveness. Bill & Melinda Gates Foundation, United States Agency for International Development

  2. The resistance of pseudomonas aeruginosa strains to fluoroquinolone group of antibiotics

    Directory of Open Access Journals (Sweden)

    Algun U

    2004-01-01

    Full Text Available Fluoroquinolones are antibiotics that are very effective against many gram negative microorganisms, including P. aeruginosa. However, resistance to these antibiotics has been reported in recent years as well. In this study, the sensivity of 136 P. aeruginosa strains, isolated from various clinical materials, to fluoroquinolones has been investigated. The lowest resistance rate was in ciprofloxacin with 12.5%. The resistance rates of the others were as follows: norfloxacin 14.7%, levofloxacin 16.9%, ofloxacin 19.9% and pefloxacin 28.7%. The 88.2% of the resistant strains to all fluoroquinolones were originated from intensive care unit.

  3. High prevalence of Fluoroquinolone- and Methicillin-resistant Staphylococcus pseudintermedius isolates from canine pyoderma and otitis externa in veterinary teaching hospital.

    Science.gov (United States)

    Yoo, Jong-Hyun; Yoon, Jang W; Lee, So-Young; Park, Hee-Myung

    2010-04-01

    Recently, a total of 74 Staphylococcus pseudintermedius isolates were collected from clinical cases of canine pyoderma and otitis externa in Korea. In this study, we examined in vitro fluoroquinolone resistance among those isolates using a standard disk diffusion technique. The results demonstrated that approximately 18.9% to 27.0% of the isolates possessed bacterial resistance to both veterinary- and human-licensed fluoroquinolones except one isolate, including moxifloxacin (18.9% resistance), levofloxacin (20.3% resistance), ofloxacin (24.3% resistance), ciprofloxacin (25.7% resistance), and enrofloxacin (27.0% resistance). Most surprisingly, 14 out of 74 (18.9%) isolates were resistant to all the five fluoroquinolones evaluated. Moreover, a PCR detection of the methicillin resistance gene (mecA) among the 74 isolates revealed that 13 out of 25 (52.0%) mecA-positive isolates, but only 7 out of 49 (14.3%) mecA-negative isolates, were resistant to one or more fluoroquinones. Taken together, our results imply that bacterial resistance to both veterinary- and human-use fluoroquinolones becomes prevalent among the S. pseudintermedius isolates from canine pyoderma and otitis externa in Korea as well as that the high prevalence of the mecA-positive S. pseudintermedius isolates carrying multiple fluoroquinolone resistance could be a potential public health problem.

  4. In vitro emergence of fluoroquinolone resistance in Cutibacterium (formerly Propionibacterium) acnes and molecular characterization of mutations in the gyrA gene.

    Science.gov (United States)

    Takoudju, Eve-Marie; Guillouzouic, Aurélie; Kambarev, Stanimir; Pecorari, Frédéric; Corvec, Stéphane

    2017-06-08

    In vitro occurrence of levofloxacin (LVX) resistance in C. acnes and characterization of its molecular background were investigated. The mutation frequency was determined by inoculation of 10(8) cfu of C. acnes ATCC 11827 (LVX MIC = 0.25 mg/L) on LVX-containing agar plates. The progressive emergence of resistance was studied by a second exposure to increasing LVX concentrations. For mutants, the QRDR regions including the gyrA and parC genes were sequenced and compared to both C. acnes ATCC 11827 and C. acnes KPA171202 reference sequences (NC006085). The importance of the efflux pump system in resistance was investigated by using inhibitors on selected resistant mutants with no mutation in the QRDR. C. acnes growth was observed on LVX-containing plates with mutation frequencies of 3. 8 cfu × 10(-8) (8 × MIC) and 1.6 cfu × 10(-7) (4 × MIC). LVX resistance emerged progressively after one-step or two-step assays. In LVX-resistant isolates, the MIC ranged from 0.75 to >32 mg/L. Mutations were detected exclusively in the gyrA gene. Ten genotypes were identified: G99 C, G99 D, D100N, D100 H, D100 G, S101L, S101W, A102 P, D105 H and A105 G. Mutants S101L and S101W were always associated with a high level of resistance. Mutants with no mutation in the QRDR were more susceptible when incubated with an efflux pump inhibitor (phenyl-arginine β-naphthylamide) only, suggesting, for the first time, the expression of such a system in C. acnes LVX-resistant mutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections.

    Science.gov (United States)

    Shah, Ansal; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2017-02-13

    The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived in patients with gram-negative bloodstream infections based on fluoroquinolone use within the past 6 months among other clinical and healthcare exposure criteria. This study aims to examine the utility of the FQRS in complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA from April 1, 2015 through July 31, 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 151 (63%) were women and 137 (58%) had cUTI due to Escherichia coli Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR] 23.4, 95% confidence intervals [CI]: 8.2-76.8, p<0.001) and within 3-12 months (aOR 13.2, 95% CI: 3.1-68.4, p<0.001) was independently associated with fluoroquinolone resistance as compared to no prior use. Area under receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRS ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI based on predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis.

  6. Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure.

    Science.gov (United States)

    Baker, Stephen; Duy, Pham Thanh; Nga, Tran Vu Thieu; Dung, Tran Thi Ngoc; Phat, Voong Vinh; Chau, Tran Thuy; Turner, A Keith; Farrar, Jeremy; Boni, Maciej F

    2013-12-10

    Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by the bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering treatment and control efforts. Using in vitro competition experiments, we assayed the fitness of eleven isogenic S. Typhi strains with resistance mutations in the FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out of 11 mutants carried a selective advantage over the antimicrobial-sensitive parent strain, indicating that FQ resistance in S. Typhi is not typically associated with fitness costs. Double-mutants exhibited higher than expected fitness as a result of synergistic epistasis, signifying that epistasis may be a critical factor in the evolution and molecular epidemiology of S. Typhi. Our findings have important implications for the management of drug-resistant S. Typhi, suggesting that FQ-resistant strains would be naturally maintained even if fluoroquinolone use were reduced. DOI: http://dx.doi.org/10.7554/eLife.01229.001.

  7. Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.

    Science.gov (United States)

    Avalos, Elisea; Catanzaro, Donald; Catanzaro, Antonino; Ganiats, Theodore; Brodine, Stephanie; Alcaraz, John; Rodwell, Timothy

    2015-01-01

    The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance. In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution. Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay. Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyr

  8. Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.

    Directory of Open Access Journals (Sweden)

    Elisea Avalos

    Full Text Available The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection

  9. 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

  10. 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

  11. Prevalence of resistance to aminoglycosides and fluoroquinolones among Pseudomonas aeruginosa strains in a University Hospital in Northeastern Poland.

    Science.gov (United States)

    Michalska, Anna Diana; Sacha, Pawel Tomasz; Ojdana, Dominika; Wieczorek, Anna; Tryniszewska, Elzbieta

    2014-01-01

    The present study was conducted to investigate the prevalence of genes encoding resistance to aminoglycosides and fluoroquinolones among twenty-five Pseudomonas aeruginosa isolated between 2002 and 2009. In PCR, following genes were detected: ant(2″)-Ia in 9 (36.0%), aac(6')-Ib in 7 (28.0%), qnrB in 5 (20.0%), aph(3″)-Ib in 2 (8.0%) of isolates.

  12. The selection of resistance to and the mutagenicity of different fluoroquinolones in Staphylococcus aureus and Streptococcus pneumoniae.

    Science.gov (United States)

    Sierra, J M; Cabeza, J G; Ruiz Chaler, M; Montero, T; Hernandez, J; Mensa, J; Llagostera, M; Vila, J

    2005-09-01

    Two quinolone-susceptible Staphylococcus aureus and five quinolone-susceptible Streptococcus pneumoniae isolates were used to obtain in-vitro quinolone-resistant mutants in a multistep resistance selection process. The fluoroquinolones used were ciprofloxacin, moxifloxacin, levofloxacin, gemifloxacin, trovafloxacin and clinafloxacin. The mutagenicity of these quinolones was determined by the Salmonella and the Escherichia coli retromutation assays. All quinolone-resistant Staph. aureus mutants had at least one mutation in the grlA gene, while 86.6% of quinolone-resistant Strep. pneumoniae mutants had mutations in either or both the gyrA and parC genes. Moxifloxacin and levofloxacin selected resistant mutants later than the other quinolones, but this difference was more obvious in Staph. aureus. Accumulation of the fluoroquinolones by Staph. aureus did not explain these differences, since levofloxacin and moxifloxacin accumulated inside bacteria to the same extent as clinafloxacin and trovafloxacin. The results also showed that moxifloxacin and levofloxacin had less mutagenic potency in both mutagenicity assays, suggesting a possible relationship between the selection of resistance to quinolones and the mutagenic potency of the molecule. Furthermore, gemifloxacin selected efflux mutants more frequently than the other quinolones used. Thus, the risk of developing quinolone resistance may depend on the density of the microorganism at the infection site and the concentration of the fluoroquinolone, and also on the mutagenicity of the quinolone used, with moxifloxacin and levofloxacin being the least mutagenic.

  13. Molecular characterization of fluoroquinolone resistance in nontypeable Haemophilus influenzae clinical isolates.

    Science.gov (United States)

    Puig, Carmen; Tirado-Vélez, José Manuel; Calatayud, Laura; Tubau, Fe; Garmendia, Junkal; Ardanuy, Carmen; Marti, Sara; de la Campa, Adela G; Liñares, Josefina

    2015-01-01

    Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267 H. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (n = 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 μg/ml, while those with three or more mutations (n = 15) had MICs of 4 to 16 μg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Prevalence and Fluoroquinolone Resistance Pattern in Escherichia coli Isolates of Urinary Tract Infection (UTI Patients

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    Tippireddypalli Gururaju,

    2015-04-01

    Full Text Available Background: Urinary tract infections (UTIs are among the most common infectious diseases all over the world. Recent studies reported an increased antibiotic resistance in Escherichia coli, primary causative agent of UTI. The resistance has emerged even to more potent antimicrobial agents like fluoroquinolones. Objectives: The present study was undertaken to evaluate the prevalence and resistance pattern of E.coli causing UTIs in patients admitted to a tertiary care hospital in South India, with reference to fluoroquinolones. Material and Methods: A total of 278 selected urine samples of urinary tract infections were processed for E.coli culture using standard methods. For these urinary E. coli isolates, susceptibility to various antibiotics including fluoroquinolones was checked by Kirby Bauer disk diffusion method according CLSI criteria. Final resistance to fluoroquinolones isolates was analyzed. Results: Out of the 278 selected UTI clinical isolates 148 (54% showed ciprofloxacin sensitive and 130 (46% clinical isolates are ciprofloxacin resistant. Of the 130 ciprofloxacin resistant urinary isolates of E. coli subjected to susceptibility test for increased generation of fluoroquinolone drugs, the pattern of resistance noticed as levofloxacin (2nd generation 79%, gatifloxacin (3rd generation 77% and moxifloxacin (4th generation 75%, respectively. The fluoroquinolone resistance in UTI clinical isolates was decreasing with increasing generations of fluoroquinolone. Quinolone drug resistance in clinical isolates was increasing with age and hospitalized patients. Conclusion: Study showed an increased fluoroquinolone resistance among uropathogenic E. coli isolates of UTI. These increased antibiotic resistance trends in UTI patients indicated that it is imperative to rationalize the use of antimicrobials and to use them conservatively.

  15. Resistance of Stenotrophomonas maltophilia to Fluoroquinolones: Prevalence in a University Hospital and Possible Mechanisms

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    Wei Jia

    2015-05-01

    Full Text Available Objective: The purpose of this study was to investigate the clinical distribution and genotyping of Stenotrophomonas maltophilia, its resistance to antimicrobial agents, and the possible mechanisms of this drug resistance. Methods: S. maltophilia isolates were collected from clinical specimens in a university hospital in Northwestern China during the period between 2010 and 2012, and were identified to the species level with a fully automated microbiological system. Antimicrobial susceptibility testing was performed for S. maltophilia with the Kirby-Bauer disc diffusion method. The minimal inhibitory concentrations (MICs of norfloxacin, ofloxacin, chloramphenicol, minocycline, ceftazidime, levofloxacin and ciprofloxacin against S. maltophilia were assessed using the agar dilution method, and changes in the MIC of norfloxacin, ciprofloxacin and ofloxacin were observed after the addition of reserpine, an efflux pump inhibitor. Fluoroquinolone resistance genes were detected in S. maltophilia using a polymerase chain reaction (PCR assay, and the expression of efflux pump smeD and smeF genes was determined using a quantitative fluorescent (QF-PCR assay. Pulsed-field gel electrophoresis (PFGE was employed to genotype identified S. maltophilia isolates. Results: A total of 426 S. maltophilia strains were isolated from the university hospital from 2010 to 2012, consisting of 10.1% of total non-fermentative bacteria. The prevalence of norfloxacin, ciprofloxacin and ofloxacin resistance was 32.4%, 21.9% and 13.2% in the 114 S. maltophilia isolates collected from 2012, respectively. Following reserpine treatment, 19 S. maltophilia isolates positive for efflux pump were identified, and high expression of smeD and smeF genes was detected in two resistant isolates. gyrA, parC, smeD, smeE and smeF genes were detected in all 114 S. maltophilia isolates, while smqnr gene was found in 25.4% of total isolates. Glu-Lys mutation (GAA-AAA was detected at the 151th

  16. Resistance of Stenotrophomonas maltophilia to Fluoroquinolones: Prevalence in a University Hospital and Possible Mechanisms

    Science.gov (United States)

    Jia, Wei; Wang, Jiayuan; Xu, Haotong; Li, Gang

    2015-01-01

    Objective: The purpose of this study was to investigate the clinical distribution and genotyping of Stenotrophomonas maltophilia, its resistance to antimicrobial agents, and the possible mechanisms of this drug resistance. Methods: S. maltophilia isolates were collected from clinical specimens in a university hospital in Northwestern China during the period between 2010 and 2012, and were identified to the species level with a fully automated microbiological system. Antimicrobial susceptibility testing was performed for S. maltophilia with the Kirby-Bauer disc diffusion method. The minimal inhibitory concentrations (MICs) of norfloxacin, ofloxacin, chloramphenicol, minocycline, ceftazidime, levofloxacin and ciprofloxacin against S. maltophilia were assessed using the agar dilution method, and changes in the MIC of norfloxacin, ciprofloxacin and ofloxacin were observed after the addition of reserpine, an efflux pump inhibitor. Fluoroquinolone resistance genes were detected in S. maltophilia using a polymerase chain reaction (PCR) assay, and the expression of efflux pump smeD and smeF genes was determined using a quantitative fluorescent (QF)-PCR assay. Pulsed-field gel electrophoresis (PFGE) was employed to genotype identified S. maltophilia isolates. Results: A total of 426 S. maltophilia strains were isolated from the university hospital from 2010 to 2012, consisting of 10.1% of total non-fermentative bacteria. The prevalence of norfloxacin, ciprofloxacin and ofloxacin resistance was 32.4%, 21.9% and 13.2% in the 114 S. maltophilia isolates collected from 2012, respectively. Following reserpine treatment, 19 S. maltophilia isolates positive for efflux pump were identified, and high expression of smeD and smeF genes was detected in two resistant isolates. gyrA, parC, smeD, smeE and smeF genes were detected in all 114 S. maltophilia isolates, while smqnr gene was found in 25.4% of total isolates. Glu-Lys mutation (GAA-AAA) was detected at the 151th amino acid of the

  17. Fluoroquinolones, the Cornerstone of Treatment of Drug-Resistant Tuberculosis : A Pharmacokinetic and Pharmacodynamic Approach

    NARCIS (Netherlands)

    Pranger, A. D.; Alffenaar, J. W. C.; Aarnoutse, R. E.

    Fluoroquinolones (FQs) are important drugs to treat drug-resistant tuberculosis. In this review we integrated pharmacokinetic properties (PK) and microbiological susceptibility against M. tuberculosis and eventually evaluated the pharmcodynamic (PD) properties, as well as the influence of

  18. Spontaneous mutation frequency and molecular mechanisms of Shigella flexneri fluoroquinolone resistance under antibiotic selective stress.

    Science.gov (United States)

    Pu, Xiao-Ying; Zhang, Qijing; Pan, Jing-Cao; Shen, Zhangqi; Zhang, Wei

    2013-02-01

    The incidence of fluoroquinolone-resistant Shigella strains has risen rapidly, presumably in response to ciprofloxacin antibiotic stress. Understanding the molecular mechanisms underlying this resistance phenotype is critical to developing novel and effective therapeutic strategies. In this study, the frequency of ciprofloxacin-induced mutation was measured in antibiotic resistance genes (gyrA, gyrB, parC, parE, marOR, and marA) of Shigella flexneri. The S. flexneri 2a strain 301 was cultured on Luria-Bertani agar plates containing one of seven different ciprofloxacin concentrations (range: 0.03125-2 μg mL(-1)). Resistant colonies were selected for gene-targeted sequencing analysis; the identified point mutations were subsequently confirmed by insertion into antibiotic cassette plasmids and growth under ciprofloxacin stress. The results demonstrated that the seven different ciprofloxacin concentrations produced dose-dependent frequencies of spontaneous mutations: 10(-8) (0.03125 and 0.0625 μg mL(-1)), 10(-9) (0.125 μg mL(-1)), and resistant colonies (minimum inhibitory concentrations (MICs) of 0.125 μg mL(-1), n = 5 and 0.25 μg mL(-1), n = 5) revealed that all colonies had mutations in the gyrA gene at either codon 83 (Ser83 → Leu) or 87 (Asp87 → Tyr or → Gly), both of which were confirmed at MIC of 0.125 μg mL(-1). None of the spontaneous mutation colonies exhibited gyrB, parC, parE, marOR, or marA mutations. In conclusion, S. flexneri is normomutable under ciprofloxacin antibiotic stress and fluoroquinolone resistance by spontaneous mutation occurs at a low rate. Codon mutations gyrA 83 and/or gyrA 87 cause a 4-fold increase in the ciprofloxacin MIC, and may represent the natural mechanism of fluoroquinolone resistance.

  19. In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae.

    Science.gov (United States)

    Daporta, Matilde Trigo; Muñoz Bellido, Juan Luis; Guirao, Genoveva Yagüe; Hernández, Manuel Segovia; García-Rodríguez, José Angel

    2004-08-01

    The effect of high-level efflux activity on the MICs of fluoroquinolones against Streptococcus pneumoniae in the absence of topoisomerase mutations leading to fluoroquinolones resistance was investigated. A S. pneumoniae ATCC 46619-derived strain with high-level efflux activity was obtained (SP-25A). Both the parent and obtained strains were tested against efflux substrates acriflavine (Acr) and ethidium bromide (EtBr), and against norfloxacin (NFX), ciprofloxacin (CFX), levofloxacin (LFX), moxifloxacin (MFX), trovafloxacin (TVX) and sitafloxacin (SFX), in presence and absence of the efflux pump inhibitor reserpine. gyrA, gyrB, parC and parE QRDR genes were amplified by PCR and sequenced. MICs of NFX and CFX against SP-25A were 64-fold higher than parent strain MICs (256 mg/L versus 4 mg/L and 64 mg/L versus 1mg/L, respectively). MIC of LFX increased from 1 to 4 mg/L and MICs of MFX, TVX and SFX remained virtually unchanged (0.1-0.2 mg/L). MICs of Acr and EtBr against SP-25A were 8- and 16-fold higher than against parent strains. In both cases, reserpine reverted MICs to the parent strain values (1 and 0.2 mg/L). Only parE showed two mutations leading to a Pro(454) --> Ser and Glu(443) changes, which have previously been shown not to lead to significant fluoroquinolones MIC increases. SP-25A showed a significant increase of MICs of the hydrophilic fluoroquinolones, apparently derived only from efflux activity. Efflux activity, at these high levels, can lead to high-level resistance to older hydrophilic fluoroquinolones, but does affect newer fluoroquinolones such as moxifloxacin, trovafloxacin and sitafloxacin.

  20. Colonization with Extraintestinal Pathogenic Escherichia coli among Nursing Home Residents and Its Relationship to Fluoroquinolone Resistance

    Science.gov (United States)

    Maslow, Joel N.; Lautenbach, Ebbing; Glaze, Thomas; Bilker, Warren; Johnson, James R.

    2004-01-01

    In a cross-sectional fecal prevalence survey involving 49 residents of a Veterans Affairs nursing home, 59% of subjects were colonized with extraintestinal pathogenic Escherichia coli (ExPEC), 22% were colonized with adhesin-positive E. coli, and 51% were colonized with fluoroquinolone-resistant E. coli. Among 80 unique isolates, adhesins correlated negatively and aerobactin correlated positively with fluoroquinolone resistance. PMID:15328142

  1. Fluoroquinolone-resistant enteric bacteria in sub-Saharan Africa: Clones, Implications and Research needs

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    Marie Anne Chattaway

    2016-04-01

    Full Text Available Fluoroquinolones came into widespread use in African countries in the early 2000s, after patents for the first generation of these drugs expired. By that time, quinolone antibacterial agents had been used intensively worldwide and resistant lineages of many bacterial species had evolved. We sought to understand which Gram negative enteric pandemic lineages have been reported from Africa, as well as the nature and transmission of any indigenous resistant clones. A systematic review of articles indexed in the Medline and AJOL literature databases was conducted. We report on the findings of 43 eligible studies documenting local or pandemic fluoroquinolone-resistant enteric clones in sub-Sahara African countries. Most reports are of invasive non-typhoidal Salmonella and Escherichia coli lineages and there have been three reports of cholera outbreaks caused by fluoroquinolone-resistant Vibrio cholerae O1. Fluoroquinolone-resistant clones have also been reported from commensals and animal isolates but there are few data for non-Enterobacteriaceae and almost none for difficult-to-culture Campylobacter spp. Fluoroquinolone-resistant lineages identified in African countries were universally resistant to multiple other classes of antibacterial agents. Although as many as 972 non-duplicate articles refer to fluoroquinolone resistance in enteric bacteria from Africa, most do not report on subtypes and therefore information on the epidemiology of fluoroquinolone-resistant clones is available from only a handful of countries in the subcontinent. When resistance is reported, resistance mechanisms and lineage information is rarely investigated. Insufficient attention has been given to molecular and sequence-based methods necessary for identifying and tracking resistant clones in Africa and more research is needed in this area.

  2. [MALDI-ToF mass-spectrometry in analysis of genetically determined resistance of Streptococcus pneumoniae to fluoroquinolones].

    Science.gov (United States)

    Malakhova, M V; Vereshchagin, V A; Il'ina, E N; Govorun, V M; Filimonova, O Iu; Grudinina, S A; Sidorenko, S V

    2007-01-01

    New fluoroquinolones with higher antipneumococcal activity are considered promising in the treatment of respiratory tract infections. Still, their wide use in clinical practice is connected with possible selection and rapid distribution of the resistance, requiring constant monitoring. Development of resistance to fluoroquinolones results from step-wise accumulation of mutations in the genes of DNA-gyrase and topoisomerase IV, the mutations of the first step being not always accompanied by a significant increase of the MIC of the new fluoroquinolones. Therefore, to detect the first signs of the resistance development, it is necessary not only to detect the susceptibility of the circulating Streptococcus pneumoniae strains phenotypically, but also to detect the genetic changes. In the present study the minisequent reaction followed by detection of the reaction products by MALD-ToF mass-spectrometry was used to reveal the mutations in the genes of the fluoroquinolone targets of 38 S. pneumoniae strains with different levels of the resistance to ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin. In the strains with high resistance to all the three fluoroquinolones (MIC 4-16 mcg/ml) there were detected mutations in GyrA (Ser81Tyr or Glu85Zys) and as well in ParC (Ser79Phe or Ser79Tyr). In the strains resistant to ofloxacin and ciprofloxacin (MIC 4-8 mcg/ml) with preserved susceptibility to levofloxacin and moxifloxacin, the mutations were detected only in GyrA (Ser114Gly). In the moderately resistant strains (MICs 4 and 2-4 mcg/ml respectively for ofloxacin and ciprofloxacin) there were detected the known mutations in ParC (Ser79Tyr or Ser79Phe or Asp83Tyr) and in GyrB (Glu475Lys) as well as the earlier not described mutations in ParE (ins Asn381a) and in Gyr B (Thr329Ala or Va1355Ile). The described method can be used in mass screening of S. pneumoniae strains for the presence of mutations in the genes of the fluoroquinolone targets.

  3. Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy.

    Science.gov (United States)

    Liss, Michael A; Taylor, Stephen A; Batura, Deepak; Steensels, Deborah; Chayakulkeeree, Methee; Soenens, Charlotte; Rao, G Gopal; Dash, Atreya; Park, Samuel; Patel, Nishant; Woo, Jason; McDonald, Michelle; Nseyo, Unwanaobong; Banapour, Pooya; Unterberg, Stephen; Ahlering, Thomas E; Van Poppel, Hendrik; Sakamoto, Kyoko; Fierer, Joshua; Black, Peter C

    2014-12-01

    Infection after transrectal prostate biopsy has become an increasing concern due to fluoroquinolone resistant bacteria. We determined whether colonization identified by rectal culture can identify men at high risk for post-transrectal prostate biopsy infection. Six institutions provided retrospective data through a standardized, web based data entry form on patients undergoing transrectal prostate biopsy who had rectal culture performed. The primary outcome was any post-transrectal prostate biopsy infection and the secondary outcome was hospital admission 30 days after transrectal prostate biopsy. We used chi-square and logistic regression statistical analysis. A total of 2,673 men underwent rectal culture before transrectal prostate biopsy from January 1, 2007 to September 12, 2013. The prevalence of fluoroquinolone resistance was 20.5% (549 of 2,673). Fluoroquinolone resistant positive rectal cultures were associated with post-biopsy infection (6.6% vs 1.6%, p Fluoroquinolone resistant positive rectal culture increased the risk of infection (OR 3.98, 95% CI 2.37-6.71, p fluoroquinolone prophylaxis, the infection and hospitalization proportion increased to 8.2% (28 of 343) and 6.1% (21 of 343), with OR 4.77 (95% CI 2.50-9.10, p fluoroquinolone resistant bacteria isolates were Escherichia coli (83.7%). Limitations include the retrospective study design, nonstandardized culture and interpretation of resistance methods. Colonization of fluoroquinolone resistant organisms in the rectum identifies men at high risk for infection and subsequent hospitalization from prostate biopsy, especially in those with fluoroquinolone prophylaxis only. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Molecular detection of fluoroquinolone-resistance in multi-drug resistant tuberculosis in Cambodia suggests low association with XDR phenotypes

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    Murray Alan

    2011-09-01

    Full Text Available Abstract Background Drug susceptibility testing (DST remains an important concern for implementing treatment of MDR tuberculosis patients. Implementation of molecular tests for drug resistance identification would facilitate DST particularly in developing countries where culturing is difficult to perform. We have characterized multidrug resistant strains in Cambodia using MDTDRsl tests, drug target sequencing and phenotypic tests. Methods A total of 65 non-MDR and 101 MDR TB isolates collected between May 2007 and June 2009 were tested for resistance to fluoroquinolones and aminoglycosides/cyclic peptides using the GenoType® MTBDRsl assay and gene sequencing. Rifampicin resistance (RMP-R was tested using gene sequencing and genotyping was assessed by spoligotyping. Results A total of 95 of the 101 MDR strains were confirmed to be RMP-R by rpoB gene sequencing. Fourteen of the 101 MDR isolates (14% carried a gyrA mutation associated with fluoroquinolone-resistance (FQ-R (detected by the MTBDRsl assay and sequencing compared with only 1 (1.5% of the 65 non-MDR strains. Only 1 (1% of the MDR isolates was found to be XDR TB. The MDR group contained a higher proportion of Beijing or Beijing like strains (58% than the non MDR group (28%. This percentage is higher in MDR FQ-R strains (71%. Conclusions The new GenoType® MTBDRsl assay combined with molecular tests to detect RMP-R and isoniazid resistance (INH-R represents a valuable tool for the detection of XDR TB. In Cambodia there is a low rate of XDR amongst MDR TB including MDR FQ-R TB. This suggests a low association between FQ-R and XDR TB. Strain spoligotyping confirms Beijing strains to be more prone to accumulate antibiotic resistance.

  5. Fluoroquinolone-metal complexes: a route to counteract bacterial resistance?

    Science.gov (United States)

    Feio, Maria J; Sousa, Isabel; Ferreira, Mariana; Cunha-Silva, Luís; Saraiva, Raúl G; Queirós, Carla; Alexandre, José G; Claro, Vasco; Mendes, Adélia; Ortiz, Rosa; Lopes, Sandra; Amaral, Ana Luísa; Lino, João; Fernandes, Patrícia; Silva, Ana João; Moutinho, Lisete; de Castro, Baltazar; Pereira, Eulália; Perelló, Lourdes; Gameiro, Paula

    2014-09-01

    Microbial resistance to antibiotics is one of the biggest public health threats of the modern world. Antibiotic resistance is an area of much clinical relevance and therefore research that has the potential to identify agents that may circumvent it or treat resistant infections is paramount. Solution behavior of various fluoroquinolone (FQ) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry and/or spectrophotometry, and are herein described. The results obtained showed that under physiological conditions (micromolar concentration range and pH7.4) only copper(II):FQ:phen ternary complexes are stable. Hence, these complexes were synthesised and characterised by means of UV-visible and IR spectroscopy, elemental analysis and single-crystal X-ray diffraction. In these complexes, the FQ acts as a bidentate ligand that coordinates the metal cation through the carbonyl and carboxyl oxygen atoms and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth position of the penta-coordinated Cu(II) centre is generally occupied axially by an oxygen atom from a water molecule or from a nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complexes and comparison with free FQ in various E. coli strains indicate that the Cu-complexes are as efficient antimicrobials as the free antibiotic. Moreover, results strongly suggest that the cell intake route of both species is different supporting, therefore, the complexes' suitability as candidates for further biological testing in FQ-resistant microorganisms.

  6. Induction of Prophages by Fluoroquinolones in Streptococcus pneumoniae: Implications for Emergence of Resistance in Genetically-Related Clones

    Science.gov (United States)

    Ferrándiz, María-José; Frias, Maria João; Ardanuy, Carmen; Ramirez, Mario; García, Ernesto; Liñares, Josefina; de la Campa, Adela G.

    2014-01-01

    Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an important role. Prophage induction by fluoroquinolones was confirmed in 4 clinical isolates by using Southern blot hybridization. Clinical isolates (105 fluoroquinolone-resistant and 160 fluoroquinolone-susceptible) were tested for lysogeny by using a PCR assay and functional prophage carriage was studied by mitomycin C induction. Fluoroquinolone-resistant strains harbored fewer inducible prophages (17/43) than fluoroquinolone-susceptible strains (49/70) (P = 0.0018). In addition, isolates of clones associated with fluoroquinolone resistance [CC156 (3/25); CC63 (2/20), and CC81 (1/19)], had lower frequency of functional prophages than isolates of clones with low incidence of fluoroquinolone resistance [CC30 (4/21), CC230 (5/20), CC62 (9/21), and CC180 (21/30)]. Likewise, persistent strains from patients with chronic respiratory diseases subjected to fluoroquinolone treatment had a low frequency of inducible prophages (1/11). Development of ciprofloxacin resistance was tested with two isogenic strains, one lysogenic and the other non-lysogenic: emergence of resistance was only observed in the non-lysogenic strain. These results are compatible with the lysis of lysogenic isolates receiving fluoroquinolones before the development of resistance and explain the inverse relation between presence of inducible prophages and fluoroquinolone-resistance. PMID:24718595

  7. Induction of prophages by fluoroquinolones in Streptococcus pneumoniae: implications for emergence of resistance in genetically-related clones.

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    Elena López

    Full Text Available Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an important role. Prophage induction by fluoroquinolones was confirmed in 4 clinical isolates by using Southern blot hybridization. Clinical isolates (105 fluoroquinolone-resistant and 160 fluoroquinolone-susceptible were tested for lysogeny by using a PCR assay and functional prophage carriage was studied by mitomycin C induction. Fluoroquinolone-resistant strains harbored fewer inducible prophages (17/43 than fluoroquinolone-susceptible strains (49/70 (P = 0.0018. In addition, isolates of clones associated with fluoroquinolone resistance [CC156 (3/25; CC63 (2/20, and CC81 (1/19], had lower frequency of functional prophages than isolates of clones with low incidence of fluoroquinolone resistance [CC30 (4/21, CC230 (5/20, CC62 (9/21, and CC180 (21/30]. Likewise, persistent strains from patients with chronic respiratory diseases subjected to fluoroquinolone treatment had a low frequency of inducible prophages (1/11. Development of ciprofloxacin resistance was tested with two isogenic strains, one lysogenic and the other non-lysogenic: emergence of resistance was only observed in the non-lysogenic strain. These results are compatible with the lysis of lysogenic isolates receiving fluoroquinolones before the development of resistance and explain the inverse relation between presence of inducible prophages and fluoroquinolone-resistance.

  8. Induction of prophages by fluoroquinolones in Streptococcus pneumoniae: implications for emergence of resistance in genetically-related clones.

    Science.gov (United States)

    López, Elena; Domenech, Arnau; Ferrándiz, María-José; Frias, Maria João; Ardanuy, Carmen; Ramirez, Mario; García, Ernesto; Liñares, Josefina; de la Campa, Adela G

    2014-01-01

    Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an important role. Prophage induction by fluoroquinolones was confirmed in 4 clinical isolates by using Southern blot hybridization. Clinical isolates (105 fluoroquinolone-resistant and 160 fluoroquinolone-susceptible) were tested for lysogeny by using a PCR assay and functional prophage carriage was studied by mitomycin C induction. Fluoroquinolone-resistant strains harbored fewer inducible prophages (17/43) than fluoroquinolone-susceptible strains (49/70) (P = 0.0018). In addition, isolates of clones associated with fluoroquinolone resistance [CC156 (3/25); CC63 (2/20), and CC81 (1/19)], had lower frequency of functional prophages than isolates of clones with low incidence of fluoroquinolone resistance [CC30 (4/21), CC230 (5/20), CC62 (9/21), and CC180 (21/30)]. Likewise, persistent strains from patients with chronic respiratory diseases subjected to fluoroquinolone treatment had a low frequency of inducible prophages (1/11). Development of ciprofloxacin resistance was tested with two isogenic strains, one lysogenic and the other non-lysogenic: emergence of resistance was only observed in the non-lysogenic strain. These results are compatible with the lysis of lysogenic isolates receiving fluoroquinolones before the development of resistance and explain the inverse relation between presence of inducible prophages and fluoroquinolone-resistance.

  9. Occurrence of the Plasmid-Mediated Fluoroquinolone Resistance qepA1 Gene in Two Clonal Clinical Isolates of CTX-M-15-Producing Escherichia coli from Algeria.

    Science.gov (United States)

    Yanat, Betitera; Dali Yahia, Radia; Yazi, Leila; Machuca, Jesús; Díaz-De-Alba, Paula; Touati, Abdelaziz; Pascual, Álvaro; Rodríguez-Martínez, José-Manuel

    2016-10-13

    QepA is a plasmid-mediated quinolone resistance determinant of low prevalence described worldwide, mainly in Enterobacteriaceae. This study describes, for the first time in Algeria, two clonally related, QepA-producing Escherichia coli clinical isolates positive for CTX-M-15. The clonal spread of these multidrug-resistant isolates is a major public health concern.

  10. 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%).

  11. Persistence and complex evolution of fluoroquinolone-resistant Streptococcus pneumoniae clone.

    Science.gov (United States)

    Ben-David, Debby; Schwaber, Mitchell J; Adler, Amos; Masarwa, Samira; Edgar, Rotem; Navon-Venezia, Shiri; Schwartz, David; Porat, Nurith; Kotlovsky, Tali; Polivkin, Nikolay; Weinberg, Irina; Lazary, Avraham; Ohana, Nissim; Dagan, Ron

    2014-05-01

    Prolonged outbreaks of multidrug-resistant Streptococcus pneumoniae in health care facilities are uncommon. We found persistent transmission of a fluroquinolone-resistant S. pneumoniae clone during 2006-2011 in a post-acute care facility in Israel, despite mandatory vaccination and fluoroquinolone restriction. Capsular switch and multiple antimicrobial nonsusceptibility mutations occurred within this single clone. The persistent transmission of fluoroquinolone-resistant S. pneumoniae during a 5-year period underscores the importance of long-term care facilities as potential reservoirs of multidrug-resistant streptococci.

  12. Fluoroquinolone Action against Mycobacteria: Effects of C-8 Substituents on Growth, Survival, and Resistance

    Science.gov (United States)

    Dong, Yuzhi; Xu, Chen; Zhao, Xilin; Domagala, John; Drlica, Karl

    1998-01-01

    Fluoroquinolones trap gyrase on DNA as bacteriostatic complexes from which lethal DNA breaks are released. Substituents at the C-8 position increase activities of N-1-cyclopropyl fluoroquinolones against several bacterial species. In the present study, a C-8-methoxyl group improved bacteriostatic action against gyrA (gyrase-resistant) strains of Mycobacterium tuberculosis and M. bovis BCG. It also enhanced lethal action against gyrase mutants of M. bovis BCG. When cultures of M. smegmatis, M. bovis BCG, and M. tuberculosis were challenged with a C-8-methoxyl fluoroquinolone, no resistant mutant was recovered under conditions in which more than 1,000 mutants were obtained with a C-8-H control. A C-8-bromo substituent also increased bacteriostatic and lethal activities against a gyrA mutant of M. bovis BCG. When lethal activity was normalized to bacteriostatic activity, the C-8-methoxyl compound was more bactericidal than its C-8-H control, while the C-8-bromo fluoroquinolone was not. The C-8-methoxyl compound was also found to be more effective than the C-8-bromo fluoroquinolone at reducing selection of resistant mutants when each was compared to a C-8-H control over a broad concentration range. These data indicate that a C-8-methoxyl substituent, which facilitates attack of first-step gyrase mutants, may help make fluoroquinolones effective antituberculosis agents. PMID:9797236

  13. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria.

    Science.gov (United States)

    Parkinson, Elizabeth I; Bair, Joseph S; Nakamura, Bradley A; Lee, Hyang Y; Kuttab, Hani I; Southgate, Emma H; Lezmi, Stéphane; Lau, Gee W; Hergenrother, Paul J

    2015-04-24

    Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections.

  14. Correlation between levofloxacin consumption and the incidence of nosocomial infections due to fluoroquinolone-resistant Escherichia coli.

    Science.gov (United States)

    Wu, Hui-Hsiu; Liu, Hsin-Yi; Lin, Yi-Chun; Hsueh, Po-Ren; Lee, Yuarn-Jang

    2016-06-01

    The relationship between fluoroquinolone resistance in Escherichia coli isolates causing nosocomial infection and hospital antibiotic consumption were investigated. Restriction of levofloxacin use was implemented to control the incidence of fluoroquinolone-resistant E coli in the hospital. The study was conducted from January 2004 to December 2010. Antimicrobial agent consumption was obtained from the pharmacy computer system and presented as the defined daily doses per 1000 patient-days every 6 months. The incidence of fluoroquinolone-resistant E coli isolates causing nosocomial infections was obtained from the Department of Infection Control every 6 months. An antimicrobial stewardship program, restricting levofloxacain use, was implemented in July 2007. The incidence of fluoroquinolone-resistant E coli causing nosocomial infections was significantly correlated with fluoroquinolone usage (p = 0.005), but not with the use of third- or fourth-generation cephalosporins, piperacillin-tazobactam, or carbapenems. Parenteral (p = 0.002), oral (p = 0.018), and total levofloxacin (p = 0.001) use were significantly correlated with the extent of fluoroquinolone resistance. With a reduction of levofloxacin use, a decrease of the incidence of fluoroquinolone resistance in E coli isolates was observed. There is a significant correlation between levofloxacin use and the incidence of nosocomial fluoroquinolone-resistant E coli isolates. The incidence of fluoroquinolone-resistant E coli could be reduced by limiting levofloxacin consumption. Copyright © 2011. Published by Elsevier B.V.

  15. Alterations in DNA Gyrase and Topoisomerase IV in Resistant Mutants of Clostridium perfringens Found after In Vitro Treatment with Fluoroquinolones

    Science.gov (United States)

    Rafii, Fatemeh; Park, Miseon; Novak, John S.

    2005-01-01

    To compare mutations in the DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes of Clostridium perfringens, which are associated with in vitro exposure to fluoroquinolones, resistant mutants were selected from eight strains by serial passage in the presence of increasing concentrations of norfloxacin, ciprofloxacin, gatifloxacin, or trovafloxacin. The nucleotide sequences of the entire gyrA, gyrB, parC, and parE genes of 42 mutants were determined. DNA gyrase was the primary target for each fluoroquinolone, and topoisomerase IV was the secondary target. Most mutations appeared in the quinolone resistance-determining regions of gyrA (resulting in changes of Asp-87 to Tyr or Gly-81 to Cys) and parC (resulting in changes of Asp-93 or Asp-88 to Tyr or Ser-89 to Ile); only two mutations were found in gyrB, and only two mutations were found in parE. More mutants with multiple gyrA and parC mutations were produced with gatifloxacin than with the other fluoroquinolones tested. Allelic diversity was observed among the resistant mutants, for which the drug MICs increased 2- to 256-fold. Both the structures of the drugs and their concentrations influenced the selection of mutants. PMID:15673722

  16. In vitro activities of five fluoroquinolone compounds against strains of Streptococcus pneumoniae with resistance to other antimicrobial agents.

    OpenAIRE

    Barry, A. L.; Fuchs, P C; Brown, S. D.

    1996-01-01

    Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents. Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro antipneumococcal activity might be particularly useful against strains that are resistant to the more traditional therapeutic agents.

  17. Detection of fluoroquinolone resistance in Mycobacterium tuberculosis clinical isolates as determined by gyrA/B gene mutation by using PCR technique

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    A. Salah Eldin

    2012-10-01

    Conclusion: The incidence of FO-resistant M. tuberculosis is gradually increasing to alarming levels this may be due to wide spread use of this vital groups of drugs in community-acquired pneumonia and urinary tract infections.

  18. Fluoroquinolone resistance of Pseudomonas aeruginosa isolates causing nosocomial infection is correlated with levofloxacin but not ciprofloxacin use.

    Science.gov (United States)

    Lee, Yuarn-Jang; Liu, Hsin-Yi; Lin, Yi-Chun; Sun, Kuo-Lun; Chun, Chi-Li; Hsueh, Po-Ren

    2010-03-01

    This study investigated the correlation between fluoroquinolone (ciprofloxacin or levofloxacin) use and rates of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from patients with nosocomial infection at a medical centre in Taiwan. Antibiotic utilisation data were extracted on a monthly basis from the inpatient pharmacy computer system records from January 2003 to December 2008. Fluoroquinolone use was expressed as defined daily dose per 1000 patient-days and was correlated with rates of fluoroquinolone-resistant P. aeruginosa every 6 months. Regression analysis was performed to explore the relationship between ciprofloxacin and levofloxacin use (both parenteral and oral forms) and resistance of P. aeruginosa isolates. During the study period, the susceptibility of P. aeruginosa to fluoroquinolones decreased after increasing use of fluoroquinolones, and increased after decreasing use of levofloxacin. Parenteral levofloxacin use was significantly positively correlated with resistance of P. aeruginosa to ciprofloxacin (P=0.015) and fluoroquinolones (either ciprofloxacin or levofloxacin, P=0.014). Use of both parenteral and oral forms of levofloxacin was also significantly positively correlated with resistance of P. aeruginosa isolates to ciprofloxacin (P=0.029), levofloxacin (P=0.031) and fluoroquinolones (P=0.010). The total amount of ciprofloxacin (oral and parenteral) and parenteral ciprofloxacin use were negatively correlated with resistance of P. aeruginosa isolates to fluoroquinolones. However, the amounts of oral ciprofloxacin, parenteral levofloxacin, oral levofloxacin and total levofloxacin use were each positively correlated with resistance of P. aeruginosa to fluoroquinolones. Levofloxacin use was associated with increased resistance of P. aeruginosa to fluoroquinolones, whereas ciprofloxacin use did not have a significant impact on fluoroquinolone resistance rates. Copyright 2009 Elsevier B.V. and the International Society of Chemotherapy

  19. Mechanisms of Resistance and Clinical Relevance of Resistance to β-Lactams, Glycopeptides, and Fluoroquinolones

    Science.gov (United States)

    Rice, Louis B.

    2012-01-01

    The widespread use of antibiotics has resulted in a growing problem of antimicrobial resistance in the community and hospital settings. Antimicrobial classes for which resistance has become a major problem include the β-lactams, the glycopeptides, and the fluoroquinolones. In gram-positive bacteria, β-lactam resistance most commonly results from expression of intrinsic low-affinity penicillin-binding proteins. In gram-negative bacteria, expression of acquired β-lactamases presents a particular challenge owing to some natural spectra that include virtually all β-lactam classes. Glycopeptide resistance has been largely restricted to nosocomial Enterococcus faecium strains, the spread of which is promoted by ineffective infection control mechanisms for fecal organisms and the widespread use of colonization-promoting antimicrobials (especially cephalosporins and antianaerobic antibiotics). Fluoroquinolone resistance in community-associated strains of Escherichia coli, many of which also express β-lactamases that confer cephalosporin resistance, is increasingly prevalent. Economic and regulatory forces have served to discourage large pharmaceutical companies from developing new antibiotics, suggesting that the antibiotics currently on the market may be all that will be available for the coming decade. As such, it is critical that we devise, test, and implement antimicrobial stewardship strategies that are effective at constraining and, ideally, reducing resistance in human pathogenic bacteria. PMID:22305032

  20. 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

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    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.

  1. Effects of fluoroquinolone treatment and group housing of pigs on the selection and spread of fluoroquinolone-resistant Campylobacter.

    Science.gov (United States)

    Usui, Masaru; Sakemi, Yoko; Uchida, Ikuo; Tamura, Yutaka

    2014-06-04

    There are concerns that the use of fluoroquinolones (FQs) and group housing of food animals may contribute to the development of bacterial FQ resistance. Here, we studied the effects of administering FQ to pigs on the selection of FQ-resistant Campylobacter. Fifteen pigs were randomly allocated to either a group treated with FQs (enrofloxacin or norfloxacin), or an untreated control group. The number of FQ-resistant Campylobacter in feces was determined using appropriate selective agar containing enrofloxacin. FQ-resistant Campylobacter from samples of both groups were observed on days 3 and 4. These bacteria persisted for up to 21 days after treatment was discontinued. To evaluate the effect of group housing on the transmission of FQ-resistant Campylobacter, five pigs infected with FQ-sensitive Campylobacter pigs and one pig infected with FQ-resistant Campylobacter were housed together. On day 3, FQ-resistant Campylobacter were isolated from all six pigs. Moreover, FQ-resistant Campylobacter were isolated from environmental samples from the pen. These results indicate that the treatment of pigs with FQs selects for and spreads FQ-resistant Campylobacter among the pen. Therefore, responsible and prudent use of FQs at pig farms is required to prevent the emergence and transmission of FQ-resistant Campylobacter.

  2. Emergence of fluoroquinolones-resistant strains of Salmonella typhi: Watch on multidrug-resistant isolates

    Directory of Open Access Journals (Sweden)

    Subhash C Arya

    2010-05-01

    Full Text Available Subhash C Arya, Nirmala Agarwal, Shekhar Agarwal, Dolly WadhwaSant Parmanand Hospital, Delhi, IndiaEmergence of multidrug-resistant Salmonella typhi has been responsible for clinical challenges for clinicians. Recently, frequent isolation and dissemination of fluoroquinolones-resistant strains of S. enterica in Surabaya, Indonesia was in the news. Subsequently, Yangai and colleagues1 recommended regular communications between laboratory professionals and clinicians. Collaboration between laboratory personnel and clinicians would be essential to offer a rational empiric antibiotic recipe while awaiting antibiotic susceptibility test results (AST for any patient.

  3. Relationship of AcrAB-TolC efflux pump and its regulatory gene mutation with fluoroquinolones resistance by Shigella.spp%志贺菌属外排泵AcrAB-TolC及其调控基因突变与氟喹诺酮耐药性的关系

    Institute of Scientific and Technical Information of China (English)

    杨贤; 董利娟; 祁伟; 程玉谦; 吕星; 梁帆

    2015-01-01

    Objective To investigate the role of AcrAB-TolC efflux pump in fluoroquinolones resistance by Shigella. spp and to explore the significance of AcrAB-TolC efflux pump on mutation of acrR, soxS and marOR as well as on drug re⁃sistence. Methods Drug resistant bacteria were selected by Kirby-Bauer disk diffusion test. After addition of efflux pump inhibitor carbonylcyanide-m-chlorophenylhydrazone (CCCP), change of minimal inhibitory concentration (MIC)s of nilidixic acid, Levofloxacin, ofloxacin, ciprofloxacin and Norfloxacin were examined. The DNA binding region of acrA, acrB, soxS, acrR and marOR gene in these mutants were amplified by PCR and sequenced. Results Among the 159 clinical isolates of Shigella,11 strains are resistant to fluoroquinolone. After the addition of CCCP, MICs of 2 fluoroquinolone resistant strains decreased; the MICs of 7 fluoroquinolone resistant strains did not change; MICs of 2 fluoroquinolone resistant strains in⁃creased. The corresponding nucleotides C, A, T, T on the 36th to 39th of marOR gene were missing, showing by sequencing, in fluoroquinolone resistent strains which might be regulated by the efflux pump gene AcrAB-TolC. Conclusion Efflux pump inhibitor could restrain the activity of efflux partially. The mutations of marOR might play an important role in fluoroquino⁃lone resistent by shigella.%目的:探讨临床分离耐氟喹诺酮志贺菌外排泵AcrAB-TolC基因及其调控基因marOR、acrR、soxS突变与耐药性的关系。方法使用K-B纸片扩散法筛选临床耐药菌,测定加入泵抑制剂羰基氢氯苯腙(CCCP)后萘啶酸、左氧氟沙星、氧氟沙星、环丙沙星、诺氟沙星的最低抑菌浓度(MIC)的变化,PCR扩增外排泵基因acrA、acrB及其调控基因marOR、acrR、soxS并测序。结果159株志贺菌中共筛选出11株氟喹诺酮耐药菌株;加入质子泵抑制剂后2株耐药菌株对氟喹诺酮类抗菌药的MIC下降;7株耐药菌对氟喹

  4. Activity of ceftazidime-avibactam against fluoroquinolone-resistant Enterobacteriaceae and Pseudomonas aeruginosa.

    Science.gov (United States)

    Pitart, C; Marco, F; Keating, T A; Nichols, W W; Vila, J

    2015-01-01

    Ceftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200 Enterobacteriaceae and 25 Pseudomonas aeruginosa strains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistant Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBL Escherichia coli (MIC90 of 0.25 mg/liter), ESBL Klebsiella pneumoniae (MIC90 of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90 of 1 mg/liter), non-ESBL E. coli (MIC90 of ≤0.125 mg/liter), non-ESBL K. pneumoniae (MIC90 of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90 of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistant P. aeruginosa strains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90 of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtained in vitro from two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90 values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains of Enterobacteriaceae and P. aeruginosa were ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affect Enterobacteriaceae and P. aeruginosa susceptibility to ceftazidime-avibactam; that is, there is no cross-resistance

  5. The role of gyrA and parC mutations in fluoroquinolones-resistant Pseudomonas aeruginosa isolates from Iran

    Directory of Open Access Journals (Sweden)

    Roghayeh Nouri

    Full Text Available Abstract The aim of this study was to examine mutations in the quinolone-resistance-determining region (QRDR of gyrA and parC genes in Pseudomonas aeruginosa isolates. A total of 100 clinical P. aeruginosa isolates were collected from different university-affiliated hospitals in Tabriz, Iran. Minimum inhibitory concentrations (MICs of ciprofloxacin and levofloxacin were evaluated by agar dilution assay. DNA sequences of the QRDR of gyrA and parC were determined by the dideoxy chain termination method. Of the total 100 isolates, 64 were resistant to ciprofloxacin. No amino acid alterations were detected in gyrA or parC genes of the ciprofloxacin susceptible or ciprofloxacin intermediate isolates. Thr-83 → Ile substitution in gyrA was found in all 64 ciprofloxacin resistant isolates. Forty-four (68.75% of them had additional substitution in parC. A correlation was found between the number of the amino acid alterations in the QRDR of gyrA and parC and the level of ciprofloxacin and levofloxacin resistance of the P. aeruginosa isolates. Ala-88 → Pro alteration in parC was generally found in high level ciprofloxacin resistant isolates, which were suggested to be responsible for fluoroquinolone resistance. These findings showed that in P. aeruginosa, gyrA was the primary target for fluoroquinolone and additional mutation in parC led to highly resistant isolates.

  6. Overexpression of patA and patB, which encode ABC transporters, is associated with fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae.

    Science.gov (United States)

    Garvey, Mark I; Baylay, Alison J; Wong, Ryan L; Piddock, Laura J V

    2011-01-01

    Fifty-seven clinical isolates of Streptococcus pneumoniae were divided into four groups based on their susceptibilities to the fluoroquinolones ciprofloxacin and norfloxacin and the dyes ethidium bromide and acriflavine. Comparative reverse transcription-PCR was used to determine the level of expression of the genes patA and patB, which encode putative ABC transporters. Overexpression was observed in 14 of the 15 isolates that were resistant to both fluoroquinolones and dyes and in only 3 of 24 of those resistant to fluoroquinolones only. Isolates overexpressing patA and patB accumulated significantly less of the fluorescent dye Hoechst 33342 than wild-type isolates, suggesting that PatA and PatB are involved in efflux. Inactivation of patA and patB by in vitro mariner mutagenesis conferred hypersusceptibility to ethidium bromide and acriflavine in all isolates tested and lowered the MICs of ciprofloxacin in the patAB-overproducing and/or fluoroquinolone-resistant isolates. These data represent the first observation of overexpression of patA and patB in clinical isolates and show that PatA and PatB play a clinically relevant role in fluoroquinolone resistance.

  7. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Escherichia coli.

    Science.gov (United States)

    Paltansing, Sunita; Tengeler, Anouk C; Kraakman, Margriet E M; Claas, Eric C J; Bernards, Alexandra T

    2013-12-01

    Resistance to ciprofloxacin in Escherichia coli is increasing parallel to increased use of fluoroquinolones both in The Netherlands and in other European countries. The objective was to investigate the contribution of active efflux and expression of outer membrane proteins (OMPs) in a collection of clinical E. coli isolates collected at a clinical microbiology department in a Dutch hospital. Forty-seven E. coli isolates a wide range of ciprofloxacin minimum inhibitory concentrations and known mutations in the quinolone resistance determining region were included. A fluorometric determination of bisbenzimide efflux was used two different efflux pump inhibitors and compared to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for the expression levels of acrA, acrB, tolC, yhiV, and mdfA efflux pump genes and the OMPs ompF and ompX. Six isolates (12.7%) showed increased efflux. Although in 35 isolates (76%), overexpression of ≥1 efflux pump genes using qRT-PCR was present. Only the combined overexpression of acrAB-TolC and mdfA correlated with the phenotypic efflux assay using glucose/carbonyl cyanide m-chlorophenylhydrazone with glucose. Thus, efflux was involved in ciprofloxacin resistance in a limited number of E. coli isolates collected at a clinical microbiology department in a Dutch hospital complementing other resistance mechanisms.

  8. Species-level assessment of the molecular basis of fluoroquinolone resistance among viridans group streptococci causing bacteraemia in cancer patients.

    Science.gov (United States)

    Sahasrabhojane, Pranoti; Galloway-Peña, Jessica; Velazquez, Luis; Saldaña, Miguel; Horstmann, Nicola; Tarrand, Jeffrey; Shelburne, Samuel A

    2014-06-01

    Viridans group streptococci (VGS) are a major cause of bacteraemia in neutropenic cancer patients, particularly those receiving fluoroquinolone prophylaxis. In this study, we sought to understand the molecular basis for fluoroquinolone resistance in VGS causing bacteraemia in cancer patients by assigning 115 VGS bloodstream isolates to specific species using multilocus sequence analysis (MLSA), by sequencing the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and parE, and by testing strain susceptibility to various fluoroquinolones. Non-susceptibility to one or more fluoroquinolones was observed for 78% of isolates, however only 68.7% of patients were receiving fluoroquinolone prophylaxis. All but one of the determinative QRDR polymorphisms occurred in GyrA or ParC, yet the pattern of determinative QRDR polymorphisms was significantly associated with the fluoroquinolone prophylaxis received. By combining MLSA and QRDR data, multiple patients infected with genetically indistinguishable fluoroquinolone-resistant Streptococcus mitis or Streptococcus oralis strains were discovered. Together these data delineate the molecular mechanisms of fluoroquinolone resistance in VGS isolates causing bacteraemia and suggest possible transmission of fluoroquinolone-resistant S. mitis and S. oralis isolates among cancer patients. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  9. Fluoroquinolone Resistance in Salmonella and the Utility of Pefloxacin Disk Diffusion [corrected].

    Science.gov (United States)

    Fang, Ferric C

    2015-11-01

    Fluoroquinolone resistance is a serious and increasingly common problem in Salmonella. Two companion studies in this issue of the Journal of Clinical Microbiology (E. Deak, R. Skov, J. A. Hindler, and R. M. Humphries, J Clin Microbiol 53:3405-3410, 2015, http://dx.doi.org/10.1128/JCM.01393-15; R. Skov, E. Matuschek, M. Sjölund-Karlsson, J. Åhman, A. Petersen, M. Stegger, M. Torpdahl, and G. Kahlmeter, J Clin Microbiol 53:3411-3417, 2015, http://dx.doi.org/10.1128/JCM.01287-15) provide data to support the use of pefloxacin disk diffusion as a convenient and inexpensive surrogate laboratory method to detect fluoroquinolone resistance in Salmonella when the direct measurement of fluoroquinolone MICs is not feasible [corrected]. Recently updated CLSI and EUCAST susceptibility breakpoints will help to optimize clinical outcomes and reduce the likelihood of emergent resistance.

  10. Bug on the back: vertebral osteomyelitis secondary to fluoroquinolone resistant Salmonella typhi in an immunocompetent patient.

    Science.gov (United States)

    Shrestha, Pragya; Mohan, Sachin; Roy, Satyajeet

    2015-11-27

    Although Salmonella osteomyelitis is commonly seen in immunocompromised patients, it may occasionally affect an immunocompetent host. Symptoms are usually non-specific, such as fever, abdominal or back pain; hence it should be considered in the differential diagnosis of patients with a history of travel to endemic regions. Fluoroquinolone resistance is rising and non-responsive patients should be treated with ampicillin, trimethoprim-sulfamethoxazole and ceftriaxone. We present a case of acute T8-T11 osteomyelitis with cord compression caused by a fluoroquinolone resistant strain of Salmonella typhi.

  11. 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.

  12. 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.

  13. Apparent involvement of a multidrug transporter in the fluoroquinolone resistance of Streptococcus pneumoniae.

    OpenAIRE

    Baranova, N N; Neyfakh, A A

    1997-01-01

    A Streptococcus pneumoniae strain selected for resistance to ethidium bromide demonstrated enhanced energy-dependent efflux of this toxic dye. Both the ethidium resistance and the ethidium efflux could be inhibited by the plant alkaloid reserpine. The ethidium-selected cells demonstrated cross-resistance to the fluoroquinolones norfloxacin and ciprofloxacin; this resistance could also be completely reversed by reserpine. Furthermore, reserpine potentiated the susceptibility of wild-type S. pn...

  14. MOLECULAR DETECTION OF CLARITHROMYCIN AND FLUOROQUINOLONES RESISTANCE IN HELICOBACTER PYLORI INFECTION, DIRECTLY APPLIED TO GASTRIC BIOPSIES, IN AN URBAN BRAZILIAN POPULATION.

    Science.gov (United States)

    Martins, Gustavo Miranda; Sanches, Bruno Squárcio Fernandes; Moretzsohn, Luciana Dias; Lima, Karine Sampaio; Cota, Bianca Della Croce V; Coelho, Luiz Gonzaga Vaz

    2016-01-01

    - Antimicrobial resistance is the major factor leading to eradication failure in H. pylori treatment. Molecular tests are useful to detect genetic mutations predictive of clarithromycin and fluoroquinolones resistance. Knowledge of the local prevalence rate of resistance is important to define the best recommended treatment. - To assess the prevalence of primary resistance of H. pylori to clarithromycin and fluoroquinolones, using a molecular test, in a Southeastern urban Brazilian population. - A total of 72 H. pylori seropositive patients [65% female, mean age 39 (19-73) years] never treated before for this infection were studied. All patients underwent gastroscopy in addition to antrum and corpus biopsies and molecular test GenoType HelicoDR (Hain Life Science, Germany) to detect H. pylori and point mutations in genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from biopsy samples, a multiplex amplification with biotinylated primers and a reverse hybridization. The most frequent point mutations involved in resistance to the two antibiotics were evaluated. - Resistance to clarithromycin was detected in nine (12.5%) patients and to fluoroquinolones in eight (11.1%) patients. The point mutation A2147G was the most common (77.8%) among resistant strains to clarithromycin. In 50% of the resistant strains to fluoroquinolones, the mutant codon couldn't be identified. - The resistance rates to clarithromycin and fluorquinolones in a large urban population in the Southeast of Brazil were acceptable, suggesting that these drugs remain appropriate options to first and second-line of H. pylori treatment. The molecular test represents an adequate diagnostic tool for monitoring H. pylori resistance.

  15. Accumulation of ciprofloxacin and lomefloxacinin fluoroquinolone-resistant strains of Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    夏培元; 冯萍; 钟利; 吕晓菊; 雷秉钧

    2002-01-01

    Objective To evaluate the role of outer membrane protein (Omp) F-deficiency and active efflux in the accumulation of hydrophilic fluoroquinolones ciprofloxacin (CPLX) and lomefloxacin (LMLX) in resistant E. coli strains. Methods Fluoroquinolone accumulation in bacteria and the effect of active efflux were measured by a fluorescence method. The outer membrane proteins of the bacteria were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). E. coli strains in this study included control strains JF701 and JF703 that are OmpC- or OmpF-deficient mutants of E. coli K-12, respectively, and the fluoroquinolone susceptible strain the fluoroquinolone susceptible strain of Escherichia coli (Ecs) and its in vitroselected resistant strains R2 and R256, and the clinical resistant isolates R5 and R6. Results The steady-state accumulation concentration of each drug in Ecs appeared to be the same as in JF701, while in the OmpF- deficient strain JF703, it was 1/5 CPLX or 1/2 LMLX lower than that in JF701, but JF703 was still susceptible to fluoroquinolones. On the other hand, compared with susceptible strains, a 2- to 10-fold decrease in the accumulation of each drug was found in the resistant strains except R2, in which the accumulation was slightly higher than in JF703. After the addition of 2,4-dinitrophenol (DNP), accumulation of each drug increased, especially in resistant strains, indicating that the function of the active efflux (pump) system in these bacteria had been enhanced dramatically. Furthermore, both OmpF and OmpC in Ecs, OmpF-deficiency in R2 and R256 and OmpC-deficiency in R5 and R6 were observed.Conclusion The decreased accumulation of hydrophilic fluoroquinolones in E. coli involved OmpF-deficiency and active efflux (pump), and the latter may be an important factor.

  16. Detection of amino acid substitutions in the GyrA protein of fluoroquinolone-resistant typhoidal Salmonella isolates using high-resolution mass spectrometry.

    Science.gov (United States)

    Hassing, Robert-Jan; Goessens, Wil H; Zeneyedpour, Lona; Sultan, Sadaf; van Kampen, Jeroen J; Verbon, Annelies; van Genderen, Perry J; Hays, John P; Luider, Theo M; Dekker, Lennard J

    2016-05-01

    Infections with typhoidal Salmonella isolates that are resistant to fluoroquinolone antibiotics have become very common in several Asian countries. In the majority of these cases, resistance to fluoroquinolone-based antibiotics is associated with genetic mutations in the quinolone resistance-determining region (QRDR) of the bacterial DNA gyrase gene gyrA. The objective of this study was to detect these amino acid substitutions by high-resolution mass spectrometry instead of sequencing of the gyrA gene. A liquid chromatography-mass spectrometry (LC-MS) methodology was developed and evaluated for the detection of amino acid substitutions in the GyrA protein of 23 typhoidal Salmonella isolates. These isolates included typhoidal Salmonella that possessed different antibiotic sensitivities to fluoroquinolone antibiotics. The LC-MS methodology correctly identified peptide sequences associated with phenotypic QRDR mutations of the GyrA protein in all 23 phenotypically diverse typhoidal Salmonella isolates tested. In conclusion, a reliable and rapid LC-MS methodology has been developed that is able to identify GyrA QRDR mutations that are involved in the development of fluoroquinolone resistance in typhoidal Salmonella spp. Furthermore, this 'proof of principle' study indicates the potential usefulness of LC-MS in future detection of antibiotic resistance. Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  17. Beijing genotype of Mycobacterium tuberculosis is significantly associated with high-level fluoroquinolone resistance in Vietnam.

    Science.gov (United States)

    Duong, Duy An; Nguyen, Thi Hong Duyen; Nguyen, Thi Ngoc Lan; Dai, Viet Hoa; Dang, Thi Minh Ha; Vo, Sy Kiet; Do, Dang Anh Thu; Nguyen, Van Vinh Chau; Nguyen, Huy Dung; Dinh, Ngoc Sy; Farrar, Jeremy; Caws, Maxine

    2009-11-01

    Consecutive fluoroquinolone (FQ)-resistant isolates (n = 109) identified at the Pham Ngoc Thach Hospital for Tuberculosis, Ho Chi Minh City, Vietnam, were sequenced in the quinolone resistance-determining regions of the gyrA and gyrB genes and typed by large sequence polymorphism typing and spoligotyping to identify the Beijing genotype of Mycobacterium tuberculosis. Beijing genotype prevalence was compared with 109 consecutive isolates from newly presenting patients with pulmonary tuberculosis from the hospital outpatient department. Overall, 82.6% (n = 90/109) of isolates had mutations in gyrAB. Nine novel mutations were identified in gyrB (S486F, N538T, T539P, D500A, D500H, D500N, G509A, E540V, and E540D). The influence of these novel gyrB mutations on FQ resistance is not proven. The Beijing genotype was significantly associated with FQ resistance (odds ratio [OR], 2.39 [95% confidence interval {CI}, 1.34 to 4.25]; P = 0.003). Furthermore, Beijing genotype FQ-resistant isolates were significantly more likely than FQ-resistant isolates of other genotypes to have gyrA mutations (OR, 7.75 [95% CI, 2.84 to 21.15]; P = 0.0001) and high-level (>8 microg/ml) FQ resistance (OR, 11.0 [95% CI, 2.6 to 47.0]; P = 0.001). The underlying mechanism of the association of the Beijing genotype with high-level FQ resistance in this setting remains to be determined. The association of the Beijing genotype with relatively high-level FQ resistance conferred by specific gyrA mutations reported here is of grave concern given the epidemic spread of the Beijing genotype and the current hopes for shorter first-line treatment regimens based on FQs.

  18. Clinical and Microbiological Features and Factors Associated with Fluoroquinolone Resistance in Men with Community-Acquired Acute Bacterial Prostatitis.

    Science.gov (United States)

    Park, Min Gu; Cho, Min Chul; Cho, Sung Yong; Lee, Jeong Woo

    2016-01-01

    To investigate the clinical and microbiological features in the patients with community-acquired acute bacterial prostatitis (CA-ABP), as well as factors that affect fluoroquinolone resistance. A retrospective analysis was performed of 209 patients hospitalized for antibiotic treatment of CA-ABP. We investigated patient age, body mass index, underlying diseases, recurrence, prostate-related factors and results of urine culture examination and antibiotic sensitivity tests. Seventeen patients (8.1%) had fluoroquinolone-resistant bacterial colonies. When we divided the subjects into groups according to the fluoroquinolone resistance, the group with resistant bacteria was significantly older, had larger prostates and had greater residual urine volumes. Bacteria were identified in 127 of 209 patients (60.8%), and the most commonly cultured included Escherichia coli (43.5%). The sensitivity of the cultured bacteria to fluoroquinolones was high compared to trimethoprim/sulfamethoxazole and gentamicin, but similar to cefotaxime. The bacteria were more sensitive to amikacin and imipenem than to fluoroquinolone. The multivariate analysis revealed that prostate volume ≥40 ml (p = 0.024) and residual urine volume >100 ml (p = 0.004) were independent predictive factors for fluoroquinolone resistance. Fluoroquinolone monotherapy might be an effective treatment in CA-ABP. However, combination antibiotic therapy is recommended in cases with prostate volume ≥40 ml or residual urine volume >100 ml, because fluoroquinolone resistance can occur. © 2016 S. Karger AG, Basel.

  19. Susceptibility of Streptococcus pneumoniae to Fluoroquinolones in Canada▿

    Science.gov (United States)

    Patel, Samir N.; McGeer, Allison; Melano, Roberto; Tyrrell, Gregory J.; Green, Karen; Pillai, Dylan R.; Low, Donald E.

    2011-01-01

    Ciprofloxacin, the first fluoroquinolone to be used to treat lower respiratory tract infections (LRTI), demonstrates poor potency against Streptococcus pneumoniae, and its use has been associated with the emergence of resistance. During the last decade, fluoroquinolones with enhanced in vitro activity against S. pneumoniae have replaced ciprofloxacin for the treatment of LRTI. Here, we analyzed the impact of more active fluoroquinolone usage on pneumococci by examining the fluoroquinolone usage, prevalence of fluoroquinolone resistance, and mutations in the genes that encode the major target sites for the fluoroquinolones (gyrA and parC) in pneumococcal isolates collected in Canada-wide surveillance. A total of 26,081 isolates were collected between 1998 and 2009. During this time period, total per capita outpatient use of fluoroquinolones increased from 64 to 96 prescriptions per 1,000 persons per year. The proportion of prescriptions for respiratory tract infection that were for fluoroquinolones increased from 5.9% to 10.7%, but the distribution changed: the proportion of prescriptions for ciprofloxacin decreased from 5.3% to 0.5%, and those for levofloxacin or moxifloxacin increased from 1.5% in 1999 to 5.9% in 2009. The prevalence of ciprofloxacin resistance (MIC ≥ 4 μg/ml), levofloxacin resistance, and moxifloxacin resistance remained unchanged at fluoroquinolones did not change during the surveillance period. If fluoroquinolone therapy is required, the preferential use of fluoroquinolones with enhanced pneumococcal activity to treat pneumococcal infections may slow the emergence of resistance in S. pneumoniae. PMID:21628545

  20. Susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada.

    Science.gov (United States)

    Patel, Samir N; McGeer, Allison; Melano, Roberto; Tyrrell, Gregory J; Green, Karen; Pillai, Dylan R; Low, Donald E

    2011-08-01

    Ciprofloxacin, the first fluoroquinolone to be used to treat lower respiratory tract infections (LRTI), demonstrates poor potency against Streptococcus pneumoniae, and its use has been associated with the emergence of resistance. During the last decade, fluoroquinolones with enhanced in vitro activity against S. pneumoniae have replaced ciprofloxacin for the treatment of LRTI. Here, we analyzed the impact of more active fluoroquinolone usage on pneumococci by examining the fluoroquinolone usage, prevalence of fluoroquinolone resistance, and mutations in the genes that encode the major target sites for the fluoroquinolones (gyrA and parC) in pneumococcal isolates collected in Canada-wide surveillance. A total of 26,081 isolates were collected between 1998 and 2009. During this time period, total per capita outpatient use of fluoroquinolones increased from 64 to 96 prescriptions per 1,000 persons per year. The proportion of prescriptions for respiratory tract infection that were for fluoroquinolones increased from 5.9% to 10.7%, but the distribution changed: the proportion of prescriptions for ciprofloxacin decreased from 5.3% to 0.5%, and those for levofloxacin or moxifloxacin increased from 1.5% in 1999 to 5.9% in 2009. The prevalence of ciprofloxacin resistance (MIC ≥ 4 μg/ml), levofloxacin resistance, and moxifloxacin resistance remained unchanged at fluoroquinolones did not change during the surveillance period. If fluoroquinolone therapy is required, the preferential use of fluoroquinolones with enhanced pneumococcal activity to treat pneumococcal infections may slow the emergence of resistance in S. pneumoniae.

  1. The Magnitude of the Association between Fluoroquinolone Use and Quinolone-Resistant Escherichia coli and Klebsiella pneumoniae May Be Lower than Previously Reported

    OpenAIRE

    Bolon, Maureen K.; Wright, Sharon B.; Gold, Howard S.; Carmeli, Yehuda

    2004-01-01

    Case-control analyses of resistant versus susceptible isolates have implicated fluoroquinolone exposure as a strong risk factor for fluoroquinolone-resistant isolates of Enterobacteriaceae. We suspect that such methodology may overestimate this association. A total of 84 cases with fluoroquinolone-resistant isolates and 578 cases with fluoroquinolone-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were compared with 608 hospitalized controls in parallel multivariable analyse...

  2. Emergence of a Streptococcus pneumoniae Clinical Isolate Highly Resistant to Telithromycin and Fluoroquinolones

    OpenAIRE

    Faccone, Diego; Andres, Patricia; Galas, Marcelo; Tokumoto, Marta; Rosato, Adriana; Corso, Alejandra

    2005-01-01

    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 μg/ml) and simultaneous resistance to FQs. Ongoing studies are oriented to elucidate the precise mechanism of res...

  3. Induction of prophages by fluoroquinolones in streptococcus pneumoniae: implications for emergence of resistance in genetically-related clones

    OpenAIRE

    Elena López; Arnau Domenech; María-José Ferrándiz; Maria João Frias; Carmen Ardanuy; Mario Ramirez; Ernesto García; Josefina Liñares; de la Campa, Adela G.

    2014-01-01

    Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an impo...

  4. Draft Genome Sequences of Streptococcus pneumoniae with High-Level Resistance to Respiratory Fluoroquinolones.

    Science.gov (United States)

    Keness, Yoram; Bisharat, Naiel

    2016-03-31

    Streptococcus pneumoniaeis the leading cause of community-acquired pneumonia. Levofloxacin is a fluoroquinolone used for treatment of severe community-acquired pneumonia. Here, we describe the draft genome sequences ofS. pneumoniaewith emerging resistance to levofloxacin, resulting in failure of treatment of pneumococcal pneumonia.

  5. Draft Genome Sequences of Streptococcus pneumoniae with High-Level Resistance to Respiratory Fluoroquinolones

    OpenAIRE

    Keness, Yoram; Bisharat, Naiel

    2016-01-01

    Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. Levofloxacin is a fluoroquinolone used for treatment of severe community-acquired pneumonia. Here, we describe the draft genome sequences of S. pneumoniae with emerging resistance to levofloxacin, resulting in failure of treatment of pneumococcal pneumonia.

  6. Fluoroquinolones, the Cornerstone of Treatment of Drug-Resistant Tuberculosis : A Pharmacokinetic and Pharmacodynamic Approach

    NARCIS (Netherlands)

    Pranger, A. D.; Alffenaar, J. W. C.; Aarnoutse, R. E.

    2011-01-01

    Fluoroquinolones (FQs) are important drugs to treat drug-resistant tuberculosis. In this review we integrated pharmacokinetic properties (PK) and microbiological susceptibility against M. tuberculosis and eventually evaluated the pharmcodynamic (PD) properties, as well as the influence of co-adminis

  7. Fluoroquinolones, the cornerstone of treatment of drug-resistant tuberculosis: a pharmacokinetic and pharmacodynamic approach.

    NARCIS (Netherlands)

    Pranger, A.D.; Alffenaar, J.W.C.; Aarnoutse, R.E.

    2011-01-01

    Fluoroquinolones (FQs) are important drugs to treat drug-resistant tuberculosis. In this review we integrated pharmacokinetic properties (PK) and microbiological susceptibility against M. tuberculosis and eventually evaluated the pharmcodynamic (PD) properties, as well as the influence of co-adminis

  8. Relationship between gyrA and parC genes and Enterococcus faecalis to fluoroquinolone resistance%gyrA和parC基因与粪肠球菌对氟喹诺酮类抗菌药物耐药的关系

    Institute of Scientific and Technical Information of China (English)

    张侠家; 沈继龙; 徐元宏; 姚杰

    2011-01-01

    Objective To study DNA gyrase and topoisomerase Ⅳ gene mutation to fluoroquinolone resistance and provide experimental evidence in treatment for clinical and developing new drugs. Methods Detected by agar dilution method against 112 strains of Enterococcus faecatis 4 fluoroquinolone antibiotics in vitro susceptibility testing,and PCR amplified QRDR of gyrA and parC that quinolone resistant strains. Then randomly selected 5 direct sequencing of PCR products were purified and compared by BLAST analysis of its amino acid sequence. Results 4 fluoroquinolone antibiotics against E.faecalis on the antibacterial activity as follows: CAT > LVX > NOR and CIP.GyrA gene had changed with Ser83→Ile( AGT→ATT )and Ser83→Tyr( ACT→TAT );parC genes occurred mutation with Ser80 Ile( AGC→ATC ),Ser48→Leu( TCA→ TTA ).Met89→Leu( ATG →CTA ),Lys94 →Ile( AAC→ATA ). Conclusion Enterococcus faecalis resistant to fluoroquinolones in serious condition. The mutation of gyrA and parC gene is an important reason of E. faecalis resistant to fluoroquinolone antibiotics.%目的 探讨粪肠球菌DNA解旋酶和拓扑异构酶Ⅳ基因与氟喹诺酮类抗菌药物的耐药的关系,为临床治疗和新药的开发提出实验依据.方法 用琼脂稀释法检测112株粪肠球菌对4种氟喹诺酮类抗菌药物的体外敏感试验,并选择对氟喹诺酮类抗菌药物耐药的菌株对其gyrA和parC的喹诺酮耐药决定区域基因进行PCR扩增,然后随机选择5株PCR产物纯化后直接测序经基因同源性分析(BLAST)分析其氨基酸序列.结果 4种氟喹诺酮类抗菌药物对粪肠球菌的抑菌效果依次为:加替沙星>左氧氟沙星>诺氟沙星、环丙沙星;5株菌的gyrA基因有4株第83位氨基酸发生了改变,parC基因均发生了突变.结论 粪肠球菌对氟喹诺酮类药物的耐药情况严重,gyrA基因和parC基因的氨基酸突变是引起粪肠球菌对氟喹诺酮类抗菌药物产生耐药的重要原因.

  9. Fluoroquinolone-Resistant Escherichia coli Infections After Transrectal Biopsy of the Prostate in the Veterans Affairs Healthcare System

    Science.gov (United States)

    Saade, Elie A.; Suwantarat, Nuntra; Zabarsky, Trina F.; Wilson, Brigid; Donskey, Curtis J.

    2016-01-01

    Background Recent reports suggest that infections due to fluoroquinolone-resistant Escherichia coli (E. coli) are an increasingly common complication of transrectal biopsy of the prostate (TBP) in the United States. A better understanding of the magnitude and scope of these infections is needed to guide prevention efforts. Our objective is to determine whether the incidence of infections due to fluoroquinolone-resistant E. coli after TBP has increased nationwide in the Veterans Affairs Health Care System and to identify risk factors for infection. Methods We performed a retrospective, observational cohort study and a nested case-control study within the US Deparment of Veterans Affairs Healthcare System. The primary outcomes were the incidence of urinary tract infection (UTI) and bacteremia with E. coli and with fluoroquinolone- resistant E. coli strains within 30 days after TBP. Secondary endpoints focused on the correlation between fluoroquinolone-resistance in all urinary E. coli isolates and post-TBP infection and risk factors for infection due to fluoroquinolone-resistant E. coli infection. Results 245 618 patients undergoing 302 168 TBP procedures from 2000 through 2013 were included in the cohort study, and 59 469 patients undergoing TBP from 2011 through 2013 were included in the nested case-control study. Between 2000 and 2013, there was a 5-fold increase in the incidence of E. coli UTI (0.18%–0.93%) and a 4-fold increase in the incidence of E. coli bacteremia (0.04%–0.18%) after TBP that was attributable to an increase in the incidence of fluoroquinolone- resistant E. coli UTI (0.03%–0.75%) and bacteremia (0.01%–0.14%). The increasing incidence of fluoroquinolone-resistant E. coli infections after TBP occurred in parallel with increasing rates of fluoroquinolone-resistance in all urinary E. coli isolates. By multivariable logistic regression analysis, independent risk factors for fluoroquinolone-resistant E. coli UTI after TBP included diabetes

  10. Association between fluoroquinolone usage and a dramatic rise in ciprofloxacin-resistant Streptococcus pneumoniae in Canada, 1997-2006.

    Science.gov (United States)

    Adam, Heather J; Hoban, Daryl J; Gin, Alfred S; Zhanel, George G

    2009-07-01

    This study evaluated the prevalence of fluoroquinolone usage and investigated the association between usage and resistance in respiratory isolates of Streptococcus pneumoniae in Canada. Fluoroquinolone susceptibility testing was conducted on S. pneumoniae collected from 25 medical centres across Canada over nine study years. Fluoroquinolone prescriptions and consumption figures were derived from data in the IMS Health, Canada CompuScript Audit. Between 1997 and 2006, 11825 S. pneumoniae isolates were collected. Ciprofloxacin resistance rates increased significantly (P or = 65 years). Outpatient ciprofloxacin and respiratory fluoroquinolone prescriptions increased by 55.6% (38.2 prescriptions/1000 population to 59.4 prescriptions/1000 population; Pfluoroquinolone consumption increased by 10.6% [1.1 defined daily doses (DDDs)/1000/day to 1.2 DDDs/1000/day; P=0.02] and 38.2% (0.5 to 0.7 DDDs/1000/day; P=0.02), respectively, from 2001 to 2006. A strong association between ciprofloxacin use and resistance (R(2)=0.89) was identified. Fluoroquinolone resistance in S. pneumoniae increased significantly in Canada from 1997 to 2006 in conjunction with increased ciprofloxacin and respiratory fluoroquinolone consumption. Ciprofloxacin usage appears to be the biggest driver of resistance; however, total fluoroquinolone usage is also important.

  11. Rising fluoroquinolone resistance in Campylobacter isolated from feedlot cattle in the United States.

    Science.gov (United States)

    Tang, Yizhi; Sahin, Orhan; Pavlovic, Nada; LeJeune, Jeff; Carlson, James; Wu, Zuowei; Dai, Lei; Zhang, Qijing

    2017-03-29

    Antibiotic resistance, particularly to fluoroquinolones and macrolides, in the major foodborne pathogen Campylobacter is considered a serious threat to public health. Although ruminant animals serve as a significant reservoir for Campylobacter, limited information is available on antibiotic-resistant Campylobacter of bovine origin. Here, we analyzed the antimicrobial susceptibilities of 320 C. jejuni and 115 C. coli isolates obtained from feedlot cattle farms in multiple states in the U.S. The results indicate that fluoroquinolone resistance reached to 35.4% in C. jejuni and 74.4% in C. coli, which are significantly higher than those previously reported in the U.S. While all fluoroquinolone resistant (FQ(R)) C. coli isolates examined in this study harbored the single Thr-86-Ile mutation in GyrA, FQ(R) C. jejuni isolates had other mutations in GyrA in addition to the Thr-86-Ile change. Notably, most of the analyzed FQ(R) C. coli isolates had similar PFGE (pulsed field gel electrophoresis) patterns and the same MLST (multilocus sequence typing) sequence type (ST-1068) regardless of their geographic sources and time of isolation, while the analyzed C. jejuni isolates were genetically diverse, suggesting that clonal expansion is involved in dissemination of FQ(R) C. coli but not C. jejuni. These findings reveal the rising prevalence of FQ(R) Campylobacter in the U.S. and provide novel information on the epidemiology of antibiotic-resistant Campylobacter in the ruminant reservoir.

  12. Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase.

    Science.gov (United States)

    Aldred, Katie J; Blower, Tim R; Kerns, Robert J; Berger, James M; Osheroff, Neil

    2016-02-16

    Mycobacterium tuberculosis is a significant source of global morbidity and mortality. Moxifloxacin and other fluoroquinolones are important therapeutic agents for the treatment of tuberculosis, particularly multidrug-resistant infections. To guide the development of new quinolone-based agents, it is critical to understand the basis of drug action against M. tuberculosis gyrase and how mutations in the enzyme cause resistance. Therefore, we characterized interactions of fluoroquinolones and related drugs with WT gyrase and enzymes carrying mutations at GyrA(A90) and GyrA(D94). M. tuberculosis gyrase lacks a conserved serine that anchors a water-metal ion bridge that is critical for quinolone interactions with other bacterial type II topoisomerases. Despite the fact that the serine is replaced by an alanine (i.e., GyrA(A90)) in M. tuberculosis gyrase, the bridge still forms and plays a functional role in mediating quinolone-gyrase interactions. Clinically relevant mutations at GyrA(A90) and GyrA(D94) cause quinolone resistance by disrupting the bridge-enzyme interaction, thereby decreasing drug affinity. Fluoroquinolone activity against WT and resistant enzymes is enhanced by the introduction of specific groups at the C7 and C8 positions. By dissecting fluoroquinolone-enzyme interactions, we determined that an 8-methyl-moxifloxacin derivative induces high levels of stable cleavage complexes with WT gyrase and two common resistant enzymes, GyrA(A90V) and GyrA(D94G). 8-Methyl-moxifloxacin was more potent than moxifloxacin against WT M. tuberculosis gyrase and displayed higher activity against the mutant enzymes than moxifloxacin did against WT gyrase. This chemical biology approach to defining drug-enzyme interactions has the potential to identify novel drugs with improved activity against tuberculosis.

  13. Intensity and Mechanisms of Fluoroquinolone Resistance within the H30 and H30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli.

    Science.gov (United States)

    Johnson, James R; Johnston, Brian; Kuskowski, Michael A; Sokurenko, Evgeni V; Tchesnokova, Veronika

    2015-08-01

    The recent expansion of the H30 subclone of Escherichia coli sequence type 131 (ST131) and its CTX-M-15-associated H30Rx subset remains unexplained. Although ST131 H30 typically exhibits fluoroquinolone resistance, so do multiple other E. coli lineages that have not expanded similarly. To determine whether H30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistant E. coli isolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistant E. coli isolates (48 non-H30 and 41 H30 [23 H30Rx and 18 H30 non-Rx]). We compared the MICs with the H30 and H30Rx status, the presence/number of nonsynonymous mutations in gyrA, parC, and parE, the presence of aac(6')-1b-cr (an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recent E. coli clinical isolates, ST131 H30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-H30 isolates, H30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations in gyrA, parC, and parE (specifically gyrA D87N, parC E84V, and parE I529L), and a numerically higher prevalence of (H30Rx-associated) aac(6')-1b-cr but lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [for aac(6')-1b-cr: ciprofloxacin and norfloxacin only]. parC D87N corresponded with ST131 H30 and parE I529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131 H30, especially H30Rx [if aac(6')-1b-cr positive], with subtle fitness advantages over other fluoroquinolone-resistant E. coli strains. This urges both parsimonious fluoroquinolone

  14. Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance

    Science.gov (United States)

    Tao, Jun; Han, Jiao; Wu, Hanyu; Hu, Xinling; Deng, Jiaoyu; Fleming, Joy; Maxwell, Anthony; Bi, Lijun; Mi, Kaixia

    2013-01-01

    DNA gyrase plays a vital role in resolving DNA topological problems and is the target of antibiotics such as fluoroquinolones. Mycobacterium fluoroquinolone resistance protein A (MfpA) from Mycobacterium smegmatis is a newly identified DNA gyrase inhibitor that is believed to confer intrinsic resistance to fluoroquinolones. However, MfpA does not prevent drug-induced inhibition of DNA gyrase in vitro, implying the involvement of other as yet unknown factors. Here, we have identified a new factor, named Mycobacterium fluoroquinolone resistance protein B (MfpB), which is involved in the protection of DNA gyrase against drugs both in vivo and in vitro. Genetic results suggest that MfpB is necessary for MfpA protection of DNA gyrase against drugs in vivo; an mfpB knockout mutant showed greater susceptibility to ciprofloxacin than the wild-type, whereas a strain overexpressing MfpA and MfpB showed higher loss of susceptibility. Further biochemical characterization indicated that MfpB is a small GTPase and its GTP bound form interacts directly with MfpA and influences its interaction with DNA gyrase. Mutations in MfpB that decrease its GTPase activity disrupt its protective efficacy. Our studies suggest that MfpB, a small GTPase, is required for MfpA-conferred protection of DNA gyrase. PMID:23275532

  15. 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.

  16. A Case of Fluoroquinolone-Resistant Leprosy Discovered after 9 Years of Misdiagnosis

    Science.gov (United States)

    Ramarozatovo, Lala S.; Ranaivo, Irina M.; Andrianarison, Malalaniaina; Cambau, Emmanuelle

    2016-01-01

    We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V). After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed. PMID:27579195

  17. A Case of Fluoroquinolone-Resistant Leprosy Discovered after 9 Years of Misdiagnosis

    Directory of Open Access Journals (Sweden)

    Onivola Raharolahy

    2016-01-01

    Full Text Available We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V. After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed.

  18. Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing transrectal ultrasound-guided prostate biopsy--should we reassess our practices for antibiotic prophylaxis?

    Science.gov (United States)

    Steensels, D; Slabbaert, K; De Wever, L; Vermeersch, P; Van Poppel, H; Verhaegen, J

    2012-06-01

    Although the estimate of the incidence of sepsis following transrectal ultrasound-guided prostate biopsy (TRUSPB) is low, fluoroquinolone-resistant infections after prostate biopsy are being increasingly noted. This study was aimed at determining the prevalence of faecal carriage of fluoroquinolone-resistant Escherichia coli strains before TRUSPB and at evaluating potential predisposing risk factors. The incidence of sepsis after prostate biopsy was determined, and our routine practice for antibiotic prophylaxis for TRUSPB was evaluated. A prospective study was conducted in 342 consecutive patients undergoing prostate biopsy between December 2009 and July 2010. Before TRUSPB, a rectal swab was cultured. The correlation between the presence of fluoroquinolone-resistant strains and plausible risk factors was investigated by the use of a questionnaire. Of the 236 patients included, 22.0% (52/236) harboured ciprofloxacin-resistant E. coli strains. The use of fluoroquinolones in the 6 months before biopsy was associated with an increased risk of faecal carriage of fluoroquinolone-resistant E. coli strains (p fluoroquinolone-resistant E. coli strains was an important risk factor for infectious complications after TRUSPB (p fluoroquinolone-resistant E. coli strains (22.0%) before TRUSPB. The use of fluoroquinolones in the previous 6 months before biopsy is a risk factor for faecal carriage of fluoroquinolone-resistant E. coli strains and for infectious complications after TRUSPB. Hence, the universal administration of fluoroquinolones should be reconsidered. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  19. Adjuvants Based on Hybrid Antibiotics Overcome Resistance in Pseudomonas aeruginosa and Enhance Fluoroquinolone Efficacy.

    Science.gov (United States)

    Gorityala, Bala Kishan; Guchhait, Goutam; Fernando, Dinesh M; Deo, Soumya; McKenna, Sean A; Zhanel, George G; Kumar, Ayush; Schweizer, Frank

    2016-01-11

    The use of adjuvants that rescue antibiotics against multidrug-resistant (MDR) pathogens is a promising combination strategy for overcoming bacterial resistance. While the combination of β-lactam antibiotics and β-lactamase inhibitors has been successful in restoring antibacterial efficacy in MDR bacteria, the use of adjuvants to restore fluoroquinolone efficacy in MDR Gram-negative pathogens has been challenging. We describe tobramycin-ciprofloxacin hybrid adjuvants that rescue the activity of fluoroquinolone antibiotics against MDR and extremely drug-resistant Pseudomonas aeruginosa isolates in vitro and enhance fluoroquinolone efficacy in vivo. Structure-activity studies reveal that the presence of both tobramycin and ciprofloxacin, which are separated by a C12 tether, is critical for the function of the adjuvant. Mechanistic studies indicate that the antibacterial modes of ciprofloxacin are retained while the role of tobramycin is limited to destabilization of the outer membrane in the hybrid. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Prediction of Fluoroquinolone Resistance in Gram-Negative Bacteria Causing Bloodstream Infections.

    Science.gov (United States)

    Dan, Seejil; Shah, Ansal; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2016-04-01

    Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve (AUC). Among 824 patients with Gram-negative BSI, 143 (17%) had BSI due to fluoroquinolone-nonsusceptible Gram-negative bacilli. Independent risk factors for FQ-R and point allocation in FQRS included male sex (adjusted odds ratio [aOR], 1.97; 95% confidence intervals [CI], 1.36 to 2.98; 1 point), diabetes mellitus (aOR, 1.54; 95% CI, 1.03 to 2.28; 1 point), residence at a skilled nursing facility (aOR, 2.28; 95% CI, 1.42 to 3.63; 2 points), outpatient procedure within 30 days (aOR, 3.68; 95% CI, 1.96 to 6.78; 3 points), prior fluoroquinolone use within 90 days (aOR, 7.87; 95% CI, 4.53 to 13.74; 5 points), or prior fluoroquinolone use within 91 to 180 days of BSI (aOR, 2.77; 95% CI, 1.17 to 6.16; 3 points). The AUC for both final logistic regression and FQRS models was 0.73. Patients with an FQRS of 0, 3, 5, or 8 had predicted probabilities of FQ-R of 6%, 22%, 39%, or 69%, respectively. The estimation of patient-specific risk of antimicrobial resistance using FQRS may improve empirical antimicrobial therapy and fluoroquinolone utilization in Gram-negative BSI. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. Evaluation of several fluoroquinolones and beta-lactams in terms of their capability to restrict the selection of fluoroquinolone-resistant Salmonella: in vitro models.

    Science.gov (United States)

    Cebríán, L; Rodríguez, J C; Escribiano, I; Royo, S G

    2007-12-01

    With a view to understanding the interaction between Salmonella and the drugs used to treat it, our aim was to compare the different capacities of various antibiotics to generate mutants resistant to fluoroquinolones following repeated exposure of the microorganisms to subinhibitory concentrations of these drugs. Mutants were generated by repeated exposure to fluoroquinolones and beta-lactams. In order to compare the different capacity to generate resistant mutants, we studied the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of the wild-type strains and of the mutants generated. These data were compared with pharmacokinetic parameters. Mutants generated following repeated exposure to fluoroquinolones exhibit an increased MPC as compared to the wild-type strains, both in strains that are nalidixic acid susceptible and in those that are nalidixic acid resistant, with repeated exposure to ciprofloxacin leading to the smallest increases. This increase in MPC is gradual and depends on the number of exposures the bacteria are subjected to. It results in a decrease in the AUC/MPC ratio, although the absolute values vary. Ciprofloxacin is the most active drug, both against nalidixic acid-susceptible and nalidixic acid-resistant strains, although in late mutants of originally nalidixic acid-resistant strains, the AUC/MPC values are low. Repeated exposure to amoxicillin and cefotaxime also produces an increase in the MPC of fluoroquinolones, with ciprofloxacin being the least affected. Exposure to amoxicillin leads to the greatest increase in the MPC of fluoroquinolones. When the AUC/MPC ratios of these mutants are compared, the values are still seen to be high (between 25 and 75). When we compare the MPC data with the antibiotic levels in humans following administration of the usual doses, it can be seen that ciprofloxacin exhibits the highest AUC/MPC and therefore the lowest risk of therapeutic failures. In addition, administration of

  2. Highly Resistant Salmonella enterica Serovar Typhi with a Novel gyrA Mutation Raises Questions about the Long-Term Efficacy of Older Fluoroquinolones for Treating Typhoid Fever

    Science.gov (United States)

    Koirala, Kanika Deshpande; Thanh, Duy Pham; Thapa, Sudeep Dhoj; Arjyal, Amit; Karkey, Abhilasha; Dongol, Sabina; Shrestha, Upendra Man; Farrar, Jeremy J.; Baker, Stephen

    2012-01-01

    As a consequence of multidrug resistance, clinicians are highly dependent on fluoroquinolones for treating the serious systemic infection typhoid fever. While reduced susceptibility to fluoroquinolones, which lessens clinical efficacy, is becoming ubiquitous, comprehensive resistance is exceptional. Here we report ofloxacin treatment failure in typhoidal patient infected with a novel, highly fluoroquinolone-resistant isolate of Salmonella enterica serovar Typhi. The isolation of this organism has serious implications for the long-term efficacy of ciprofloxacin and ofloxacin for typhoid treatment. PMID:22371897

  3. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones

    Science.gov (United States)

    Malik, Muhammad; Mustaev, Arkady; Schwanz, Heidi A.; Luan, Gan; Shah, Nirali; Oppegard, Lisa M.; de Souza, Ernane C.; Hiasa, Hiroshi; Zhao, Xilin; Kerns, Robert J.; Drlica, Karl

    2016-01-01

    Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance. PMID:26984528

  4. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones.

    Science.gov (United States)

    Malik, Muhammad; Mustaev, Arkady; Schwanz, Heidi A; Luan, Gan; Shah, Nirali; Oppegard, Lisa M; de Souza, Ernane C; Hiasa, Hiroshi; Zhao, Xilin; Kerns, Robert J; Drlica, Karl

    2016-04-20

    Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance.

  5. A case of atypical nocardia asteroides sclerouveitis resistant to fourth-generation fluoroquinolones

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    Túlio Frade Reis

    Full Text Available ABSTRACT We describe an unusual case of Nocardia spp scleritis in a health girl resistant to topical fourth-generation fluoroquinolones. Clinically, there was only partial response of the scleritis to initial therapy. Treatment was changed to meropenem intravenously and topical amikacin. Following several weeks of antibiotic treatment, the patient's infection resolved but her vision was reduced to no light perception. Nocardia asteroides must be considered as a possible agent in cases of necrotizing scleritis in patients without a clear source. Antibiotic sensitivity testing has a definitive role in view of the resistance to these new medications.

  6. Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella pneumophila and Humans

    Science.gov (United States)

    Shadoud, Lubana; Almahmoud, Iyad; Jarraud, Sophie; Etienne, Jérôme; Larrat, Sylvie; Schwebel, Carole; Timsit, Jean-François; Schneider, Dominique; Maurin, Max

    2015-01-01

    Background Infectious diseases are the leading cause of human morbidity and mortality worldwide. One dramatic issue is the emergence of microbial resistance to antibiotics which is a major public health concern. Surprisingly however, such in vivo adaptive ability has not been reported yet for many intracellular human bacterial pathogens such as Legionella pneumophila. Methods We examined 82 unrelated patients with Legionnaire's disease from which 139 respiratory specimens were sampled during hospitalization and antibiotic therapy. We both developed a real time PCR assay and used deep-sequencing approaches to detect antibiotic resistance mutations in L. pneumophila and follow their selection and fate in these samples. Findings We identified the in vivo selection of fluoroquinolone resistance mutations in L. pneumophila in two infected patients treated with these antibiotics. By investigating the mutational dynamics in patients, we showed that antibiotic resistance occurred during hospitalization most likely after fluoroquinolone treatment. Interpretation In vivo selection of antibiotic resistances in L. pneumophila may be associated with treatment failures and poor prognosis. This hidden resistance must be carefully considered in the therapeutic management of legionellosis patients and in the control of the gradual loss of effectiveness of antibiotics. PMID:26501115

  7. Fluoroquinolone-resistant Escherichia coli carriage in long-term care facility.

    Science.gov (United States)

    Maslow, Joel N; Lee, Betsy; Lautenbach, Ebbing

    2005-06-01

    We conducted a cross-sectional study to determine the prevalence of, and risk factors for, colonization with fluoroquinolone (FQ)-resistant Escherichia coli in residents in a long-term care facility. FQ-resistant E. coli were identified from rectal swabs for 25 (51%) of 49 participants at study entry. On multivariable analyses, prior FQ use was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures in the previous 3, 6, 9, or 12 months. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified clonal spread of 1 strain among 16 residents. Loss (6 residents) or acquisition (7 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. Unlike the case in the hospital setting, FQ-resistant E. coli carriage in long-term care facilities is associated with clonal spread.

  8. Genetic profiles of fluoroquinolone-resistant Escherichia coli isolates obtained from patients with cystitis: phylogeny, virulence factors, PAIusp subtypes, and mutation patterns.

    Science.gov (United States)

    Takahashi, Akira; Muratani, Tetsuro; Yasuda, Mitsuru; Takahashi, Satoshi; Monden, Koichi; Ishikawa, Kiyohito; Kiyota, Hiroshi; Arakawa, Soichi; Matsumoto, Tetsuro; Shima, Hiroki; Kurazono, Hisao; Yamamoto, Shingo

    2009-03-01

    The low virulence of quinolone- and fluoroquinolone-resistant Escherichia coli strains is known, although the reasons for this remain unclear. We surveyed the mutation patterns of quinolone resistance determining regions (QRDRs), phylogenetic distribution, prevalence of 18 urovirulence genes, and PAIusp subtypes in 89 fluoroquinolone-resistant E. coli (FQREC) isolates obtained from patients with cystitis and compared them with those of their fluoroquinolone-susceptible counterparts (FQSEC). Phylogenetic group B2 was significantly less prevalent in FQREC than in FQSEC (49% versus 78%; P=0.0138), but it still dominated, followed by phylogroup D (35%), in FQREC. When the prevalences of virulence factor (VF) genes were compared between FQREC and FQSEC, sfa/foc, cnf1, hly, kpsMT, ompT, ibeA, usp, and iroN showed significantly lower prevalences in FQREC than in FQSEC (1.1% versus 24% [Presistance, e.g., mutations in QRDRs, might be a specific event in limited strains, such as those that possess PAIusp subtype 2a in phylogroup B2.

  9. Isolation of novel IncA/C and IncN fluoroquinolone resistance plasmids from an antibiotic-polluted lake.

    Science.gov (United States)

    Flach, Carl-Fredrik; Johnning, Anna; Nilsson, Ida; Smalla, Kornelia; Kristiansson, Erik; Larsson, D G Joakim

    2015-10-01

    Antibiotic-polluted environments may function as reservoirs for novel resistance plasmids not yet encountered in pathogens. The aims of this study were to assess the potential of resistance transfer between bacteria from such environments and Escherichia coli, and to characterize the conjugative elements involved. Sediment samples from Kazipally lake and Asanikunta tank, two Indian lakes with a history of severe pollution with fluoroquinolones, were investigated. Proportions of resistant bacteria were determined by selective cultivation, while horizontal gene transfer was studied using a GFP-tagged E. coli as recipient. Retrieved transconjugants were tested for susceptibility by Etest(®) and captured conjugative resistance elements were characterized by WGS. The polluted lakes harboured considerably higher proportions of ciprofloxacin-resistant and sulfamethoxazole-resistant bacteria than did other Indian and Swedish lakes included for comparison (52% versus 2% and 60% versus 7%, respectively). Resistance plasmids were captured from Kazipally lake, but not from any of the other lakes; in the case of Asanikunta tank because of high sediment toxicity. Eight unique IncA/C and IncN resistance plasmids were identified among 11 sequenced transconjugants. Five plasmids were fully assembled, and four of these carried the quinolone resistance gene qnrVC1, which has previously only been found on chromosomes. Acquired resistance genes, in the majority of cases associated with class 1 integrons, could be linked to decreased susceptibility to several different classes of antibiotics. Our study shows that environments heavily polluted with antibiotics contain novel multiresistance plasmids transferrable to E. coli. © 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.

  10. Life-Threatening Infantile Diarrhea from Fluoroquinolone-Resistant Salmonella enteric Typhimurium with Mutations in Both gyrA and parC

    OpenAIRE

    Nakaya, Hideo; Yasuhara, Akihiro; Yoshimura, Ken; Oshihoi, Yukio; Izumiya, Hidemasa; Watanabe, Haruo

    2003-01-01

    Salmonella Typhimurium DT12, isolated from a 35-day-old infant with diarrhea, was highly resistant to ampicillin, tetracycline, chloramphenicol, streptomycin, gentamycin, sulfamethoxazole/trimethoprim, nalidixic acid, and fluoroquinolones. The patient responded to antibiotic therapy with fosfomycin. Multidrug-resistance may become prevalent in Salmonella infections in Japan, as shown in this first case of a patient infected with fluoroquinolone-resistant Salmonella.

  11. Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase

    Science.gov (United States)

    Aldred, Katie J.; Kerns, Robert J.; Berger, James M.; Osheroff, Neil

    2016-01-01

    Mycobacterium tuberculosis is a significant source of global morbidity and mortality. Moxifloxacin and other fluoroquinolones are important therapeutic agents for the treatment of tuberculosis, particularly multidrug-resistant infections. To guide the development of new quinolone-based agents, it is critical to understand the basis of drug action against M. tuberculosis gyrase and how mutations in the enzyme cause resistance. Therefore, we characterized interactions of fluoroquinolones and related drugs with WT gyrase and enzymes carrying mutations at GyrAA90 and GyrAD94. M. tuberculosis gyrase lacks a conserved serine that anchors a water–metal ion bridge that is critical for quinolone interactions with other bacterial type II topoisomerases. Despite the fact that the serine is replaced by an alanine (i.e., GyrAA90) in M. tuberculosis gyrase, the bridge still forms and plays a functional role in mediating quinolone–gyrase interactions. Clinically relevant mutations at GyrAA90 and GyrAD94 cause quinolone resistance by disrupting the bridge–enzyme interaction, thereby decreasing drug affinity. Fluoroquinolone activity against WT and resistant enzymes is enhanced by the introduction of specific groups at the C7 and C8 positions. By dissecting fluoroquinolone–enzyme interactions, we determined that an 8-methyl-moxifloxacin derivative induces high levels of stable cleavage complexes with WT gyrase and two common resistant enzymes, GyrAA90V and GyrAD94G. 8-Methyl-moxifloxacin was more potent than moxifloxacin against WT M. tuberculosis gyrase and displayed higher activity against the mutant enzymes than moxifloxacin did against WT gyrase. This chemical biology approach to defining drug–enzyme interactions has the potential to identify novel drugs with improved activity against tuberculosis. PMID:26792518

  12. Temporal Changes in Resistance Mechanisms in Colonizing Escherichia coli Isolates with Reduced Susceptibility to Fluoroquinolones

    Science.gov (United States)

    Han, Jennifer H.; Nachamkin, Irving; Tolomeo, Pam; Mao, Xiangqun; Bilker, Warren B.; Lautenbach, Ebbing

    2013-01-01

    The objective of this study was to characterize the temporal variability of fluoroquinolone resistance mechanisms among Escherichia coli colonizing the gastrointestinal tract of hospitalized patients. Patients with new fluoroquinolone-resistant E. coli (FQREC) colonization were followed with serial fecal sampling until discharge or death. Genetic mechanism(s) of resistance for all FQREC isolates were characterized, including mutations in gyrA and parC and efflux pump overexpression. Of 451 subjects, 73 (16.2%) became newly colonized with FQREC. There was significant variability in regard to temporal changes in resistance mechanisms and levofloxacin MICs among isolates from individual patients. Compared to patients with transient colonization, patients with persistent colonization were more likely to have a urinary catheter (P=0.04), diarrhea (P=0.04), and a longer duration of hospitalization (22 and 9.0 mean days, respectively; P=0.01) prior to sampling. Our data demonstrate the significant variability of resistance mechanisms in colonizing E. coli isolates among hospitalized patients. PMID:23719087

  13. Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones

    Science.gov (United States)

    Yamaguchi, Yuko; Tomoyasu, Toshifumi; Takaya, Akiko; Morioka, Mizue; Yamamoto, Tomoko

    2003-01-01

    Background It is well known that expression of certain bacterial genes responds rapidly to such stimuli as exposure to toxic chemicals and physical agents. It is generally believed that the proteins encoded in these genes are important for successful survival of the organism under the hostile conditions. Analogously, the proteins induced in bacterial cells exposed to antibiotics are believed to affect the organisms' susceptibility to these agents. Results We demonstrated that Escherichia coli cells exposed to levofloxacin (LVFX), a fluoroquinolone (FQ), induce the syntheses of heat shock proteins and RecA. To examine whether the heat shock proteins affect the bactericidal action of FQs, we constructed E. coli strains with mutations in various heat shock genes and tested their susceptibility to FQs. Mutations in dnaK, groEL, and lon increased this susceptibility; the lon mutant exhibited the greatest effects. The increased susceptibility of the lon mutant was corroborated by experiments in which the gene encoding the cell division inhibitor, SulA, was subsequently disrupted. SulA is induced by the SOS response and degraded by the Lon protease. The findings suggest that the hypersusceptibility of the lon mutant to FQs could be due to abnormally high levels of SulA protein resulting from the depletion of Lon and the continuous induction of the SOS response in the presence of FQs. Conclusion The present results show that the bactericidal action of FQs is moderately affected by the DnaK and GroEL chaperones and strongly affected by the Lon protease. FQs have contributed successfully to the treatment of various bacterial infections, but their widespread use and often misuse, coupled with emerging resistance, have gradually compromised their utility. Our results suggest that agents capable of inhibiting the Lon protease have potential for combination therapy with FQs. PMID:12911840

  14. Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones

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    Morioka Mizue

    2003-08-01

    Full Text Available Abstract Background It is well known that expression of certain bacterial genes responds rapidly to such stimuli as exposure to toxic chemicals and physical agents. It is generally believed that the proteins encoded in these genes are important for successful survival of the organism under the hostile conditions. Analogously, the proteins induced in bacterial cells exposed to antibiotics are believed to affect the organisms' susceptibility to these agents. Results We demonstrated that Escherichia coli cells exposed to levofloxacin (LVFX, a fluoroquinolone (FQ, induce the syntheses of heat shock proteins and RecA. To examine whether the heat shock proteins affect the bactericidal action of FQs, we constructed E. coli strains with mutations in various heat shock genes and tested their susceptibility to FQs. Mutations in dnaK, groEL, and lon increased this susceptibility; the lon mutant exhibited the greatest effects. The increased susceptibility of the lon mutant was corroborated by experiments in which the gene encoding the cell division inhibitor, SulA, was subsequently disrupted. SulA is induced by the SOS response and degraded by the Lon protease. The findings suggest that the hypersusceptibility of the lon mutant to FQs could be due to abnormally high levels of SulA protein resulting from the depletion of Lon and the continuous induction of the SOS response in the presence of FQs. Conclusion The present results show that the bactericidal action of FQs is moderately affected by the DnaK and GroEL chaperones and strongly affected by the Lon protease. FQs have contributed successfully to the treatment of various bacterial infections, but their widespread use and often misuse, coupled with emerging resistance, have gradually compromised their utility. Our results suggest that agents capable of inhibiting the Lon protease have potential for combination therapy with FQs.

  15. Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype

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    Melissa Agnello

    2016-10-01

    Full Text Available Fluoroquinolone (FQ resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains containing the exoS gene, as well as more likely to acquire resistance-conferring mutations in gyrA/B and parC/E. We hypothesize that FQ-resistance imposes a lower fitness cost on exoU compared to exoS strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in parC from 3 exoU and 3 exoS clinical isolates and tested fitness in vitro using head-to-head competition assays. The mutation differentially affected fitness in the exoU and exoS strains tested. While the addition of the parC mutation dramatically increased fitness in one of the exoU strains leaving the other two unaffected, all three exoS strains displayed a general decrease in fitness. In addition, we found that exoU strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the exoS strains. These results may provide a biological explanation for the observed predominance of the virulent exoU genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of P. aeruginosa. Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance.

  16. Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype

    Science.gov (United States)

    Agnello, Melissa; Finkel, Steven E.; Wong-Beringer, Annie

    2016-01-01

    Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains containing the exoS gene, as well as more likely to acquire resistance-conferring mutations in gyrA/B and parC/E. We hypothesize that FQ-resistance imposes a lower fitness cost on exoU compared to exoS strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in parC from three exoU to three exoS clinical isolates and tested fitness in vitro using head-to-head competition assays. The mutation differentially affected fitness in the exoU and exoS strains tested. While the addition of the parC mutation dramatically increased fitness in one of the exoU strains leaving the other two unaffected, all three exoS strains displayed a general decrease in fitness. In addition, we found that exoU strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the exoS strains. These results may provide a biological explanation for the observed predominance of the virulent exoU genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of P. aeruginosa. Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance.

  17. The quest for the best metric of antibiotic use and its correlation with the emergence of fluoroquinolone resistance in children.

    Science.gov (United States)

    Rose, Lucia; Coulter, Marissa M; Chan, Shannon; Hossain, Jobayer; Di Pentima, M Cecilia

    2014-06-01

    We evaluated the correlation between fluoroquinolone use, measured by doses administered and days of therapy, with the emergence of ciprofloxacin and levofloxacin resistance among Gram-negative bacilli infections in children hospitalized at one pediatric center between April 2001 and March 2009. Both metrics and drug resistance were highly correlated.

  18. Impact of fluoroquinolones on human microbiota. Focus on the emergence of antibiotic resistance.

    Science.gov (United States)

    de Lastours, Victoire; Fantin, Bruno

    2015-01-01

    The aggregate of microorganisms residing on the surface of the skin, in the oropharynx and in the GI tract, known as the human microbiota, play a major role as natural reservoirs for bacterial resistance to antibiotics. Fluoroquinolones (FQ) are among the most prescribed antibiotics and a major increase in FQ resistance is occurring worldwide. High concentrations of FQ are found in microbial ecosystems explaining their profound effect on the clinically relevant bacteria that compose them. Yet, because of different local pharmacokinetics, distinct selective pressures occur in the different microbiota. Here we review the qualitative and quantitative impact of FQ on the three main human microbiota and their consequences, particularly in terms of emergence of antibiotic resistance. Finally, we review potential actions that could decrease the impact of FQs on microbiota.

  19. The role of fluoroquinolones in the promotion of alginate synthesis and antibiotic resistance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Piña, S E; Mattingly, S J

    1997-08-01

    Treatment of nonmucoid Pseudomonas aeruginosa with gyrase inhibitors such as ciprofloxacin, norfloxacin, and ofloxacin, which target the A subunit of topoisomerase II, resulted in 100% conversion to the mucoid phenotype. However, antibiotics that partially inhibited growth and macromolecular synthesis (DNA, RNA, protein, or peptidoglycan) of nonmucoid isolates in a gluconate-limited chemostat culture system did not promote conversion to mucoid subpopulations. An increase in resistance was observed in populations that expressed the mucoid phenotype. Both mucoid conversion and antibiotic resistance were completely reversible when ciprofloxacin pressure was withdrawn, but only partially reversible by the removal of norfloxacin and ofloxacin. Thus, these experiments indicate that in the presence of some fluoroquinolones, a conditional response resulting in mucoid conversion and antibiotic resistance may occur.

  20. Effects of fluoroquinolone restriction (from 2007 to 2012) on resistance in Enterobacteriaceae: interrupted time-series analysis.

    Science.gov (United States)

    Sarma, J B; Marshall, B; Cleeve, V; Tate, D; Oswald, T; Woolfrey, S

    2015-09-01

    Antibiotic stewardship is a key component in the effort to reduce healthcare-associated infections. To describe the implementation and analyse the impact of fluoroquinolone restriction on resistance in Enterobacteriaceae, focusing on urinary isolates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, which were historically almost universally resistant to fluoroquinolones. ESBL-producing E. coli hospital and community isolates, obtained between April 2009 and March 2012 from consecutive non-duplicate urine samples, were included in an interrupted time-series analysis based on a Poisson distribution model. Periods before and after fluoroquinolone restriction were compared. The trend in fluoroquinolone resistance in all urinary isolates of Enterobacteriaceae (N ≈ 20,000 per year) and blood culture isolates of E. coli (N ≈ 350) between 2009 and 2013 were also analysed. A large decline in the percentage of ciprofloxacin-resistant ESBL-producing urinary E. coli isolates was observed in both hospital (risk ratio: 0.473; 95% confidence interval: 0.315-0.712) and community settings (0.098; 0.062-0.157). The decline was also marked in all urinary isolates of Enterobacteriaceae and E. coli isolates from blood cultures. We conclude that reducing fluoroquinolone usage to a level of ≤2 defined daily doses per 100 occupied bed-days in hospital sufficiently removed selection pressure to allow resistant Enterobacteriaceae – specifically, the UK endemic strains of ESBL-producing E. coli – to revert back to fluoroquinolone susceptibility within a short span of four months. This was accompanied with a concomitant reduction in overall ESBL burden. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  1. Inhibitory effects of reserpine and carbonyl cyanide m-chloro-phenylhydrazone on fluoroquinolone resistance of Acinetobacter baumannii

    Institute of Scientific and Technical Information of China (English)

    SHI Wei-feng; JIANG Jian-ping; XU Ning; HUANG Zhi-mi; WANG Yu-yue

    2005-01-01

    @@ Mechanisms of bacterial resistance to fluoro-quinolones may be grouped into three principal categories: gene mutations of DNA topoisomerase Ⅱ (GyrA or GyrB), DNA topoisomerase Ⅳ (ParC or ParE), decrease of outer membrane permeation and upregulation of multi-drug efflux pump (active efflux system).1 Efflux pumps are transport proteins removing toxic substrates (including virtually all classes of clinically relevant antibiotics) from cells to the external environment. These proteins exist in both Gram positive bacteria and Gram negative bacteria as well as in fungi and mammalian (tumour) cells.2-4 It has been reported that alkaloid reserpine and carbonyl cyanide m-chlorophenylhydrazone (CCCP) can inhibit NorA multi-drug efflux.5,6 In order to explore the universality of drug efflux in microorganisms, 85 strains of Acinetobacter baumannii (A. Baumannii) were tested using reserpine and CCCP. The quinolone-resistant-determining region (QRDR) of gyrA and parC genes in 35 isolates of A. Baumannii were amplified by polymerase chain reaction (PCR) and sequenced by DNA sequencer. The correlation between resistant mutation regularity and bacterial drug efflux were analysed.

  2. Rapid and sensitive detection of fluoroquinolone-resistant Escherichia coli from urine samples using a genotyping DNA microarray.

    Science.gov (United States)

    Yu, Xiaolei; Susa, Milorad; Weile, Jan; Knabbe, Cornelius; Schmid, Rolf D; Bachmann, Till T

    2007-10-01

    Urinary tract infections (UTI) are among the most common bacterial infections in humans, with Escherichia coli being the major cause of infection. Fluoroquinolone resistance of uropathogenic E. coli has increased significantly over the last decade. In this study a microarray-based assay was developed and applied, which provides a rapid, sensitive and specific detection of fluoroquinolone-resistant E. coli in urine. The capture probes were designed against previously identified and described hotspots for quinolone resistance (codons 83 and 87 of gyrA). The key goals of this development were to reduce assay time while increasing the sensitivity and specificity as compared with a pilot version of a gyrA genotyping DNA microarray. The performance of the assay was demonstrated with pure cultures of 30 E. coli isolates as well as with urine samples spiked with 6 E. coli isolates. The microarray results were confirmed by standard DNA sequencing and were in full agreement with the phenotypic antimicrobial susceptibility testing using standard methods. The DNA microarray test displayed an assay time of 3.5h, a sensitivity of 100CFU/ml, and the ability to detect fluoroquinolone-resistant E. coli in the presence of a 10-fold excess of fluoroquinolone-susceptible E. coli cells. As a consequence, we believe that this microarray-based determination of antibiotics resistance has a true potential for the application in clinical routine laboratories in the future.

  3. Antimicrobial resistance in invasive non-typhoid Salmonella from the Democratic Republic of the Congo: emergence of decreased fluoroquinolone susceptibility and extended-spectrum beta lactamases.

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    Octavie Lunguya

    Full Text Available BACKGROUND: Co-resistance against the first-line antibiotics ampicillin, chloramphenicol and trimethoprim/sulphamethoxazole or multidrug resistance (MDR is common in non typhoid Salmonella (NTS. Use of alternative antibiotics, such as fluoroquinolones or third generation cephalosporins is threatened by increasing resistance, but remains poorly documented in Central-Africa. METHODOLOGY/PRINCIPAL FINDINGS: As part of a microbiological surveillance study in DR Congo, blood cultures were collected between 2007 and 2011. Isolated NTS were assessed for serotype and antimicrobial resistance including decreased ciprofloxacin susceptibility and extended-spectrum beta-lactamase (ESBL production. In total, 233 NTS isolates (representing 23.6% of clinically significant organisms were collected, mainly consisting of Salmonella Typhimurium (79% and Salmonella Enteritidis (18%. The majority of NTS were isolated in the rainy season, and recovered from children ≤2 years old. MDR, decreased ciprofloxacin susceptibility, azithromycin and cefotaxime resistance were 80.7%, 4.3%, 3.0% and 2.1% respectively. ESBL production was noted in three (1.3% isolates. Decreased ciprofloxacin susceptibility was associated with mutations in codon 87 of the gyrA gene, while ESBLs all belonged to the SHV-2a type. CONCLUSIONS/SIGNIFICANCE: Presence of almost full MDR among NTS isolates from blood cultures in Central Africa was confirmed. Resistance to fluoroquinolones, azithromycin and third generation cephalosporins is still low, but emerging. Increased microbiological surveillance in DR Congo is crucial for adapted antibiotic therapy and the development of treatment guidelines.

  4. Fluoroquinolone and multidrug resistance phenotypes associated with the overexpression of AcrAB and an orthologue of MarA in Yersinia enterocolitica.

    Science.gov (United States)

    Fàbrega, Anna; Roca, Ignasi; Vila, Jordi

    2010-11-01

    Quinolone resistance among clinical isolates is of increasing importance. This phenotype particularly affects the nalidixic acid resistance levels and is also increasing among Yersinia enterocolitica strains. This study investigated the quinolone resistance mechanisms acquired in vitro by a Y. enterocolitica clinical isolate exposed to increasing concentrations of ciprofloxacin in a multi-step selection process. The fluoroquinolone-susceptible clinical isolate, Y.83-wt, the fluoroquinolone-resistant mutant, Y.83-64, and intermediate mutants were analysed by QRDR sequencing and MIC determination. Four different QRDRs (quinolone resistance-determining regions) mutations were characterised in Y.83-64: one in gyrA, one in gyrB, and two in parC. A significant increase in the MICs of ciprofloxacin, norfloxacin, nalidixic acid, and other unrelated antibiotics was detected in Y.83-64. Furthermore, the bacterial growth rate was assessed for strains Y.83-wt and Y.83-64. The analysis reported no significant differences between both strains. Cell envelope protein approach revealed an overexpression of both AcrA and AcrB proteins in Y.83-64. RT-PCR analyses were also carried out as was sequencing of known AcrAB regulators in Yersinia. The RT-PCR analysis showed an increased transcriptional level of a marA orthologue, marA(Ye), in Y.83-64. The sequencing results reported no change in the acrR gene or in the promoter sequence of the acrAB operon when comparing Y.83-wt with Y.83-64. One differential mutation was detected within the marA(Ye) promoter in Y.83-64. Thus, the fluoroquinolone resistance phenotype acquired by Y.83-64 relies on the acquisition of 4 QRDR mutations in addition to the overexpression of AcrAB, which is likely triggered by increased expression levels of marA(Ye).

  5. A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure.

    Science.gov (United States)

    Pham Thanh, Duy; Karkey, Abhilasha; Dongol, Sabina; Ho Thi, Nhan; Thompson, Corinne N; Rabaa, Maia A; Arjyal, Amit; Holt, Kathryn E; Wong, Vanessa; Tran Vu Thieu, Nga; Voong Vinh, Phat; Ha Thanh, Tuyen; Pradhan, Ashish; Shrestha, Saroj Kumar; Gajurel, Damoder; Pickard, Derek; Parry, Christopher M; Dougan, Gordon; Wolbers, Marcel; Dolecek, Christiane; Thwaites, Guy E; Basnyat, Buddha; Baker, Stephen

    2016-03-11

    The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(pS. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure.

  6. Antimicrobial susceptibility testing of Escherichia coli strains isolated from urinary tract infections to fluoroquinolones and detection of gyrA mutations in resistant strains

    Directory of Open Access Journals (Sweden)

    Akbari-Nakhjavani F.

    2007-05-01

    Full Text Available Widespread uses of fluoroquinolones have resulted in increasing incidences of resistance against these agents all over the world. The aim of this study was to assess, susceptibility of Escherichia coli strains from patients with Urinary Tract Infection against common fluoroquinolones and detection of mutations in the gyrA gene. Antimicrobial susceptibility testing of 164 E.coli isolates from patients with UTI, was evaluated by disk agar diffusion (DAD and MIC methods. Polymerase chain reaction of E.coli strains were performed by amplification of Quinolone Resistance Determining Region (QRDR of gyrA gene. PCR products were tested by Conformational Sensitive Gel Electrophoresis (CSGE and those with hetrodublexes were selected and examined by DNA sequencing. According to disc agar diffusion, 49.3% were resistant to nalidixic acid, 41.4% to norfloxacin, 44.5% to ofloxacin and 40.2 % to ciprofloxacin. By Minimal Inhibitory Concentration (MIC testing a high-level of resistance (42.1% to ciprofloxacin was observed. Mutations in codons 83 and 87 in all 81 isolates were positive by CSGE method.

  7. Comparative dynamics of the emergence of fluoroquinolone resistance in staphylococci from the nasal microbiota of patients treated with fluoroquinolones according to their environment.

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    Munier, Anne-Lise; de Lastours, Victoire; Barbier, François; Chau, Françoise; Fantin, Bruno; Ruimy, Raymond

    2015-12-01

    Fluoroquinolone-resistant staphylococci (FQRS) are primarily selected in the nasal microbiota during fluoroquinolone (FQ) treatment. To gain insight into the dynamics of the emergence of FQRS, 49 hospitalised patients (HPs) and 62 community patients (CPs) treated with FQs were studied. Nasal swabs were collected before (T0), at the end of (T1) and 1 month after (T2) FQ treatment. FQRS were identified by mass spectrometry. Antibiotic resistance was determined. Pre- and post-exposure staphylococci populations were compared phenotypically and by MLST to determine the origin of FQRS. At T0, 33/49 HPs (67%) and 24/62 CPs (39%) carried FQRS (OR=3.3, 95% CI: 1.4-7.9; P<0.001). Among patients with no FQRS at T0, 15/16 HPs (94%) and 16/38 CPs (42%) had FQRS detected at T1 and/or T2 (OR=19.6, 95% CI: 2.5-902; P<0.001). Among FQRS having emerged, co-resistance to meticillin was detected in 87% and 82% of HPs and CPs, respectively. No selection of resistance emerging from the initial microbiota was evidenced. FQRS showed decreased species diversity in favour of Staphylococcus haemolyticus and Staphylococcus epidermidis. As a consequence of FQ treatment, acquisition of FQRS in the nasal microbiota is frequent in the community and almost inevitable in hospitals. Acquisition from extranasal sites prevails. A restriction in species diversity in favour of more pathogenic and resistant species occurs. This highlights the major impact of FQ treatment on nasal microbiota, the role of the ecological environment in the emergence of FQRS, and the high-risk of dissemination of resistant staphylococci. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  8. [Treatment of drug resistant destructive pulmonary tuberculosis: gemifloxacin and other fluoroquinolones clinical efficiency and tolerance at the end of initial phase of treatment].

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    Petrenko, V I; Radysh, H V

    2013-12-01

    Gemifloxacin efficiency and tolerance in comparison to the ofloxacin, levofloxacin and gatifloxacin during the intensive phase of the antituberculosis therapy for drug resistant cases was evaluated. 156 drug resistant TB patients were examined in the open, prospective, randomized research, being divided into 2 groups with similar drug resistance profile. The 1st group received gemifloxacin, the 2nd--other fluoroquinolones. Gemifloxacin efficiency in the treatment regimen for the drug resistant TB patients did not differ from the efficiency of the use of other fluoroquinolones of the 4th generation and was significantly higher in comparison to ofloxacin. At the same time the identical level of side effects was registered in the course of treatment with mentioned drugs. Gemifloxacin is effective and safe at treatment of tuberculosis in comparison to other fluoroquinolones that allows considering it as the drug of choice among fluoroquinolones for treatment of drug resistant TB, including multidrug-resistant TB.

  9. Fluoroquinolone Resistance Mechanisms and population structure of Enterobacter cloacae non-susceptible to Ertapenem in North-Eastern France.

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    Thomas eGuillard

    2015-10-01

    Full Text Available Fluoroquinolone (FQ agents are a potential resort to treat infection due to Enterobacteriaceae producing extended spectrum β-lactamase and susceptible to FQ. In a context of increase of non-susceptibility to carbapenems among Enterobacteriaceae, we characterized FQ resistance mechanisms in 75 Enterobacter cloacae isolates non-susceptible to ertapenem in North-Eastern France in 2012 and describe the population structure by pulsed field gel electrophoresis (PFGE and multilocus sequence typing (MLST.Among them, 14.7% (12/75 carried a carbapenemase-encoding gene. Except one isolate producing VIM-1, the carbapenemase-producing isolates carried the well-known IncL/M pOXA48a plasmid. Most of the isolates (59/75 harbored at least a FQ-R determinant. qnr genes were predominant (40%, 30/75. The MLST study revealed that E. cloacae isolates’ clonality was wide (24 different STs. The more widespread STs were ST74, ST101, ST110, ST114 and ST133. Carbapenem MICs were higher for E. cloacae ST74 than for other E. cloacae isolates. PMQR determinants were more often observed in E. cloacae ST74 isolates. These findings showed that (i pOXA-48a is spreading in North-Eastern France, (ii qnr is preponderant in E. cloacae, (iii E. cloacae comprised a large amount of lineages spreading in North-Eastern France and (iv FQ as an alternative to β-lactams to treat ertapenem non-susceptible Enterobacteriaceae are compromised.

  10. Fluoroquinolones for the treatment of tuberculosis in children.

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    Thee, S; Garcia-Prats, A J; Donald, P R; Hesseling, A C; Schaaf, H S

    2015-05-01

    The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens as well as in the prevention of drug-resistant TB. The objective of this review was to identify existing evidence for the use of the fluoroquinolones ofloxacin, levofloxacin and moxifloxacin in the treatment of TB in children. Existing data from in vitro, animal and human studies consistently demonstrate the efficacy of the fluoroquinolones against Mycobacterium tuberculosis, with superiority of levofloxacin and moxifloxacin compared to ofloxacin. In vitro and murine studies demonstrated the potential of moxifloxacin to shorten drug-susceptible TB treatment, but in multiple randomized controlled trials shortened fluoroquinolone-containing regimens have not been non-inferior compared to standard therapy. Resistance occurs frequently via mutations in the gyrA gene, and emerges rapidly depending on the fluoroquinolone concentration, with newer more potent fluoroquinolones less likely to develop resistance. Emerging data from paediatric studies underlines the importance of fluoroquinolones in the treatment of MDR-TB in children. There is a paucity of pharmacokinetic data especially in children Fluoroquinolone use has been restricted in children due to concerns about drug-induced arthropathy. The available data does not demonstrate any serious arthropathy or other severe toxicity in children. Although there is limited paediatric safety data for the prolonged treatment of MDR-TB, extended administration of fluoroquinolones in adults with MDR-TB does not show serious adverse effects and there is no evidence suggesting less tolerability of fluoroquinolones in children. Additional study of moxifloxacin and levofloxacin for TB treatment and prevention in children is an urgent priority. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Salmonella Typhimurium exhibits fluoroquinolone resistance mediated by the accumulation of the antioxidant molecule H2S in a CysK-dependent manner.

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    Frávega, J; Álvarez, R; Díaz, F; Inostroza, O; Tejías, C; Rodas, P I; Paredes-Sabja, D; Fuentes, J A; Calderón, I L; Gil, F

    2016-12-01

    To evaluate the contribution of cysK and cysM to the fluoroquinolone (ofloxacin) antibiotic resistance in Salmonella Typhimurium, and their impact on H2S and cysteine production through targeted mutagenesis. Salmonella Typhimurium 14028s and its cysK and cysM mutants were tested for their susceptibility to ofloxacin, as determined by a broth microdilution test (to determine the MIC) and survival curves. H2S levels were measured by the Pb(AC)2 method and cysteine levels were determined using 5,5-dithio-bis-2-nitrobenzoic acid. DNA damage induced by antibiotic treatment was determined by PFGE. Finally, expression of cysK and cysM genes under antibiotic treatment was determined by real-time reverse transcription PCR. As determined by MIC, the ΔcysK strain was more resistant to ofloxacin, a reactive oxygen species (ROS)-producing fluoroquinolone, than the WT and ΔcysM strains, which correlates with survival curves. Moreover, the ΔcysK strain exhibited higher H2S levels and lower cysteine levels than the WT strain. Finally, the ΔcysK strain exhibited lower DNA damage upon challenge with ofloxacin than the WT and ΔcysM strains. These results are in accordance with lower expression of cysK under ofloxacin treatment in the WT strain. This work demonstrated that cysteine metabolism in Salmonella Typhimurium modulated H2S levels, conferring resistance to second-generation fluoroquinolones. © The Author 2016. 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.

  12. Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia

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    Bayeh Abera

    2014-01-01

    Full Text Available Aim: To determine profiles of non-chlamydia conjunctival bacteria and their antimicrobial susceptibility from adults who underwent trachomatous trichiasis surgery in rural areas of Ethiopia. Materials and Methods: A cross-sectional study was conducted in rural districts in West Gojjam administrative zone. Conjunctival swabs were collected during surgery and transported using Stuart transport broth (Oxoid, UK. Antibiotic susceptibility of conjunctival isolates was determined using the Kirby-Bauer disc-diffusion method. Results: Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31% participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G, Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4% were observed to ceftriaxone, tetracycline and cotrimoxazole. Conclusion: Fluoroquinolones that have activity against the majority of bacterial isolates were potent at in vitro. However, unacceptably high levels of resistance to azithromycin and chloramphenicol in rural community indicated a need for further study and antimicrobial resistance surveillance.

  13. Low rate of fluoroquinolone resistance in Mycobacterium tuberculosis isolates from northern Tanzania

    NARCIS (Netherlands)

    Boogaard, J. van den; Semvua, H.H.; Ingen, J. van; Mwaigwisya, S.; Laan, T. van der; Soolingen, D. van; Kibiki, G.S.; Boeree, M.J.; Aarnoutse, R.E.

    2011-01-01

    OBJECTIVES: Fluoroquinolones are used in second-line treatment of tuberculosis (TB) and have a potential role in shortening TB treatment duration. The wide use of fluoroquinolones in the treatment of other infections, including respiratory tract infections in patients with (undiagnosed) active TB,

  14. Low rate of fluoroquinolone resistance in Mycobacterium tuberculosis isolates from northern Tanzania

    NARCIS (Netherlands)

    Boogaard, J. van den; Semvua, H.H.; Ingen, J. van; Mwaigwisya, S.; Laan, T. van der; Soolingen, D. van; Kibiki, G.S.; Boeree, M.J.; Aarnoutse, R.E.

    2011-01-01

    OBJECTIVES: Fluoroquinolones are used in second-line treatment of tuberculosis (TB) and have a potential role in shortening TB treatment duration. The wide use of fluoroquinolones in the treatment of other infections, including respiratory tract infections in patients with (undiagnosed) active TB, c

  15. Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions.

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    Shen, Gwan-Han; Tsao, Thomas Chang-Yao; Kao, Shang-Jyh; Lee, Jen-Jyh; Chen, Yen-Hsu; Hsieh, Wei-Chung; Hsu, Gwo-Jong; Hsu, Yen-Tao; Huang, Ching-Tai; Lau, Yeu-Jun; Tsao, Shih-Ming; Hsueh, Po-Ren

    2012-03-01

    The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1-7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥ 7 days) of symptoms, a history of night sweats, lack of fever (> 38 °C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  16. Increased fluoroquinolone resistance with time in Escherichia coli from >17,000 patients at a large county hospital as a function of culture site, age, sex, and location

    Science.gov (United States)

    Boyd, Lauren Becnel; Atmar, Robert L; Randall, Graham L; Hamill, Richard J; Steffen, David; Zechiedrich, Lynn

    2008-01-01

    Background Escherichia coli infections are common and often treated with fluoroquinolones. Fluoroquinolone resistance is of worldwide importance and is monitored by national and international surveillance networks. In this study, we analyzed the effects of time, culture site, and patient age, sex, and location on fluoroquinolone resistance in E. coli clinical isolates. Methods To understand how patient factors and time influenced fluoroquinolone resistance and to determine how well data from surveillance networks predict trends at Ben Taub General Hospital in Houston, TX, we used Perl to parse and MySQL to house data from antibiograms (n ≅ 21,000) for E. coli isolated between 1999 to 2004 using Chi Square, Bonferroni, and Multiple Linear Regression methods. Results Fluoroquinolone resistance (i) increased with time; (ii) exceeded national averages by 2- to 4-fold; (iii) was higher in males than females, largely because of urinary isolates from male outpatients; (iv) increased with patient age; (v) was 3% in pediatric patients; (vi) was higher in hospitalized patients than outpatients; (vii) was higher in sputum samples, particularly from inpatients, than all other culture sites, including blood and urine, regardless of patient location; and (viii) was lowest in genital isolates than all other culture sites. Additionally, the data suggest that, with regard to susceptibility or resistance by the Dade Behring MicroScan system, a single fluoroquinolone suffices as a "surrogate marker" for all of the fluoroquinolone tested. Conclusion Large surveillance programs often did not predict E. coli fluoroquinolone resistance trends at a large, urban hospital with a largely indigent, ethnically diverse patient population or its affiliated community clinics. PMID:18197977

  17. Increased fluoroquinolone resistance with time in Escherichia coli from >17,000 patients at a large county hospital as a function of culture site, age, sex, and location

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    Hamill Richard J

    2008-01-01

    Full Text Available Abstract Background Escherichia coli infections are common and often treated with fluoroquinolones. Fluoroquinolone resistance is of worldwide importance and is monitored by national and international surveillance networks. In this study, we analyzed the effects of time, culture site, and patient age, sex, and location on fluoroquinolone resistance in E. coli clinical isolates. Methods To understand how patient factors and time influenced fluoroquinolone resistance and to determine how well data from surveillance networks predict trends at Ben Taub General Hospital in Houston, TX, we used Perl to parse and MySQL to house data from antibiograms (n ≅ 21,000 for E. coli isolated between 1999 to 2004 using Chi Square, Bonferroni, and Multiple Linear Regression methods. Results Fluoroquinolone resistance (i increased with time; (ii exceeded national averages by 2- to 4-fold; (iii was higher in males than females, largely because of urinary isolates from male outpatients; (iv increased with patient age; (v was 3% in pediatric patients; (vi was higher in hospitalized patients than outpatients; (vii was higher in sputum samples, particularly from inpatients, than all other culture sites, including blood and urine, regardless of patient location; and (viii was lowest in genital isolates than all other culture sites. Additionally, the data suggest that, with regard to susceptibility or resistance by the Dade Behring MicroScan system, a single fluoroquinolone suffices as a "surrogate marker" for all of the fluoroquinolone tested. Conclusion Large surveillance programs often did not predict E. coli fluoroquinolone resistance trends at a large, urban hospital with a largely indigent, ethnically diverse patient population or its affiliated community clinics.

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

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    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.

  19. Characterization of ESBL- and AmpC-Producing and Fluoroquinolone-Resistant Enterobacteriaceae Isolated from Mouflons (Ovis orientalis musimon in Austria and Germany.

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    Igor Loncaric

    Full Text Available The aim of this study was to investigate the presence of β-lactamase producing or fluoroquinolone-resistant members of the family Enterobacteriaceae in European mouflons (Ovis orientalis musimon. The mouflon samples originated from nasal and perineal swabs and/or organ samples in cases of a suspected infection. Only one of the 32 mouflons was tested positive for the presence of Enterobacteriaceae that displayed either an ESBL/AmpC phenotype or were resistant to ciprofloxacin. The positively tested swab originated from a sample of the jejunal mucosa of a four-year old female mouflon. Two different colony morphotypes were identified as Escherichia coli and Klebsiella pneumoniae. These isolates were phenotypically and genotypically characterized in detail by a polyphasic approach. Both isolates were multi-drug resistant. The E. coli isolate belonged to the phylogenetic group B1 and sequence type (ST 744 and harboured the β-lactamase genes blaCTX-M-15 and blaOXA-1. The K. pneumoniae, identified as ST11, harboured the β-lactamase genes blaSHV-11, blaOXA-1, and blaDHA-1 as well as the plasmid-mediated quinolone resistance (PMQR gene qnrB55. The present study demonstrates that wild animals can acquire human-derived resistance determinants and such findings may indicate environmental pollution with resistance determinants from other sources.

  20. The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients.

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    Kandemir, Özlem; Bozlu, Murat; Efesoy, Ozan; Güntekin, Onur; Tek, Mesut; Akbay, Erdem

    2016-08-01

    We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P = 0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization.

  1. Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study

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    Düzgün Nurşen

    2009-10-01

    Full Text Available Abstract Background The aims of this study were to determine the antimicrobial susceptibility patterns of urinary isolates from community acquired acute uncomplicated urinary tract infections (uUTI and to evaluate which antibiotics were empirically prescribed in the outpatient management of uUTI. Methods Among the patients which were admitted to outpatient clinics of Ankara University Medical Faculty, Ibni-Sina Hospital during 2005-2006, a total of 429 women between the age of 18 and 65 years old who were clinically diagnosed with uUTI and to whom prescribed empirical antibiotics were enrolled in this prospective observational study. Patients' demographical data, urine culture results, resistance rates to antimicrobial agents and prescribed empiric antimicrobial therapy were analyzed. Results Totally 390 (90.9% patients among all study population were requested for urine culture by their physicians. 150 (38.5% of these urine cultures were positive. The most common isolated uropathogen was Escherichia coli (E. coli (71.3%. The variations of uropathogens according to age and menopause status were not significantly different. The resistance rates of E. coli isolates for ampicillin, ampicillin-sulbactam, amoxicillin-clavulonate, cefuroxime, ceftriaxone, fluoroquinolones (FQ, co-trimoxazole (TMP-SMX and gentamicin were 55.1%, 32.7%, 32.7%, 23.4%, 15.9%, 25.2%, 41.1%, 6.1% respectively. FQ were the most common prescribed antibiotics (77.9% (P P Conclusion Empirical use of FQ in uUTI should be discouraged because of increased antimicrobial resistance rates.

  2. Occurrence, fate and antibiotic resistance of fluoroquinolone antibacterials in hospital wastewaters in Hanoi, Vietnam.

    Science.gov (United States)

    Duong, Hong Anh; Pham, Ngoc Ha; Nguyen, Hoang Tung; Hoang, Thi Thuong; Pham, Hung Viet; Pham, Van Ca; Berg, Michael; Giger, Walter; Alder, Alfredo C

    2008-06-01

    Occurrence and behavior of fluoroquinolone antibacterial agents (FQs) were investigated in hospital wastewaters in Hanoi, Vietnam. Hospital wastewater in Hanoi is usually not treated and this untreated wastewater is directly discharged into one of the wastewater channels of the city and eventually reaches the ambient aquatic environment. The concentrations of the FQs, ciprofloxacin (CIP) and norfloxacin (NOR) in six hospital wastewaters ranged from 1.1 to 44 and from 0.9 to 17 micrgl(-1), respectively. Total FQ loads to the city sewage system varied from 0.3 to 14 g d(-1). Additionally, the mass flows of CIP and NOR were investigated in the aqueous compartment in a small wastewater treatment facility of one hospital. The results showed that the FQ removal from the wastewater stream was between 80 and 85%, probably due to sorption on sewage sludge. Simultaneously, the numbers of Escherichia coli (E. coli) were measured and their resistance against CIP and NOR was evaluated by determining the minimum inhibitory concentration. Biological treatment lead to a 100-fold reduction in the number of E. coli but still more than a thousand E. coli colonies per 100ml of wastewater effluent reached the receiving water. The highest resistance was found in E. coli strains of raw wastewater and the lowest in isolates of treated wastewater effluent. Thus, wastewater treatment is an efficient barrier to decrease the residual FQ levels and the number of resistant bacteria entering ambient waters. Due to the lack of municipal wastewater treatment plants, the onsite treatment of hospital wastewater before discharging into municipal sewers should be considered as a viable option and consequently implemented.

  3. [Increase in antimicrobial resistance of Salmonella from food to fluoroquinolones and cephalosporins--a review of data from ten years].

    Science.gov (United States)

    Tenhagen, Bernd-Alois; Schroeter, Andreas; Szabo, Istvan; Dorn, Christina; Appel, Bernd; Helmuth, Reiner; Käsbohrer, Annemarie

    2014-01-01

    Animal derived food is a relevant source of human infections with Salmonella enterica. In this paper we analyse the presence of Salmonella in meat with respect to the observed serovars and their resistance to the fluoroquinolone ciprofloxacin and 3rd generation cephalosporins in the years 2003 to 2012. Data originated from 8176 isolates that were isolated from meat, characterized in the National Reference Laboratory for Salmonella and tested for antimicrobial resistance in the National Reference Laboratory for antimicrobial resistance in this time period. The analysis reveals substantial differences in resistance patterns between isolates from different types of meat and different serovars. Frequent serovars were mostly associated with one type of meat, suggesting an additional influence of specific characteristics of the serovars besides the effect of selection pressure excerted by antimicrobial treatments. Results show a clear increase in resistance to fluoroquinolones and 3rd generation cephalosporins that was most prominent in isolates from poultry meat. Although the number of human infections with Salmonella in Germany decreased sharply in recent years, results indicate a substantial exposure of consumers to Salmonella that are resistant to important antimicrobials via meat.

  4. Estimation of transmission parameters of a fluoroquinolone-resistant Escherichia coli strain between pigs in experimental conditions

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    Andraud Mathieu

    2011-03-01

    Full Text Available Abstract Antimicrobial resistance is of primary importance regarding public and animal health issues. Persistence and spread of resistant strains within a population contribute to the maintenance of a reservoir and lead to treatment failure. An experimental trial was carried out to study the horizontal transmission of a fluoroquinolone-resistant Escherichia coli strain from inoculated to naïve pigs. All naïve contact pigs had positive counts of fluoroquinolone-resistant E. coli after only two days of contact. Moreover, re-infections of inoculated pigs caused by newly contaminated animals were suspected. A maximum likelihood method, based on a susceptible-infectious-susceptible (SIS model, was used to determine the transmission parameters. Two transmission levels were identified depending on the quantity of bacteria shed by infected individuals: (i low-shedders with bacterial counts of resistant E. coli in the faeces between 5*103 and 106 CFU/g (βL = 0.41 [0.27; 0.62], (ii high shedders with bacterial counts above 106 CFU/g (βH = 0.98 [0.59; 1.62]. Hence, transmission between animals could be pivotal in explaining the persistence of resistant bacteria within pig herds.

  5. Virulence determinants, phylogenetic groups and fluoroquinolone resistance in Escherichia coli isolated from cystitis and pyelonephritis.

    Science.gov (United States)

    Ferjani, S; Saidani, M; Ennigrou, S; Hsairi, M; Ben Redjeb, S

    2012-10-01

    The aim of this study is to assess the relation between virulence genotype, phylogenetic group and susceptibility to fluoroquinolones and the urinary tract infection type including pyelonephritis and cystitis due to Escherichia coli. Between 2006 and 2007, 129 non-duplicate E. coli isolates from pyelonephritis (n=56) and cystitis (n=73) were prospectively collected. The antibiotic susceptibility was done by disk diffusion method. The phylogenetic groups, A, B1, B2 and D and 18 virulence genes were determined by multiplex PCR. Statistical analysis was done with the Pearson χ2 test, Mann-Whitney U-test, Kruskal-Wallis test and stepwise multivariable logistic regression analysis, P values below 0.05 were considered statistically significant. For the pyelonephritis group, sex ratio was 0.3, the median age for women was 30 years and for men it was 54 years. For the cystitis group, sex ratio was 0.4, the median age for women was 41.5 years and for men it was 67.8 years. Significant statistical correlations were found between pyelonephritis isolates and susceptibility to ciprofloxacin (P=4 10(-5)), papG allele II (P=2 10(-6)), hlyA (P=10(-03)), iroN (P=0.04), iha (P=0.03) and ompT (P=0.03) virulence genes, high virulence score (P=0.008) and B2 phylogenetic group (P=0.03). In multivariate logistic regression analysis, papG II as predictor of pyelonephritis, no correlation could be established for the cystitis group. Our findings argue for a direct link between pyelonephritis, virulence factors, susceptibility to fluroquinolones and B2 phylogenetic group among uropthogenic E. coli. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  6. Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin-capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens.

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    Hillemann, Doris; Rüsch-Gerdes, Sabine; Richter, Elvira

    2009-06-01

    The new GenoType Mycobacterium tuberculosis drug resistance second line (MTBDRsl) assay (Hain Lifescience, Nehren, Germany) was tested on 106 clinical isolates and directly on 64 sputum specimens for the ability to detect resistance to fluoroquinolones, injectable drugs (amikacin or capreomycin), and ethambutol in Mycobacterium tuberculosis strains. A total of 63 strains harboring fluoroquinolone, amikacin/capreomycin, or ethambutol resistance and 43 fully susceptible strains were comparatively analyzed with the new MTBDRsl assay, by DNA sequencing, and by conventional drug susceptibility testing in liquid and solid media. No discrepancies were obtained in comparison with the DNA sequencing results. Fluoroquinolone resistance was detected in 29 (90.6%) of 32, amikacin/capreomycin resistance was detected in 39/39 (84.8%/86.7%) of 46/45, and ethambutol resistance was detected in 36 (69.2%) of 52 resistant strains. A total of 64 sputum specimens (42 smear positive, 12 scanty, and 10 smear negative) were tested with the new MTBDRsl assay, and the results were compared with those of conventional drug susceptibility testing. Fluoroquinolone resistance was detected in 8 (88.9%) of 9, amikacin/capreomycin resistance was detected in 6/7 (75.0%/87.5%) of 8, and ethambutol resistance was detected in 10 (38.5%) of 26 resistant strains. No mutation was detected in susceptible strains. The new GenoType MTBDRsl assay represents a reliable tool for the detection of fluoroquinolone and amikacin/capreomycin resistance and to a lesser extent also ethambutol resistance. In combination with a molecular test for detection of rifampin and isoniazid resistance, the potential for the detection of extensively resistant tuberculosis within 1 to 2 days can be postulated.

  7. PatA and PatB form a functional heterodimeric ABC multidrug efflux transporter responsible for the resistance of Streptococcus pneumoniae to fluoroquinolones.

    Science.gov (United States)

    Boncoeur, Emilie; Durmort, Claire; Bernay, Benoît; Ebel, Christine; Di Guilmi, Anne Marie; Croizé, Jacques; Vernet, Thierry; Jault, Jean-Michel

    2012-10-02

    All bacterial multidrug ABC transporters have been shown to work as either homodimers or heterodimers. Two possibly linked genes, patA and patB from Streptococcus pneumococcus, that encode half-ABC transporters have been shown previously to be involved in fluoroquinolone resistance. We showed that the ΔpatA, ΔpatB, or ΔpatA/ΔpatB mutant strains were more sensitive to unstructurally related compounds, i.e., ethidium bromide or fluoroquinolones, than the wild-type R6 strain. Inside-out vesicles prepared from Escherichia coli expressing PatA and/or PatB transported Hoechst 33342, a classical substrate of multidrug transporters, only when both PatA and PatB were coexpressed. This transport was inhibited either by orthovanadate or by reserpine, and mutation of the conserved Walker A lysine residue of either PatA or PatB fully abrogated Hoechst 33342 transport. PatA, PatB, and the PatA/PatB heterodimer were purified from detergent-solubilized E. coli membrane preparations. Protein dimers were identified in all cases, albeit in different proportions. In contrast to the PatA/PatB heterodimers, homodimers of PatA or PatB failed to show a vanadate-sensitive ATPase activity. Thus, PatA and PatB need to interact together to make a functional drug efflux transporter, and they work only as heterodimers.

  8. Impact of preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria on the incidence of sepsis following transrectal ultrasound guided prostate biopsy

    Science.gov (United States)

    Farrell, John J; Hicks, Jennifer L; Wallace, Stephanie E; Seftel, Allen D

    2017-01-01

    With the universal adoption of antibiotic prophylaxis prior to prostate biopsy, the current risk of post-biopsy infection (including sepsis) is study of preoperative rectal cultures to screen for rectal colonization with fluoroquinolone-resistant bacteria using ciprofloxacin-supplemented MacConkey agar culture media. To evaluate the feasibility and practicality of this test, one provider used the results of rectal swab cultures collected during the preoperative outpatient evaluation to adjust each patient’s preoperative antibiotic prophylaxis when fluoroquinolone-resistant enteric bacteria were detected, whereas two other providers continued usual preoperative care and empiric antimicrobial prophylaxis. Rectal colonization with fluoroquinolone-resistant bacteria was detected in 19/152 (12.5%) of patients. In our intention-to-treat analysis (N=268), the rate of post-biopsy sepsis was 3.6% lower in the group that was screened for rectal colonization with fluoroquinolone-resistant bacteria prior to transrectal prostate biopsy. The observed risk reduction in the rectal screening group trended toward, but did not achieve, statistical significance. We suggest that preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria may be a useful step toward mitigating post-prostate biopsy sepsis. PMID:28280717

  9. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014.

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    Pieter-Jan Ceyssens

    Full Text Available We present the results of a longitudinal surveillance study (1995-2014 on fluoroquinolone resistance (FQ-R among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602. For many years, the switch to respiratory fluoroquinolones for the treatment of (atypical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25, parC (n = 46 and parE (n = 3 in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%. Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance.

  10. Diagnosis of Drug Resistance to Fluoroquinolones, Amikacin, Capreomycin, Kanamycin and Ethambutol with Genotype MTBDRsl Assay: a Meta-Analysis.

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    Mao, Xiaolu; Ke, Zunqiong; Shi, Xiaoyan; Liu, Shuiyi; Tang, Beibei; Wang, Jin; Huang, Hao

    2015-01-01

    The Genotype MTBDRsl is a new-generation PCR-based line-probe assay for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. The aim of this meta-analysis was to evaluate the performance of Genotype MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol in comparison with the phenotypic drug susceptibility test. We searched Pubmed, Embase and the Cochrane Library and calculated the sensitivity, the specificity, the positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), corresponding 95% confidence interval (CI), and the area under the summary receiver operating characteristic (SROC) curves (AUC), and tested heterogeneity in accuracy estimates with the Spearman correlation coefficient and Chi-square. The summarized sensitivity (95% CI), specificity (95% CI), and AUC (standard error) were 0.869 (0.847-0.890), 0.973 (0.965-0.979) and 0.9690 (0.0188) for fluoroquinolones, 0.868 (0.829-0.900), 0.998 (0.994-0.999) and 0.9944 (0.0050) for amikacin, 0.879 (0.838-0.914), 0.970 (0.958-0.978) and 0.9791 (0.0120) for capreomycin, 0.501 (0.461-0.541), 0.991 (0.983-0.996) and 0.9814 (0.0114) for kanamycin and 0.686 (0.663-0.709), 0.871 (0.852-0.888) and 0.7349 (0.0639) for ethambutol, respectively. The genotype MTBDRsl demonstrate excellent accuracy for detecting drug resistance to fluoroquinolones, amikacin, and capreomycin, but it may not be an appropriate choice for detection of kanamycin and ethambutol. © 2015 by the Association of Clinical Scientists, Inc.

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

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    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.

  12. Sale of fluoroquinolones in northern Tanzania: a potential threat for fluoroquinolone use in tuberculosis treatment.

    NARCIS (Netherlands)

    Boogaard, J. van den; Semvua, H.H.; Boeree, M.J.; Aarnoutse, R.E.; Kibiki, G.S.

    2010-01-01

    OBJECTIVES: Fluoroquinolones have a potential role in shortening tuberculosis (TB) treatment duration. They are currently used in the treatment of other infections. This has raised concerns about development of mycobacterial resistance. The current study evaluates the sale of fluoroquinolones (among

  13. Sale of fluoroquinolones in northern Tanzania: a potential threat for fluoroquinolone use in tuberculosis treatment.

    NARCIS (Netherlands)

    Boogaard, J. van den; Semvua, H.H.; Boeree, M.J.; Aarnoutse, R.E.; Kibiki, G.S.

    2010-01-01

    OBJECTIVES: Fluoroquinolones have a potential role in shortening tuberculosis (TB) treatment duration. They are currently used in the treatment of other infections. This has raised concerns about development of mycobacterial resistance. The current study evaluates the sale of fluoroquinolones (among

  14. Contribution of different mechanisms to the resistance to fluoroquinolones in clinical isolates of Salmonella enterica

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    Abeer Ahmed Rushdy

    Full Text Available OBJECTIVES: To study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates. METHODS: Antimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated. RESULTS: Five Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F. Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2-4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC. CONCLUSIONS: Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gramnegative clinical isolates.

  15. Changes in concentrations of fluoroquinolones and of ciprofloxacin-resistant Enterobacteriaceae in chicken feces and manure stored in a heap.

    Science.gov (United States)

    Moraru, Ramona; Pourcher, Anne-Marie; Jadas-Hecart, Alain; Kempf, Isabelle; Ziebal, Christine; Kervarrec, Magalie; Comunal, Pierre-Yves; Mares, Mihai; Dabert, Patrick

    2012-01-01

    This study evaluated the impact of storing chicken manure on the degradation of enrofloxacin (ENR) and ciprofloxacin (CIP), and on the survival of CIP-resistant Enterobacteriaceae. At 24 d of age, half of 8900 chickens received ENR for 5 d. After the animals departed, their manure was stored in two heaps for 63 d. Enterobacteriaceae were cultured on media containing 0 to 32 mg L⁻¹ of CIP. A total of 320 isolates were fingerprinted using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) to evaluate community structure. Initial concentrations of ENR and CIP in the heap were 22 and 1.8 mg kg⁻¹, respectively. Seventy-three percent of the two fluoroquinolones were eliminated during storage. The administration of ENR led to a 5.1 log₋₁₀ decrease in Enterobacteriaceae concentrations and emergence of CIP-resistant bacteria, which became dominant in the feces. concentrations decreased 1.2 to 2.3 log₋₁₀ 2 d after the heaps were made and continued to decline during storage. No resistant were found by Day 63. The highest CIP minimum inhibitory concentration (MIC) values observed among isolates of and of both and sp. were 128 and 4 mg L⁻¹, respectively. The dominant ERIC-PCR profiles changed over time. There was no relationship between genotype and resistance-isolated strains to CIP. Storing chicken manure in heaps appeared to be an effective way of limiting the entrance of CIP-resistant E. coli into the environment but did not prevent the dissemination of fluoroquinolones after land spreading. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  16. Fluoroquinolone Prophylaxis Against Febrile Neutropenia in Areas With High Fluoroquinolone Resistance—An Asian Perspective

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    Esther Shu-Ting Ng

    2010-09-01

    Full Text Available Febrile neutropenia remains a major cause of morbidity and mortality in patients receiving chemotherapy. Major prophylactic strategies include granulocyte colony-stimulating factor and antibiotics, the most widely used of which are fluoroquinolones. While fluoroquinolone prophylaxis has been shown to be effective in areas where fluoroquinolone resistance is low, this same efficacy has not been proven in areas where resistance is high, such as in Asia. Given the increase in antimicrobial resistance with the use of prophylaxis, the risks and benefits of this strategy need to be carefully considered. This review presents the evidence for and against fluoroquinolone prophylaxis in areas of high fluoroquinolone resistance.

  17. Fluoroquinolone-Resistant Sequence Type 131 Subgroups O25b and O16 Among Extraintestinal Escherichia coli Isolates from Community-Acquired Urinary Tract Infections.

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    Hefzy, Enas Mamdouh; Hassuna, Noha Anwar

    2017-03-01

    The multidrug-resistant sequence type 131 (ST131) Escherichia coli is a spreading epidemiological burden particularly among isolates resistant to fluoroquinolones. We aimed to evaluate the commonality of ST131-O25b and ST131-O16 among fluoroquinolone-resistant E. coli isolates causing community-acquired urinary tract infections (UTIs) at Fayoum University Hospital, in Egypt. Ninety-two fluoroquinolone-resistant E. coli isolates were subjected to multiplex PCR for detection of ST131 of either O25b or O16 subgroups. Positive isolates were then assessed for antimicrobial susceptibility and virulence genotyping. Out of 92 fluoroquinolone-resistant E. coli isolates, 56 (60.9%) isolates were O25b/O16 subgroups of ST131, including 44 (78.6%) ST131-O25b and 12 (21.4%) ST131-O16 subgroups. All the O25b/O16 ST131 isolates were sensitive to meropenem, where ST131-O25b isolates were significantly more resistant to extended spectrum cephalosporins compared to S131-O16 strains. All the O25b/O16 ST131 isolates harbored three or more of the virulence factors associated with extraintestinal pathogenic E. coli status. ST131-O16 showed a significantly higher virulence score than ST131-O25b isolates. Our results bring to highlight the emergence of O25b/O16 ST131 isolates between community acquired UTIs among Egyptian patients. This is the first report for the presence of O16 isolates in Egypt, showing a lower predominance than the O25b subgroup. The high prevalence of O25b/O16 ST131 isolates requires strict stewardship on antimicrobial use, notably fluoroquinolones, to control the endemicity of such emerging multidrug-resistant clone in the community.

  18. Increase in fluoroquinolone non-susceptibility among clinical Streptococcus pyogenes in Belgium during 2007-10.

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    Van Heirstraeten, Liesbet; Leten, Gert; Lammens, Christine; Goossens, Herman; Malhotra-Kumar, Surbhi

    2012-11-01

    To study the temporal evolution of fluoroquinolone non-susceptibility among Streptococcus pyogenes during 2007-10 in Belgium. S. pyogenes (n = 4690) recovered from patients with tonsillopharyngitis or skin, wound or invasive infections were screened for fluoroquinolone non-susceptibility. A selection of fluoroquinolone-non-susceptible strains was investigated for resistance mechanisms: reserpine-sensitive efflux and mutations in topoisomerase genes parC and gyrA. Clonality was determined by emm typing. Fluoroquinolone non-susceptibility (ciprofloxacin MIC ≥2 mg/L) was identified in 535 (11.4%) of 4690 S. pyogenes recovered during 2007-10 in Belgium. The proportion of fluoroquinolone-non-susceptible S. pyogenes increased significantly from 4.3% (2008) to 10.9% (2009) to 21.6% (2010) and coincided with a significant increase in emm6 strains among fluoroquinolone-non-susceptible S. pyogenes. Ciprofloxacin MICs of 2-8 mg/L correlated with first-step ParC substitutions. Two high-level fluoroquinolone-resistant S. pyogenes strains (ciprofloxacin MICs 32 mg/L) showed second-step substitutions in GyrA (Ser-81→Phe or Tyr) in addition to first-step mutations in parC. Reserpine-sensitive efflux was not observed. We report an unprecedented increase in fluoroquinolone-non-susceptible S. pyogenes in Belgium, a country with high quinolone use, as well as emergence of two high-level fluoroquinolone-resistant S. pyogenes strains with second-step mutations in gyrA, warning us of the need for more prudent use of fluoroquinolones and for continued resistance surveillance.

  19. Molecular Typing of Fluoroquinolone-Resistant Campylobacter jejuni Isolated from Broilers in Japan Using Multilocus Sequence Typing and Pulsed-Field Gel Electrophoresis.

    Science.gov (United States)

    Ozawa, Manao; Hiki, Mototaka; Kawanishi, Michiko; Abo, Hitoshi; Kojima, Akemi; Asai, Tetsuo; Hamamoto, Shuichi

    2016-01-01

    Fluoroquinolone-resistant Campylobacter jejuni isolates from broilers in Japan were characterized using multilocus sequence typing and pulsed-field gel electrophoresis (PFGE) in order to elucidate the genetic relationship between these strains. Forty-three of the isolates were classified into 20 sequence types and were clustered into 21 PFGE types with 70% similarity. The most dominant clonal complex (CC) was CC-21 (41.9%). Diverse PFGE patterns were observed within the same CC, but the combined analysis of PFGE type and CC revealed that the strains with the same combination were isolated from the same district or neighboring districts. On the other hand, strains with the same combination pattern were also isolated from geographically distant districts. Our results elucidate two possible reasons for the prevalence of fluoroquinolone-resistant C. jejuni among broiler farms: (1) the resistant C. jejuni is clonally disseminated within the limited area, and (2) susceptible C. jejuni acquired fluoroquinolone resistance during the use of fluoroquinolone on the farms.

  20. Resistance to fluoroquinolones and treatment failure/short-term relapse of community-acquired urinary tract infections caused by Escherichia coli.

    Science.gov (United States)

    Gagliotti, Carlo; Buttazzi, Rossella; Sforza, Stefano; Moro, Maria Luisa

    2008-09-01

    This study aims to evaluate the impact of resistance to fluoroquinolones on the short-term outcome of community-acquired urinary tract infections (UTIs) caused by Escherichia coli. Patients were identified and followed, during 2006, using the health care databases of the Emilia-Romagna Region. The outcome of interest was the treatment failure/short-term relapse (the re-isolation of E. coli from urine between 4 and 30 days after the first isolation). Resistance to fluoroquinolones increases the risk of treatment failure/short-term relapse in women with uncomplicated community-acquired UTIs caused by E. coli (Rate Ratio=1.85, 95% CI 1.32-2.60). The efficacy of fluoroquinolones for community-acquired UTIs of men was significantly modified by the resistance status of E. coli. Prescription of these agents was associated with a reduced occurrence of the outcome only in men with a ciprofloxacin sensitive first isolate (Rate Ratio=0.50, 95% CI 0.25-0.99). Resistance to fluoroquinolones of E. coli is a growing problem with a negative impact on the outcome of community-acquired UTIs; therefore, the prescription of these agents should be limited to infections for which they are recommended, avoiding their use in uncomplicated UTIs.

  1. Impact of preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria on the incidence of sepsis following transrectal ultrasound guided prostate biopsy

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    Farrell JJ

    2017-02-01

    Full Text Available John J Farrell,1,2 Jennifer L Hicks,3 Stephanie E Wallace,2 Allen D Seftel4,5 1Department of Medicine, Division of Infectious Diseases, University of Illinois College of Medicine, 2Department of Laboratory Medicine, Division of Clinical Microbiology & Serology, OSF/Saint Francis Medical Center, 3Department of Urology, OSF /Saint Francis Medical Center, Peoria, IL, 4Department of Urology, Cooper University Hospital, 5Department of Surgery, Cooper University School of Medicine, Camden, NJ, USA Abstract: With the universal adoption of antibiotic prophylaxis prior to prostate biopsy, the current risk of post-biopsy infection (including sepsis is <2%. Preoperative prophylactic antibiotic regimens can vary, and although fluoroquinolones have emerged as the standard of care, there is no universally agreed upon preoperative antibiotic regimen. Recently, an increase in the proportion of postoperative infections caused by fluoroquinolone-resistant Escherichia coli (as well as other Enterobacteriaceae has led to the exploration of simple, practical, and cost-effective methods to minimize this postoperative infection risk. We performed a prospective, nonrandomized, controlled study of preoperative rectal cultures to screen for rectal colonization with fluoroquinolone-resistant bacteria using ciprofloxacin-supplemented MacConkey agar culture media. To evaluate the feasibility and practicality of this test, one provider used the results of rectal swab cultures collected during the preoperative outpatient evaluation to adjust each patient’s preoperative antibiotic prophylaxis when fluoroquinolone-resistant enteric bacteria were detected, whereas two other providers continued usual preoperative care and empiric antimicrobial prophylaxis. Rectal colonization with fluoroquinolone-resistant bacteria was detected in 19/152 (12.5% of patients. In our intention-to-treat analysis (N=268, the rate of post-biopsy sepsis was 3.6% lower in the group that was screened

  2. Clinical impact of fluoroquinolone-resistant Escherichia coli in the fecal flora of hematological patients with neutropenia and levofloxacin prophylaxis.

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    Yong Chong

    Full Text Available BACKGROUND: Fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated. METHODS: We prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times. RESULTS: In this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P = 0.65. Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum β-lactamase (ESBL producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis. CONCLUSIONS: Levofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis.

  3. Detection and coexistence of six categories of resistance genes in Escherichia coli strains from chickens in Anhui Province, China

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    Lin Li

    2015-12-01

    Full Text Available The aim of this study was to characterise the prevalence of class 1 integrons and gene cassettes, tetracycline-resistance genes, phenicol-resistance genes, 16S rRNA methylase genes, extended-spectrum β-lactamase genes and plasmid-mediated fluoroquinolone resistance determinants in 184 Escherichia coli isolates from chickens in Anhui Province, China. Susceptibility to 15 antimicrobials was determined using broth micro-dilution. Polymerase chain reaction and DNA sequencing were used to characterise the molecular basis of the antibiotic resistance. High rates of antimicrobial resistance were observed; 131 out of the 184 (72.3% isolates were resistant to at least six antimicrobial agents. The prevalences of class 1 integrons, tetracycline-resistance genes, phenicol-resistance genes, 16S rRNA methylase genes, extended-spectrum β-lactamase genes and plasmid-mediated fluoroquinolone resistance determinants were 49.5, 17.4, 15.8, 0.5, 57.6 and 46.2%, respectively. In 82 isolates, 48 different kinds of coexistence of the different genes were identified. Statistical (χ2 analysis showed that the resistance to amoxicillin, doxycycline, florfenicol, ofloxacin and gentamicin had significant differences (P<0.01 or 0.01resistance genes, which showed a certain correlation between antimicrobial resistance and the presence of resistance genes.

  4. Analysis of the Fluoroquinolone Antibiotic Resistance Mechanism of Salmonella enterica Isolates.

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    Kim, Soo-Young; Lee, Si-Kyung; Park, Myeong-Soo; Na, Hun-Taek

    2016-09-28

    Quinolone-resistant Salmonella strains were isolated from patient samples, and several quinolone-sensitive strains were used to analyze mutations in the quinolone resistance-determining region (QRDR) of gyrA, gyrB, parC, and parE and to screen for plasmid-mediated quinolone resistance. Among the 21 strains that showed resistance to nalidixic acid and ciprofloxacin (MIC 0.125-2.0 μg/ml), 17 strains had a mutation in QRDR codon 87 of gyrA, and 3 strains had a single mutation (Ser83 → Phe). Another cause of resistance, efflux pump regulation, was studied by examining the expression of acrB, ramA, marA, and soxS. Five strains, including Sal-KH1 and Sal-KH2, showed no increase in relative expression in an analysis using the qRT-PCR method (p < 0.05). In order to determine the genes involved in the resistance, the Sal-9 isolate that showed decreased susceptibility and did not contain a mutation in the gyrA QRDR was used to make the STM (MIC 8 μg/ml) and STH (MIC 16 μg/ml) ciprofloxacin-resistant mutants. The gyrA QRDR Asp87 → Gly mutation was identified in both the STM and STH mutants by mutation analysis. qRT-PCR analysis of the efflux transporter acrB of the AcrAB-TolC efflux system showed increased expression levels in both the STM (1.79-fold) and STH (2.0-fold) mutants. In addition, the expression of the transcriptional regulator marA was increased in both the STM (6.35-fold) and STH (21.73-fold) mutants. Moreover, the expression of soxS was increased in the STM (3.41-fold) and STH (10.05-fold) mutants (p < 0.05). Therefore, these results indicate that AcrAB-TolC efflux pump activity and the target site mutation in gyrA are involved in quinolone resistance.

  5. Overexpression of SOS genes in ciprofloxacin resistant Escherichia coli mutants.

    Science.gov (United States)

    Pourahmad Jaktaji, Razieh; Pasand, Shirin

    2016-01-15

    Fluoroquinolones are important antibiotics for the treatment of urinary tract infections caused by Escherichia coli. Mutational studies have shown that ciprofloxacin, a member of fluoroquinolones induces SOS response and mutagenesis in pathogenic bacteria which in turn develop antibiotic resistance. However, inhibition of SOS response can increase recombination activity which in turn leads to genetic variation. The aim of this study was to measure 5 SOS genes expressions in nine E. coli mutants with different MICs for ciprofloxacin following exposure to ciprofloxacin. Gene expression was assessed by quantitative real time PCR. Gene alteration assessment was conducted by PCR amplification and DNA sequencing. Results showed that the expression of recA was increased in 5 mutants. This overexpression is not related to gene alteration, and enhances the expression of polB and umuCD genes encoding nonmutagenic and mutagenic polymerases, respectively. The direct relationship between the level of SOS expression and the level of resistance to ciprofloxacin was also indicated. It was concluded that novel therapeutic strategy that inhibits RecA activity would enhance the efficiency of common antibiotics against pathogenic bacteria. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. 鱼源病原菌对氟喹诺酮类药物的耐药性分析%Analysis of the Fluoroquinolone Resistance of Pathogens Isolated from Fish

    Institute of Scientific and Technical Information of China (English)

    王小亮; 徐立蒲; 曹欢; 王静波; 王姝

    2013-01-01

    本试验旨在了解北京地区鱼源病原菌对氟喹诺酮类药物的耐药现状,提供氟喹诺酮类药物在防制鱼类疾病上合理规范使用的依据.从北京地区具有典型症状的病鱼脏器或病灶分离出16株病原菌,采用纸片扩散法检测病原菌对7种氟喹诺酮类药物的耐药表型,运用PCR法分析病原菌的喹诺酮类耐药基因gyrA、qnrA和qnrS的携带情况.结果表明,鱼源病原菌对氟喹诺酮的耐药基因阳性率显著高于耐药表型检出率,可能耐药基因检测比耐药表型检测更能推测病原菌的耐药现状.50%的病原菌至少耐受1种氟喹诺酮类药物,87.5%的病原菌至少携带1种喹诺酮耐药基因,显示北京地区鱼源病原菌对氟喹诺酮类药物已在基因水平呈现出严重的耐药,有必要严格控制此类药物在鱼类养殖上的应用.%In order to survey the status quo of fish pathogens resistant to fluoroquinolones sourced from Beijing area, and provide the basis to regulate the fluoroquinolones used in fish farming,there were 16 pathogens isolated from diseased fish organs or focus with typical symtom in Beijing, and then the resistance phenotype of fish pathogens on seven kinds of fluoroquinolones were assayed by Kirby-Bauer disk diffusion method according to CLSI and the status of which carried gyrA,qnrA and qnrS genes were detected by PCR method. The data results showed that, on one hand, the rate of fish pathogens detected quino-lones resistance gene-positive was higher than that of resistance phenotype,and the reason might be that the resistance genes detection were more exact than resistance phenotype tested. On the other hand, half of the fish pathogens resistant to a kind of fluoroquinolones at least, while 87. 5% of the pathogens carried a quinolones resistance gene at any rate. Thereby.it was serious that the fish pathogens sourced from Beijing resistant to fluoroquinolones at genetic level, and it was necessary to strictly

  7. Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H30R and O1-ST648.

    Science.gov (United States)

    Sato, Toyotaka; Suzuki, Yuuki; Shiraishi, Tsukasa; Honda, Hiroyuki; Shinagawa, Masaaki; Yamamoto, Soh; Ogasawara, Noriko; Takahashi, Hiroki; Takahashi, Satoshi; Tamura, Yutaka; Yokota, Shin-Ichi

    2017-02-01

    Tigecycline (TGC) is a last-line drug for multidrug-resistant Enterobacteriaceae We investigated the mechanism(s) underlying TGC nonsusceptibility (TGC resistant/intermediate) in Escherichia coli clinical isolates. The MIC of TGC was determined for 277 fluoroquinolone-susceptible isolates (ciprofloxacin [CIP] MIC, resistant isolates (CIP MIC, >2 mg/liter). The MIC50 and MIC90 for TGC in fluoroquinolone-resistant isolates were 2-fold higher than those in fluoroquinolone-susceptible isolates (MIC50, 0.5 mg/liter versus 0.25 mg/liter; MIC90, 1 mg/liter versus 0.5 mg/liter, respectively). Two fluoroquinolone-resistant isolates (O25b:H4-ST131-H30R and O125:H37-ST48) were TGC resistant (MICs of 4 and 16 mg/liter, respectively), and four other isolates of O25b:H4-ST131-H30R and an isolate of O1-ST648 showed an intermediate interpretation (MIC, 2 mg/liter). No TGC-resistant/intermediate strains were found among the fluoroquinolone-susceptible isolates. The TGC-resistant/intermediate isolates expressed higher levels of acrA and acrB and had lower intracellular TGC concentrations than susceptible isolates, and they possessed mutations in acrR and/or marR The MICs of acrAB-deficient mutants were markedly lower (0.25 mg/liter) than those of the parental strain. After continuous stepwise exposure to CIP in vitro, six of eight TGC-susceptible isolates had reduced TGC susceptibility. Two of them acquired TGC resistance (TGC MIC, 4 mg/liter) and exhibited expression of acrA and acrB and mutations in acrR and/or marR In conclusion, a population of fluoroquinolone-resistant E. coli isolates, including major extraintestinal pathogenic lineages O25b:H4-ST131-H30R and O1-ST648, showed reduced susceptibility to TGC due to overexpression of the efflux pump AcrAB-TolC, leading to decreased intracellular concentrations of the antibiotics that may be associated with the development of fluoroquinolone resistance.

  8. Pharmacodynamic assessment based on mutant prevention concentrations of fluoroquinolones to prevent the emergence of resistant mutants of Streptococcus pneumoniae.

    Science.gov (United States)

    Homma, Tomoyuki; Hori, Toshihiko; Sugimori, Giichi; Yamano, Yoshinori

    2007-11-01

    The objective of this study was to investigate the relationship between pharmacokinetic and pharmacodynamic parameters, on the basis of the mutant prevention concentration (MPC) concept, and the emergence of resistant mutants of Streptococcus pneumoniae to fluoroquinolone antibacterials. Some clinical isolates with various MIC and MPC values of moxifloxacin and levofloxacin were exposed under conditions simulating the time-concentration curves observed when moxifloxacin (400 or 80 mg, once a day) or levofloxacin (200 mg, twice a day) was orally administered by using an in vitro pharmacodynamic model. The decrease in susceptibility was evaluated by altering the population analysis profiles after moxifloxacin or levofloxacin treatment for 72 h. When the area under the concentration-time curve from 0 to 24 h (AUC(0-24))/MPC and peak concentration (C(max))/MPC were above 13.41 and 1.20, respectively, complete eradication occurred and no decrease in susceptibility was observed. On the other hand, when AUC(0-24)/MPC and C(max)/MPC were below 0.84 and 0.08, respectively, the susceptibility decreased. However, the time inside the mutant selective window and the time above the MPC did not show any correlation with the decrease in susceptibility. These results suggest that AUC(0-24)/MPC and C(max)/MPC are important parameters for predicting the emergence of resistant mutants and that higher values indicate greater effectiveness.

  9. Pseudo-outbreak of pre-extensively drug-resistant (Pre-XDR) tuberculosis in Kinshasa: collateral damage caused by false detection of fluoroquinolone resistance by GenoType MTBDRsl.

    Science.gov (United States)

    Kaswa, Michel K; Aloni, Muriel; Nkuku, Léontine; Bakoko, Brian; Lebeke, Rossin; Nzita, Albert; Muyembe, Jean Jacques; de Jong, Bouke C; de Rijk, Pim; Verhaegen, Jan; Boelaert, Marleen; Ieven, Margareta; Van Deun, Armand

    2014-08-01

    Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDRsl and is thus falsely scored as resistance. Our findings suggest that MTBDRsl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.

  10. Comparative Evaluation of Sloppy Molecular Beacon and Dual-Labeled Probe Melting Temperature Assays to Identify Mutations in Mycobacterium tuberculosis Resulting in Rifampin, Fluoroquinolone and Aminoglycoside Resistance

    Science.gov (United States)

    Lee, Jong Seok; Via, Laura E.; Barry, Clifton E.; Alland, David; Chakravorty, Soumitesh

    2015-01-01

    Several molecular assays to detect resistance to Rifampin, the Fluoroquinolones, and Aminoglycosides in Mycobacterium tuberculosis (M. tuberculosis) have been recently described. A systematic approach for comparing these assays in the laboratory is needed in order to determine the relative advantage of each assay and to decide which ones should be advanced to evaluation. We performed an analytic comparison of a Sloppy Molecular Beacon (SMB) melting temperature (Tm) assay and a Dual labeled probe (DLP) Tm assay. Both assays targeted the M. tuberculosis rpoB, gyrA, rrs genes and the eis promoter region. The sensitivity and specificity to detect mutations, analytic limit of detection (LOD) and the detection of heteroresistance were tested using a panel of 56 clinical DNA samples from drug resistant M. tuberculosis strains. Both SMB and DLP assays detected 29/29 (100%) samples with rpoB RRDR mutations and 3/3 (100%) samples with eis promoter mutations correctly. The SMB assay detected all 17/17 gyrA mutants and 22/22 rrs mutants, while the DLP assay detected 16/17 (94%) gyrA mutants and 12/22 (55%) rrs mutants. Both assays showed comparable LODs for detecting rpoB and eis mutations; however, the SMB assay LODs were at least two logs better for detecting wild type and mutants in gyrA and rrs targets. The SMB assay was also moderately better at detecting heteroresistance. In summary, both assays appeared to be promising methods to detect drug resistance associated mutations in M. tuberculosis; however, the relative advantage of each assay varied under each test condition. PMID:25938476

  11. Comparative Evaluation of Sloppy Molecular Beacon and Dual-Labeled Probe Melting Temperature Assays to Identify Mutations in Mycobacterium tuberculosis Resulting in Rifampin, Fluoroquinolone and Aminoglycoside Resistance.

    Directory of Open Access Journals (Sweden)

    Sandy S Roh

    Full Text Available Several molecular assays to detect resistance to Rifampin, the Fluoroquinolones, and Aminoglycosides in Mycobacterium tuberculosis (M. tuberculosis have been recently described. A systematic approach for comparing these assays in the laboratory is needed in order to determine the relative advantage of each assay and to decide which ones should be advanced to evaluation. We performed an analytic comparison of a Sloppy Molecular Beacon (SMB melting temperature (Tm assay and a Dual labeled probe (DLP Tm assay. Both assays targeted the M. tuberculosis rpoB, gyrA, rrs genes and the eis promoter region. The sensitivity and specificity to detect mutations, analytic limit of detection (LOD and the detection of heteroresistance were tested using a panel of 56 clinical DNA samples from drug resistant M. tuberculosis strains. Both SMB and DLP assays detected 29/29 (100% samples with rpoB RRDR mutations and 3/3 (100% samples with eis promoter mutations correctly. The SMB assay detected all 17/17 gyrA mutants and 22/22 rrs mutants, while the DLP assay detected 16/17 (94% gyrA mutants and 12/22 (55% rrs mutants. Both assays showed comparable LODs for detecting rpoB and eis mutations; however, the SMB assay LODs were at least two logs better for detecting wild type and mutants in gyrA and rrs targets. The SMB assay was also moderately better at detecting heteroresistance. In summary, both assays appeared to be promising methods to detect drug resistance associated mutations in M. tuberculosis; however, the relative advantage of each assay varied under each test condition.

  12. Polyamines Inhibit Porin-Mediated Fluoroquinolone Uptake in Mycobacteria

    Science.gov (United States)

    Sarathy, Jansy Passiflora; Lee, Edmund; Dartois, Véronique

    2013-01-01

    Polyamines decrease the permeability of the outer membrane of Escherichia coli to fluoroquinolones and β-lactams. In this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in Mycobacterium bovis BCG. Our results show that polyamines are also capable of reducing the permeability of the mycobacterial outer membrane to fluoroquinolones. Spermidine was most effective and demonstrated reversible dose- and pH-dependent inhibition of ciprofloxacin accumulation. The extent of this inhibition was demonstrated across the fluoroquinolone compound class to varying degrees. Furthermore, we have shown that the addition of spermidine increases the survival of M. bovis BCG after a 5-day exposure to ciprofloxacin by up to 25 times. The treatment of actively-replicating Mycobacterium tuberculosis with spermidine reduced ciprofloxacin accumulation by half while non-replicating nutrient-starved M. tuberculosis cultures lacked similar sensitivity to polyamines. Gene expression studies showed that several outer membrane proteins are significantly down–regulated during the shift to non–replication. Collectively, these characteristics of fluoroquinolone uptake in M. bovis BCG are consistent with facilitated transport by porin-like proteins and suggest that a reduction in intracellular uptake contributes to the phenotypic drug resistance demonstrated by M. tuberculosis in the non-replicating state. PMID:23755283

  13. Has the use of fluoroquinolones facilitated the widespread dissemination of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing Klebsiella pneumoniae in the healthcare setting?

    Science.gov (United States)

    Füzi, Miklós

    2014-12-01

    Our group recently demonstrated that diverse fitness cost associated with resistance to fluoroquinolones allowed the extensive dissemination of the major international clones of both methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Klebsiella pneumoniae in the healthcare setting. The mechanism described by us was subsequently confirmed by British authors investigating the dynamics of MRSA clones in England. Our results imply that the use of fluoroquinolones should impact the incidence for both MRSA and multiresistant K. pneumoniae. A review of the related clinical studies mostly support this notion and shows that changes in the consumption of fluoroquinolone type antibiotics and the rates for both MRSA and multiresistant ESBL-producing K. pneumoniae remain usually in accordance. Though the association seems strong and the mechanism behind it unequivocal the use of fluoroquinolones should not be abandoned; a more judicious application can be recommended.

  14. 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.

  15. Systemic use of fluoroquinolone in children

    Directory of Open Access Journals (Sweden)

    Soo-Han Choi

    2013-05-01

    Full Text Available Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.

  16. 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.

  17. Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella pneumophila and Humans

    Directory of Open Access Journals (Sweden)

    Lubana Shadoud

    2015-09-01

    Interpretation: In vivo selection of antibiotic resistances in L. pneumophila may be associated with treatment failures and poor prognosis. This hidden resistance must be carefully considered in the therapeutic management of legionellosis patients and in the control of the gradual loss of effectiveness of antibiotics.

  18. Presence of an Active Efflux System in the Fluoroquinolones Resistance of Mycoplasma Hominis

    Institute of Scientific and Technical Information of China (English)

    姚艳冰; 吴移谋; 朱翠明; 曾铁兵; 曾焱华

    2003-01-01

    Objective: To investigate the possible presence of an active efflux system in resistance to fluoroqninolones in Mycoplasma hominis. Methods: The resistant strains of M. hominis were selected from one hundred and three clinical strains of M. homlnls by broth microdilution method. The ac-cumulation of ciprofloxacin in M. hominis and the in-fluence of carbonyl cyanide m-chlorophenyl- hydrazone (CCCP) and reserpine were measured by a fluores-cence method. Results: Two resistant strains and two susceptible strains of M. hominis were selected in vitro. The accu-mulation of ciprofloxacin for resistant strains is lower than that of susceptible strains. CCCP and reserpine had different influence on clinical strains of M.hominis. Reserpine could dramatically increase the accumulation of ciprofloxacin, however CCCP had a little effect on it. Conclusion: These results suggest that the pres-ence of an active efflux system implicated in the fluoroouinolones-resistant in M. hominis.

  19. Emergence of fluoroquinolone-resistant Neisseria gonorrhoeae in São Paulo, Brazil Emergência de Neisseria gonorrhoeae resistente à fluoroquinolona em São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    Walter Belda Junior

    2007-06-01

    Full Text Available Continued monitoring of antimicrobial resistance patterns is essential in order for Sexually Transmitted Diseases (STD treatment to be effective. Gonococci isolates from 65 patients in São Paulo were submitted to susceptibility testing, and a decreased susceptibility or resistance to ciprofloxacin was observed in 8.7% of these patients, indicating that Neisseria gonorrhoeae fluoroquinolone resistance is emerging in Brazil.O monitoramento contínuo de resistência antimicrobiana é essencial para a efetividade do tratamento das Doenças Sexualmente Transmissíveis (DST. Gonococosisolados de 65 pacientes de São Paulo foram submetidos a teste de susceptibilidade verificando-se que 8,7% apresentavam susceptibilidade diminuída ou resistência ao ciprofloxacino, o que indica que a resistência da Neisseria gonorrhoeae às fluoroquinolonas é emergente no Brasil.

  20. Emergence of quinolone-resistant strains in Streptococcus pneumoniae isolated from paediatric patients since the approval of oral fluoroquinolones in Japan.

    Science.gov (United States)

    Takeuchi, Noriko; Ohkusu, Misako; Hoshino, Tadashi; Naito, Sachiko; Takaya, Akiko; Yamamoto, Tomoko; Ishiwada, Naruhiko

    2017-04-01

    Tosufloxacin (TFLX) is a fluoroquinolone antimicrobial agent. TFLX granules for children were initially released in Japan in 2010 to treat otitis media and pneumonia caused by drug-resistant bacteria, e.g. penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae. The evolution of bacterial resistance since TFLX approval is not known. To clarify the influence of quinolones administered to children since their approval, we examined the resistance mechanism of TFLX-resistant S. pneumoniae isolated from paediatric patients as well as patient clinical characteristics. TFLX-resistant strains (MIC ≥ 2 mg/L) were detected among clinical isolates of S. pneumoniae derived from children (≤15 years old) between 2010 and 2014. These strains were characterised based on quinolone resistance-determining regions (QRDRs), i.e. gyrA, gyrB, parC, and parE. In addition, the antimicrobial susceptibility, serotype, and multilocus sequence type of strains were determined, pulsed-field gel electrophoresis was performed, and patient clinical characteristics based on medical records were assessed for cases with underling TFLX-resistant strains. Among 1168 S. pneumoniae isolates, two TFLX-resistant strains were detected from respiratory specimens obtained from paediatric patients with frequent exposure to TFLX. Both strains had mutations in the QRDRs of gyrA and parC. One case exhibited gradual changes in the QRDR during the clinical course. This is the first study of quinolone-resistant S. pneumoniae isolated from children, including clinical data, in Japan. These data may help prevent increases in infections of quinolone-resistant S. pneumoniae in children; specifically, the results emphasise the importance of administering fluoroquinolones only in appropriate cases. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. A single-center evaluation of the risk for colonization or bacteremia with piperacillin-tazobactam- and cefepime-resistant bacteria in patients with acute leukemia receiving fluoroquinolone prophylaxis.

    Science.gov (United States)

    Nguyen, A D; Heil, E L; Patel, N K; Duffy, A; Gilmore, S

    2016-04-01

    Fluoroquinolone prophylaxis is indicated to prevent neutropenic fever in patients with acute leukemia. However, fluoroquinolone use has been associated with development of multi-drug-resistant Pseudomonas aeruginosa and extended spectrum β-lactamase producing gram-negative bacilli. Due to a presumed risk of multi-drug resistance associated with fluoroquinolone prophylaxis, patients admitted to our hospital with neutropenic fever receive empiric carbapenem therapy until cultures are negative for 72 h or identification of an organism. Our study seeks to identify the incidence of multi-drug-resistant organism colonization and bacteremia among patients who receive fluoroquinolone prophylaxis and to evaluate duration of empiric carbapenem therapy. A retrospective review of adult patients with acute leukemia receiving a fluoroquinolone as outpatient infection prophylaxis, admitted to our tertiary cancer center for treatment of neutropenic fever was completed. Surveillance and blood cultures were reviewed for antibiotic resistance. Duration of empiric carbapenem therapy was reviewed. One hundred patients and 177 admissions for neutropenic fever were included. Six patients harbored a piperacillin-tazobactam-resistant organism found during routine surveillance. Among these patients, two bacteremias were identified, one of which was a piperacillin-tazobactam-resistant organism. Five bacteremias were identified among 83 patients with negative surveillance cultures. Among the bloodstream infections, five organisms isolated were fluoroquinolone resistant. No cefepime-resistant organism was isolated on surveillance or bloodstream cultures. Adherence to the institution guideline of narrowing antibiotics after 72 h of negative cultures occurred in only 13% of neutropenic fever cases. The average duration of carbapenem therapy in 177 neutropenic fever episodes was 4.4 days. Our findings show that among our patient population, there is a low risk of bacteremia with a

  2. Changes in fluoroquinolone-resistant Streptococcus pneumoniae after 7-valent conjugate vaccination, Spain.

    Science.gov (United States)

    de la Campa, Adela G; Ardanuy, Carmen; Balsalobre, Luz; Pérez-Trallero, Emilio; Marimón, Jose M; Fenoll, Asunción; Liñares, Josefina

    2009-06-01

    Among 4,215 Streptococcus pneumoniae isolates obtained in Spain during 2006, 98 (2.3%) were ciprofloxacin resistant (3.6% from adults and 0.14% from children). In comparison with findings from a 2002 study, global resistance remained stable. Low-level resistance (30 isolates with MIC 4-8 microg/mL) was caused by a reserpine-sensitive efflux phenotype (n = 4) or single topoisomerase IV (parC [n = 24] or parE [n = 1]) changes. One isolate did not show reserpine-sensitive efflux or mutations. High-level resistance (68 isolates with MIC >or=16 microg/mL) was caused by changes in gyrase (gyrA) and parC or parE. New changes in parC (S80P) and gyrA (S81V, E85G) were shown to be involved in resistance by genetic transformation. Although 49 genotypes were observed, clones Spain9V-ST156 and Sweden15A-ST63 accounted for 34.7% of drug-resistant isolates. In comparison with findings from the 2002 study, clones Spain14-ST17, Spain23F-ST81, and ST8819F decreased and 4 new genotypes (ST9710A, ST57016, ST43322, and ST71733) appeared in 2006.

  3. Correlation of different phenotypic drug susceptibility testing methods for four fluoroquinolones in Mycobacterium tuberculosis.

    Science.gov (United States)

    Coeck, Nele; de Jong, Bouke C; Diels, Maren; de Rijk, Pim; Ardizzoni, Elisa; Van Deun, Armand; Rigouts, Leen

    2016-05-01

    Molecular resistance testing fails to explain all fluoroquinolone resistance, with a continued need for a suitable rapid phenotypic drug susceptibility testing method. To evaluate the optimal method for phenotypic fluoroquinolone susceptibility testing. Using Löwenstein-Jensen medium, Middlebrook 7H11 agar, BACTEC-MGIT 960 and the resazurin microtitre plate assay, we determined susceptibility to fluoroquinolones in Mycobacterium tuberculosis and investigated cross-resistance between ofloxacin, levofloxacin, moxifloxacin and gatifloxacin. We compared MICs of all four fluoroquinolones for 91 strains on Löwenstein-Jensen (as the gold standard) with their MICs in resazurin plates, and with ofloxacin susceptibility at a single concentration in MGIT and on 7H11 agar, in addition to sequencing of the gyrAB genes. Applying a cut-off of 2 mg/L ofloxacin, 1 mg/L levofloxacin and 0.5 mg/L moxifloxacin and gatifloxacin in all methods, some discordance between solid medium and MGIT methods was observed, yet this tended to be explained by MICs around the cut-off. The high discordance between Löwenstein-Jensen (LJ) and resazurin plates suggests that the currently applied cut-offs for all fluoroquinolones in the resazurin method should decrease and minor changes in colour (from blue to purple) be considered as meaningful. High-level resistance in all assays to all drugs correlated well with the presence of gyrA mutations, in support of recent findings that fluoroquinolone resistance should be tested at different concentrations, as patients with lower levels of resistance may continue to benefit from high-dose fluoroquinolone-based therapy. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  4. The global establishment of a highly-fluoroquinolone resistant Salmonella enterica serotype Kentucky ST198 strain

    Directory of Open Access Journals (Sweden)

    Simon eLe Hello

    2013-12-01

    Full Text Available While the spread of Salmonella enterica serotype Kentucky resistant to ciprofloxacin across Africa and the Middle-East has been described recently, the presence of this strain in humans, food, various animal species (livestock, pets, and wildlife and in environment is suspected in other countries of different continents. Here, we report results of an in-depth molecular epidemiological study on a global human and non-human collection of S. Kentucky (n=70.We performed XbaI-pulsed field gel electrophoresis and multilocus sequence typing, assessed mutations in the quinolone resistance-determining regions, detected β-lactam resistance mechanisms, and screened the presence of the Salmonella genomic island 1 (SGI1. In this study, we highlight the rapid and extensive worldwide dissemination of the ciprofloxacin-resistant S. Kentucky ST198-X1-SGI1 strain since the mid-2000s in an increasingly large number of contaminated sources, including the environment. This strain has accumulated an increasing number of chromosomal and plasmid resistance determinants and has been identified in the Indian subcontinent, Southeast Asia and Europe since 2010. The second substitution at position 87 in GyrA (replacing the amino acid Asp appeared helpful for epidemiological studies to track the origin of contamination.This global study provides evidence leading to the conclusion that high-level resistance to ciprofloxacin in S. Kentucky is a simple microbiological trait that facilitates the identification of the epidemic clone of interest, ST198-X1-SGI1. Taking this into account is essential in order to detect and monitor it easily and to take rapid measures in livestock to ensure control of this infection.

  5. Distribution of gyrA mutations in fluoroquinolone-resistant Helicobacter pylori strains

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the resistance of Helicobacter pylori(H.pylori) to ciprofloxacin(CIP),levofloxacin(LVX) and moxifloxacin(MOX) in the Beijing area and to elucidate the resistance mechanisms.METHODS:Seventy-nine H.pylori clinical strains,isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009,were tested for their susceptibility to CIP,LVX and MOX using the E-test method.H.pylori strain 26695 was included in the susceptibility testing ...

  6. Persistence of fluoroquinolone-resistant Salmonella enterica serovar Kentucky from poultry and poultry sources in Nigeria

    DEFF Research Database (Denmark)

    Raufu, Ibrahim A.; Fashae, Kayode; Ameh, James A.

    2014-01-01

    Introduction: This study investigated the antimicrobial resistance and clonality of Salmonella enterica serotype Kentucky in poultry and poultry sources in Nigeria, and compared the isolates with the clone of S. Kentucky STI98-X1 CIPR using (PFGE) and (MIC). Methodology: Fecal samples from chicke...

  7. Fluoroquinolone resistance of Streptococcus pneumoniae isolates causing invasive disease: special focus on zabofloxacin.

    Science.gov (United States)

    Kim, Tark; Park, Su-Jin; Chong, Yong Pil; Park, Ki-Ho; Lee, Yu-Mi; Hong, Hyo-Lim; Kim, Hee Seung; Kim, Eun Sil; Lee, Sungkyoung; Choi, Dong Rack; Kim, Sung-Han; Jeong, Jin-Yong; Lee, Sang-Oh; Choi, Sang-Ho; Woo, Jun Hee; Kim, Yang Soo

    2016-10-01

    The present study examined the in vitro activity of various antibiotics including zabofloxacin, against isolates responsible for invasive pneumococcal diseases. Between 1997 and 2008, a total of 208 isolates were collected from sterile fluids, including blood (n=196, 94.2%), pleural fluid (n=5, 2.4%), cerebrospinal fluid (n=5, 2.4%), and ascites (n=2, 1.0%). Zabofloxacin showed the lowest MIC50 (0.015μg/mL) and MIC90 (0.025μg/mL) values of all the tested antibiotics. Rates of isolates resistant to penicillin (MIC ≥8μg/mL), ceftriaxone (MIC ≥4μg/mL) and levofloxacin (MIC ≥8μg/mL) were 3.4%, 0.4% and 2.0%, respectively. Four isolates (2.0%) were resistant to levofloxacin, and zabofloxacin showed low MICs (range, 0.025-0.125μg/mL). Zabofloxacin shows potent in vitro activity against S. pneumoniae isolates that caused invasive disease, even strains that are resistant to levofloxacin.

  8. High rates of intestinal colonisation with fluoroquinolone-resistant ESBL-harbouring Enterobacteriaceae in hospitalised patients with antibiotic-associated diarrhoea.

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    Vervoort, J; Gazin, M; Kazma, M; Kotlovsky, T; Lammens, C; Carmeli, Y; Goossens, H; Malhotra-Kumar, S

    2014-12-01

    The purposes of this study were to investigate the intestinal carriage of extended-spectrum β-lactamase-harbouring Enterobacteriaceae (ESBL-EN) and associated fluoroquinolone resistance (FQ-R) in 120 hospitalised patients with antibiotic-associated diarrhoea, and to investigate a correlation between Clostridium difficile (C. difficile) infection and intestinal colonisation with ESBL-EN in these patients. Stool samples were screened for C. difficile infection by toxin A/B enzyme-linked immunosorbent assay (ELISA) and for the presence of enterobacterial isolates producing β-lactamases by plating on β-lactamase screening (BLSE) agar. Recovered isolates were confirmed pheno- and genotypically for the presence of ESBL genes (bla CTX-M, bla TEM, bla SHV) by the double-disc synergy test and polymerase chain reaction (PCR) sequencing, and tested for the presence of topoisomerase mutations (gyrA, parC) and plasmid-mediated quinolone resistance (PMQR) determinants [qnrA, qnrB, qnrS, qepA, aac(6')-Ib-cr] by PCR sequencing. ESBL-EN were detected in 44/120 (37 %) stool samples. C. difficile-infected patients showed a significantly higher frequency of intestinal colonisation with ESBL-EN compared to C. difficile non-infected patients (62 % vs. 31 %, p = 0.008). Of the 73 ESBL-EN recovered, 46 (63 %) showed high-level FQ-R [ciprofloxacin minimum inhibitory concentration (MIC) ≥32 mg/L]. The largest group consisted of 21 bla CTX-M-15-harbouring Enterobacteriaceae (ciprofloxacin MIC ≥64 mg/L) with multiple topoisomerase mutations in gyrA and parC, in combination with co-carriage of aac(6')-Ib-cr. Most of them were Escherichia coli isolates belonging to sequence types ST131 and ST410. We found remarkably high rates of intestinal colonisation with high-level FQ-R ESBL-EN in hospitalised patients with antibiotic-associated diarrhoea, especially among C. difficile-infected patients. These data underscore the need for stringent infection control to contain this potentially

  9. Increasing Trend of Resistance to Penicillin, Tetracycline, and Fluoroquinolone Resistance in Neisseria gonorrhoeae from Pakistan (1992–2009

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    Kauser Jabeen

    2011-01-01

    Full Text Available Emergence and spread of drug resistant Neisseria gonorrhoeae is global concern. We evaluated trends of antimicrobial resistance in Neisseria gonorrhoeae over years 1992–2009 in Pakistan. Resistance rates were compared between years (2007–2009 and (1992–2006. Antimicrobial susceptibility testing was performed and interpreted according to Clinical Laboratory Standards Institute (CLSI criteria using the disk diffusion methodology against penicillin, ceftriaxone, tetracycline and ofloxacin. Additional antibiotics tested in 100 strains isolated during 2007–2009, included cefotaxime, cefoxitin, cefuroxime, cefipime, ceftazidime, ceftizoxime, cefixime, cefpodoxime, spectinomycin and azithromycin. Neisseria gonorrhoeae ATCC 49226 was used as control. Chi-square for trend analysis was conducted to assess resistance trend over the study period. During study period significant increase in combined resistance to penicillin, tetracycline and ofloxacin was observed (P value <0.01. Resistance rates during the two study period also increased significantly (P value <0.01. Ceftriaxone resistance was not observed. None of the isolates were found to be resistant or with intermediate sensitivity to additional antibiotics. Our findings suggest that penicillin, ciprofloxacin, tetracycline should not be used in the empirical treatment of gonorrhea in Pakistan. Ceftriaxone and cefixime should be the first line therapy; however periodic MICs should be determined to identify emergence of strains with reduced susceptibility.

  10. Resistance mechanism of Haemophilus influenzae against β- lactam antibiotics and fluoroquinolone%流感嗜血杆菌对β内酰胺类和氟喹诺酮类药物的耐药机制

    Institute of Scientific and Technical Information of China (English)

    马池; 吕媛

    2012-01-01

    Objective To investigate the susceptibility of Haemophilus influenzae to p - lactam antimicrobial agents and fluoroquinolones and to explore the resistance mechanism. Methods Minimal inhibitory concentrations ( MIC)of clinical isolate Haemophilus influenzaes against p - lactam antimicrobial agents and fluoroquinolones were evaluated by the serial two - fold agar dilution method. The production or presence of P - lacta-mase was studied by the rapid method utilizing ihe chromogenic cephalo-sporin compound nitrocefin in cultures of Haemophilus influenzaes. Then TEM -1 and ROB - 1 type of p - lactamase genes and quinolones - resistant determining regions ( QRDR) of fluoroquinolone resistant strain were detected by polymerase chain reaction ( PCR) amplification and product sequencing. Results The susceptible rate of the 183 strains Haemophilus influenzae to ampicillin was 73.2% . Otherwise, all the strains were all susceptible to ampicillin - sulbactam, cefotaxime and cefepim. Two ciprofloxacin and 3 moxifloxacin resistance strains were detected, and one of them was not susceptible to both ciprofloxacin and moxifloxacin. Of the 183 strains Haemophilus influenzae, 34 isolates (18. 6% ) were determinated as p - lactamase producing strains. One hundred percent of the p - lactainase positive strains gave a positive result with specific primers for the TEM - 1 gene. None strain was detected for the ROB -1 gene with in 34 strains in all the 183 strains. One or more mutations in GyrA and ParC in QRDR were detected in all the fluoroquinolone resistance Haemophilus influenzaes, even the change of ami-no acids in position 84 or (and) 88 of GyrA occurred more frequently. Conclusion Other than ampicillin, cephalospo-rins and fluoroquinolones show potent activities against Haemophilus influenzae. The major mechanism of Haemophilus influenzae resistance to p - lactam antibiotics is mainly the presence of β - lactamase, mainly TEM - 1 type enzyme. ROB -1 gene should be persistently

  11. 介导对氟喹诺酮类药物耐药的金黄色葡萄球菌norA基因的研究%Study on drug resistance of Staphylococcus aureus mediated by norA gene to fluoroquinolones

    Institute of Scientific and Technical Information of China (English)

    陈寒冬; 房雷; 钟利; 闫宏钧; 彭勋; 王守云; 杨丽敏; 赵培利; 苗亮; 李丹

    2012-01-01

    Objective To study the mechanism of fluoropuinolone resistance mediated by norA gene in Staphylococcus aureus. Methods The susceptibility test was performed by Kirby-Bauer disk diffusion method. FQNS can be issued fluorescence by laser excitation at a certain wavelength, and the relationship of fluorescence value and the concentration of FQNS was linear. The accumulation concentration of two FQNS in bacteria were measured by fluorescene measured method. Study on norA gene of S. aureus. Total RNA was extracted by Trizol reagent, Reverse transcription was done by TOYOBO's reverse transcriptase kit. For RT-PCR, the volume of reaction is 25μL, 10μL of the product of reverse transcription of total RNA, 1μL of upstream primer,1μL of downstream primer, 12.5uL of 2×PCR Master Mix, up to 25μL of double distilled H2O. PCR products were visualized on horizontal agarose gels after electrophoresis. Then the PCR products were purified and were sequencing and diluted series of gradient, as a quantitative standard reference. Expression level of norA gene was detected by Fluorescence quantitative RT-PCR of TaqMan probe. The volume of PCR reaction is 25μL, luL of probe, 4uL of upstream primer,4μL of downstream primer, 5μL of cDNA or standard reference, 25μL of Realtime PCR Master Mix and 11μL of double distilled water and carried out as hot start at 95℃ for 60s, 40 cycles of denaturation at 95℃ for 15s, renaturation at 60℃ for 60s, extension at 60℃ for lmin. Results There are MDR and CDR in Four FQNS. The steadystate accumulation concentration of two drugs in the sensitive bacteria was significantly higher than that of the resistant bacteria. norA gene were detected in all experimental strains. The expression level of nor A gene in bad resistant strain were 0~8 times more than the average expression in sensitive stains. Conclusion There is CDR to four different quinolones in S. aureus, while there is MDR to other antibacterials.The decrease of accumulation

  12. The Use of Systemic and Topical Fluoroquinolones.

    Science.gov (United States)

    Jackson, Mary Anne; Schutze, Gordon E

    2016-11-01

    Appropriate prescribing practices for fluoroquinolones, as well as all antimicrobial agents, are essential as evolving resistance patterns are considered, additional treatment indications are identified, and the toxicity profile of fluoroquinolones in children has become better defined. Earlier recommendations for systemic therapy remain; expanded uses of fluoroquinolones for the treatment of certain infections are outlined in this report. Prescribing clinicians should be aware of specific adverse reactions associated with fluoroquinolones, and their use in children should continue to be limited to the treatment of infections for which no safe and effective alternative exists or in situations in which oral fluoroquinolone treatment represents a reasonable alternative to parenteral antimicrobial therapy. Copyright © 2016 by the American Academy of Pediatrics.

  13. Fungal treatment for the removal of antibiotics and antibiotic resistance genes in veterinary hospital wastewater.

    Science.gov (United States)

    Lucas, D; Badia-Fabregat, M; Vicent, T; Caminal, G; Rodríguez-Mozaz, S; Balcázar, J L; Barceló, D

    2016-06-01

    The emergence and spread of antibiotic resistance represents one of the most important public health concerns and has been linked to the widespread use of antibiotics in veterinary and human medicine. The overall elimination of antibiotics in conventional wastewater treatment plants is quite low; therefore, residual amounts of these compounds are continuously discharged to receiving surface waters, which may promote the emergence of antibiotic resistance. In this study, the ability of a fungal treatment as an alternative wastewater treatment for the elimination of forty-seven antibiotics belonging to seven different groups (β-lactams, fluoroquinolones, macrolides, metronidazoles, sulfonamides, tetracyclines, and trimethoprim) was evaluated. 77% of antibiotics were removed after the fungal treatment, which is higher than removal obtained in conventional treatment plants. Moreover, the effect of fungal treatment on the removal of some antibiotic resistance genes (ARGs) was evaluated. The fungal treatment was also efficient in removing ARGs, such as ermB (resistance to macrolides), tetW (resistance to tetracyclines), blaTEM (resistance to β-lactams), sulI (resistance to sulfonamides) and qnrS (reduced susceptibility to fluoroquinolones). However, it was not possible to establish a clear link between concentrations of antibiotics and corresponding ARGs in wastewater, which leads to the conclusion that there are other factors that should be taken into consideration besides the antibiotic concentrations that reach aquatic ecosystems in order to explain the emergence and spread of antibiotic resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Fluoroquinolone resistance: relation between drug use and evolution of resistance in some Units of the “San Bassiano” hospital from 2007 to 2008

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    Claudia Mascotto

    2010-06-01

    Full Text Available There is substantial evidence that the overuse of antibiotics is a major cause for the emergence in antimicrobial resistance. This study analyzes the evolution of antimicrobial resistance to ciprofloxacin and levofloxacin from 2007 to 2008 in some Units of the “San Bassiano” hospital and compares this evolution among the consumption of the same antibiotics. The study involved the collection of all first isolates in blood, urine and transtracheal samples between 2007 and 2008; three microorganisms were chosen: Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Microorganisms investigations concerned Geriatrics, Medicine, Surgery and Intensive Care Unit (ICU with 48, 48, 44 and 10 beds respectively. Identification and antimicrobial susceptibility testing was performed using the Phoenix automated system (Becton Dickinson. If the ciprofloxacin susceptibility was (S and levofloxacin susceptibility was (I/R antimicrobial susceptibility was confirmed by the E-Test method (bioMérieux on Muller Hilton agar and cell density of 0.5 MacFarland. Control strains were E. Coli ATCC 25922, P. aeruginosa ATCC 27853 and S. aureus ATCC 29213. The antibiotics consumed in the hospital between January 2007 and December 2008 were transformed into Defined Daily Dose (DDD, which corresponds to the quantity of antibiotics consumed by a patient in 24 h. Ciprofloxacin and levofloxacin demonstrated a similar pattern of increasing resistance in some units between 2007 and 2008. Fluoroquinolone resistance increase for E. coli, varies from 10% in Geriatrics to 15% in ICU, for S. aureus varies from 15% in Medicine Unit to 5% in ICU. P. aeruginosa maintained the same percentage of resistance from 2007 to 2008, but there was a significantly increase of strains with intermediate sensitivity (I up to 30%. The consumption of Ciprofloxacin didn’t increase in any of the units and in some case decreased. The consumption of levofloxacin increased in every units

  15. Resistance of canine methicillin-resistant Staphylococcus pseudintermedius strains to pradofloxacin.

    Science.gov (United States)

    Kizerwetter-Świda, Magdalena; Chrobak-Chmiel, Dorota; Rzewuska, Magdalena; Binek, Marian

    2016-09-01

    We investigated in vitro activity of a novel veterinary fluoroquinolone, pradofloxacin, against methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates and compared with other fluoroquinolones. A total of 38 MRSP isolates were subjected to agar disk diffusion tests for sensitivity to pradofloxacin, orbifloxacin, marbofloxacin, enrofloxacin, and ciprofloxacin. The minimal inhibitory concentration (MIC) values of pradofloxacin, ciprofloxacin, and enrofloxacin were determined. Mutations in the genes encoding DNA gyrase subunit A (GyrA) and topoisomerase IV (GrlA) proteins associated with fluoroquinolone resistance were studied by an analysis of partial sequences of the genes encoding these proteins. Two MRSP isolates were susceptible in disk diffusion and microdilution test to all fluoroquinolones tested, including pradofloxacin. Based on the results of the disk diffusion testing, 33 of 38 isolates showed resistance to pradofloxacin and 3 were intermediate, whereas, by pradofloxacin MIC testing, 35 isolates were classified as resistant and 1 as intermediate. Single alterations in GyrA and GrlA proteins were observed in the 35 resistant isolates and the 1 intermediate isolate (MIC results). These same 36 isolates were also resistant to the other tested fluoroquinolones. The results of the current study showed that MRSP isolates are usually resistant to all fluoroquinolones, including pradofloxacin. Therefore, in routine susceptibility testing to pradofloxacin by disk diffusion, the results should be carefully interpreted for MRSP isolates, especially those resistant to other fluoroquinolones and, in questionable cases, the pradofloxacin MIC should be determined to confirm the susceptibility testing results. © 2016 The Author(s).

  16. Sale of fluoroquinolones in northern Tanzania: a potential threat for fluoroquinolone use in tuberculosis treatment.

    Science.gov (United States)

    van den Boogaard, Jossy; Semvua, Hadija H; Boeree, Martin J; Aarnoutse, Rob E; Kibiki, Gibson S

    2010-01-01

    Fluoroquinolones have a potential role in shortening tuberculosis (TB) treatment duration. They are currently used in the treatment of other infections. This has raised concerns about development of mycobacterial resistance. The current study evaluates the sale of fluoroquinolones (among other antibacterials) in Moshi, Tanzania, a country with one of the highest burdens of TB in the world. Trained pharmacy assistants registered the sale of fluoroquinolones during February and March 2009 to outpatients in Moshi in all 14 pharmacies that are authorized to sell antibacterials for systemic use. The sale of all antibacterials of the Anatomical Therapeutic Chemical (ATC) J01 class was expressed in defined daily doses (DDDs) per 1000 inhabitants per day (DID). The availability of fluoroquinolones in drug outlets that are not authorized to sell antibacterials for systemic use was assessed in 15 randomly selected outlets in Moshi. The sale of antibacterials to outpatients in Moshi by authorized pharmacies was 4.99 DID. The sale of fluoroquinolones was 0.62 DID (12% of total antibacterial sales). Ciprofloxacin was available in all 15 unauthorized drug outlets. The substantial sales of fluoroquinolones by authorized pharmacies and the wide availability of fluoroquinolones in unauthorized drug outlets in Moshi constitute a challenge to the use of fluoroquinolones in TB treatment in Tanzania. Control of antibacterial use in Tanzania requires the implementation of surveillance systems for antibacterial use and resistance, and adequate restriction of antibacterial sales to authorized pharmacies only.

  17. Contribution of oqxAB and aac(6’Ib-cr to fluoroquinolone resistance in Salmonella Typhimurium

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    Marcus Ho-yin eWong

    2014-10-01

    Full Text Available Emergence of multidrug-resistant S. Typhimurium strains, especially the ACSSuT and nalidixic acid R types, has significantly compromised the effectiveness of current strategies to control Salmonella infections, resulting in increased morbidity and mortality. Clinical S. Typhimurium isolates recovered in Hong Kong during the period of 2005-2011 were increasingly resistant to ciprofloxacin and antibiotics of the ACSSuT group. Our data revealed that oqxAB and aac(6’Ib-cr were encoded on plasmids of various sizes and the presence of these two elements together with a single gyrA mutation in S. Typhimurium were sufficient to mediate resistance to ciprofloxacin. Acquisition of the oqxAB and aac(6'Ib-cr encoding plasmids by S. Typhimurium caused a 4-fold increase in CIP MIC. Furthermore, the presence of oqxAB and aac(6'Ib-cr in Salmonella dramatically increased the mutation prevention concentration (MPC of ciprofloxacin which may due to mutational changes in the drug target genes. In conclusion, possession of oqxAB and aac(6’Ib-cr encoding plasmid facilitate the selection of ciprofloxacin resistant S. Typhimurium, thereby causing a remarkable increase of ciprofloxacin resistance among clinical Salmonella strains in Hong Kong.

  18. Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones.

    Science.gov (United States)

    van der Heijden, Yuri F; Maruri, Fernanda; Blackman, Amondrea; Mitchel, Ed; Bian, Aihua; Shintani, Ayumi K; Eden, Svetlana; Warkentin, Jon V; Sterling, Timothy R

    2013-09-01

    Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case-control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002-December 2009). Each fluoroquinolone-resistant case (n=25) was matched to two fluoroquinolone-susceptible controls (n=50). Ciprofloxacin and ofloxacin were classified as older-generation fluoroquinolones; levofloxacin, moxifloxacin and gatifloxacin were considered newer agents. There was no difference between median ofloxacin MIC for isolates from 9 patients exposed only to older fluoroquinolones, 25 exposed only to newer fluoroquinolones, 6 exposed to both and 35 fluoroquinolone-unexposed patients (Kruskal-Wallis, P=0.35). Using multivariate proportional odds logistic regression adjusting for age and sex, duration of exposure to newer fluoroquinolones was independently associated with higher MIC (OR=1.79, 95% CI 1.22-2.64), but duration of exposure to older fluoroquinolones was not (OR=0.94, 95% CI 0.50-1.78). Isolates from patients exposed only to newer fluoroquinolones tended to have mutations at gyrA codons 90, 91 or 94 more frequently than those exposed only to older fluoroquinolones (44% vs. 11%). We were surprised to find that duration of exposure to newer fluoroquinolones, but not older ones, was independently associated with higher ofloxacin MIC. This suggests that the mutant selection window lower boundary is likely to have clinical relevance; caution is warranted when newer fluoroquinolones are prescribed to patients with TB risk factors. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  19. SOS response induces persistence to fluoroquinolones in Escherichia coli.

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    Tobias Dörr

    2009-12-01

    Full Text Available Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo.

  20. Constitutive SoxS expression in a fluoroquinolone-resistant strain with a truncated SoxR protein and identification of a new member of the marA-soxS-rob regulon, mdtG.

    Science.gov (United States)

    Fàbrega, Anna; Martin, Robert G; Rosner, Judah L; Tavio, M Mar; Vila, Jordi

    2010-03-01

    Elevated levels of fluoroquinolone resistance are frequently found among Escherichia coli clinical isolates. This study investigated the antibiotic resistance mechanisms of strain NorE5, derived in vitro by exposing an E. coli clinical isolate, PS5, to two selection steps with increasing concentrations of norfloxacin. In addition to the amino acid substitution in GyrA (S83L) present in PS5, NorE5 has an amino acid change in ParC (S80R). Furthermore, we now find by Western blotting that NorE5 has a multidrug resistance phenotype resulting from the overexpression of the antibiotic resistance efflux pump AcrAB-TolC. Microarray and gene fusion analyses revealed significantly increased expression in NorE5 of soxS, a transcriptional activator of acrAB and tolC. The high soxS activity is attributable to a frameshift mutation that truncates SoxR, rendering it a constitutive transcriptional activator of soxS. Furthermore, microarray and reverse transcription-PCR analyses showed that mdtG (yceE), encoding a putative efflux pump, is overexpressed in the resistant strain. SoxS, MarA, and Rob activated an mdtG::lacZ fusion, and SoxS was shown to bind to the mdtG promoter, showing that mdtG is a member of the marA-soxS-rob regulon. The mdtG marbox sequence is in the backward or class I orientation within the promoter, and its disruption resulted in a loss of inducibility by MarA, SoxS, and Rob. Thus, chromosomal mutations in parC and soxR are responsible for the increased antibiotic resistance of NorE5.

  1. Risk Factors for the Development of Gastrointestinal Colonization With Fluoroquinolone-Resistant Escherichia coli in Residents of Long-Term Care Facilities

    Science.gov (United States)

    Han, Jennifer H.; Maslow, Joel; Han, Xiaoyan; Xie, Sharon X.; Tolomeo, Pam; Santana, Evelyn; Carson, Lesley; Lautenbach, Ebbing

    2014-01-01

    Background. The objective of this study was to assess risk factors for the development of fluoroquinolone (FQ)–resistant Escherichia coli gastrointestinal tract colonization in long-term care facility (LTCF) residents. Methods. A prospective cohort study was conducted from 2006 to 2008 at 3 LTCFs. Residents initially colonized with FQ-susceptible E. coli were followed by means of serial fecal sampling for new FQ-resistant E. coli colonization for up to 12 months or until discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQ-resistant E. coli colonization, with antibiotic and device exposures modeled as time-varying covariates. Results. Fifty-seven (47.5%) of 120 residents became newly colonized with FQ-resistant E. coli, with a median time to colonization of 57 days. Fecal incontinence (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.04–3.06; P = .04) was significantly associated with FQ-resistant E. coli acquisition. Receipt of amoxicillin-clavulanate (HR, 6.48; 95% CI, 1.43–29.4; P = .02) and the presence of a urinary catheter (HR, 3.81; 95% CI, 1.06–13.8; P = .04) during LTCF stay increased the risk of new FQ-resistant E. coli colonization. Conclusions. Acquisition of FQ-resistant E. coli was common, with nearly half of LTCF residents developing new FQ-resistant E. coli colonization. Further studies are needed on interventions to limit the emergence of FQ-resistant E. coli in LTCFs. PMID:23986544

  2. BC4707 is a major facilitator superfamily multidrug resistance transport protein from Bacillus cereus implicated in fluoroquinolone tolerance.

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    Roger Simm

    Full Text Available Transcriptional profiling highlighted a subset of genes encoding putative multidrug transporters in the pathogen Bacillus cereus that were up-regulated during stress produced by bile salts. One of these multidrug transporters (BC4707 was selected for investigation. Functional characterization of the BC4707 protein in Escherichia coli revealed a role in the energized efflux of xenobiotics. Phenotypic analyses after inactivation of the gene bc4707 in Bacillus cereus ATCC14579 suggested a more specific, but modest role in the efflux of norfloxacin. In addition to this, transcriptional analyses showed that BC4707 is also expressed during growth of B. cereus under non-stressful conditions where it may have a role in the normal physiology of the bacteria. Altogether, the results indicate that bc4707, which is part of the core genome of the B. cereus group of bacteria, encodes a multidrug resistance efflux protein that is likely involved in maintaining intracellular homeostasis during growth of the bacteria.

  3. An Intrinsic Pattern of Reduced Susceptibility to Fluoroquinolones in Pediatric Isolates of Streptococcus pyogenes

    Science.gov (United States)

    Yan, S. Steve; Schreckenberger, Paul C.; Zheng, Xiaotian; Nelson, Nancy A.; Harrington, Susan M.; Tjhio, Joyce; Fedorko, Daniel P.

    2008-01-01

    A total of 116 clinical isolates collected in 2003 from a tertiary pediatric hospital and a primary pediatric department in Chicago, Illinois were screened for reduced susceptibility to selected fluoroquinolones by disc diffusion. Correlation between reduced susceptibility and point mutations in the quinolone resistance-determining region of parC and gyrA genes were evaluated, and point mutations were compared with other reports of isolates derived from adult or mixed patient populations. 9% of isolates had reduced susceptibility to one or more of these fluoroquinolones by Etest: ciprofloxacin, levofloxacin, moxifloxacin. A single point mutation (Ser-79) in parC seemed responsible for the reduced susceptibility. Resistant S. pyogenes isolates were compared using M/emm type, RepPCR, and pulsed-field gel electrophoresis (PFGE). RepPCR provided no more separation of strains than M/emm typing and PFGE results with SgrA1 were more discriminatory than with SmaI. The majority of these isolates were M/emm type 6. PFGE analysis using SgrA1 demonstrated 2 different resistant strains among the M/emm type 6 isolates. The findings suggest that a population of S. pyogenes with an intrinsic reduced susceptibility to fluoroquinolones exists in pediatric clinical isolates. Monitoring of amino acid changes in both parC and gyrA will assist in the prediction of emergence of high level fluoroquinolone resistance. PMID:18554840

  4. Rapid detection of fluoroquinolone-resistant and heteroresistant Mycobacterium tuberculosis by use of sloppy molecular beacons and dual melting-temperature codes in a real-time PCR assay.

    Science.gov (United States)

    Chakravorty, Soumitesh; Aladegbami, Bola; Thoms, Kimberley; Lee, Jong Seok; Lee, Eun Gae; Rajan, Vignesh; Cho, Eun-Jin; Kim, Hyunchul; Kwak, Hyunkyung; Kurepina, Natalia; Cho, Sang-Nae; Kreiswirth, Barry; Via, Laura E; Barry, Clifton E; Alland, David

    2011-03-01

    Fluoroquinolones (FQ) are important second-line drugs to treat tuberculosis; however, FQ resistance is an emerging problem. Resistance has been mainly attributed to mutations in a 21-bp region of the Mycobacterium tuberculosis gyrA gene, often called the quinolone resistance-determining region (QRDR). We have developed a simple, rapid, and specific assay to detect FQ resistance-determining QRDR mutations. The assay amplifies the M. tuberculosis gyrA QRDR in an asymmetrical PCR followed by probing with two sloppy molecular beacons (SMBs) spanning the entire QRDR. Mutations are detected by melting temperature (T(m)) shifts that occur when the SMBs bind to mismatched sequences. By testing DNA targets corresponding to all known QRDR mutations, we found that one or both of the SMBs produced a T(m) shift of at least 3.6°C for each mutation, making mutation detection very robust. The assay was also able to identify mixtures of wild-type and mutant DNA, with QRDR mutants identified in samples containing as little as 5 to 10% mutant DNA. The assay was blindly validated for its ability to identify the QRDR mutations on DNA extracted from clinical M. tuberculosis strains. Fifty QRDR wild-type samples, 34 QRDR mutant samples, and 8 heteroresistant samples containing mixtures of wild-type and mutant DNA were analyzed. The results showed 100% concordance to conventional DNA sequencing, including a complete identification of all of the mixtures. This SMB T(m) shift assay will be a valuable molecular tool to rapidly detect FQ resistance and to detect the emergence of FQ heteroresistance in clinical samples from tuberculosis patients.

  5. First evaluation of drug-resistant Mycobacterium tuberculosis clinical isolates from Congo revealed misdetection of fluoroquinolone resistance by line probe assay due to a double substitution T80A-A90G in GyrA.

    Directory of Open Access Journals (Sweden)

    Alexandra Aubry

    Full Text Available BACKGROUND: Tuberculosis (TB is one of the major public health problems in Congo. However, data concerning Mycobacterium tuberculosis drug resistance are lacking because of the insufficient processing capacity. So, the aim of this study was to investigate for the first time the resistance patterns and the strain lineages of a sample of M. tuberculosis complex (MTBC isolates collected in the two main cities of Congo. METHODS: Over a 9-day period, 114 smear-positive sputa isolated from 114 patients attending centers for the diagnosis and treatment of TB in Brazzaville and Pointe Noire were collected for culture and drug susceptibility testing (DST. Detection of mutations conferring drug resistance was performed by using line probe assays (GenoType MTBDRplus and MTBDRsl and DNA sequencing. Strain lineages were determined by MIRU-VNTR genotyping. RESULTS: Of the 114 sputa, 46 were culture positive for MTBC. Twenty-one (46% were resistant to one or more first-line antiTB drugs. Of these, 15 (71% were multidrug resistant (MDR. The most prevalent mutations involved in rifampin and isoniazid resistance, D516V (60% in rpoB and S315T (87% in katG respectively, were well detected by MTBDRplus assay. All the 15 MDR strains were susceptible to fluoroquinolone and injectable second-line drug. No mutation was detected in the rrs locus involved in resistance to amikacin and capreomycin by both the MTBDRsl assay and DNA sequencing. By contrast, 9 MDR strains belonging to the same cluster related to T-family were identified as being falsely resistant to fluoroquinolone by the MTBDRsl assay due to the presence of a double substitution T80A-A90G in GyrA. CONCLUSIONS: Taken together, these data revealed a possible spread of a particular MDR clone in Congo, misidentified as fluoroquinolone resistant by MTBDRsl assay. Thus, this test cannot replace gold-standard culture method and should be interpreted carefully in view of the patient's native land.

  6. Obesity genes and insulin resistance

    Science.gov (United States)

    Belkina, Anna C.; Denis, Gerald V.

    2011-01-01

    Purpose of review The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of ‘metabolically healthy but obese’ (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. Recent findings The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Summary Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients. PMID:20585247

  7. 耐氟喹诺酮类铜绿假单胞菌GyrA的变异%A study on GyrA mutant in fluoroquinolone - resistant clinical isolates of Pseudomonas aeruginosa

    Institute of Scientific and Technical Information of China (English)

    杨茁; 刘原; 张利侠; 孙莉

    2011-01-01

    目的 研究铜绿假单胞菌DNA旋转酶A亚单位(GyrA)的变异与其耐氟喹诺酮类(FQNL)的关系.方法 收集临床分离耐喹诺酮铜绿假单胞菌30株及敏感株10株,测定其对萘啶酸、环丙沙星、氧氟沙星的最低抑菌浓度(MIC),并对此30株菌GyrA的基因(gyrA)进行PCR扩增.对PCR产物进行限制性片断长度多态性(PCR-RFLP)分析,检测gyrA突变情况.结果 30株耐喹诺酮菌株都检测到gyrA基因突变,PCR-RFLP均显示两条不同于敏感株的电泳带,而10株敏感菌均未检测到gyrA基因突变.结论 铜绿假单胞菌对喹诺酮类药物耐药性与gyrA基因突变有关,gyrA基因第83位氨基酸密码子突变可能为其耐药的主要原因.%Objective To study the relation between the alterations in the DNA gyrase subunit A (GyrA) and fluoroquinolones (FQNL) resistance in Pseudomonas aeruginosa. Methods Using age the micro broth diluent to determine the MICs of three quinolones of 30 quinolone-resistant and 10 quinolone-susceptible isolates. The genes of GyrA (gyrA) in the30 strains were amplified by PCR. then by restrictive fragments length polymorphism(RFLP) to detect the mutation of gyrA gene. Results All 30 quinolone-resistant isolates were detected the mutation of gyrA gene,the results of PCR-RFLP of them revealed two from 10 quinolone - susceptible isolates. No mutation in gyrA gene of 10 quinolone - susceptible isolates and ATCC10031 was detected by PCR-RFLP. Conclusions Mutation of gyrA gene in clinical iso-lates of Pseudomonas aeruginosa implicated in resistance to quinolones, the mutation of DNA gyrase at the 83rd amino acid may be play a principle role in the resistant to quinolones of Pseudomonas aeruginosa isolates.

  8. Presence of qnr gene in Escherichia coli and Klebsiella pneumoniae resistant to ciprofloxacin isolated from pediatric patients in China

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    Wang Chuanqing

    2008-05-01

    Full Text Available Abstract Background Quinolone resistance in Enterobacteriaceae results mainly from mutations in type II DNA topoisomerase genes and/or changes in the expression of outer membrane and efflux pumps. Several recent studies have indicated that plasmid-mediated resistance mechanisms also play a significant role in fluoroquinolone resistance, and its prevalence is increasing worldwide. In China, the presence of the qnr gene in the clinical isolates of Enterobacteriaceae has been reported, but this transmissible quinolone resistance gene has not been detected in strains isolated singly from pediatric patients. Because quinolones associated with a variety of adverse side effects on children, they are not authorized for pediatric use. This study therefore aimed to investigate the presence of the qnr gene in clinical isolates of E. coli and K. pneumoniae from pediatric patients in China. Methods A total 213 of non-repetitive clinical isolates resistant to ciprofloxacin from E. coli and K. pneumoniae were collected from hospitalized patients at five children's hospital in Beijing, Shanghai, Guangzhou, and Chongqing. The isolates were screened for the plasmid-mediated quinolone resistance genes of qnrA, qnrB, and qnrS by PCR. Transferability was examined by conjugation with the sodium azide-resistant E. coli J53. All qnr-positive were analyzed for clonality by enterobacterial repetitive intergenic consensus (ERIC-PCR. Results The study found that 19 ciprofloxacin-resistant clinical isolates of E. coli and K. pneumoniae were positive for the qnr gene, and most of the qnr positive strains were ESBL producers. Conjugation experiments showed that quinolone resitance could be transferred to recipients. Apart from this, different DNA banding patterns were obtained by ERIC-PCR from positive strains, which means that most of them were not clonally related. Conclusion This report on transferable fluoroquinolone resistance due to the qnr gene among E. coli and K

  9. Call for the international adoption of microbiological breakpoints for fluoroquinolones and Streptococcus pneumoniae.

    Science.gov (United States)

    Schurek, Kristen N; Adam, Heather J; Hoban, Daryl J; Zhanel, George G

    2006-09-01

    The use of current Clinical and Laboratory Standards Institute levofloxacin breakpoints for assessing fluoroquinolone resistance in Streptococcus pneumoniae is inadequate for detecting isolates possessing first-step parC mutations. Consequently, the risk for development of fluoroquinolone resistance is greatly underestimated. Adopting microbiological breakpoints for fluoroquinolones and S. pneumoniae, where parC mutations are rare in susceptible isolates, more accurately describes the emergence of resistance and may help to prevent a number of future fluoroquinolone treatment failures. Additionally, we propose that the use of a second fluoroquinolone marker, such as ciprofloxacin, offers the best prediction for detecting an isolate possessing a first-step parC mutation.

  10. Eliminação de resistência a drogas por fluorquinolonas em Staphylococcus aureus de origem bovina Elimination of resistance to drugs by fluoroquinolones in bovine strains of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Maria S.V. Pereira

    2004-03-01

    Full Text Available Cepas de Staphylococcus aureus de origem bovina foram submetidas ao tratamento com quatro fluoquinolonas na concentração subinibitória (1/2 x CMI, para avaliar a influência desses agentes sobre plasmídios. A ciprofloxacina mostrou ser a fluorquinolona mais eficiente, eliminando marcas de resistência para estreptomicina, tetraciclina, penicilina e cádmio. A norfloxacina e a pefloxacina eliminaram resistência para penicilina e tetraciclina, respectivamente; no entanto, não foi evidenciada a eliminação de plasmídio com ofloxacina. Os resultados confirmam a eficácia das fluor-quinolonas em eliminar plasmídios de resistência mostrando a importância desses estudos como contribuição para o entendimento da prevenção de linhagens multiresistentes, uma vez que as quinolonas em concentrações subinibitórias podem aumentar a sensibilidade das linhagens a outros agentes antimicrobianos.Bovine strains of Staphylococcus aureus were submitted to treatment with four fluoro-quinolones in subinhibitory concentrations (1/2 x MICs to evaluate their influence on the curing of plasmids. Ciprofloxacin showed to be the most efficient by eliminating resistance to streptomycin, tetracyclin, penicillin, and cadmium nitrate. Norfloxacin and pefloxacin eliminated penicillin- and tetracyclin-resistance respectively. Otherwise, plasmids elimination by ofloxacin was not evidenced. The results obtained in this study confirm the potential of fluoroquinolones to eliminate antibiotic-resistant plasmids, and showed to be a valuable contribution for the prevention of multi-resistant strains, and may even enhance their sensitivity to other chemotherapeutic agents.

  11. Correction: Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

    LENUS (Irish Health Repository)

    Costa, Sofia S

    2013-06-06

    AbstractAfter the publication of our study [1], we became aware that the mutations in the quinolone resistance-determining region (QRDR) of the gene grlA were incorrectly described for some of the Staphylococcus aureus clinical isolates studied in this work. In particular, isolates SM1, SM10, SM14, SM17, SM25, SM27, SM43, SM46, SM47 and SM48 carry the GrlA double mutation S80Y\\/E84G; isolate SM52 carries the GrlA mutation S80Y; isolates SM3 and SM5 carry the GrlA double mutation S80F\\/E84G. The correct data can be found in Table 1.

  12. Fluoroquinolone resistance in non-multidrug-resistant tuberculosis—a surveillance study in New South Wales, Australia, and a review of global resistance rates

    Directory of Open Access Journals (Sweden)

    Jennifer Ho

    2014-09-01

    Conclusions: FQ resistance in non-MDR-TB is uncommon in NSW, Australia. The existing global evidence suggests that FQ resistance remains largely confined to MDR-TB strains. In the majority of TB endemic regions, however, FQ resistance in non-MDR-TB has not been assessed. Knowledge of the prevalence of FQ resistance in MTB is essential to guide the rational use of these drugs, including their feasibility as first-line agents.

  13. The evolution of resistance gene in plants

    Institute of Scientific and Technical Information of China (English)

    BEN Haiyan; LIU Xuemin; LI Lijun; LIU Li

    2007-01-01

    Resistance genes enable plants to fight against plant pathogens. Plant resistance genes (R gene) are organized complexly in genome. Some resistance gene sequence data enable an insight into R gene structure and gene evolution. Some sites like Leucine-Rich Repeat (LRR) are of specific interest since homologous recombination can happen. Crossing over, transposon insertion and excision and mutation can produce new specificity. Three models explaining R gene evolution were discussed. More information needed for dissection of R gene evolution though some step can be inferred from genetic and sequence analysis.

  14. Fluoroquinolone-Gyrase-DNA Complexes

    Science.gov (United States)

    Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M.; Hiasa, Hiroshi; Marks, Kevin R.; Kerns, Robert J.; Berger, James M.; Drlica, Karl

    2014-01-01

    DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys466 gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly81 and GyrB-Glu466 residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases. PMID:24497635

  15. 氟喹诺酮类药物体外诱导大肠埃希菌耐药性观察%Observation of Escherichia coli induced resistance to fluoroquinolones in vitro

    Institute of Scientific and Technical Information of China (English)

    赵磊; 荆鹏伟

    2011-01-01

    Aim: To observe the induced resistance of Escherichia coli to a variety of fluoroquinolones in drug concentration of sub-M/C. Methods-.The experiments on induced resistance to ciprofloxacin.levofloxacin or gatifloxacin were performed, in thrity-two Escherichia coli sensitived to fluoroquinolones from clinic,respectively, by multiple-step method. The susceptibility of the induced strains resistant to fluoroquinolones was measured by determining the MIC using agar dilution method. Results:The strains highly resistant to fluoroquinolone were obtained from 22 tested strain of Escherichia coli,the MICs of these laboratory resistant strains were with 32 to 3 000 fold increase, respectively, when compared with parent strains. All six induced highly resistant strains examined carried two gyrA mutations affecting residues 83Ser→Leu,Asp87→ Asn and one parC mutation of 80Ser→Ile. No mutation was found in a susceptible isolate. Conclusion :Acquired resistance could be occurred when exposing to low level of some fluoroquinolones for long term.%目的:探讨大肠埃希菌在氟喹若酮类最低抑菌浓度(MIC)下耐药性的产生,以指导临床合理使用抗生素.方法:采用多步诱导法,对32株临床分离的氟喹诺酮类敏感大肠埃希菌分别进行环丙沙星、左氧氟沙星和加替沙星的诱导性耐药试验;用琼脂稀释法测定诱导前后敏感菌株的药物敏感性;用PCR方法测定耐药基因序列.结果:22株大肠埃希菌诱导出稳定的高耐氟喹诺酮菌株;与原株比较,耐药株的MIC分别增加了32~3 000倍;进行测序的6株诱导耐药菌株均发生gyrA的83Ser→Leu、87Asp→Ash和parc的80Ser→Ile突变,而测序的1株敏感菌株未发现基因突变.结论:在低浓度抗菌药物的长期压力下,可诱导大肠埃希菌产生对氟喹诺酮类的获得性耐药.

  16. Transgenic Cotton and Disease Resistance Genes

    Institute of Scientific and Technical Information of China (English)

    RAJASEKARAN; Kanniah

    2008-01-01

    Success in conventional breeding for resistance to mycotoxin-producing or other phytopathogenic fungi is dependent on the availability of resistance gene(s) in the germplasm.Even when it is available,breeding for disease-resistant crops is very time consuming,especially in perennial crops such as

  17. Fluoroquinolones in community-acquired pneumonia: guide to selection and appropriate use.

    Science.gov (United States)

    Frei, Christopher R; Labreche, Matthew J; Attridge, Russell T

    2011-04-16

    Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Over a relatively brief period of time, the respiratory fluoroquinolones have supplanted other first-line options as the predominant community-acquired pneumonia (CAP) therapy in hospitals. This article discusses the rise of the fluoroquinolone era, debates the comparative effectiveness of fluoroquinolones for CAP therapy, examines fluoroquinolone resistance and adverse drug reactions, and discusses new trends in pneumonia epidemiology and outcomes assessment. Overall, published data suggest that fluoroquinolone monotherapy is associated with improved patient survival compared with β-lactam monotherapy and similar survival to β-lactam plus macrolide combination therapy. Fluoroquinolone monotherapy may be associated with shorter hospital length of stay compared with β-lactam plus macrolide combination therapy, particularly in severe pneumonia or with high-dose therapy. There is insufficient evidence to conclude that any individual fluoroquinolone therapy is better than another with regards to patient mortality. Fluoroquinolones are generally well tolerated and Streptococcus pneumoniae resistance remains low; however, rare but serious adverse effects have been reported. Some members of the fluoroquinolone class have been removed from the market amidst safety concerns. Pneumonia classifications have changed and antipseudomonal fluoroquinolones may have a role in healthcare-associated pneumonia when administered in combination with other antipseudomonal and anti-methicillin-resistant Staphylococcus aureus therapies.

  18. Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

    Science.gov (United States)

    Thompson, Corinne N; Thieu, Nga Tran Vu; Vinh, Phat Voong; Duc, Anh Nguyen; Wolbers, Marcel; Vinh, Ha; Campbell, James I; Ngoc, Dung Tran Thi; Hoang, Nguyen Van Minh; Thanh, Tuyen Ha; The, Hao Chung; Nguyen, To Nguyen Thi; Lan, Nguyen Phu Huong; Parry, Christopher M; Chau, Nguyen Van Vinh; Thwaites, Guy; Thanh, Duy Pham; Baker, Stephen

    2016-03-01

    We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  19. Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India

    Directory of Open Access Journals (Sweden)

    Johan eBengtsson-Palme

    2014-12-01

    Full Text Available There is increasing evidence for an environmental origin of many antibiotic resistance genes. Consequently, it is important to identify environments of particular risk for selecting and maintaining such resistance factors. In this study, we described the diversity of antibiotic resistance genes in an Indian lake subjected to industrial pollution with fluoroquinolone antibiotics. We also assessed the genetic context of the identified resistance genes, to try to predict their genetic transferability. The lake harbored a wide range of resistance genes (81 identified gene types against essentially every major class of antibiotics, as well as genes responsible for mobilization of genetic material. Resistance genes were estimated to be 7000 times more abundant than in a Swedish lake included for comparison, where only eight resistance genes were found. The sul2 and qnrD genes were the most common resistance genes in the Indian lake. Twenty-six known and twenty-one putative novel plasmids were recovered in the Indian lake metagenome, which, together with the genes found, indicate a large potential for horizontal gene transfer through conjugation. Interestingly, the microbial community of the lake still included a wide range of taxa, suggesting that, across most phyla, bacteria has adapted relatively well to this highly polluted environment. Based on the wide range and high abundance of known resistance factors we have detected, it is plausible that yet unrecognized resistance genes are also present in the lake. Thus, we conclude that environments polluted with waste from antibiotic manufacturing could be important reservoirs for mobile antibiotic resistance genes.

  20. Molecular typing, antibiotic resistance, virulence gene and biofilm formation of different Salmonella enterica serotypes.

    Science.gov (United States)

    Turki, Yousra; Mehr, Ines; Ouzari, Hadda; Khessairi, Amel; Hassen, Abdennaceur

    2014-01-01

    Salmonella enterica isolates representing commonly isolated serotypes in Tunisia were analyzed using genotyping and phenotyping methods. ERIC and ITS-PCR applied to 48 Salmonella spp. isolates revealed the presence of 12 and 10 different profiles, respectively. The distribution of profiles among serotypes demonstrated the presence of strains showing an identical fingerprinting pattern. All Salmonella strains used in this study were positive for the sdiA gene. Three Salmonella isolates belonging to serotypes Anatum, Enteritidis and Amsterdam were negative for the invA gene. The spvC gene was detected in thirteen isolates belonging to serotypes Anatum, Typhimurium, Enteritidis, Gallinarum and Montevideo. Antibiotic resistance was frequent among the recovered Salmonella isolates belonging to serotypes Anatum, Typhimurium, Enteritidis, Zanzibar and Derby. The majority of these isolates exhibited resistance to at least two antibiotic families. Four multidrug-resistant isolates were recovered from food animals and poultry products. These isolates exhibited not only resistance to tetracycline, sulphonamides, and ampicillin, but also have shown resistance to fluoroquinolones. Common resistance to nalidixic acid, ciprofloxacin and ofloxacin in two S. Anatum and S. Zanzibar strains isolated from raw meat and poultry was also obtained. Furthermore, wastewater and human isolates exhibited frequent resistance to nalidixic acid and tetracycline. Of all isolates, 33.5% were able to form biofilm.

  1. Acquired antibiotic resistance genes: an overview.

    Directory of Open Access Journals (Sweden)

    Angela H.A.M. van Hoek

    2011-09-01

    Full Text Available In this review an overview is given on antibiotic resistance mechanisms with special attentions to the antibiotic resistance genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is paid to mobile genetic elements such as plasmids, transposons and integrons, which are associated with antibiotic resistance genes, and involved in the dispersal of antimicrobial determinants between different bacteria.

  2. Acquired antibiotic resistance genes: an overview.

    OpenAIRE

    Hoek, Angela H.A.M. van; Dik eMevius; Beatriz eGuerra; Peter eMullany; Adam Paul Roberts; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance mechanisms with special attentions to the antibiotic resistance genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is paid to mobile genetic elements such as plasmids, transposons and integrons, which are associated with antibiotic resistance genes, and involved in the dispersal of anti...

  3. Epidemiology and characteristics of Escherichia coli sequence type 131 (ST131) from long-term care facility residents colonized intestinally with fluoroquinolone-resistant Escherichia coli.

    Science.gov (United States)

    Han, Jennifer H; Garrigan, Charles; Johnston, Brian; Nachamkin, Irving; Clabots, Connie; Bilker, Warren B; Santana, Evelyn; Tolomeo, Pam; Maslow, Joel; Myers, Janice; Carson, Lesley; Lautenbach, Ebbing; Johnson, James R

    2017-03-01

    The objective of this study was to evaluate molecular and epidemiologic factors associated with Escherichia coli sequence type 131 (ST131) among long-term care facility (LTCF) residents who acquired gastrointestinal tract colonization with fluoroquinolone-resistant E. coli (FQREC). Colonizing isolates from 37 residents who newly developed FQREC colonization at three LTCFs from 2006 to 2008 were evaluated. Twenty-nine (78%) of 37 total FQREC colonizing isolates were ST131. Most ST131 isolates had a distinctive combination of gyrA and parC replacement mutations. The ST131 and non-ST131 isolates differed significantly for the prevalence of many individual virulence factors but not for the proportion that qualified molecularly as extraintestinal pathogenic E. coli (ExPEC) or aggregate virulence factor scores. E. coli ST131 was highly prevalent among LTCF residents with FQREC colonization. Future studies should determine the risk factors for infection among ST131-colonized residents, and assess the potential for increased transmissibility of ST131 in the long-term care setting.

  4. [Pharmacodynamic and pharmacokinetic evaluation of respiratory fluoroquinolones. Guideline to selection of the most appropriate fluoroquinolone].

    Science.gov (United States)

    Parra-Ruiz, Jorge; Hernández-Quero, José

    2012-12-01

    Since its approval, fluoroquinolones have become one of the most prescribed antibacterial agents. Because of its widespread use, serious concerns about the emergence of resistance in Streptococcus pneumoniae, Pseudomonas spp, and entrobacteriaceae, has arisen, especially because of cross-resistance between fluoroquinolones. Huge efforts has been done to identify pharmacokinetic (PK) parameters like maximum serum concentration (Cmax), area under the curve of serum concentrations (AUC) and pharmacodynamic (PD) parameters like the minimum inhibitory concentration (MIC) or the mutant prevention concentration (MPC), to optimize the use of the new fluoroquinolones, especially against these difficult to treat microorganisms. The new fluoroquinolones commercially available in Spain, levofloxacin and moxifloxacin, have significant differences in their PK (Cmax, half-life, volume of distribution, etc), PD (MIC, MPC,) and in their PK/PD parameters (AUC/MIC; AUC/MPC) that allow clinicians to establish clear preference for the utilization of one of them. Proper use of these new fluoroquinolones according to these PK/PD parameters will result in better management of respiratory infections with a reduction in the emergence of resistance. Based on data reviewed in this paper moxifloxacin use, with best PK/PD characteristics, should be preferred over levofloxacin. Should levofloxacin be used, alternative dosing strategies would be recommended to avoid selection of resistant variants.

  5. Overexpression of the novel MATE fluoroquinolone efflux pump FepA in Listeria monocytogenes is driven by inactivation of its local repressor FepR.

    Directory of Open Access Journals (Sweden)

    François Guérin

    Full Text Available Whereas fluoroquinolone resistance mainly results from target modifications in gram-positive bacteria, it is primarily due to active efflux in Listeria monocytogenes. The aim of this study was to dissect a novel molecular mechanism of fluoroquinolone resistance in this important human pathogen. Isogenic L. monocytogenes clinical isolates BM4715 and BM4716, respectively susceptible and resistant to fluoroquinolones, were studied. MICs of norfloxacin and ciprofloxacin were determined in the presence or in the absence of reserpine (10 mg/L. Strain BM4715 was susceptible to norfloxacin (MIC, 4 mg/L and ciprofloxacin (MIC, 0.5 mg/L whereas BM4716 was highly resistant to both drugs (MICs 128 and 32 mg/L, respectively. Reserpine was responsible for a 16-fold decrease in both norfloxacin and ciprofloxacin MICs against BM4716 suggesting efflux associated resistance. Whole-genome sequencing of the strains followed by comparative genomic analysis revealed a single point mutation in the gene for a transcriptional regulator, designated fepR (for fluoroquinolone efflux protein regulator belonging to the TetR family. The frame-shift mutation was responsible for the introduction of a premature stop codon resulting in an inactive truncated protein. Just downstream from fepR, the structural gene for an efflux pump of the MATE family (named FepA was identified. Gene expression was quantified by qRT-PCR and demonstrated that fepA expression was more than 64-fold higher in BM4716 than in BM4715. The clean deletion of the fepR gene from BM4715 was responsible for an overexpression of fepA with resistance to norfloxacin and ciprofloxacin, confirming the role of FepR as a local repressor of fepA. In conclusion, we demonstrated that overexpression of the new MATE efflux pump FepA is responsible for fluoroquinolone resistance in L. monocytogenes and secondary to inactivation of the FepR repressor.

  6. PCR-restriction fragment length polymorphism assay for detection of gyrA mutations associated with fluoroquinolone resistance in Campylobacter coli.

    Science.gov (United States)

    Alonso, Rodrigo; Mateo, Estibaliz; Girbau, Cecilia; Churruca, Estibaliz; Martinez, Irati; Fernández-Astorga, Aurora

    2004-12-01

    A fragment of the gyrA gene was sequenced from 34 isolates of Campylobacter coli, including 23 isolates resistant to ciprofloxacin. All ciprofloxacin-resistant isolates examined by DNA sequencing carried a point mutation at position Thr-86 on the gyrA gene product, involving the replacement of Thr-86 by Ile. A combined PCR-restriction fragment length polymorphism technique using RsaI was developed to detect this mutation.

  7. Gene flow from glyphosate-resistant crops.

    Science.gov (United States)

    Mallory-Smith, Carol; Zapiola, Maria

    2008-04-01

    Gene flow from transgenic glyphosate-resistant crops can result in the adventitious presence of the transgene, which may negatively impact markets. Gene flow can also produce glyphosate-resistant plants that may interfere with weed management systems. The objective of this article is to review the gene flow literature as it pertains to glyphosate-resistant crops. Gene flow is a natural phenomenon not unique to transgenic crops and can occur via pollen, seed and, in some cases, vegetative propagules. Gene flow via pollen can occur in all crops, even those that are considered to be self-pollinated, because all have low levels of outcrossing. Gene flow via seed or vegetative propagules occurs when they are moved naturally or by humans during crop production and commercialization. There are many factors that influence gene flow; therefore, it is difficult to prevent or predict. Gene flow via pollen and seed from glyphosate-resistant canola and creeping bentgrass fields has been documented. The adventitious presence of the transgene responsible for glyphosate resistance has been found in commercial seed lots of canola, corn and soybeans. In general, the glyphosate-resistant trait is not considered to provide an ecological advantage. However, regulators should consider the examples of gene flow from glyphosate-resistant crops when formulating rules for the release of crops with traits that could negatively impact the environment or human health.

  8. Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis.

    Science.gov (United States)

    Blower, Tim R; Williamson, Benjamin H; Kerns, Robert J; Berger, James M

    2016-02-16

    Mycobacterium tuberculosis (Mtb) infects one-third of the world's population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-Å resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone-gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone-enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance.

  9. Transgenic Cotton and Disease Resistance Genes

    Institute of Scientific and Technical Information of China (English)

    RAJASEKARAN Kanniah

    2008-01-01

    @@ Success in conventional breeding for resistance to mycotoxin-producing or other phytopathogenic fungi is dependent on the availability of resistance gene(s) in the germplasm.Even when it is available,breeding for disease-resistant crops is very time consuming,especially in perennial crops such as tree nut crops,and does not lend itself ready to combat the evolution of new virulent fungal races.

  10. Correlation Analysis of Fluoroquinolone Antibacterial Use and Resistance Rate of Common Bacteria%氟喹诺酮类抗菌药使用频度与常见细菌耐药率的相关研究

    Institute of Scientific and Technical Information of China (English)

    叶云

    2015-01-01

    Objective To statistically analyze utilization of fluoroquinolone antibiotic drugs and resistance rate of bacteria in a hospital from 2011 to 2013, and study the relationship between them, so as to reduce bacterial resistance and provide references for clinical rational use of antibacterial drugs. Methods Retrospective investigation method was used to statistically analyze the pathogenic bacteria culture results, antibacterial cumulative frequency and results of drug resistance test. SPSS 17.0 software was used to analyze Pearson correlation coefficient of the resistant rates of bacteria and antibacterial consumption. Results The frequency of fluoroquinolone antibacterial drug use decreased from 29 237.90 DDDs in 2009 to 11 296.65 DDDs in 2013, cumulatively declined by 61.36%. In addition to the fluoroquinolone use and Staphylococcus haemolyticus (r=-0.68) and Enterococcus faecium (r=-0.86) resistance rate were negatively correlated, positive correlation has been found with the common bacteria resistance rate, there is a significant positive correlation with E. coli (r=0.95), Enterobacter cloacae (r=0.88) and Enterococcus faecalis (R=0.95). Conclusion The frequency of fluoroquinolone antibacterial drug use showed a declining trend in a hospital. In addition to Staphylococcus haemolyticus and Enterococcus faecium, drug use of fluoroquinolones and common pathogenic bacteria was positively correlated, the frequency of fluoroquinolone antibacterial drug use may be a main factor to increase certain bacteria resistance rate.%目的:统计分析某三甲医院2009~2013年氟喹诺酮类抗菌药使用情况及细菌耐药率,并分析两者之间的相关性,为降低细菌耐药性和合理使用抗菌药提供参考依据。方法采用回顾性调查方法对2009~2013年送检病原菌培养结果、同期抗菌药物累计使用频度和细菌耐药率情况进行统计分析,并利用SPSS 17.0软件统计细菌耐药率和抗菌药物消耗量之间

  11. The global establishment of a highly-fluoroquinolone resistant Salmonella enterica serotype Kentucky ST198 strain

    DEFF Research Database (Denmark)

    Le Hello, Simon; Bekhit, Amany; Granier, Sophie A.

    2013-01-01

    While the spread of Salmonella enterica serotype Kentucky resistant to ciprofloxacin across Africa and the Middle-East has been described recently, the presence of this strain in humans, food, various animal species (livestock, pets, and wildlife) and in environment is suspected in other countrie...

  12. RNA expression analysis of efflux pump genes in clinical isolates of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis in South Korea.

    Science.gov (United States)

    Oh, Tae Sang; Kim, Young Jin; Kang, Hee Yoon; Kim, Chang-Ki; Cho, Sun Young; Lee, Hee Joo

    2017-04-01

    Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is an important communicable disease. Various mechanisms of resistance to antituberculosis drugs have been reported; these are principally mutations in target genes. However, not all M. tuberculosis resistance can be explained by mutations in such genes. Other resistance mechanisms associated with drug transport, such as efflux pumps, have also been reported. In this study, we investigated the expression levels of three putative efflux pumps and mutations in target genes associated with injectable agents and fluoroquinolones with clinical MDR and XDR-TB isolates. Thirty clinical isolates of M. tuberculosis that had been phenotypically characterized were obtained from the Korean Institute of Tuberculosis. Of these, 14 were MDR-TB isolates resistant to at least one injectable aminoglycoside (amikacin; AMK, kanamycin; KAN, and/or capreomycin; CPM) and 16 were XDR-TB isolates. M. tuberculosis H37Rv (ATCC 27249) was used as a reference strain. Five putative genes (Rv1258c, Rv2686c, Rv2687c, Rv2688c and pstB) were selected for analysis in this study. Sequencing was performed to detect mutations in rrs and eis genes. qRT-PCR was performed to investigate expression levels of five efflux pump genes. Of the 30 isolates, 25 strains had mutations in rrs associated with resistance to KAN, CPM and AMK and two strains had eis mutations, as well as mutations in rrs. pstB (Rv0933) exhibited increased expression and Rv2687c and Rv2688c exhibited decreased expression compared to the reference strain. Increased expression of pstB in clinical drug-resistant tuberculosis isolates may contribute to drug resistance in M. tuberculosis. In our case, overexpression of Rv1258c may have been associated with resistance to kanamycin. No correlation was evident between Rv2686c, Rv2687c or Rv2688c expression and fluoroquinolone resistance. To explore the details of efflux pump drug-resistance mechanisms, further studies on

  13. Fluoroquinolone susceptibilities to methicillin-resistant and susceptible coagulase-negative Staphylococcus isolated from eye infection Suscetibilidade dos Staphylococcus coagulase negativo meticilina-resistentes e suscetíveis isolados em infecções oculares

    Directory of Open Access Journals (Sweden)

    Adália Dias Dourado Oliveira

    2007-03-01

    Full Text Available PURPOSE: To evaluate the fluoroquinolone susceptibilities of ocular isolate coagulase-negative staphylococci (CoNS, identified at the Microbiology Laboratory - UNIFESP. DESIGN: Experimental laboratory investigation. METHODS: The minimum inhibitory concentrations (MICs of 21 strains of methicillin-resistant coagulase-negative staphylococci (MRCoNS and 22 methicillin-sensitive coagulase-negative staphylococci (MSCoNS to ciprofloxacin, ofloxacin, gatifloxacin and moxifloxacin were determined, using the E-test method standardized by the Clinical and Laboratory Standards Institute (CLSI/NCCLS. RESULTS: The MIC90s (µg/ml for the second generation of tested fluoroquinolones were higher than the fourth generation, especially for the methicillin-resistant coagulase-negative staphylococci group. CONCLUSION: Our results indicate that methicillin-sensitive coagulase-negative staphylococci are more susceptible to quinolones than are methicillin-resistant coagulase-negative staphylococci and that fourth generation fluoroquinolones appear to be more potent, affecting even coagulase-negative staphylococcal strains resistant to second generation fluoroquinolones.OBJETIVOS: Avaliar a suscetibilidade a fluorquinolonas dos Staphylococcus coagulase-negativo (SCoN identificados no Laboratório de Microbiologia Ocular da Unifesp. MÉTODOS: Foi determinada a concentração inibitória mínima de 21 cepas de SCoN meticilina-resistentes e 22 meticilina-sensíveis para ciprofloxacina, ofloxacina, gatifloxacina e moxifloxacina, utilizando o E-test estandartizado pelo CLSI/NCCLS. RESULTADOS: Os MIC90 (µg/ml de 43 SCoN isolados para fluorquinolonas de segunda geração foram maiores do que os de quarta geração, principalmente para o grupo dos meticilina-resistentes. CONCLUSÃO: Nossos resultados indicam que Staphylococcus coagulase-negativo meticilina-sensíveis são mais suscetíveis às quinolonas do que os Staphylococcus coagulase-negativo meticilina

  14. Tagging Blast Resistance Gene Pi 1 in Rice (Oryza sativa) Using Candidate Resistance Genes

    Institute of Scientific and Technical Information of China (English)

    LI Ai-hong; WU Jian-li; XU Xin-ping; Menchu BERNADO; DAI Zheng-yuan; ZHUANG Jie-yun; CHEN Zong-xiang; ZHENG Kang-le; LI Bao-jian; Hei LEUNG; ZHANG Hong-xi; PAN Xue-biao

    2004-01-01

    An F3 population derived from C101LAC/CO39 containing 90 lines was analyzed for blast resistance with 48 candidate genes developed from resistance gene analogs (RGA) and suppression subtractive library. Genetic analysis confirmed that blast resistance of the population was controlled by a single gene Pi 1. One of the candidate genes, R10 was identified as associated with the blast resistance gene on the long arm of chromosome 11 and mapped using a DH population derived from Azucena/IR64.A pair of PCR based primers was designed based on the sequence of R10 for marker-aided selection of the blast resistance gene.The recombination frequency between Pi 1 and the marker was estimated as 1.28%. It suggested that strategy of employing candidate genes is useful for gene identification and mapping. A new RFLP marker and the corresponding PCR marker for tagging of Pi 1 were provided.

  15. Disease Resistance Gene Analogs (RGAs in Plants

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Sekhwal

    2015-08-01

    Full Text Available Plants have developed effective mechanisms to recognize and respond to infections caused by pathogens. Plant resistance gene analogs (RGAs, as resistance (R gene candidates, have conserved domains and motifs that play specific roles in pathogens’ resistance. Well-known RGAs are nucleotide binding site leucine rich repeats, receptor like kinases, and receptor like proteins. Others include pentatricopeptide repeats and apoplastic peroxidases. RGAs can be detected using bioinformatics tools based on their conserved structural features. Thousands of RGAs have been identified from sequenced plant genomes. High-density genome-wide RGA genetic maps are useful for designing diagnostic markers and identifying quantitative trait loci (QTL or markers associated with plant disease resistance. This review focuses on recent advances in structures and mechanisms of RGAs, and their identification from sequenced genomes using bioinformatics tools. Applications in enhancing fine mapping and cloning of plant disease resistance genes are also discussed.

  16. Disease Resistance Gene Analogs (RGAs) in Plants.

    Science.gov (United States)

    Sekhwal, Manoj Kumar; Li, Pingchuan; Lam, Irene; Wang, Xiue; Cloutier, Sylvie; You, Frank M

    2015-08-14

    Plants have developed effective mechanisms to recognize and respond to infections caused by pathogens. Plant resistance gene analogs (RGAs), as resistance (R) gene candidates, have conserved domains and motifs that play specific roles in pathogens' resistance. Well-known RGAs are nucleotide binding site leucine rich repeats, receptor like kinases, and receptor like proteins. Others include pentatricopeptide repeats and apoplastic peroxidases. RGAs can be detected using bioinformatics tools based on their conserved structural features. Thousands of RGAs have been identified from sequenced plant genomes. High-density genome-wide RGA genetic maps are useful for designing diagnostic markers and identifying quantitative trait loci (QTL) or markers associated with plant disease resistance. This review focuses on recent advances in structures and mechanisms of RGAs, and their identification from sequenced genomes using bioinformatics tools. Applications in enhancing fine mapping and cloning of plant disease resistance genes are also discussed.

  17. Mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis%结核分枝杆菌耐氟喹诺酮类药物的分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    张玉娇; 李晓静; 米凯霞

    2016-01-01

    Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world’s deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.%结核病是由结核分枝杆菌(Mycobacterium tuberculosis)通过空气传播引起人类感染的慢性传染病,耐药结核分枝杆菌的流行是目前结核病防治的世界难题。氟喹诺酮类药物是人工合成药物,应用于耐药结核的临床治疗中,在治疗中起着核心的作用。但近年来,氟喹诺酮类药物的抗性菌株不断出现,愈发增加了结核病治疗的困难与治疗失败风险。在临床中氟喹诺酮药物的靶点比较清楚,是结核分枝杆菌的DNA旋转酶。目前发现结核分枝杆菌耐氟喹诺酮类药物的机制主要包括药物靶点DNA旋转酶的关键氨基酸改变、

  18. Acquired Antibiotic Resistance Genes: An Overview

    OpenAIRE

    Hoek, Angela H.A.M. van; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants betw...

  19. Identification of acquired antimicrobial resistance genes

    DEFF Research Database (Denmark)

    Zankari, Ea; Hasman, Henrik; Cosentino, Salvatore

    2012-01-01

    ObjectivesIdentification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic laborato......ObjectivesIdentification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic...... laboratories and is anticipated to substitute traditional methods for resistance gene identification. Thus, the current challenge is to extract the relevant information from the large amount of generated data.MethodsWe developed a web-based method, ResFinder that uses BLAST for identification of acquired...... antimicrobial resistance genes in whole-genome data. As input, the method can use both pre-assembled, complete or partial genomes, and short sequence reads from four different sequencing platforms. The method was evaluated on 1862 GenBank files containing 1411 different resistance genes, as well as on 23 de...

  20. Acquired antibiotic resistance genes:an overview

    NARCIS (Netherlands)

    Hoek, A.H. van; Mevius, D.; Guerra, B.; Mullany, P.; Robberts, A.P.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance,

  1. Acquired antibiotic resistance genes: an overview

    NARCIS (Netherlands)

    Hoek, van A.H.; Mevius, D.J.; Guerra, B.; Mullany, P.; Roberts, A.P.; Aarts, H.J.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance,

  2. Acquired antibiotic resistance genes:an overview

    NARCIS (Netherlands)

    Hoek, A.H. van; Mevius, D.; Guerra, B.; Mullany, P.; Robberts, A.P.

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance,

  3. Acquired antibiotic resistance genes: an overview

    NARCIS (Netherlands)

    Hoek, van A.H.; Mevius, D.J.; Guerra, B.; Mullany, P.; Roberts, A.P.; Aarts, H.J.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance,

  4. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients.

    Science.gov (United States)

    Werner, Nicole L; Hecker, Michelle T; Sethi, Ajay K; Donskey, Curtis J

    2011-07-05

    Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for Clostridium difficile infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use. We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy. Of 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens). In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for management of urinary syndromes could

  5. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients

    Science.gov (United States)

    2011-01-01

    Background Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for Clostridium difficile infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use. Methods We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy. Results Of 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens). Conclusions In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for

  6. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients

    Directory of Open Access Journals (Sweden)

    Donskey Curtis J

    2011-07-01

    Full Text Available Abstract Background Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for Clostridium difficile infection (CDI. In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use. Methods We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy. Results Of 1,773 days of fluoroquinolone therapy, 690 (39% were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy and administration of antimicrobials for longer than necessary durations (234 days-of-therapy. The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy. Twenty-seven percent (60/227 of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens, colonization by resistant pathogens (8% of regimens, and CDI (4% of regimens. Conclusions In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial

  7. Detection and characterization of antibiotic-resistance genes in Arcanobacterium pyogenes strains from abscesses of forest musk deer.

    Science.gov (United States)

    Zhao, Ke-Lei; Liu, Yang; Zhang, Xiu-Yue; Palahati, Paha'erding; Wang, Hong-Ning; Yue, Bi-Song

    2011-12-01

    Arcanobacterium pyogenes is commonly isolated from ruminant animals as an opportunistic pathogen that co-infects with other bacteria, normally causing surface or internal abscesses. Twenty-eight strains of A. pyogenes isolated from forest musk deer suppurative samples were identified by their 16S rRNA gene sequences, and confirmed by amplification of the pyolysin-encoding gene (plo) in all isolates. The MICs of 14 commonly used antibiotics were determined by an agar dilution method. Class 1 and 2 intI genes were amplified to determine whether integrons were present in the A. pyogenes genome. Class 1 gene cassettes were detected by specific primers and analysed by sequencing. All of the strains were susceptible to most fluoroquinolone antibiotics; however, high resistance rates were observed for β-lactams and trimethoprim. A total of 18 of the isolates (64.3%) were positive for the class 1 intI gene, and 16 (57.1%) contained class 1 gene cassettes with the aacC, aadA1, aadA2, blaP1 and dfr2a genes. Most were present in the multi-resistant isolates, indicating a general concordance between the presence of gene cassettes and antibiotic resistance, and that the integrons have played an important role in the dissemination of antimicrobial resistance in this species.

  8. Antibiotics, Antibiotic Resistance Genes, and Bacterial Community Composition in Fresh Water Aquaculture Environment in China.

    Science.gov (United States)

    Xiong, Wenguang; Sun, Yongxue; Zhang, Tong; Ding, Xueyao; Li, Yafei; Wang, Mianzhi; Zeng, Zhenling

    2015-08-01

    Environmental antibiotic resistance has drawn increasing attention due to its great threat to human health. In this study, we investigated concentrations of antibiotics (tetracyclines, sulfonamides and (fluoro)quinolones) and abundances of antibiotic resistance genes (ARGs), including tetracycline resistance genes, sulfonamide resistance genes, and plasmid-mediated quinolone resistance genes, and analyzed bacterial community composition in aquaculture environment in Guangdong, China. The concentrations of sulfametoxydiazine, sulfamethazine, sulfamethoxazole, oxytetracycline, chlorotetracycline, doxycycline, ciprofloxacin, norfloxacin, and enrofloxacin were as high as 446 μg kg(-1) and 98.6 ng L(-1) in sediment and water samples, respectively. The relative abundances (ARG copies/16S ribosomal RNA (rRNA) gene copies) of ARGs (sul1, sul2, sul3, tetM, tetO, tetW, tetS, tetQ, tetX, tetB/P, qepA, oqxA, oqxB, aac(6')-Ib, and qnrS) were as high as 2.8 × 10(-2). The dominant phyla were Proteobacteria, Bacteroidetes, and Firmicutes in sediment samples and Proteobacteria, Actinobacteria and Bacteroidetes in water samples. The genera associated with pathogens were also observed, such as Acinetobacter, Arcobacter, and Clostridium. This study comprehensively investigated antibiotics, ARGs, and bacterial community composition in aquaculture environment in China. The results indicated that fish ponds are reservoirs of ARGs and the presence of potential resistant and pathogen-associated taxonomic groups in fish ponds might imply the potential risk to human health.

  9. Exploring Antibiotic Resistance Genes and Metal Resistance Genes in Plasmid Metagenomes from Wastewater Treatment Plants

    Directory of Open Access Journals (Sweden)

    An-Dong eLi

    2015-09-01

    Full Text Available Plasmids operate as independent genetic elements in microorganism communities. Through horizontal gene transfer, they can provide their host microorganisms with important functions such as antibiotic resistance and heavy metal resistance. In this study, six metagenomic libraries were constructed with plasmid DNA extracted from influent, activated sludge and digested sludge of two wastewater treatment plants. Compared with the metagenomes of the total DNA extracted from the same sectors of the wastewater treatment plant, the plasmid metagenomes had significantly higher annotation rates, indicating that the functional genes on plasmids are commonly shared by those studied microorganisms. Meanwhile, the plasmid metagenomes also encoded many more genes related to defense mechanisms, including ARGs. Searching against an antibiotic resistance genes (ARGs database and a metal resistance genes (MRGs database revealed a broad-spectrum of antibiotic (323 out of a total 618 subtypes and metal resistance genes (23 out of a total 23 types on these plasmid metagenomes. The influent plasmid metagenomes contained many more resistance genes (both ARGs and MRGs than the activated sludge and the digested sludge metagenomes. Sixteen novel plasmids with a complete circular structure that carried these resistance genes were assembled from the plasmid metagenomes. The results of this study demonstrated that the plasmids in wastewater treatment plants could be important reservoirs for resistance genes, and may play a significant role in the horizontal transfer of these genes.

  10. Occurrence of antibiotics and antibiotic resistance genes in hospital and urban wastewaters and their impact on the receiving river.

    Science.gov (United States)

    Rodriguez-Mozaz, Sara; Chamorro, Sara; Marti, Elisabet; Huerta, Belinda; Gros, Meritxell; Sànchez-Melsió, Alexandre; Borrego, Carles M; Barceló, Damià; Balcázar, Jose Luis

    2015-02-01

    Antibiotic resistance has become a major health concern; thus, there is a growing interest in exploring the occurrence of antibiotic resistance genes (ARGs) in the environment as well as the factors that contribute to their emergence. Aquatic ecosystems provide an ideal setting for the acquisition and spread of ARGs due to the continuous pollution by antimicrobial compounds derived from anthropogenic activities. We investigated, therefore, the pollution level of a broad range of antibiotics and ARGs released from hospital and urban wastewaters, their removal through a wastewater treatment plant (WWTP) and their presence in the receiving river. Several antimicrobial compounds were detected in all water samples collected. Among antibiotic families, fluoroquinolones were detected at the highest concentration, especially in hospital effluent samples. Although good removal efficiency by treatment processes was observed for several antimicrobial compounds, most antibiotics were still present in WWTP effluents. The results also revealed that copy numbers of ARGs, such as blaTEM (resistance to β-lactams), qnrS (reduced susceptibility to fluoroquinolones), ermB (resistance to macrolides), sulI (resistance to sulfonamides) and tetW (resistance to tetracyclines), were detected at the highest concentrations in hospital effluent and WWTP influent samples. Although there was a significant reduction in copy numbers of these ARGs in WWTP effluent samples, this reduction was not uniform across analyzed ARGs. Relative concentration of ermB and tetW genes decreased as a result of wastewater treatment, whereas increased in the case of blaTEM, sulI and qnrS genes. The incomplete removal of antibiotics and ARGs in WWTP severely affected the receiving river, where both types of emerging pollutants were found at higher concentration in downstream waters than in samples collected upstream from the discharge point. Taken together, our findings demonstrate a widespread occurrence of

  11. Resistance Genes in Global Crop Breeding Networks.

    Science.gov (United States)

    Garrett, K A; Andersen, K F; Asche, F; Bowden, R L; Forbes, G A; Kulakow, P A; Zhou, B

    2017-08-31

    Resistance genes are a major tool for managing crop diseases. The networks of crop breeders who exchange resistance genes and deploy them in varieties help to determine the global landscape of resistance and epidemics, an important system for maintaining food security. These networks function as a complex adaptive system, with associated strengths and vulnerabilities, and implications for policies to support resistance gene deployment strategies. Extensions of epidemic network analysis can be used to evaluate the multilayer agricultural networks that support and influence crop breeding networks. Here, we evaluate the general structure of crop breeding networks for cassava, potato, rice, and wheat. All four are clustered due to phytosanitary and intellectual property regulations, and linked through CGIAR hubs. Cassava networks primarily include public breeding groups, whereas others are more mixed. These systems must adapt to global change in climate and land use, the emergence of new diseases, and disruptive breeding technologies. Research priorities to support policy include how best to maintain both diversity and redundancy in the roles played by individual crop breeding groups (public versus private and global versus local), and how best to manage connectivity to optimize resistance gene deployment while avoiding risks to the useful life of resistance genes. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

  12. Fluoroquinolone antibiotics and type 2 diabetes mellitus.

    Science.gov (United States)

    Telfer, Stephen J

    2014-09-01

    Exposure to fluoroquinolone antibiotics is postulated as a risk factor for subsequent development of type 2 diabetes. It is hypothesized that fluoroquinolones induce an intracellular magnesium deficit that can lead to insulin resistance. A temporal correlation is reported between the rate of outpatient prescription of quinolones and the incidence of diabetes during the period 1980-2011 with a lag of approximately two years (R(2)=0.86, Pfluoroquinolone prescription rates. A geographical correlation is reported (adj. R(2)=0.7, Pfluoroquinolone prescription, local rates of increase in the prevalence of obesity, and local rates of population growth as predictor variables. Prescription rates of non-quinolone antibiotics correlated less well with the local rates of increase in prevalence of diabetes. The data are consistent with fluoroquinolone exposure predisposing an individual to develop diabetes with a probability that strongly depends upon factors that also lead to an increase in obesity. According to the hypothesis, much of the increase in the incidence of type 2 diabetes in the U.S. from 1990 to the present can be attributed to fluoroquinolone exposure. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  13. [Fluoroquinolones. Drug interactions].

    Science.gov (United States)

    Rusu, G; Dănilă, G

    2000-01-01

    This review summarizes clinically relevant drug-drug interactions for fluoroquinolones: antiacids containing aluminum and magnesium salts, iron or zinc preparations, sucralfate, cimetidine, ranitidine, warfarina, cyclosporin, rifampin, oral contraceptive steroids, benzodiazepine, probenecid, beta-lactam antibiotics, nonsteroidal anti-inflammatory drugs, metronidazole, theophylline, caffeine.

  14. High prevalence and variability of CTX-M-15-producing and fluoroquinolone-resistant Escherichia coli observed in stray dogs in rural Angola.

    Science.gov (United States)

    Albrechtova, Katerina; Kubelova, Michaela; Mazancova, Jana; Dolejska, Monika; Literak, Ivan; Cizek, Alois

    2014-08-01

    Antimicrobial resistance (AMR) represents a serious problem globally, but it is especially pronounced in the tropics, where pressure of infectious diseases is high. We examined resistance in Escherichia coli colonizing gastrointestinal tracts of 17 dogs which have never received antimicrobial treatment, living in central rural Angola. Emphasis was placed on extended-spectrum beta-lactamases (ESBL) and plasmid-mediated quinolone resistance (PMQR). Resistance-carrying plasmids were characterized in size, group of incompatibility and ability to conjugate. Isolates were compared by their pulsed-field gel electrophoresis (PFGE) profiles. Detailed description of 19 E. coli isolates with either ESBL or PMQR genes carried on multiresistant plasmids of different groups of incompatibility indicates that dogs, despite never being treated by antibiotics, are important reservoirs and transmitters of AMR in the study area.

  15. Study of Antibiotic Resistance Pattern and Mutation in Genes gyrA and parC of Escherichia Coli Causing Urinary Tract Infection

    Directory of Open Access Journals (Sweden)

    J. Faghri

    2016-07-01

    Full Text Available Introduction & Objective: Fluoroquinolones are essential antimicrobial agents used to treat UTIs. Clinical experiences have shown a high rate of antibiotic resistance among uropatho-gens. These resistance are usually the consequence of mutations involving genes encoding gyrA and parC. The aim of this study was to determine antimicrobial resistance pattern and the presence of mutations in regions that code for quinolone resistance in the genes gyrA and parC in clinical isolates of E. coli from a hospital in Isfahan, Iran. Materials & Methods: A total of 135 isolates of E.coli (from urine were collected from Sep-tember to February 2013 from Alzahra Hospital (Isfahan, Iran. Bacterial susceptibility to an-timicrobial agents was determined using disk diffusion method. PCR was performed to detect genes gyrA and parC. Then, 13 isolates were randomly chosen for genetic characterization of the quinolone-determining region (QRDR of the parC and gyrA genes. Results: Among 135 E. coli isolates, 61 isolates ( 45 % were resistant to fluoroquinolones. From 13 isolates, 11 isolates showed two mutations (Ser83Leu/ Asp87Asn and 2 isolates showed a single mutation (Ser83Leu in gyrA gene. Also, five different mutations were de-tected in parC gene in the E. coli isolates, encoding Ser80Ile, Ser80Val, Ser80Arg, Glu84Val, Gly78Ser. Conclusion: More research on the molecular basis of FQ resistance is required to develop new therapeutic strategies for FQ-resistant E. coli. To overcome antibiotic resistance antibiotic therapy should be limited and based on the susceptibility patterns of microorganisms. (Sci J Hamadan Univ Med Sci 2016; 23 (2:118-125

  16. Exploring antibiotic resistance genes and metal resistance genes in plasmid metagenomes from wastewater treatment plants.

    Science.gov (United States)

    Li, An-Dong; Li, Li-Guan; Zhang, Tong

    2015-01-01

    Plasmids operate as independent genetic elements in microorganism communities. Through horizontal gene transfer (HGT), they can provide their host microorganisms with important functions such as antibiotic resistance and heavy metal resistance. In this study, six metagenomic libraries were constructed with plasmid DNA extracted from influent, activated sludge (AS) and digested sludge (DS) of two wastewater treatment plants (WWTPs). Compared with the metagenomes of the total DNA extracted from the same sectors of the wastewater treatment plant, the plasmid metagenomes had significantly higher annotation rates, indicating that the functional genes on plasmids are commonly shared by those studied microorganisms. Meanwhile, the plasmid metagenomes also encoded many more genes related to defense mechanisms, including ARGs. Searching against an antibiotic resistance genes (ARGs) database and a metal resistance genes (MRGs) database revealed a broad-spectrum of antibiotic (323 out of a total 618 subtypes) and MRGs (23 out of a total 23 types) on these plasmid metagenomes. The influent plasmid metagenomes contained many more resistance genes (both ARGs and MRGs) than the AS and the DS metagenomes. Sixteen novel plasmids with a complete circular structure that carried these resistance genes were assembled from the plasmid metagenomes. The results of this study demonstrated that the plasmids in WWTPs could be important reservoirs for resistance genes, and may play a significant role in the horizontal transfer of these genes.

  17. High prevalence of multidrug-tolerant bacteria and associated antimicrobial resistance genes isolated from ornamental fish and their carriage water.

    Directory of Open Access Journals (Sweden)

    David W Verner-Jeffreys

    Full Text Available BACKGROUND: Antimicrobials are used to directly control bacterial infections in pet (ornamental fish and are routinely added to the water these fish are shipped in to suppress the growth of potential pathogens during transport. METHODOLOGY/PRINCIPAL FINDINGS: To assess the potential effects of this sustained selection pressure, 127 Aeromonas spp. isolated from warm and cold water ornamental fish species were screened for tolerance to 34 antimicrobials. Representative isolates were also examined for the presence of 54 resistance genes by a combination of miniaturized microarray and conventional PCR. Forty-seven of 94 Aeromonas spp. isolates recovered from tropical ornamental fish and their carriage water were tolerant to > or =15 antibiotics, representing seven or more different classes of antimicrobial. The quinolone and fluoroquinolone resistance gene, qnrS2, was detected at high frequency (37% tested recent isolates were positive by PCR. Class 1 integrons, IncA/C broad host range plasmids and a range of other antibiotic resistance genes, including floR, bla(TEM-1, tet(A, tet(D, tet(E, qacE2, sul1, and a number of different dihydrofolate reductase and aminoglycoside transferase coding genes were also detected in carriage water samples and bacterial isolates. CONCLUSIONS: These data suggest that ornamental fish and their carriage water act as a reservoir for both multi-resistant bacteria and resistance genes.

  18. Salmonella enterica serotypes isolated from squabs reveal multidrug resistance and a distinct pathogenicity gene repertoire.

    Science.gov (United States)

    Osman, K M; Marouf, S H; Mehana, O A; AlAtfeehy, N

    2014-12-01

    The consumption of squab (young unfledged pigeons) as part of the cuisine of many countries, together with the observation that squabs are vectors of zoonotic agents, may make them a public health risk. This study was designed to determine the serotypes, distribution of 11 virulence genes (invA, avrA, ssaQ, mgtC, siiD, sopB, gipA, sodC1, sopE1, spvC, bcfC) and the antimicrobial resistance profiles of salmonellae recovered from squabs. Six isolates were identified from among 45 (13.3%) squabs sampled. Three serotypes were identified according to the Kauffmann-White serotyping scheme: Salmonella Typhimurium (4/6; 66.7%), S. Braenderup (1/6; 16.7%) and S. Lomita (1/6; 16.7%). Polymerase chain reaction analyses revealed the presence of invA, sopB and bcfC in all six isolates, whereas sopE1 and gipA were absent. All six isolates were resistant to lincomycin and streptomycin, but all were susceptible to ciprofloxacin, colistin sulphate and gentamicin. Among the S. Typhimurium isolates, seven resistance profiles were identified: penicillins,aminoglycosides,fluoroquinolones, lincosamides,phenicols, tetracyclines and sulphonamides; four resistance profiles were identified in the isolates of S. Braenderup and S. Lomita: aminoglycosides, fluoroquinolones, lincosamides and polymyxin. Thus, the distribution of resistance to the antibiotics was largely dependent on serotype identity. The presence of invA, avrA, ssaQ, mgtC, siiD, sopB and bcfC was associated with resistance to chloramphenicol; invA, sopB and bcfC with resistance to streptomycin and lincosamide; and invA and sodC1 with resistance to trimethoprim-sulfamethoxazole. The identification of serotypes S. Typhimurium, S. Braenderup and S. Lomita in the squab samples has important implications because these serotypes are significant causes of food poisoning and enteric fever in humans.

  19. Quinolone Resistance among Salmonella enterica from Cattle, Broilers and Swine in Denmark

    DEFF Research Database (Denmark)

    Wiuff, C.; Baggesen, Dorte Lau; Madsen, M.

    2000-01-01

    This study was conducted to determine the susceptibility to nalidixic acid and fluoroquinolones of Salmonella Dublin, S. Enteritidis, and S. Typhimurium isolates from cattle, broilers, and pigs over time in Denmark and to characterise the gyrA, gyrB, and parC genes in quinolone-resistant isolates......, and one from 1999 were resistant to nalidixic acid. All the nalidixic acid-resistant isolates had reduced susceptibility to fluoroquinolones. Sequence analysis of the gyrA gene in 37 nalidixic-resistant isolates identified two different base substitutions at codon serine-83 and two at aspartate-87...

  20. Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis

    Science.gov (United States)

    Williamson, Benjamin H.; Kerns, Robert J.; Berger, James M.

    2016-01-01

    Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-Å resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone–gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone–enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance. PMID:26792525

  1. Antibiotic resistance genes in the environment

    Directory of Open Access Journals (Sweden)

    Jianqiang Su

    2013-07-01

    Full Text Available Antibiotic resistance and its spread in bacteria are topics of great importance in global research. In this paper, we review recent progress in understanding sources, dissemination, distribution and discovery of novel antibiotics resistance genes (ARGs in the environment. Bacteria exhibiting intrinsic resistance and antibiotic resistant bacteria in feces from humans and animals are the major sources of ARGs occurring in the environment. A variety of novel ARGs have been discovered using functional metagenomics. Recently, the long-term overuse of antibotics in drug therapy and animal husbandry has led to an increase in diversity and abundance of ARGs, causing the environmental dissemination of ARGs in aquatic water, sewage treatmentplants, rivers, sediment and soil. Future research should focus on dissemination mechanisms of ARGs, the discovery of novel ARGs and their resistant mechanisms, and the establishment of environmental risk assessment systems for ARGs.

  2. Efficient Reduction of Antibacterial Activity and Cytotoxicity of Fluoroquinolones by Fungal-Mediated N-Oxidation.

    Science.gov (United States)

    Rusch, Marina; Spielmeyer, Astrid; Meißner, Jessica; Kietzmann, Manfred; Zorn, Holger; Hamscher, Gerd

    2017-04-19

    Extensive usage of fluoroquinolone antibiotics in livestock results in their occurrence in manure and subsequently in the environment. Fluoroquinolone residues may promote bacterial resistance and are toxic to plants and aquatic organisms. Moreover, fluoroquinolones may enter the food chain through plant uptake, if manure is applied as fertilizer. Thus, the presence of fluoroquinolones in the environment may pose a threat to human and ecological health. In this study, the biotransformation of enrofloxacin, marbofloxacin, and difloxacin by the fungus X. longipes (Xylaria) was investigated. The main metabolites were unequivocally identified as the respective N-oxides by mass spectrometry and nuclear magnetic resonance spectroscopy. Fungal-mediated N-oxidation of fluoroquinolones led to a 77-90% reduction of the initial antibacterial activity. In contrast to their respective parent compounds, N-oxides showed low cytotoxic potential and had a reduced impact on cell proliferation. Thus, biotransformation by X. longipes may represent an effective method for inactivating fluoroquinolones.

  3. Characterization of Antimicrobial Resistance Patterns and Detection of Virulence Genes in Campylobacter Isolates in Italy

    Science.gov (United States)

    Di Giannatale, Elisabetta; Di Serafino, Gabriella; Zilli, Katiuscia; Alessiani, Alessandra; Sacchini, Lorena; Garofolo, Giuliano; Aprea, Giuseppe; Marotta, Francesca

    2014-01-01

    Campylobacter has developed resistance to several antimicrobial agents over the years, including macrolides, quinolones and fluoroquinolones, becoming a significant public health hazard. A total of 145 strains derived from raw milk, chicken faeces, chicken carcasses, cattle faeces and human faeces collected from various Italian regions, were screened for antimicrobial susceptibility, molecular characterization (SmaI pulsed-field gel electrophoresis) and detection of virulence genes (sequencing and DNA microarray analysis). The prevalence of C. jejuni and C. coli was 62.75% and 37.24% respectively. Antimicrobial susceptibility revealed a high level of resistance for ciprofloxacin (62.76%), tetracycline (55.86%) and nalidixic acid (55.17%). Genotyping of Campylobacter isolates using PFGE revealed a total of 86 unique SmaI patterns. Virulence gene profiles were determined using a new microbial diagnostic microarray composed of 70-mer oligonucleotide probes targeting genes implicated in Campylobacter pathogenicity. Correspondence between PFGE and microarray clusters was observed. Comparisons of PFGE and virulence profiles reflected the high genetic diversity of the strains examined, leading us to speculate different degrees of pathogenicity inside Campylobacter populations. PMID:24556669

  4. Antibiotic resistance genes occurrence and bacterial community composition in the Liuxi River

    Directory of Open Access Journals (Sweden)

    Wenguang eXiong

    2014-12-01

    Full Text Available Antibiotic resistance genes (ARGs in the environment have paid great concern due to their health risk. We investigated antibiotics concentrations (tetracyclines, sulfonamides and fluoroquinolones, ARGs abundances (tetracycline, sulfonamide and plasmid-mediated quinolone resistance (PMQR genes, and bacterial community composition in sediment and water samples in the Liuxi River, China. Antibiotics concentrations were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry. ARGs abundances were quantified by a culture-independent method. Bacterial community composition was analyzed by metagenomic approach based on Ion Torrent Personal Genome Machine platform. Antibiotics concentrations were at the levels of 1.19 to 622 ug kg-1 in sediment samples and below the limit of detection to 127 ng L-1 in water samples. Relative abundances (ARGs copies/16S rRNA gene copies of detected ARGs were at the range of 10-5 to 10-2. The dominant phyla were Proteobacteria, Bacteroidetes and Verrucomicrobia in sediment samples, and were Proteobacteria, Actinobacteria and Bacteroidetes in water samples. The results indicated that the river environment was contaminated by antibiotics and may be as a reservoir of ARGs. This study provided quantitative data on antibiotics, ARGs and bacterial community composition in the Liuxi River, a geographical location different from the reported studies.

  5. Characterization of Antimicrobial Resistance Patterns and Detection of Virulence Genes in Campylobacter Isolates in Italy

    Directory of Open Access Journals (Sweden)

    Elisabetta Di Giannatale

    2014-02-01

    Full Text Available Campylobacter has developed resistance to several antimicrobial agents over the years, including macrolides, quinolones and fluoroquinolones, becoming a significant public health hazard. A total of 145 strains derived from raw milk, chicken faeces, chicken carcasses, cattle faeces and human faeces collected from various Italian regions, were screened for antimicrobial susceptibility, molecular characterization (SmaI pulsed-field gel electrophoresis and detection of virulence genes (sequencing and DNA microarray analysis. The prevalence of C. jejuni and C. coli was 62.75% and 37.24% respectively. Antimicrobial susceptibility revealed a high level of resistance for ciprofloxacin (62.76%, tetracycline (55.86% and nalidixic acid (55.17%. Genotyping of Campylobacter isolates using PFGE revealed a total of 86 unique SmaI patterns. Virulence gene profiles were determined using a new microbial diagnostic microarray composed of 70-mer oligonucleotide probes targeting genes implicated in Campylobacter pathogenicity. Correspondence between PFGE and microarray clusters was observed. Comparisons of PFGE and virulence profiles reflected the high genetic diversity of the strains examined, leading us to speculate different degrees of pathogenicity inside Campylobacter populations.

  6. The fluoroquinolone levofloxacin triggers the transcriptional activation of iron transport genes that contribute to cell death in Streptococcus pneumoniae.

    Science.gov (United States)

    Ferrándiz, María-José; de la Campa, Adela G

    2014-01-01

    We studied the transcriptomic response of Streptococcus pneumoniae to levofloxacin (LVX) under conditions inhibiting topoisomerase IV but not gyrase. Although a complex transcriptomic response was observed, the most outstanding result was the upregulation of the genes of the fatDCEB operon, involved in iron (Fe(2+) and Fe(3+)) uptake, which were the only genes varying under every condition tested. Although the inhibition of topoisomerase IV by levofloxacin did not have a detectable effect in the level of global supercoiling, increases in general supercoiling and fatD transcription were observed after topoisomerase I inhibition, while the opposite was observed after gyrase inhibition with novobiocin. Since fatDCEB is located in a topological chromosomal domain downregulated by DNA relaxation, we studied the transcription of a copy of the 422-bp (including the Pfat promoter) region located upstream of fatDCEB fused to the cat reporter inserted into the chromosome 106 kb away from its native position: PfatfatD was upregulated in the presence of LVX in its native location, whereas no change was observed in the Pfatcat construction. Results suggest that topological changes are indeed involved in PfatfatDCE transcription. Upregulation of fatDCEB would lead to an increase of intracellular iron and, in turn, to the activation of the Fenton reaction and the increase of reactive oxygen species. In accordance, we observed an attenuation of levofloxacin lethality in iron-deficient media and in a strain lacking the gene coding for SpxB, the main source of hydrogen peroxide. In addition, we observed an increase of reactive oxygen species that contributed to levofloxacin lethality.

  7. High Resolution Melting Analysis for Rapid Mutation Screening in Gyrase and Topoisomerase IV Genes in Quinolone-Resistant Salmonella enterica

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    Soo Tein Ngoi

    2014-01-01

    Full Text Available The increased Salmonella resistance to quinolones and fluoroquinolones is a public health concern in the Southeast Asian region. The objective of this study is to develop a high resolution melt curve (HRM assay to rapidly screen for mutations in quinolone-resistant determining region (QRDR of gyrase and topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations were detected in QRDR of gyrA (n=52; S83F, S83Y, S83I, D87G, D87Y, and D87N and parE (n=1; M438I. Salmonella strains with mutations within QRDR of gyrA are generally more resistant to nalidixic acid (MIC 16>256 μg/mL. Mutations were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay, mutants can be distinguished from the wild-type strains based on the transition of melt curves, which is more prominent when the profiles are displayed in difference plot. In conclusion, HRM analysis allows for rapid screening for mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This assay markedly reduced the sequencing effort involved in mutational studies of quinolone-resistance genes.

  8. [Cyclooxigenase-1 gene polymorphism and aspirin resistance].

    Science.gov (United States)

    Bondar', T N; Kravchenko, N A

    2012-01-01

    The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 gene polymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

  9. Relationship Between Resistance Gene Analogue and Blast Resistance in Rice

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-min; FAN Cheng-ming; YANG Yan; HE Yue-qiu

    2009-01-01

    DNA fragments of 43 rice varieties were amplified with 11 pairs of primers designed based on resistance gene analogue (RGA) of plants, and the blast resistance of the varieties was identified by inoculation with 33 isolates of Magnaporthe grisea collected from Yunnan Province, China. Clustering results revealed a significant correlation between the blast resistance and DNA bands with a correlation coefficient of 0.6117 (α=0.01), indicating that the resistance analysis based on RGA-PCR clustering analysis coincided with that based on inoculation. The correlation coefficients, ranging from 0.1701 to 0.535, however, depended on the primers. Five pairs of primers, S1/AS3, S1 INV/S2 INV, XLRR For/XLRR Rev, Pto-Kin1 IN/Pto-Kin2 IN, and NLRR For/NLRR Rev might be applied for blast resistance identification in consideration of their band numbers and polymorphisms, and their correlation coefficients with blast resistance were 0.5305, 0.4898, 0.4059, 0.3719 and 0.3524, respectively. Besides, indica and japonica rice except two highly susceptible varieties, CO39 and Lijiangxintuanheigu, could be well classified by the 11 pairs of primers.

  10. Transposon tagging of disease resistance genes

    Energy Technology Data Exchange (ETDEWEB)

    Michelmore, R.W. (California Univ., Davis, CA (USA). Dept. of Physics)

    1989-01-01

    We are developing a transposon mutagenesis system for lettuce to clone genes for resistance to the fungal pathogen, Bremia lactucae. Activity of heterologous transposons is being studied in transgenic plants. Southern analysis of T{sub 1} and T{sub 2} plants containing Tam3 from Antirrhinum provided ambiguous results. Multiple endonuclease digests indicated that transposition had occurred; however, in no plant were all endonuclease digests consistent with a simple excision event. Southern or PCR analysis of over 50 plans containing Ac from maize have also failed to reveal clear evidence of transposition; this is contrast to experiments by others with the same constructs who have observed high rates of Ac excision in other plant species. Nearly all of 65 T{sub 2} families containing Ac interrupting a chimeric streptomycin resistance gene (Courtesy J. Jones, Sainsbury Lab., UK) clearly segregated for streptomycin resistance. Southern analyses, however, showed no evidence of transposition, indicating restoration of a functional message by other mechanisms, possibly mRNA processing. Transgenic plants have also been generated containing CaMV 35S or hsp70 promoters fused to transposase coding sequences or a Ds element interrupting a chimeric GUS gene (Courtesy M. Lassner, UC Davis). F{sub 1} plants containing both constructs were analyzed for transposition. Only two plants containing both constructs were obtained from 48 progeny, far fewer than expected, and neither showed evidence of transposition in Southerns and GUS assays. We are currently constructing further chimeric transposase fusions. To test for the stability of the targeted disease resistance genes, 50,000 F{sub 1} plants heterozygous for three resistance genes were generated; no mutants have been identified in the 5000 so far screened.

  11. Occurrence and persistence of antibiotic resistance genes in river biofilms after wastewater inputs in small rivers.

    Science.gov (United States)

    Proia, Lorenzo; von Schiller, Daniel; Sànchez-Melsió, Alexandre; Sabater, Sergi; Borrego, Carles M; Rodríguez-Mozaz, Sara; Balcázar, José Luis

    2016-03-01

    The extensive use of antibiotics in human and veterinary medicine and their subsequent release into the environment may have direct consequences for autochthonous bacterial communities, especially in freshwater ecosystems. In small streams and rivers, local inputs of wastewater treatment plants (WWTPs) may become important sources of organic matter, nutrients and emerging pollutants, such as antibiotic resistance genes (ARGs). In this study, we evaluated the effect of WWTP effluents as a source of ARGs in river biofilms. The prevalence of genes conferring resistance to main antibiotic families, such as beta-lactams (blaCTX-M), fluoroquinolones (qnrS), sulfonamides (sul I), and macrolides (ermB), was determined using quantitative PCR (qPCR) in biofilm samples collected upstream and downstream WWTPs discharge points in four low-order streams. Our results showed that the WWTP effluents strongly modified the hydrology, physico-chemistry and biological characteristics of the receiving streams and favoured the persistence and spread of antibiotic resistance in microbial benthic communities. It was also shown that the magnitude of effects depended on the relative contribution of each WWTP to the receiving system. Specifically, low concentrations of ARGs were detected at sites located upstream of the WWTPs, while a significant increase of their concentrations was observed in biofilms collected downstream of the WWTP discharge points (particularly ermB and sul I genes). These findings suggest that WWTP discharges may favour the increase and spread of antibiotic resistance among streambed biofilms. The present study also showed that the presence of ARGs in biofilms was noticeable far downstream of the WWTP discharge (up to 1 km). It is therefore reasonable to assume that biofilms may represent an ideal setting for the acquisition and spread of antibiotic resistance determinants and thus be considered suitable biological indicators of anthropogenic pollution by active

  12. Identification of plasmid-mediated quinolone resistance genes qnrA1, qnrB1 and aac(6′-1b-cr in a multiple drug-resistant isolate of Klebsiella pneumoniae from Chennai

    Directory of Open Access Journals (Sweden)

    H Magesh

    2011-01-01

    Full Text Available Purpose: Resistance to fluoroquinolones, a commonly prescribed antimicrobial for Gram-negative and Gram-positive microorganisms, is of importance in therapy. The purpose of this study was to screen for the presence of Plasmid-Mediated Quinolone Resistance (PMQR determinants in clinical isolates of Klebsiella pneumoniae. Materials and Methods: Extended-Spectrum Beta-Lactamase (ESBL isolates of K. pneumoniae collected during October 2009 were screened by the antimicrobial susceptibility test. The plasmids from these isolates were analysed by specific Polymerase chain Reaction (PCR for qnrA, qnrB and aac(6′-1b. The amplified products were sequenced to confirm the allele. Results: Our analysis showed that 61% out of the 23 ESBL K. pneumoniae isolates were resistant to ciprofloxacin and 56% to levofloxacin. The PMQR was demonstrated by transforming the plasmids from two isolates P12 and P13 into E. coli JM109. The PMQR gene qnrA was found in 16 isolates and qnrB in 11 isolates. The plasmid pKNMGR13 which conferred an minimum inhibitory concentration (MIC of more than 240 ΅g/ml in sensitive E. coli was found to harbour the qnrA1 and qnrB1 allele. Furthermore, the gene aac(6′-1b-cr encoding a variant aminoglycoside 6′-N Acetyl transferase which confers resistance to fluoroquinolones was found in the same plasmid. Conclusions: Our report shows the prevalence of PMQR mediated by qnrA and qnrB in multidrug-resistant K. pneumoniae isolates from Chennai. A multidrug-resistant plasmid conferring high resistance to ciprofloxacin was found to harbour another PMQR gene, aac(6′-1b-cr mutant gene. This is the first report screening for PMQR in K. pneumoniae isolates from India.

  13. Quadruple-first line drug resistance in Mycobacterium tuberculosis in Vietnam: What can we learn from genes?

    Science.gov (United States)

    Nguyen, Huy Quang; Nguyen, Nhung Viet; Contamin, Lucie; Tran, Thanh Hoa Thi; Vu, Thuong Thi; Nguyen, Hung Van; Nguyen, Ngoc Lan Thi; Nguyen, Son Thai; Dang, Anh Duc; Bañuls, Anne-Laure; Nguyen, Van Anh Thi

    2017-02-21

    In Vietnam, a country with high tuberculosis (137/100.000 population) and multidrug-resistant (MDR)-TB burdens (7.8/100.000 population), little is known about the molecular signatures of drug resistance in general and more particularly of second line drug (SLD) resistance. This study is specifically focused on Mycobacterium tuberculosis isolates resistant to four first-line drugs (FLDs) that make TB much more difficult to treat. The aim is to determine the proportion of SLD resistance in these quadruple drug resistant isolates and the genetic determinants linked to drug resistance to better understand the genetic processes leading to quadruple and extremely drug resistance (XDR). 91 quadruple (rifampicin, isoniazid, ethambutol and streptomycin) FLD resistant and 55 susceptible isolates were included. Spoligotyping and 24-locus MIRU-VNTR techniques were performed and 9 genes and promoters linked to FLD and SLD resistance were sequenced. SLD susceptibility testing was carried out on a subsample of isolates. High proportion of quadruple-FLD resistant isolates was resistant to fluoroquinolones (27%) and second-line injectable drugs (30.2%) by drug susceptibility testing. The sequencing revealed high mutation diversity with prevailing mutations at positions katG315, inhA-15, rpoB531, embB306, rrs1401, rpsL43 and gyrA94. The sensitivity and specificity were high for most drug resistances (>86%), but the sensitivity was lower for injectable drug resistances (<69%). The mutation patterns revealed 23.1% of pre-XDR and 7.7% of XDR isolates, mostly belonging to Beijing family. The genotypic diversity and the variety of mutations reflect the existence of various evolutionary paths leading to FLD and SLD resistance. Nevertheless, particular mutation patterns linked to high-level resistance and low fitness costs seem to be favored.

  14. Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones☆

    Science.gov (United States)

    van der Heijden, Yuri F.; Maruri, Fernanda; Blackman, Amondrea; Mitchel, Ed; Bian, Aihua; Shintani, Ayumi K.; Eden, Svetlana; Warkentin, Jon V.; Sterling, Timothy R.

    2013-01-01

    Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case–control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002–December 2009). Each fluoroquinolone-resistant case (n = 25) was matched to two fluoroquinolone-susceptible controls (n = 50). Ciprofloxacin and ofloxacin were classified as older-generation fluoroquinolones; levofloxacin, moxifloxacin and gatifloxacin were considered newer agents. There was no difference between median ofloxacin MIC for isolates from 9 patients exposed only to older fluoroquinolones, 25 exposed only to newer fluoroquinolones, 6 exposed to both and 35 fluoroquinolone-unexposed patients (Kruskal–Wallis, P = 0.35). Using multivariate proportional odds logistic regression adjusting for age and sex, duration of exposure to newer fluoroquinolones was independently associated with higher MIC (OR = 1.79, 95% CI 1.22–2.64), but duration of exposure to older fluoroquinolones was not (OR = 0.94, 95% CI 0.50–1.78). Isolates from patients exposed only to newer fluoroquinolones tended to have mutations at gyrA codons 90, 91 or 94 more frequently than those exposed only to older fluoroquinolones (44% vs. 11%). We were surprised to find that duration of exposure to newer fluoroquinolones, but not older ones, was independently associated with higher ofloxacin MIC. This suggests that the mutant selection window lower boundary is likely to have clinical relevance; caution is warranted when newer fluoroquinolones are prescribed to patients with TB risk factors. PMID:23806638

  15. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).

    Science.gov (United States)

    Effa, Emmanuel E; Lassi, Zohra S; Critchley, Julia A; Garner, Paul; Sinclair, David; Olliaro, Piero L; Bhutta, Zulfiqar A

    2011-10-05

    Typhoid and paratyphoid are febrile illnesses, due to a bacterial infection, which remain common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends the fluoroquinolone antibiotics in areas with known resistance to the older first-line antibiotics. To evaluate fluoroquinolone antibiotics for treating children and adults with enteric fever. We searched The Cochrane Infectious Disease Group Specialized Register (February 2011); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2011, Issue 2); MEDLINE (1966 to February 2011); EMBASE (1974 to February 2011); and LILACS (1982 to February 2011). We also searched the metaRegister of Controlled Trials (mRCT) in February 2011. Randomized controlled trials examining fluoroquinolone antibiotics, in people with blood, stool or bone marrow culture-confirmed enteric fever. Two authors independently assessed the trial's methodological quality and extracted data. We calculated risk ratios (RR) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI).Comparative effectiveness has been interpreted in the context of; length of treatment, dose, year of study, known levels of antibiotic resistance, or proxy measures of resistance such as the failure rate in the comparator arm. Twenty-six studies, involving 3033 patients, are included in this review.Fluoroquinolones versus older antibiotics (chloramphenicol, co-trimoxazole, amoxicillin and ampicillin)In one study from Pakistan in 2003-04, high clinical failure rates were seen with both chloramphenicol and co-trimoxazole, although resistance was not confirmed microbiologically. A seven-day course of either ciprofloxacin or ofloxacin were found to be superior. Older studies of these comparisons failed to show a difference (six trials, 361 participants).In small studies conducted almost two decades ago, the fluoroquinolones were demonstrated to have fewer

  16. Retrospective analysis of fluoroquinolone prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Simondsen, Katherine A; Reed, Michael P; Mably, Mary S; Zhang, Yang; Longo, Walter L

    2013-12-01

    Patients undergoing allogeneic hematopoietic stem cell transplant are at a high risk for infection-related mortality in the immediate post-transplantation phase. Prophylaxis with a fluoroquinolone is now recommended to reduce this risk with the stipulation that surveillance for increased fluoroquinolone resistance Clostridium difficile associated diarrhea be conducted. We conducted a retrospective chart review of 48 patients who underwent an allogeneic hematopoietic stem cell transplant and received a fluoroquinolone for prophylaxis and 48 patients who underwent an allogeneic hematopoietic stem cell transplant who did not receive a fluoroquinolone for prophylaxis. All patients received the same standard antifungal, antiviral and anti-pneumocystis prophylaxis. Patients receiving fluoroquinolone prophylaxis had a lower incidence of febrile neutropenia than those not receiving prophylaxis, though the difference was not found to be statistically significant (83% vs. 67%, p = 0.098). Similar non-significant improvements in the number of positive cultures recovered during an episode of febrile neutropenia and antimicrobial days were noted. No significant increase in fluoroquinolone resistance, Clostridium difficile associated diarrhea, or in methicillin resistant Staphylococcus aureus infections were noted. Our single institution experience with fluoroquinolone prophylaxis for allogeneic hematopoietic stem cell transplant patients supports continuation of this practice. Expansion to autologous hematopoietic stem cell transplant patients may be appropriate based on guideline recommendations and our institution-specific experience with fluoroquinolone prophylaxis.

  17. Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella enterica Serotype Enteritidis: Reduced Infectivity Associated with Decreased Expression of Salmonella Pathogenicity Island 1 Genes

    Science.gov (United States)

    The fitness costs associated with high-level fluoroquinolone resistance were examined in phenotypically and genotypically characterized ciprofloxacin-resistant Salmonella Enteritidis mutants (104-cip and 5408-cip, MIC > 32 µg/ml). The stability of the fluoroquinolone resistance phenotype in both mut...

  18. Topical ocular delivery of fluoroquinolones.

    Science.gov (United States)

    Pawar, Pravin; Katara, Rajesh; Mishra, Sushil; Majumdar, Dipak K

    2013-05-01

    Topical fluoroquinolones are used in ophthalmology to treat ocular infections. They are bactericidal and inhibit bacterial DNA replication by inhibiting DNA gyrase and topoisomerase. Fluoroquinolones possess two ionizable groups: a carboxylic group (pKa1 = 5.5 - 6.34) and a heterocyclic group (pKa2 = 7.6 - 9.3), in the nucleus, which acquire charge at pH above and below the isoelectric point (pI = 6.75 - 7.78). At isoelectric point, fluoroquinolones remain unionized and show enhanced corneal penetration but exhibit reduced aqueous solubility and the drug may precipitate from aqueous solution. Aqueous ophthalmic solutions of fluoroquinolones are obtained by using hydrochloride or mesylate salt which is acidic and irritating to the eyes. Hence, pH of the solution is kept between 5 and 7 to ensure aqueous solubility and minimum ocular irritation. This review gives an overview of various physicochemical and formulation factors affecting the ocular delivery of fluoroquinolones and strategies for getting higher ocular bioavailability for ocular delivery of fluoroquinolones. These strategies could be employed to improve efficacy of fluoroquinolones in eye preparation. Broad-spectrum antibacterials, such as the ophthalmic fluoroquinolones, are powerful weapons for treating and preventing potentially sight-threatening infections. The fourth-generation fluoroquinolones have quickly assumed an outstanding place in the ophthalmic applications. Especially valuable for their broad-spectrum coverage against Gram-positive and Gram-negative organisms, these agents have become the anti-infective of preference for many ophthalmologists. Moxifloxacin seems to be a promising powerful molecule among all fluoroquinolones for treatment of bacterial infections.

  19. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and

  20. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veter

  1. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veter

  2. Structure based in silico analysis of quinolone resistance in clinical isolates of Salmonella Typhi from India.

    Science.gov (United States)

    Kumar, Manoj; Dahiya, Sushila; Sharma, Priyanka; Sharma, Sujata; Singh, Tej P; Kapil, Arti; Kaur, Punit

    2015-01-01

    Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC) of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase.

  3. Structure Based In Silico Analysis of Quinolone Resistance in Clinical Isolates of Salmonella Typhi from India

    Science.gov (United States)

    Sharma, Priyanka; Sharma, Sujata; Singh, Tej P.; Kapil, Arti; Kaur, Punit

    2015-01-01

    Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC) of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase. PMID:25962113

  4. Structure based in silico analysis of quinolone resistance in clinical isolates of Salmonella Typhi from India.

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    Full Text Available Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase.

  5. Whole-Genome Sequence of Multidrug-Resistant Campylobacter coli Strain COL B1-266, Isolated from the Colombian Poultry Chain.

    Science.gov (United States)

    Bernal, Johan F; Donado-Godoy, Pilar; Arévalo, Alejandra; Duarte, Carolina; Realpe, María E; Díaz, Paula L; Gómez, Yolanda; Rodríguez, Fernando; Agarwala, Richa; Landsman, David; Mariño-Ramírez, Leonardo

    2016-03-17

    Campylobacter coli is considered one of the main causes of food-borne illness worldwide. We report here the whole-genome sequence of multidrug-resistant Campylobacter coli strain COL B1-266, isolated from the Colombian poultry chain. The genome sequences encode genes for a variety of antimicrobial resistance genes, including aminoglycosides, β-lactams, lincosamides, fluoroquinolones, and tetracyclines.

  6. Diagnostic Performance of the New Version (v2.0) of GenoType MTBDRsl Assay for Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs: a Multicenter Study

    Science.gov (United States)

    Tagliani, Elisa; Cabibbe, Andrea M.; Miotto, Paolo; Borroni, Emanuele; Toro, Juan Carlos; Mansjö, Mikael; Hoffner, Sven; Hillemann, Doris; Zalutskaya, Aksana; Skrahina, Alena

    2015-01-01

    Resistance to fluoroquinolones (FLQ) and second-line injectable drugs (SLID) is steadily increasing, especially in eastern European countries, posing a serious threat to effective tuberculosis (TB) infection control and adequate patient management. The availability of rapid molecular tests for the detection of extensively drug-resistant TB (XDR-TB) is critical in areas with high rates of multidrug-resistant TB (MDR-TB) and XDR-TB and limited conventional drug susceptibility testing (DST) capacity. We conducted a multicenter study to evaluate the performance of the new version (v2.0) of the Genotype MTBDRsl assay compared to phenotypic DST and sequencing on a panel of 228 Mycobacterium tuberculosis isolates and 231 smear-positive clinical specimens. The inclusion of probes for the detection of mutations in the eis promoter region in the MTBDRsl v2.0 test resulted in a higher sensitivity for detection of kanamycin resistance for both direct and indirect testing (96% and 95.4%, respectively) than that seen with the original version of the assay, whereas the test sensitivities for detection of FLQ resistance remained unchanged (93% and 83.6% for direct and indirect testing, respectively). Moreover, MTBDRsl v2.0 showed better performance characteristics than v1.0 for the detection of XDR-TB, with high specificity and sensitivities of 81.8% and 80.4% for direct and indirect testing, respectively. MTBDRsl v2.0 thus represents a reliable test for the rapid detection of resistance to second-line drugs and a useful screening tool to guide the initiation of appropriate MDR-TB treatment. PMID:26179309

  7. 耐头孢他啶大肠埃希菌与肺炎克雷伯菌对氟喹诺酮类药物的耐药性分析%Drug resistance of ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae to fluoroquinolones antibiotics

    Institute of Scientific and Technical Information of China (English)

    饶冠利; 周文聪; 季青; 张德忠

    2013-01-01

    目的 了解临床耐头孢他啶大肠埃希菌与肺炎克雷伯菌分离株对氟喹诺酮类抗菌药物的耐药性,以合理使用氟喹诺酮类抗菌药物,采取有效措施控制耐药株的出现.方法 采用K-B和MIC法测定耐头孢他啶大肠埃希菌与肺炎克雷伯菌对8种常见氟喹诺酮类抗菌药物的敏感性.结果 共分离出耐头孢他啶大肠埃希菌与肺炎克雷伯菌276株,对加替沙星、莫西沙星、吉米沙星、左氧氟沙星、氧氟沙星、环丙沙星、帕珠沙星、司帕沙星的耐药率分别为46.38%、43.48%、42.72%、55.43%、65.22%、61.96%、52.54%、53.62%,且均明显高于头孢他啶敏感株(P<0.05);呼吸道、非呼吸道标本的耐头孢他啶大肠埃希菌与肺炎克雷伯菌分离株对加替沙星、莫西沙星、氧氟沙星、司帕沙星的耐药率不同,差异均有统计学意义(P<0.05).结论 耐头孢他啶大肠埃希菌与肺炎克雷伯菌分离株对氟喹诺酮类抗菌药物的耐药率较高,呼吸道、非呼吸道标本分离株对多种常见氟喹诺酮抗菌药物的耐药率不同.%OBJECTIVE To understand the drug resistance of ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae strains to fluoroquinolones so as to reasonably use fluoroquinolones and take effective measures to control the drug resistant strains. METHODS The drug susceptibility testing for E . coli and K. pneumoniae to 8 common fluoroquinolone antimicrobial drugs were determined by K-B and MIC. RESULTS A total of 276 strains of ceftazidime-resistant E. coli and K. pneumoniae were isolated, the drug resistance rates to gatifloxacin, moxifloxacin, gemifloxacin, levofloxacin, ofloxacin, ciprofloxacin, pazufloxacin, and sparfloxacin were 46. 38%, 43. 48%,42. 72%, 55. 43% ,65. 22% , 61.96%, 52.54%, and 53.62%, respectively, significantly higher than that of the ceftazidime-sensitive E. coli and K. pneumoniae strains (P<0. 05). The ceftazidime-resistant E. coli and

  8. Organization of a resistance gene cluster linked to rhizomania resistance in sugar beet

    Science.gov (United States)

    Genetic resistance to rhizomania has been in use for over 40 years. Characterization of the molecular basis for susceptibility and resistance has proved challenging. Nucleotide-binding leucine-rich-repeat-containing (NB-LRR) genes have been implicated in numerous gene-for-gene resistance interaction...

  9. Polycyclic aromatic hydrocarbons (PAHs) enriching antibiotic resistance genes (ARGs) in the soils.

    Science.gov (United States)

    Chen, Baowei; He, Rong; Yuan, Ke; Chen, Enzhong; Lin, Lan; Chen, Xin; Sha, Sha; Zhong, Jianan; Lin, Li; Yang, Lihua; Yang, Ying; Wang, Xiaowei; Zou, Shichun; Luan, Tiangang

    2017-01-01

    The prevalence of antibiotic resistance genes (ARGs) in modern environment raises an emerging global health concern. In this study, soil samples were collected from three sites in petrochemical plant that represented different pollution levels of polycyclic aromatic hydrocarbons (PAHs). Metagenomic profiling of these soils demonstrated that ARGs in the PAHs-contaminated soils were approximately 15 times more abundant than those in the less-contaminated ones, with Proteobacterial being the preponderant phylum. Resistance profile of ARGs in the PAHs-polluted soils was characterized by the dominance of efflux pump-encoding ARGs associated with aromatic antibiotics (e.g., fluoroquinolones and acriflavine) that accounted for more than 70% of the total ARGs, which was significantly different from representative sources of ARG pollution due to wide use of antibiotics. Most of ARGs enriched in the PAHs-contaminated soils were not carried by plasmids, indicating the low possibilities of them being transferred between bacteria. Significant correlation was observed between the total abundance of ARGs and that of Proteobacteria in the soils. Proteobacteria selected by PAHs led to simultaneously enriching of ARGs carried by them in the soils. Our results suggested that PAHs could serve as one of selective stresses for greatly enriching of ARGs in the human-impacted environment.

  10. Safety of Fluoroquinolones: An Update

    Directory of Open Access Journals (Sweden)

    L Mandell

    2002-01-01

    Full Text Available The fluoroquinolone class of antimicrobials has been in clinical use for over 13 years. During that period, some representatives of the class have been extensively prescribed, such as ciprofloxacin and levofloxacin, while others have seen minimal use and have been restricted or withdrawn, namely, trovafloxacin and grepafloxacin. Manipulation of the fluoroquinolone structure by substituting a range of moieties around the core has yielded enhanced antibacterial activity, but in some cases this has come at a price. Specific substitutions are discussed in relation to particular recognized adverse events. In the present paper, newly introduced fluoroquinolones, such as moxifloxacin and gatifloxacin, are examined in terms of anticipated class effects and recent clinical experience. These antimicrobials are associated with reactions such as diarrhea, nausea, headache and other typical antimicrobial phenomena at rates less than 5%. New fluoroquinolone agents should be examined carefully in light of structural findings until adequate clinical data are amassed.

  11. Extremely Drug-Resistant Salmonella enterica Serovar Senftenberg Infections in Patients in Zambia

    DEFF Research Database (Denmark)

    Hendriksen, Rene S.; Joensen, Katrine Grimstrup; Lukwesa-Musyani, Chileshe

    2013-01-01

    Two cases of extremely drug-resistant Salmonella enterica serovar Senftenberg isolated from patients in Zambia were investigated by utilizing MIC determinations and whole-genome sequencing. The isolates were resistant to, and harbored genes toward, nine drug classes, including fluoroquinolones...

  12. Genetic characteristics of vancomycin resistance gene cluster in Enterococcus spp.

    Science.gov (United States)

    Chunhui, Chen; Xiaogang, Xu

    2015-05-01

    Vancomycin resistant enterococci has become an important nosocomial pathogen since it is discovered in late 1980s. The products, encoded by vancomycin resistant gene cluster in enterococci, catalyze the synthesis of peptidoglycan precursors with low affinity with glycopeptide antibiotics including vancomycin and teicoplanin and lead to resistance. These vancomycin resistant gene clusters are classified into nine types according to their gene sequences and organization, or D-Ala:D-Lac (VanA, VanB, VanD and VanM) and D-Ala:D-Ser (VanC, VanE, VanG, VanL and VanN) ligase gene clusters based on the differences of their encoded ligases. Moreover, these gene clusters are characterized by their different resistance levels and infection models. In this review, we summarize the classification, gene organization and infection model of vancomycin resistant gene cluster in Enterococcus spp.

  13. Mutation analysis of induced fluoroquinolone-resistant mutants of Streptococcus suis in vitro%人工诱导猪链球菌氟喹诺酮耐药株的靶位突变分析

    Institute of Scientific and Technical Information of China (English)

    张雨菡; 姚杰; 陆承平; 王丽平

    2009-01-01

    To perform a systematic analysis of point mutations in the quinolone resistance determining regions (QRDRs) of the DNA gyrase and topoisomerase genes of Streptococcus suis type 2 strain after in vitro exposure to stepwise increasing concentrations of enrofloxacin and ciprofloxacin. Four parent strains of S. suis type 2 were chosen for stepwise exposure to increasing levels of enro-floxacin and ciprofloxacin followed by selection of resistant mutants. The QRDRs of gyrA, gyrB, parC and parE correlating to mutants with increased MICs were analysed for point mutations. Multiple mutants with significantly increased MICs (128 mg· L~(-1)) were generated from each parent strain. Most of the amino acid substitutions identified were Ser79Phe of ParC, Ser81 Arg of GyrA, Asp315Asn, Ser285Leu, Glu354Lys of GryB and Pro278Ser of ParE, which were consistent to the mechanisms of resistance reported in clinical isolates of S. pneumoniae. However, it has some mutable points Glnll8His of GyrA, Asn297Tyr of ParE as well as the deletions 288 -291 amino acids of GyrB and 62 amino acid of ParC, which haven't been documented and whether these nuleoti-de mutations associated with fluoroquinolone resistance are not clear. The number of induction/selection cycles required for the emergence of key point mutations in gyrA and parC was variable among strains. The results indicate that stepwise increasing concentration of enrofloxacin and ciprofloxacin can easily select resistant strains of S. suis.%以4株临床分离的对环丙沙星和恩诺沙星敏感的猪链球菌2型菌株为研究对象,采用体外递增药物浓度的方法分别诱导了其对环丙沙星和恩诺沙星耐药的菌株,按CLSI推荐方法测定了环丙沙星和恩诺沙星对亲本敏感株和诱导耐药株的MIC,测定了亲本株和诱导耐药株的生长曲线,并采用PCR和基因测序的方法分析了诱导耐药株的DNA回旋酶(GyrA和GyrB)和拓扑异构酶Ⅳ(ParC和ParE)

  14. Efflux pump genes of the resistance-nodulation-division family in Burkholderia cenocepacia genome

    Directory of Open Access Journals (Sweden)

    Manina Giulia

    2006-07-01

    Full Text Available Abstract Background Burkholderia cenocepacia is recognized as opportunistic pathogen that can cause lung infections in cystic fibrosis patients. A hallmark of B. cenocepacia infections is the inability to eradicate the organism because of multiple intrinsic antibiotic resistance. As Resistance-Nodulation-Division (RND efflux systems are responsible for much of the intrinsic multidrug resistance in Gram-negative bacteria, this study aims to identify RND genes in the B. cenocepacia genome and start to investigate their involvement into antimicrobial resistance. Results Genome analysis and homology searches revealed 14 open reading frames encoding putative drug efflux pumps belonging to RND family in B. cenocepacia J2315 strain. By reverse transcription (RT-PCR analysis, it was found that orf3, orf9, orf11, and orf13 were expressed at detectable levels, while orf10 appeared to be weakly expressed in B. cenocepacia. Futhermore, orf3 was strongly induced by chloramphenicol. The orf2 conferred resistance to fluoroquinolones, tetraphenylphosphonium, streptomycin, and ethidium bromide when cloned and expressed in Escherichia coli KAM3, a strain lacking the multidrug efflux pump AcrAB. The orf2-overexpressing E. coli also accumulate low concentrations of ethidium bromide, which was restored to wild type level in the presence of CCCP, an energy uncoupler altering the energy of the drug efflux pump. Conclusion The 14 RND pumps gene we have identified in the genome of B. cenocepacia suggest that active efflux could be a major mechanism underlying antimicrobial resistance in this microorganism. We have characterized the ORF2 pump, one of these 14 potential RND efflux systems. Its overexpression in E. coli conferred resistance to several antibiotics and to ethidium bromide but it remains to be determined if this pump play a significant role in the antimicrobial intrinsic resistance of B. cenocepacia. The characterization of antibiotic efflux pumps in B

  15. Major gene for field stem rust resistance co-locates with resistance gene Sr12 in "Thatcher" wheat

    Science.gov (United States)

    Stem rust, caused by Puccinia graminis (Pgt), is a damaging disease of wheat that can be controlled by utilizing effecting stem rust resistance genes. "Thatcher" wheat carries complex resistance to stem rust that is enhanced in the presence of the resistance gene Lr34. The purpose of this study was ...

  16. Fluoroquinolone prophylaxis in preventing BK polyomavirus infection after renal transplant: A systematic review and meta-analysis.

    Science.gov (United States)

    Song, Tu-Run; Rao, Zheng-Sheng; Qiu, Yang; Liu, Jin-Peng; Huang, Zhong-Li; Wang, Xian-Ding; Lin, Tao

    2016-03-01

    Previous studies regarding the prevention of BK viremia following renal transplantation with fluoroquinolone have yielded conflicting results. The purpose of this systematic review was to examine the evidence regarding the efficacy of fluoroquinolone in preventing BK polyomavirus infection following renal transplantation. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for research articles published prior to January 2015 using keywords such as "fluoroquinolone," "BK viremia," and "renal transplantation." We extracted all types of study published in English. The primary outcome was BK viremia and viruria at 1 year post-transplantation. Secondary outcomes were BK virus-associated nephropathy (BKVN), graft failure, and fluoroquinolone-resistant infection. We identified eight trials, including a total of 1477 participants with a mean duration of fluoroquinolone prophylaxis of >1 month. At 1 year, fluoroquinolone prophylaxis was not associated with a decreased incidence of BK viremia [risk ratio (RR), 0.84; 95% confidence interval (95% CI), 0.58-1.20). No significant differences in BKVN (RR, 0.88; 95% CI, 0.37-2.11), risk of graft failure due to BKVN (RR, 0.68; 95% CI, 0.29-1.59), or fluoroquinolone-resistant infection (RR, 1.08; 95% CI, 0.64-1.83) were observed between the fluoroquinolone prophylaxis and control groups. The results of this study suggest that fluoroquinolone is ineffective in preventing BK polyomavirus infection following renal transplantation. Copyright © 2016. Published by Elsevier Taiwan.

  17. Fluoroquinolone resistance determining region mutation in Streptococcus pneumonia isolates%肺炎链球菌氟喹诺酮耐药决定区突变位点研究

    Institute of Scientific and Technical Information of China (English)

    张菲菲; 赵春江; 王辉

    2013-01-01

    目的 调查我国肺炎链球菌对不同氟喹诺酮类抗生素(FQ)的耐药性,研究耐药突变位点与FQ耐药性的关系.方法 收集2010年6-12月我国9个城市12家教学医院临床分离的232株肺炎链球菌,用琼脂稀释法测定环丙沙星、左氧氟沙星和莫西沙星等16种抗菌药物的抗菌活性.选取左氧氟沙星MIC≥1 mg/L的菌株进行parC、parE和gyrA基因喹诺酮耐药决定区(QRDR)PCR扩增和序列分析.结果 环丙沙星、左氧氟沙星和莫西沙星的敏感度分别53.9% (125/232)、98.7% (229/232)和98.7% (229/232).选取19株左氧氟沙星MIC≥2 mg/L的菌株并筛选出24株左氧氟沙星MIC值为1 mg/L的菌株,在选取的43株肺炎链球菌中,当parE靶点发生单一突变时,左氧氟沙星的MIC值为1~2 mg/L,环丙沙星的MIC值为2 mg/L,莫西沙星的MIC值为0.125~0.25 mg/L.当parE和parC靶点均有突变时,大部分菌株左氧氟沙星的MIC值为2 mg/L,环丙沙星的MIC值为4 mg/L,莫西沙星的MIC值为0.25 mg/L或0.50 mg/L.当parE和gyrA靶点同时突变时,左氧氟沙星的MIC值为16 mg/L,环丙沙星的MIC≥16 mg/L,莫西沙星的MIC值为4 mg/L.卡方检验结果发现,parE基因和parC基因双突变比parE基因单突变更能导致左氧氟沙星耐药性升高.结论 当parE/parC靶点产生突变时,左氧氟沙星和环丙沙星的MIC值已有升高,但莫西沙星MIC值还处于低水平;只有当parC/parE和gyrA双位点突变时,莫西沙星才达到耐药水平.%Objective To investigate the relationship between different fluoroquinolone (FQ) resistance of Streptococcus pneumoniae and the mutations of target genes.Methods A total of 232 Streptococcus pneumoniae isolates were collected from 12 teaching hospitals at 9 cities between June and December 2010.The antibacterial activities of 16 antimicrobial agents were determined by agar dilution method.The ciprofloxacin,levofloxacin and moxifloxacin MIC≥1 mg/L isolates were selected to detect the

  18. Absence of tmRNA Has a Protective Effect against Fluoroquinolones in Streptococcus pneumoniae.

    Science.gov (United States)

    Brito, Liliana; Wilton, Joana; Ferrándiz, María J; Gómez-Sanz, Alicia; de la Campa, Adela G; Amblar, Mónica

    2016-01-01

    The transfer messenger RNA (tmRNA), encoded by the ssrA gene, is a small non-coding RNA involved in trans-translation that contributes to the recycling of ribosomes stalled on aberrant mRNAs. In most bacteria, its inactivation has been related to a decreased ability to respond to and recover from a variety of stress conditions. In this report, we investigated the role of tmRNA in stress adaptation in the human pathogen Streptococcus pneumoniae. We constructed a tmRNA deletion mutant and analyzed its response to several lethal stresses. The ΔssrA strain grew slower than the wild type, indicating that, although not essential, tmRNA is important for normal pneumococcal growth. Moreover, deletion of tmRNA increased susceptibility to UV irradiation, to exogenous hydrogen peroxide and to antibiotics that inhibit protein synthesis and transcription. However, the ΔssrA strain was more resistant to fluoroquinolones, showing twofold higher MIC values and up to 1000-fold higher survival rates than the wild type. Deletion of SmpB, the other partner in trans-translation, also reduced survival to levofloxacin in a similar extent. Accumulation of intracellular reactive oxygen species associated to moxifloxacin and levofloxacin treatment was also highly reduced (∼100-fold). Nevertheless, the ΔssrA strain showed higher intracellular accumulation of ethidium bromide and levofloxacin than the wild type, suggesting that tmRNA deficiency protects pneumococcal cells from fluoroquinolone-mediated killing. In fact, analysis of chromosome integrity revealed that deletion of tmRNA prevented the fragmentation of the chromosome associated to levofloxacin treatment. Moreover, such protective effect appears to relay mainly on inhibition of protein synthesis, since a similar effect was observed with antibiotics that inhibit that process. The emergence and spread of drug-resistant pneumococci is a matter of concern and these results contribute to a better comprehension of the mechanisms

  19. Absence of tmRNA Has a Protective Effect against Fluoroquinolones in Streptococcus pneumoniae

    Science.gov (United States)

    Brito, Liliana; Wilton, Joana; Ferrándiz, María J.; Gómez-Sanz, Alicia; de la Campa, Adela G.; Amblar, Mónica

    2017-01-01

    The transfer messenger RNA (tmRNA), encoded by the ssrA gene, is a small non-coding RNA involved in trans-translation that contributes to the recycling of ribosomes stalled on aberrant mRNAs. In most bacteria, its inactivation has been related to a decreased ability to respond to and recover from a variety of stress conditions. In this report, we investigated the role of tmRNA in stress adaptation in the human pathogen Streptococcus pneumoniae. We constructed a tmRNA deletion mutant and analyzed its response to several lethal stresses. The ΔssrA strain grew slower than the wild type, indicating that, although not essential, tmRNA is important for normal pneumococcal growth. Moreover, deletion of tmRNA increased susceptibility to UV irradiation, to exogenous hydrogen peroxide and to antibiotics that inhibit protein synthesis and transcription. However, the ΔssrA strain was more resistant to fluoroquinolones, showing twofold higher MIC values and up to 1000-fold higher survival rates than the wild type. Deletion of SmpB, the other partner in trans-translation, also reduced survival to levofloxacin in a similar extent. Accumulation of intracellular reactive oxygen species associated to moxifloxacin and levofloxacin treatment was also highly reduced (∼100-fold). Nevertheless, the ΔssrA strain showed higher intracellular accumulation of ethidium bromide and levofloxacin than the wild type, suggesting that tmRNA deficiency protects pneumococcal cells from fluoroquinolone-mediated killing. In fact, analysis of chromosome integrity revealed that deletion of tmRNA prevented the fragmentation of the chromosome associated to levofloxacin treatment. Moreover, such protective effect appears to relay mainly on inhibition of protein synthesis, since a similar effect was observed with antibiotics that inhibit that process. The emergence and spread of drug-resistant pneumococci is a matter of concern and these results contribute to a better comprehension of the mechanisms

  20. Fluoroquinolone consumption and -resistance trends in Mycobacterium tuberculosis and other respiratory pathogens: Ecological antibiotic pressure and consequences in Pakistan, 2009–2015

    Directory of Open Access Journals (Sweden)

    S Shakoor

    2016-01-01

    Conclusion: We discuss the possible reasons for the decrease in resistance rates in TB, putative drivers of resistance other than volume of FQ consumption, and the possible impact of the National Tuberculosis Programme and drug regulatory activities.

  1. Fluoroquinolone-associated tendinopathy.

    Science.gov (United States)

    Tsai, Wen-Chung; Yang, Yun-Ming

    2011-01-01

    The fluoroquinolones (FQs) are used to treat a wide range of infections because of their excellent gastrointestinal absorption, superior tissue penetration and broad-spectrum activity. Recently, FQ-associated tendinopathy and tendon rupture have been reported, especially in the elderly and patients with diabetes and renal failure. However, these adverse effects do not appear to be widely known among physicians. Because of the frequent use of FQs in clinical practice, physicians should be aware of their potential for severe disability from tendon rupture. Achilles tendinopathy or rupture is among the most serious side effects associated with FQ use, with reports markedly increasing, especially with the use of ciprofloxacin. The histopathologic findings include degenerative lesions, fissures, interstitial edema without cellular infiltration, necrosis and neovascularization. There are possible molecular mechanisms accounting for FQ-associated tendinopathy. First, ciprofloxacin mediates inhibition of cell proliferation and G2/M cell cycle arrest in tendon cells by down-regulation of cyclin B and cyclin-dependent kinase 1. Second, ciprofloxacin inhibits the spead and migration of tenocytes by down-regulation of focal adhesion kinase phosphorylation. Third, ciprofloxacin enhances the enzymatic activity of matrix metalloproteinase-2 with degradation of type I collagen. Management of FQ-associated tendinopathy includes immediate discontinuation of FQs, rest, non-steroidal anti-inflammatory drugs, physical modalities and eccentric strengthening exercise. Tendon rupture may require surgical intervention.

  2. Detection of the common resistance genes in Gram-negative bacteria using gene chip technology

    Directory of Open Access Journals (Sweden)

    C Ting

    2013-01-01

    Full Text Available Objective: To design a resistance gene detection chip that could, in parallel, detect common clinical drug resistance genes of Gram-negative bacteria. Materials and Methods: Seventy clinically significant Gram-negative bacilli (Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii were collected. According to the known resistance gene sequences, we designed and synthesized primers and probes, which were used to prepare resistance gene detection chips, and finally we hybridized and scanned the gene detection chips. Results: The results between the gene chip and polymerase chain reaction (PCR were compared. The rate was consistently 100% in the eight kinds of resistance genes tested (TEM, SHV, CTX-M, DHA, CIT, VIM, KPC, OXA-23. One strain of Pseudomonas aeruginosa had the IMP, but it was not found by gene chip. Conclusion: The design of Gram-negative bacteria-resistant gene detection chip had better application value.

  3. In vitro study on drug-resistance characteristics of Aeromonas hydrophila to tetracyclines and fluoroquinolones%嗜水气单胞菌对四环素类和氟喹诺酮类药物的耐药性研究

    Institute of Scientific and Technical Information of China (English)

    王美珍; 陈昌福; 刘振兴; 谭晶晶; 高宇; 李革雷

    2011-01-01

    在离体条件下进行患病鱼体内分离的嗜水气单胞菌3个菌株对四环素类和氟喹诺酮类药物的耐药性获得、稳定性、保存条件和交叉耐药性研究.结果表明:分别在含有盐酸多西环素、盐酸四环素、诺氟沙星和左氧氟沙星的药物培养基中连续传代9次(在28℃条件下培养72 h为1代)后,四环素类对3个菌株的最小抑菌浓度上升倍数为8~32倍,氟喹诺酮类组MIC上升倍数为125~7 997倍,且耐药获得后保持稳定.同时嗜水气单胞菌对四环素类和氟喹诺酮类药物存在交叉耐药.耐药菌4℃保存10和20 d耐药性保持稳定,30 d耐药性均有不同程度的下降.%The aims of this study were to investigate the development, stability, cross-resistance and preservation of Aeromonas hydrophila resistance to tetracyclines and fluoroquinolones. A. hydrophilawas grown at 28 ℃ for 72 h and used it to test for the development of resistance after 9 sequential subcultures in sub-inhibitory concentrations of two tetracyclines(doxycycline and tetracycline) and two fluoroquinolones (norfloxacin and levofloxacin). After 9 subcultures the minimal inhibitory concentrations (MIC) to tetracyclines were 8-32 times greater than the initial values, MIC values to fluoroquinolones were 125-7 997 times greater than the initial values, and drug-resistance were stable. The doxycycline-resistant isolate was resistant to tetracycline and fluoroquinolones, and the levofloxacin-resistant isolate was resistant to tetracyclines and norfloxacin. The drug-resistance stability test indicated that long-term storage of the bacteria at 4 ℃ could reduce their resistance to antimicrobials.

  4. Mosaic tetracycline resistance genes encoding ribosomal protection proteins.

    Science.gov (United States)

    Warburton, Philip J; Amodeo, Nina; Roberts, Adam P

    2016-12-01

    First reported in 2003, mosaic tetracycline resistance genes are a subgroup of the genes encoding ribosomal protection proteins (RPPs). They are formed when two or more RPP-encoding genes recombine resulting in a functional chimera. To date, the majority of mosaic genes are derived from sections of three RPP genes, tet(O), tet(W) and tet(32), with others comprising tet(M) and tet(S). In this first review of mosaic genes, we report on their structure, diversity and prevalence, and suggest that these genes may be responsible for an under-reported contribution to tetracycline resistance in bacteria.

  5. Antibiotic resistance gene discovery in food-producing animals.

    Science.gov (United States)

    Allen, Heather K

    2014-06-01

    Numerous environmental reservoirs contribute to the widespread antibiotic resistance problem in human pathogens. One environmental reservoir of particular importance is the intestinal bacteria of food-producing animals. In this review I examine recent discoveries of antibiotic resistance genes in agricultural animals. Two types of antibiotic resistance gene discoveries will be discussed: the use of classic microbiological and molecular techniques, such as culturing and PCR, to identify known genes not previously reported in animals; and the application of high-throughput technologies, such as metagenomics, to identify novel genes and gene transfer mechanisms. These discoveries confirm that antibiotics should be limited to prudent uses.

  6. Identification of genes contributing to quantitative disease resistance in rice

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Despite the importance of quantitative disease resistance during a plant’s life, little is known about the molecular basis of this type of host-pathogen interaction, because most of the genes underlying resistance quantitative trait loci (QTLs) are unknown. To identify genes contributing to resistance QTLs in rice, we analyzed the colocalization of a set of characterized rice defense-responsive genes and resistance QTLs against different pathogens. We also examined the expression patterns of these genes in response to pathogen infection in the parents of the mapping populations, based on the strategy of validation and functional analysis of the QTLs. The results suggest that defense-responsive genes are important resources of resistance QTLs in rice. OsWRKY45-1 is the gene contributing to a major resistance QTL.NRR,OsGH3-1,and OsGLP members on chromosome 8 contribute alone or collectively to different minor resistance QTLs. These genes function in a basal resistance pathway or in major disease resistance gene-mediated race-specific pathways.

  7. Responses of plasmid-mediated quinolone resistance genes and bacterial taxa to (fluoro)quinolones-containing manure in arable soil.

    Science.gov (United States)

    Xiong, Wenguang; Sun, Yongxue; Ding, Xueyao; Zhang, Yiming; Zhong, Xiaoxia; Liang, Wenfei; Zeng, Zhenling

    2015-01-01

    The aim of the present study was to investigate the fate of plasmid-mediated quinolone resistance (PMQR) genes and the disturbance of soil bacterial communities posed by (fluoro)quinolones (FQNs)-containing manure in arable soil. Representative FQNs (enrofloxacin (ENR), ciprofloxacin (CIP) and norfloxacin (NOR)), PMQR genes (qepA, oqxA, oqxB, aac(6')-Ib-cr and qnrS) and bacterial communities in untreated soil, +manure and +manure+FQNs groups were analyzed using culture independent methods. The significantly higher abundance of oqxA, oqxB and aac(6')-Ib-cr, and significantly higher abundance of qnrS in +manure group than those in untreated soil disappeared at day 30 and day 60, respectively. All PMQR genes (oqxA, oqxB, aac(6')-Ib-cr and qnrS) dissipated 1.5-1.7 times faster in +manure group than those in +manure+FQNs group. The disturbance of soil bacterial communities posed by FQNs-containing manure was also found. The results indicated that significant effects of PMQR genes (oqxA, oqxB, aac(6')-Ib and qnrS) on arable soils introduced by manure disappeared 2 month after manure application. FQNs introduced by manure slowed down the dissipation of PMQR genes. The presence of high FQNs provided a selective advantage for species affiliated to the phylum including Acidobacteria, Verrucomicrobia and Planctomycetes while suppressing Proteobacteria and Actinobacteria.

  8. Horizontal gene transfer—emerging multidrug resistance in hospital bacteria

    Institute of Scientific and Technical Information of China (English)

    SenkaDZIDIC; VladimirBEDEKOVIC

    2003-01-01

    The frequency and spectrum of antibiotic resistant infections have increased worldwide during the past few decades. This increase has been attributed to a combination of microbial characteristics, the selective pressure of antimicrobial use, and social and technical changes that enhance the transmission of resistant organisms. The resistance is acquired by mutational changer or by the acquisition of resistance-encoding genetic material which is transfered from another bacteria. The spread of antibiotic resistance genes may be causally related to the overuse of antibiotics in human health care and in animal feeds, increased use of invasive devices and procedures, a greater number of susceptible hosts, and lapses in infection control practices leading to increased transmission of resistant organisms. The resistance gene sequences are integrated by recombination into several classes of naturally occurring gene expression cassettes and disseminated within the microbial population by horizontal gene transfer mechanisms: transformation, conjugation or transduction. In the hospital, widespread use of antimicrobials in the intensive care units (ICU) and for immunocompromised patients has resulted in the selection of multidrug-resistant organisms. Methicilin-resistant Staphylococci, vancomycin resistant Enterococci and extended-spectrum betalactamase(ESBL) producing Gram negative bacilli are identified as major phoblem in nosocomial infections. Recent surveillance studies have demonstrated trend towares more seriously ill patients suffering from multidrug-resistant nosocomial infections. Emergence of multiresistant bacteria and spread of resistance genes should enforce the aplication of strict prevention strategies, including changes in antibiotic treatment regimens, hygiene measures, infection prevention and control of horizontal nosocomial transmission of organisms.

  9. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes

    DEFF Research Database (Denmark)

    Venkatesan, Meera; Gadalla, Nahla B; Stepniewska, Kasia

    2014-01-01

    Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated...

  10. Occurrence of integrons and resistance genes among sulphonamide-resistant Shigella spp. from Brazil

    DEFF Research Database (Denmark)

    Peirano, G.; Agersø, Yvonne; Aarestrup, Frank Møller

    2005-01-01

    Objectives: To determine the occurrence of class 1 and 2 integrons and antimicrobial resistance genes among sulphonamide-resistant Shigella strains isolated in Brazil during 1999-2003. Methods: Sixty-two Shigella (Shigella flexneri, n = 47 and Shigella sonnei, n = 15) were tested against 21....... Conclusions: The detection of class 1 and 2 integrons and additional antimicrobial resistance genes allowed us to identify the most frequent antimicrobial resistance patterns of Shigella spp. isolated in Brazil....

  11. Antimicrobial resistance gene distribution: a socioeconomic and sociocultural perspective

    Science.gov (United States)

    Ojo, Kayode K.; Sapkota, Amy R.; Ojo, Tokunbo B.; Pottinger, Paul S.

    2008-01-01

    The appearance of resistance to many first-line antimicrobial agents presents a critical challenge to the successful treatment of bacterial infections. Antimicrobial resistant bacteria and resistance genes are globally distributed, but significant variations in prevalence have been observed in different geographical regions. This article discusses possible relationships between socioeconomic and sociocultural factors and regional differences in the prevalence of antibiotic-resistant bacteria and their associated resistance genes. Findings indicate that the few studies that have been conducted to understand relationships between socioeconomic and sociocultural factors and antimicrobial resistance have focused on patterns of phenotypic antibiotic resistance. Yet, a critical need exists for molecular studies of human influences on bacterial resistance and adaptation. We propose that the results of these studies, coupled with well-coordinated culturally appropriate interventions that address specific socioeconomic and sociocultural needs may be necessary to reduce the scourge of antimicrobial resistance in both developing and developed countries. PMID:20204098

  12. The tomato I-3 gene: a novel gene for resistance to Fusarium wilt disease.

    Science.gov (United States)

    Catanzariti, Ann-Maree; Lim, Ginny T T; Jones, David A

    2015-07-01

    Plant resistance proteins provide race-specific immunity through the recognition of pathogen effectors. The resistance genes I, I-2 and I-3 have been incorporated into cultivated tomato (Solanum lycopersicum) from wild tomato species to confer resistance against Fusarium oxysporum f. sp. lycopersici (Fol) races 1, 2 and 3, respectively. Although the Fol effectors corresponding to these resistance genes have all been identified, only the I-2 resistance gene has been isolated from tomato. To isolate the I-3 resistance gene, we employed a map-based cloning approach and used transgenic complementation to test candidate genes for resistance to Fol race 3. Here, we describe the fine mapping and sequencing of genes at the I-3 locus, which revealed a family of S-receptor-like kinase (SRLK) genes. Transgenic tomato lines were generated with three of these SRLK genes and one was found to confer Avr3-dependent resistance to Fol race 3, confirming it to be I-3. The finding that I-3 encodes an SRLK reveals a new pathway for Fol resistance and a new class of resistance genes, of which Pi-d2 from rice is also a member. The identification of I-3 also allows the investigation of the complex effector-resistance protein interaction involving Avr1-mediated suppression of I-2- and I-3-dependent resistance in tomato.

  13. Multiple Drug Resistance Pump and Its Regulatory Proteins in Salmonella Typhimurium on the Role of Fluoroquinolone Resistance%多重耐药泵及其调控蛋白在鼠伤寒沙门氏菌对氟喹诺酮类耐药中的作用

    Institute of Scientific and Technical Information of China (English)

    刘莹

    2016-01-01

    To study the multiple drug resistance pump and its regulatory proteins in mouse salmonella typhi to the role of fluoroquinoloneresistance, selectting ciprofloxacin hydrochloride, and grace and salmonella typhimurium, norfloxacin and other drugs, such as salmonella bacteriophage induction in vitro identification, thia paper detected multiple drug-resistant bacteria induction of pump expression level, and at the same time, analyzed the role of regulatory proteins in multiple drug-resistant bacteria, and investigated the RamA for the influence of different drugs. The results showed that salmonella typhimurium of fluoroquinolone resistance was mainly implemented in synergy with MdtK with aCrab; Outside fluoroquinolone multi-resistant pump main regulation system was for RamR - RamA; The impact of new GyrB bacteria by gumming point, made its sensitivity to fluoroquinolone declined; And RamA to ciprofloxacin mutant strains had certain influence, promoted its mutant strains. It followed that multiple drug-resistant pump and its regulatory proteins in salmonella typhimurium of fluoroquinolone resistance had a positive role.%为探讨多重耐药泵及其调控蛋白在鼠伤寒沙门氏菌对氟喹诺酮类耐药中的作用,选取盐酸环丙沙星、恩诺沙星、诺氟沙星等药物以及鼠伤寒沙门氏菌、沙门氏菌噬菌体等,开展体外诱导鉴定、检测诱导菌中多种耐药泵表达水平,同时分析调控蛋白在多重耐药菌中的作用,并且探讨RamA对不同药物的影响。结果表明:鼠伤寒沙门氏菌对氟喹诺酮类耐药主要是在MdtK与AcrAB协同作用下实现的;外排氟喹诺酮类多重耐药泵的主要调控体系为RamR-RamA;细菌受新GyrB靶位点的影响,而使其对氟喹诺酮类敏感性有所下降;同时RamA对环丙沙星突变株有一定的影响,促进了其突变株产生。由此得出,多重耐药泵及其调控蛋白在鼠伤寒沙门氏菌对氟喹诺酮类耐药中具有积极的作用。

  14. New resistance genes in the Zea mays: exserohilum turcicum pathosystem

    Directory of Open Access Journals (Sweden)

    Juliana Bernardi Ogliari

    2005-09-01

    Full Text Available The use of monogenic race-specific resistance is widespread for the control of maize (Zea mays L. helminthosporiosis caused by Exserohilum turcicum. Inoculation of 18 Brazilian isolates of E. turcicum onto elite maize lines containing previously identified resistance genes and onto differential near-isogenic lines allowed the identification of new qualitative resistance genes. The inoculation of one selected isolate on differential near-isogenic lines, F1 generations and a BC1F1 population from the referred elite lines enabled the characterization of the resistance spectrum of three new genes, one dominant (HtP, one recessive (rt and a third with non-identified genetic action. Three physiological races of the pathogen were also identified including two with new virulence factors capable of overcoming the resistance of one of the resistance genes identified here (rt.

  15. Presence of quinolone resistance to qnrB1 genes and blaOXA-48 carbapenemase in clinical isolates of Klebsiella pneumoniae in Spain.

    Science.gov (United States)

    Rodríguez Martínez, J M; Díaz-de Alba, P; Lopez-Cerero; Ruiz-Carrascoso, G; Gomez-Gil, R; Pascual, A

    2014-01-01

    A study is presented on the presence of quinolone resistance qnrB1 genes in clinical isolates belonging to the largest series of infections caused by OXA-48-producing Klebsiella pneumoniae in a single-centre outbreak in Spain. Evidence is also provided, according to in vitro results, that there is a possibility of co-transfer of plasmid harbouring blaOXA-48 with an other plasmid harbouring qnrB1 in presence of low antibiotic concentrations of fluoroquinolones, showing the risk of multi-resistance screening. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Comparison of clinical categories for Escherichia coli harboring specific qnr and chromosomal-mediated fluoroquinolone resistance determinants according to CLSI and EUCAST.

    Science.gov (United States)

    Machuca, Jesús; Briales, Alejandra; Díaz-de-Alba, Paula; Martínez-Martínez, Luis; Rodríguez-Martínez, José-Manuel; Pascual, Álvaro

    2016-03-01

    EUCAST breakpoints are more restrictive than those defined by CLSI. This study highlights the discrepancies between CLSI and EUCAST in a well characterized isogenic Escherichia coli collection and their correlations with specific quinolone resistance mechanisms. The greatest number of discrepancies was observed in strains containing 2-4 resistance mechanisms (MIC values on the borderline of clinical resistance). Bearing in mind that quinolones are concentration dependent antimicrobial agents, small changes in MIC may have relevant consequences for treatment outcomes. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. The Vf gene for scrab resistance in apple is linked to sub-lethal genes

    NARCIS (Netherlands)

    Gao, Z.S.; Weg, van de W.E.

    2006-01-01

    V f is the most widely used resistance gene in the breeding for scab resistant apple cultivars. Distorted segregation ratios for V f -resistance have frequently been reported. Here we revealed that sub-lethal genes caused the distorted segregation. The inheritance of V f was examined in six progenie

  18. A comparison of interview methods to ascertain fluoroquinolone exposure before tuberculosis diagnosis.

    Science.gov (United States)

    Van Der Heijden, Y F; Maruri, F; Holt, E; Mitchel, E; Warkentin, J; Sterling, T R

    2015-04-01

    SUMMARY Fluoroquinolone use before tuberculosis (TB) diagnosis delays the time to diagnosis and treatment, and increases the risk of fluoroquinolone-resistant TB and death. Ascertainment of fluoroquinolone exposure could identify such high-risk patients. We compared four methods of ascertaining fluoroquinolone exposure in the 6 months prior to TB diagnosis in culture-confirmed TB patients in Tennessee from January 2007 to December 2009. The four methods included a simple questionnaire administered to all TB suspects by health department personnel (FQ-Form), an in-home interview conducted by research staff, outpatient and inpatient medical record review, and TennCare pharmacy database review. Of 177 TB patients included, 72 (41%) received fluoroquinolones during the 6 months before TB diagnosis. Fluoroquinolone exposure determined by review of inpatient and outpatient medical records was considered the gold standard for comparison. The FQ-Form had 61% [95% confidence interval (CI) 48-73] sensitivity and 93% (95% CI 85-98) specificity (agreement 79%, kappa = 0.56) while the in-home interview had 28% (95% CI 18-40) sensitivity and 99% (94-100%) specificity (agreement 68%, kappa = 0.29). A simple questionnaire administered by health department personnel identified fluoroquinolone exposure before TB diagnosis with moderate reliability.

  19. 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.

  20. [Differences between species involved and fluoroquinolone resistance patterns of strains isolated from bacteriuria according to nosocomial, health-related or community-acquired onset].

    Science.gov (United States)

    Tassain, Jérome; N'Guyen, Yohan; Batalla, Anne-Sophie; Duval, Véronique; Guillard, Thomas; De Champs, Christophe; Strady, Christophe

    2012-12-01

    To describe and to compare species and antibiotics resistance patterns of bacteria involved among bacteriuria from hospital and city laboratories and among health-related and community-acquired bacteriuria. Epidemiologic transversal study conducted among Bacteriology laboratories of University Hospital (UH) and the whole city of Reims, during the week 21 to 26 June 2010. A standardized investigation form was completed after telephonical interview with the prescriber. One hundred and eighty-nine strains have been isolated among 179 urocultures. One hundred and seven strains were isolated in city laboratories and 82 in UH laboratory. Strains were community-acquired, health-related and nosocomial in 136, 22 and 31 cases, respectively. More Gram positive bacteria and ofloxacin resistant strains were isolated among UH strains (P=0.001 and P=0.015, respectively) and among health-related strains (P=0.01 and P=0.003, respectively). When analysis was restricted only to Enterobacteriaceae or to Escherichia coli, the ofloxacin resistance rate was no more elevated among health-related or UH strains. Ofloxacin resistant Enterobacteriaceae were more frequently resistant to all other classes of antibiotics except nitrofurans. Strains isolated in health-related bacteriuria are more frequently ofloxacin resistant principally because of the greater proportion of Gram positive bacteria and because of a non-significant higher ofloxacin resistance rate among Enterobacteriaceae. Numerous studies only focus on Enterobacteriaceae, and the data from our study need to be confirmed on larger samples, in order to validate the predictive value of health-related bacteriuria for ofloxacin resistance. Copyright © 2012. Published by Elsevier Masson SAS.

  1. Sponge microbiota are a reservoir of functional antibiotic resistance genes

    Directory of Open Access Journals (Sweden)

    Dennis Versluis

    2016-11-01

    Full Text Available Wide application of antibiotics has contributed to the evolution of multi-drug resistant human pathogens, resulting in poorer treatment outcomes for infections. In the marine environment, seawater samples have been investigated as a resistance reservoir; however, no studies have methodically examined sponges as a reservoir of antibiotic resistance. Sponges could be important in this respect because they often contain diverse microbial communities that have the capacity to produce bioactive metabolites. Here, we applied functional metagenomics to study the presence and diversity of functional resistance genes in the sponges Aplysina aerophoba, Petrosia ficiformis and Corticium candelabrum. We obtained 37 insert sequences facilitating resistance to D-cycloserine (n=6, gentamicin (n=1, amikacin (n=7, trimethoprim (n=17, chloramphenicol (n=1, rifampicin (n=2 and ampicillin (n=3. Fifteen of 37 inserts harboured resistance genes that shared <90% amino acid identity with known gene products, whereas on 13 inserts no resistance gene could be identified with high confidence, in which case we predicted resistance to be mainly mediated by antibiotic efflux. One marine-specific ampicillin-resistance-conferring β-lactamase was identified in the genus Pseudovibrio with 41% global amino acid identity to the closest β-lactamase with demonstrated functionality, and subsequently classified into a new family termed PSV. Taken together, our results show that sponge microbiota host diverse and novel resistance genes that may be harnessed by phylogenetically distinct bacteria.

  2. Fluoroquinolones and second-line injectable anti-TB drug susceptibility analysis in 30 multidrug-resistant Mycobacterium tuberculosis clinical isolates%耐多药结核分枝杆菌临床分离株30株对氟喹诺酮类及二线注射类抗结核药敏感性的分析

    Institute of Scientific and Technical Information of China (English)

    刘一典; 桂徐蔚; 景玲杰; 郝晓晖; 姚岚; 韩敏; 陈晋; 唐神结

    2013-01-01

    目的 了解耐多药结核分枝杆菌对氟喹诺酮类和(或)二线注射类抗结核药物的敏感性情况.方法 收集2011年6~9月采用Bactec-MGIT 960检测的30株耐多药结核分枝杆菌临床分离株,检测其对氟喹诺酮类及二线注射类抗结核药的药敏结果并进行分析.结果 30株耐多药结核分枝杆菌菌株对氟喹诺酮类和二线注射类抗结核药物耐药共21株(70%).单药耐药依次为:氧氟沙星耐药19株(63.33%),莫西沙星耐药13株(耐药率43.33%),左氧氟沙星耐药10株(耐药率33.33%),阿米卡星耐药9株(耐药率30%),卷曲霉素最少(26.67%).氧氟沙星耐药率高于左氧氟沙星耐药和三种氟喹诺酮类药同时耐药,差异有统计学意义(P=0.038).氟喹诺酮类任意耐药及两种注射类药物任意耐药共8株[即广泛耐药结核病(XDR-TB)].氟喹诺酮类任意耐药及两种注射类药物敏感为11株,氟喹诺酮类均敏感及两种注射类药物任意耐药为2株,相比差异有统计学意义(P =0.001).结论 耐多药结核病(MDR-TB)临床分离株对氟喹诺酮类药物耐药严重,氟喹诺酮类药物的耐药也是早期XDR-TB菌株的耐药主要形式.因此,氧氟沙星不建议作为MDR-TB的治疗用药.而MDR-TB临床分离株对阿米卡星和卷曲霉素敏感性较好,推荐可用于MDR-TB的首选药物.%Objective To investigate the drug susceptibility of fluoroquinolones and/or second-line injectable anti-TB drugs in multidrug resistant (MDR) Mycobacterium tuberculosis.Methods A total of 30 clinical isolates of MDR Mycobacterium tuberculosis were gathered,identificated by Bactec-MGIT 960,tested for drug susceptibility of fluoroquinolones and second-line injectable anti-TB drug,and the results were analysed.Results Twenty one isolates were resistant to fluoroquinolones or second-line injectable anti-TB drug in 30 MDR Mycobacterium tuberculosis isolates.Single drug resistance followed by:ofloxacin resistance was 19 isolates(resistance

  3. 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.

  4. Diverse antibiotic resistance genes in dairy cow manure.

    Science.gov (United States)

    Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

    2014-04-22

    Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. IMPORTANCE The increasing prevalence of antibiotic resistance among bacteria is one of the most intractable challenges in 21st-century public health. The origins of resistance are complex, and a better understanding of the impacts of antibiotics used on farms would produce a more robust platform for public policy. Microbiomes of farm animals are reservoirs of antibiotic resistance genes, which may affect distribution of antibiotic resistance genes in human pathogens. Previous studies have focused on antibiotic resistance genes in manures of animals subjected

  5. Associations between Antimicrobial Resistance Phenotypes, Antimicrobial Resistance Genes, and Virulence Genes of Fecal Escherichia coli Isolates from Healthy Grow-Finish Pigs ▿

    OpenAIRE

    2009-01-01

    Escherichia coli often carries linked antimicrobial resistance genes on transmissible genetic elements. Through coselection, antimicrobial use may select for unrelated but linked resistance or virulence genes. This study used unconditional statistical associations to investigate the relationships between antimicrobial resistance phenotypes and antimicrobial resistance genes in 151 E. coli isolates from healthy pigs. Phenotypic resistance to each drug was significantly associated with phenotyp...

  6. Amplification of a Gene Related to Mammalian mdr Genes in Drug-Resistant Plasmodium falciparum

    Science.gov (United States)

    Wilson, Craig M.; Serrano, Adelfa E.; Wasley, Annemarie; Bogenschutz, Michael P.; Shankar, Anuraj H.; Wirth, Dyann F.

    1989-06-01

    The malaria parasite Plasmodium falciparum contains at least two genes related to the mammalian multiple drug resistance genes, and at least one of the P. falciparum genes is expressed at a higher level and is present in higher copy number in a strain that is resistant to multiple drugs than in a strain that is sensitive to the drugs.

  7. Computational gene network study on antibiotic resistance genes of Acinetobacter baumannii.

    Science.gov (United States)

    Anitha, P; Anbarasu, Anand; Ramaiah, Sudha

    2014-05-01

    Multi Drug Resistance (MDR) in Acinetobacter baumannii is one of the major threats for emerging nosocomial infections in hospital environment. Multidrug-resistance in A. baumannii may be due to the implementation of multi-combination resistance mechanisms such as β-lactamase synthesis, Penicillin-Binding Proteins (PBPs) changes, alteration in porin proteins and in efflux pumps against various existing classes of antibiotics. Multiple antibiotic resistance genes are involved in MDR. These resistance genes are transferred through plasmids, which are responsible for the dissemination of antibiotic resistance among Acinetobacter spp. In addition, these resistance genes may also have a tendency to interact with each other or with their gene products. Therefore, it becomes necessary to understand the impact of these interactions in antibiotic resistance mechanism. Hence, our study focuses on protein and gene network analysis on various resistance genes, to elucidate the role of the interacting proteins and to study their functional contribution towards antibiotic resistance. From the search tool for the retrieval of interacting gene/protein (STRING), a total of 168 functional partners for 15 resistance genes were extracted based on the confidence scoring system. The network study was then followed up with functional clustering of associated partners using molecular complex detection (MCODE). Later, we selected eight efficient clusters based on score. Interestingly, the associated protein we identified from the network possessed greater functional similarity with known resistance genes. This network-based approach on resistance genes of A. baumannii could help in identifying new genes/proteins and provide clues on their association in antibiotic resistance.

  8. First characterisation of plasmid-mediated quinolone resistance-qnrS1 co-expressed bla CTX-M-15 and bla DHA-1 genes in clinical strain of Morganella morganii recovered from a Tunisian Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    S Mahrouki

    2012-01-01

    Full Text Available Purpose: Aim of this study was to show the emergence of the qnr genes among fluoroquinolone-resistant, AMPC and ESBL (extended-spectrum-beta-lactamase co-producing Morganella morganii isolate. Materials and Methods: A multi resistant Morganella morganii SM12012 isolate was recovered from pus from a patient hospitalized in the intensive care unit at the Military hospital, Tunisia. Antibiotic susceptibility was tested with the agar disk diffusion method according to Clinical and Laboratory Standards Institute guidelines. ESBLs were detected using a standard double-disk synergy test. The characterization of beta-lactamases and associated resistance genes were performed by isoelectric focusing, polymerase chain reaction and nucleotide sequencing. Results: The antimicrobial susceptibility testing showed the high resistance to penicillins, cephalosporins (MICs: 64-512 μg/ml and fluoroquinolones (MICs: 32-512 μg/ml. But M. morganii SM12012 isolate remained susceptible to carbapenems (MICs: 4-<0.25 μg/ml. The double-disk synergy test confirmed the phenotype of extended-spectrum β-lactamases (ESBLs. Three identical β-lactamases with pI values of 6.5, 7.8 and superior to 8.6 were detected after isoelectric focusing analysis. These β-lactamases genes can be successfully transferred by the conjugative plasmid. Molecular analysis demonstrated the co-production of bla DHA-1, bla CTX-M-15 and qnrS1 genes on the same plasmid. The detection of an associated chromosomal quinolone resistance revealed the presence of a parC mutation at codon 80 (Ser80-lle80. Conclusion: This is the first report in Tunisia of nosocomial infection due to the production of CTX-M-15 and DHA-1 β-lactamases in M. morganii isolate with the association of quinolone plasmid resistance. The incidence of these strains invites continuous monitoring of such multidrug-resistant strains and the further study of their epidemiologic evolution.

  9. Fluoroquinolone and Quinazolinedione Activities against Wild-Type and Gyrase Mutant Strains of Mycobacterium smegmatis▿

    Science.gov (United States)

    Malik, Muhammad; Marks, Kevin R.; Mustaev, Arkady; Zhao, Xilin; Chavda, Kalyan; Kerns, Robert J.; Drlica, Karl

    2011-01-01

    Quinazolinediones (diones) are fluoroquinolone-like inhibitors of bacterial gyrase and DNA topoisomerase IV. To assess activity against mycobacteria, C-8-methoxy dione derivatives were compared with cognate fluoroquinolones by using cultured Mycobacterium smegmatis. Diones exhibited higher MIC values than fluoroquinolones; however, MICs for fluoroquinolone-resistant gyrA mutants, normalized to the MIC for wild-type cells, were lower. Addition of a 3-amino group to the 2,4-dione core increased relative activity against mutants, while alteration of the 8-methoxy group to a methyl or of the 2,4-dione core to a 1,3-dione core lowered activity against mutants. A GyrA G89C bacterial variant was strikingly susceptible to most of the diones tested; in contrast, low susceptibility to fluoroquinolones was observed. Many of the bacteriostatic differences between diones and fluoroquinolones were explained by interactions at the N terminus of GyrA helix IV revealed by recently published X-ray structures of drug-topoisomerase-DNA complexes. When lethal activity was normalized to the MIC in order to minimize the effects of drug uptake, efflux, and ternary complex formation, a 3-amino-2,4-dione exhibited killing activity comparable to that of a cognate fluoroquinolone. Surprisingly, the lethal activity of the dione was inhibited less by chloramphenicol than that of the cognate fluoroquinolone. This observation adds the 2,4-dione structural motif to the list of structural features known to impart lethality to fluoroquinolone-like compounds in the absence of protein synthesis, a phenomenon that is not explained by X-ray structures of drug-enzyme-DNA complexes. PMID:21383100

  10. Exploiting natural variation to identify insect-resistance genes.

    Science.gov (United States)

    Broekgaarden, Colette; Snoeren, Tjeerd A L; Dicke, Marcel; Vosman, Ben

    2011-10-01

    Herbivorous insects are widespread and often serious constraints to crop production. The use of insect-resistant crops is a very effective way to control insect pests in agriculture, and the development of such crops can be greatly enhanced by knowledge on plant resistance mechanisms and the genes involved. Plants have evolved diverse ways to cope with insect attack that has resulted in natural variation for resistance towards herbivorous insects. Studying the molecular genetics and transcriptional background of this variation has facilitated the identification of resistance genes and processes that lead to resistance against insects. With the development of new technologies, molecular studies are not restricted to model plants anymore. This review addresses the need to exploit natural variation in resistance towards insects to increase our knowledge on resistance mechanisms and the genes involved. We will discuss how this knowledge can be exploited in breeding programmes to provide sustainable crop protection against insect pests. Additionally, we discuss the current status of genetic research on insect-resistance genes. We conclude that insect-resistance mechanisms are still unclear at the molecular level and that exploiting natural variation with novel technologies will contribute greatly to the development of insect-resistant crop varieties.

  11. Sponge Microbiota are a Reservoir of Functional Antibiotic Resistance Genes

    DEFF Research Database (Denmark)

    Versluis, Dennis; de Evgrafov, Mari Cristina Rodriguez; Sommer, Morten Otto Alexander

    2016-01-01

    Wide application of antibiotics has contributed to the evolution of multi-drug resistant human pathogens, resulting in poorer treatment outcomes for infections. In the marine environment, seawater samples have been investigated as a resistance reservoir; however, no studies have methodically...... examined sponges as a reservoir of antibiotic resistance. Sponges could be important in this respect because they often contain diverse microbial communities that have the capacity to produce bioactive metabolites. Here, we applied functional metagenomics to study the presence and diversity of functional......). Fifteen of 37 inserts harbored resistance genes that shared resistance gene could be identified with high confidence, in which case we predicted resistance to be mainly mediated by antibiotic efflux. One marine-specific ampicillin-resistance...

  12. Staphyloferrin A as siderophore-component in fluoroquinolone-based Trojan horse antibiotics.

    Science.gov (United States)

    Milner, Stephen J; Seve, Alexandra; Snelling, Anna M; Thomas, Gavin H; Kerr, Kevin G; Routledge, Anne; Duhme-Klair, Anne-Kathrin

    2013-06-07

    A series of fluoroquinolone conjugates was synthesised by linking the carboxylic acid functionality of the carboxylate-type siderophore staphyloferrin A and its derivatives to the piperazinyl nitrogen of ciprofloxacin and norfloxacin via amide bond formation. Four siderophore-drug conjugates were screened against a panel of bacteria associated with infection in humans. Whilst no activity was found against ciprofloxacin- or norfloxacin-resistant bacteria, one of the conjugates retained antibacterial activity against fluoroquinolone-susceptible strains although the structure of its lysine-based siderophore component differs from that of the natural siderophore staphyloferrin A. In contrast, three ornithine-based siderophore conjugates showed significantly reduced activity against strains that are susceptible to their respective parent fluoroquinolones, regardless of the type of fluoroquinolone attached or chirality at the ornithine Cα-atom. The loss of potency observed for the (R)- and (S)-ornithine-based ciprofloxacin conjugates correlates with their reduced inhibitory activity against the target enzyme DNA gyrase.

  13. AMINOGLYCOSIDE RESISTANCE GENES IN Pseudomonas aeruginosa ISOLATES FROM CUMANA, VENEZUELA.

    Science.gov (United States)

    Teixeira, Bertinellys; Rodulfo, Hectorina; Carreño, Numirin; Guzmán, Militza; Salazar, Elsa; De Donato, Marcos

    2016-01-01

    The enzymatic modification of aminoglycosides by aminoglycoside-acetyltransferases (AAC), aminoglycoside-adenyltransferases (AAD), and aminoglycoside-phosphotransferases (APH), is the most common resistance mechanism in P. aeruginosa and these enzymes can be coded on mobile genetic elements that contribute to their dispersion. One hundred and thirty seven P. aeruginosa isolates from the University Hospital, Cumana, Venezuela (HUAPA) were evaluated. Antimicrobial susceptibility was determined by the disk diffusion method and theaac, aadB and aph genes were detected by PCR. Most of the P. aeruginosa isolates (33/137) were identified from the Intensive Care Unit (ICU), mainly from discharges (96/137). The frequency of resistant P. aeruginosaisolates was found to be higher for the aminoglycosides tobramycin and amikacin (30.7 and 29.9%, respectively). Phenotype VI, resistant to these antibiotics, was the most frequent (14/49), followed by phenotype I, resistant to all the aminoglycosides tested (12/49). The aac(6´)-Ib,aphA1 and aadB genes were the most frequently detected, and the simultaneous presence of several resistance genes in the same isolate was demonstrated. Aminoglycoside resistance in isolates ofP. aeruginosa at the HUAPA is partly due to the presence of the aac(6´)-Ib, aphA1 andaadB genes, but the high rates of antimicrobial resistance suggest the existence of several mechanisms acting together. This is the first report of aminoglycoside resistance genes in Venezuela and one of the few in Latin America.

  14. AMINOGLYCOSIDE RESISTANCE GENES IN Pseudomonas aeruginosa ISOLATES FROM CUMANA, VENEZUELA

    Science.gov (United States)

    TEIXEIRA, Bertinellys; RODULFO, Hectorina; CARREÑO, Numirin; GUZMÁN, Militza; SALAZAR, Elsa; DONATO, Marcos DE

    2016-01-01

    The enzymatic modification of aminoglycosides by aminoglycoside-acetyltransferases (AAC), aminoglycoside-adenyltransferases (AAD), and aminoglycoside-phosphotransferases (APH), is the most common resistance mechanism in P. aeruginosa and these enzymes can be coded on mobile genetic elements that contribute to their dispersion. One hundred and thirty seven P. aeruginosa isolates from the University Hospital, Cumana, Venezuela (HUAPA) were evaluated. Antimicrobial susceptibility was determined by the disk diffusion method and theaac, aadB and aph genes were detected by PCR. Most of the P. aeruginosa isolates (33/137) were identified from the Intensive Care Unit (ICU), mainly from discharges (96/137). The frequency of resistant P. aeruginosaisolates was found to be higher for the aminoglycosides tobramycin and amikacin (30.7 and 29.9%, respectively). Phenotype VI, resistant to these antibiotics, was the most frequent (14/49), followed by phenotype I, resistant to all the aminoglycosides tested (12/49). The aac(6´)-Ib,aphA1 and aadB genes were the most frequently detected, and the simultaneous presence of several resistance genes in the same isolate was demonstrated. Aminoglycoside resistance in isolates ofP. aeruginosa at the HUAPA is partly due to the presence of the aac(6´)-Ib, aphA1 andaadB genes, but the high rates of antimicrobial resistance suggest the existence of several mechanisms acting together. This is the first report of aminoglycoside resistance genes in Venezuela and one of the few in Latin America. PMID:27007556

  15. Mapping of the apple scab-resistance gene Vb.

    Science.gov (United States)

    Erdin, N; Tartarini, S; Broggini, G A L; Gennari, F; Sansavini, S; Gessler, C; Patocchi, A

    2006-10-01

    Apple scab, caused by the fungus Venturia inaequalis, is the major production constraint in temperate zones with humid springs. Normally, its control relies on frequent and regular fungicide applications. Because this control strategy has come under increasing criticism, major efforts are being directed toward the breeding of scab-resistant apple cultivars. Modern apple breeding programs include the use of molecular markers, making it possible to combine several different scab-resistance genes in 1 apple cultivar (pyramiding) and to speed up the breeding process. The apple scab-resistance gene Vb is derived from the Siberian crab apple 'Hansen's baccata #2', and is 1 of the 6 "historical" major apple scab-resistance genes (Vf, Va, Vr, Vbj, Vm, and Vb). Molecular markers have been published for all these genes, except Vr. In testcross experiments conducted in the 1960s, it was reported that Vb segregated independently from 3 other major resistance genes, including Vf. Recently, however, Vb and Vf have both been mapped on linkage group 1, a result that contrasts with the findings from former testcross experiments. In this study, simple sequence repeat (SSR) markers were used to identify the precise position of Vb in a cross of 'Golden Delicious' (vbvb) and 'Hansen's baccata #2' (Vbvb). A genome scanning approach, a fast method already used to map apple scab-resistance genes Vr2 and Vm, was used, and the Vb locus was identified on linkage group 12, between the SSR markers Hi02d05 and Hi07f01. This finding confirms the independent segregation of Vb from Vf. With the identification of SSR markers linked to Vb, another major apple scab-resistance gene has become available; breeders can use it to develop durable resistant cultivars with several different resistance genes.

  16. Quinolone Resistance among Salmonella enterica from Cattle, Broilers and Swine in Denmark

    DEFF Research Database (Denmark)

    Wiuff, C.; Baggesen, Dorte Lau; Madsen, M.

    2000-01-01

    This study was conducted to determine the susceptibility to nalidixic acid and fluoroquinolones of Salmonella Dublin, S. Enteritidis, and S. Typhimurium isolates from cattle, broilers, and pigs over time in Denmark and to characterise the gyrA, gyrB, and parC genes in quinolone-resistant isolates...

  17. Are duplicated genes responsible for anthracnose resistance in common bean?

    Science.gov (United States)

    Costa, Larissa Carvalho; Nalin, Rafael Storto; Ramalho, Magno Antonio Patto; de Souza, Elaine Aparecida

    2017-01-01

    The race 65 of Colletotrichum lindemuthianum, etiologic agent of anthracnose in common bean, is distributed worldwide, having great importance in breeding programs for anthracnose resistance. Several resistance alleles have been identified promoting resistance to this race. However, the variability that has been detected within race has made it difficult to obtain cultivars with durable resistance, because cultivars may have different reactions to each strain of race 65. Thus, this work aimed at studying the resistance inheritance of common bean lines to different strains of C. lindemuthianum, race 65. We used six C. lindemuthianum strains previously characterized as belonging to the race 65 through the international set of differential cultivars of anthracnose and nine commercial cultivars, adapted to the Brazilian growing conditions and with potential ability to discriminate the variability within this race. To obtain information on the resistance inheritance related to nine commercial cultivars to six strains of race 65, these cultivars were crossed two by two in all possible combinations, resulting in 36 hybrids. Segregation in the F2 generations revealed that the resistance to each strain is conditioned by two independent genes with the same function, suggesting that they are duplicated genes, where the dominant allele promotes resistance. These results indicate that the specificity between host resistance genes and pathogen avirulence genes is not limited to races, it also occurs within strains of the same race. Further research may be carried out in order to establish if the alleles identified in these cultivars are different from those described in the literature.

  18. Molecular characterization of clinical Streptococcus pneumoniae isolates with reduced susceptibility to fluoroquinolones emerging in Italy.

    Science.gov (United States)

    Montanari, Maria Pia; Tili, Emily; Cochetti, Ileana; Mingoia, Marina; Manzin, Aldo; Varaldo, Pietro Emanuele

    2004-01-01

    Fifteen Streptococcus pneumoniae clinical isolates with reduced fluoroquinolone susceptibility (defined as a ciprofloxacin MIC of > or = 4 microg/ml), all collected in Italy in 2000-2003, were typed and subjected to extensive molecular characterization to define the contribution of drug target alterations and efflux mechanisms to their resistance. Serotyping and pulsed-field gel electrophoresis analysis indicated substantial genetic unrelatedness among the 15 isolates, suggesting that the new resistance traits arise in multiple indigenous strains rather than through clonal dissemination. Sequencing of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE demonstrated that point mutations producing single amino acid changes were more frequent in topoisomerase IV (parC mutations in 14 isolates and parE mutations in 13) than in DNA gyrase subunits (gyrA mutations in 7 isolates and no gyrB mutations observed). No isolate displayed a quinolone efflux system susceptible to carbonyl cyanide m-chlorophenylhydrazone; conversely, four-fold or greater MIC reductions in the presence of reserpine were observed in all 15 isolates with ethidium bromide, in 13 with ulifloxacin, in 9 with ciprofloxacin, in 5 with norfloxacin, and in none with five other fluoroquinolones. The effect of efflux pump activity on the level and profile of fluoroquinolone resistance in our strains was minor compared with that of target site modifications. DNA mutations and/or efflux systems other than those established so far might contribute to the fluoroquinolone resistance expressed by our strains. Susceptibility profiles to nonquinolone class antibiotics and resistance-associated phenotypic and genotypic characteristics were also determined and correlated with fluoroquinolone resistance. A unique penicillin-binding protein profile was observed in all five penicillin-resistant isolates, whereas the same PBP profile as S. pneumoniae R6 was exhibited by all six penicillin

  19. Genes for resistance to zucchini yellow mosaic in tropical pumpkin.

    Science.gov (United States)

    Pachner, Martin; Paris, Harry S; Lelley, Tamas

    2011-01-01

    Four cultigens of Cucurbita moschata resistant to zucchini yellow mosaic virus were crossed with the susceptible 'Waltham Butternut' and with each other in order to clarify the mode of inheritance of resistance and relationships among the genes involved. Five loci were segregating, with genes for resistance Zym-0 and Zym-4 carried by 'Nigerian Local' and one of them also carried by 'Nicklow's Delight,' Zym-1 carried by 'Menina,' and zym-6 carried by 'Soler.' A recessive gene carried by 'Waltham Butternut,' zym-5, is complementary with the dominant Zym-4 of 'Nigerian Local,' that is, the resistance conferred by Zym-4 is only expressed in zym-5/zym-5 individuals. Gene zym-6 appears to be linked to either Zym-0 or Zym-4, and it is also possible that Zym-1 is linked to one of them as well.

  20. The impact of insulin resistance, gender, genes, glucocorticoids and ...

    African Journals Online (AJOL)

    The impact of insulin resistance, gender, genes, glucocorticoids and ethnicity on body ... The metabolic consequences of obesity are highly dependent on body fat ... it has been suggested that insulin sensitivity at the level of the adipocyte may ...

  1. Differential Expression of Salinity Resistance Gene on Cotton

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Salinity resistance and differential gene expression associated with salinity in cotton germplasm were studied,because of the large scale area of salinity in China,and its significant negative effects on

  2. Salmonella typhi in the democratic republic of the congo: fluoroquinolone decreased susceptibility on the rise.

    Directory of Open Access Journals (Sweden)

    Octavie Lunguya

    Full Text Available BACKGROUND: Drug resistance of Salmonella enterica serovar Typhi (Salmonella Typhi to first-line antibiotics is emerging in Central Africa. Although increased use of fluoroquinolones is associated with spread of resistance, Salmonella Typhi with decreased ciprofloxacin susceptibility (DCS has rarely been reported in Central Africa. METHODOLOGY/PRINCIPAL FINDINGS: As part of a microbiological surveillance study in the Democratic Republic of the Congo (DR Congo, Salmonella Typhi isolates from bloodstream infections were collected prospectively between 2007 and 2011. The genetic relationship of the Salmonella Typhi isolates was assessed by pulsed-field gel electrophoresis (PFGE. The antimicrobial resistance profile of the isolates was determined and mutations associated with DCS were studied. In total, 201 Salmonella Typhi isolates were collected. More than half of the Salmonella Typhi isolates originated from children and young adults aged 5-19. Thirty different PFGE profiles were identified, with 72% of the isolates showing a single profile. Multidrug resistance, DCS and azithromycin resistance were 30.3%, 15.4% and 1.0%, respectively. DCS was associated with point mutations in the gyrA gene at codons 83 and 87. CONCLUSIONS/SIGNIFICANCE: Our study describes the first report of widespread multidrug resistance and DCS among Salmonella Typhi isolates from DR Congo. Our findings highlight the need for increased microbiological diagnosis and surveillance in DR Congo, being a prerequisite for rational use of antimicrobials and the development of standard treatment guidelines.

  3. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.

    2016-01-01

    Combination therapy with several antibiotics is one strategy that has been applied in order to limit the spread of antimicrobial resistance. We compared the de novo evolution of resistance during combination therapy with the β-lactam ceftazidime and the fluoroquinolone ciprofloxacin with the resi......Combination therapy with several antibiotics is one strategy that has been applied in order to limit the spread of antimicrobial resistance. We compared the de novo evolution of resistance during combination therapy with the β-lactam ceftazidime and the fluoroquinolone ciprofloxacin...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

  4. Resistance gene management: concepts and practice

    Science.gov (United States)

    Christopher C. Mundt

    2012-01-01

    There is now a very long history of genetics/breeding for disease resistance in annual crops. These efforts have resulted in conceptual advances and frustrations, as well as practical successes and failures. This talk will review this history and its relevance to the genetics of resistance in forest species. All plant breeders and pathologists are familiar with boom-...

  5. Fluoroquinolones in children: update of the literature.

    Science.gov (United States)

    Bacci, Caterina; Galli, Luisa; de Martino, Maurizio; Chiappini, Elena

    2015-10-01

    The use of fluoroquinolones (FQ), antibiotics, which have excellent pharmacokinetic and pharmacodynamic characteristics and a broad spectrum of action, has increased dramatically in recent years, both in adults and children. Numerous safety and efficacy data are now available on FQ use in children, particularly regarding the treatment of complicated infections of the urinary tract, typhoid fever, pneumonia, acute external otitis, acute media otitis, meningoencephalitis, sepsis in neutropenic children and multidrug-resistant tuberculosis (MDR-TB), though sometimes studies have the limitations that they were conducted in selected populations, such as children with cystic fibrosis. Despite available safety data are encouraging, there is still an open debate on the toxicity of this class of antibiotics on weight-bearing joints in children. Not being able to exclude the possibility that, in rare cases, this event is likely to occur, their use in children should be limited to cases where the cost-benefit has been carefully examined, for example, in the case of sepsis or other severe infections from multi-resistant bacteria and not responsive to other classes of drugs. Furthermore, considering the increased use of FQ in children, it is possible that there is an increase in the incidence of infections from resistant germs (such as Escherichia coli, and pneumococci), as occurred in adults. In order to limit the diffusion of resistance, a judicious and appropriate use of this class of drugs is recommended.

  6. The antimicrobial resistance crisis: management through gene monitoring

    Science.gov (United States)

    2016-01-01

    Antimicrobial resistance (AMR) is an acknowledged crisis for humanity. Its genetic origins and dire potential outcomes are increasingly well understood. However, diagnostic techniques for monitoring the crisis are currently largely limited to enumerating the increasing incidence of resistant pathogens. Being the end-stage of the evolutionary process that produces antimicrobial resistant pathogens, these measurements, while diagnostic, are not prognostic, and so are not optimal in managing this crisis. A better test is required. Here, using insights from an understanding of evolutionary processes ruling the changing abundance of genes under selective pressure, we suggest a predictive framework for the AMR crisis. We then discuss the likely progression of resistance for both existing and prospective antimicrobial therapies. Finally, we suggest that by the environmental monitoring of resistance gene frequency, resistance may be detected and tracked presumptively, and how this tool may be used to guide decision-making in the local and global use of antimicrobials. PMID:27831476

  7. Apple contains receptor-like genes homologous to the Cladosporium fulvum resistance gene family of tomato with a cluster of genes cosegregating with Vf apple scab resistance.

    Science.gov (United States)

    Vinatzer, B A; Patocchi, A; Gianfranceschi, L; Tartarini, S; Zhang, H B; Gessler, C; Sansavini, S

    2001-04-01

    Scab caused by the fungal pathogen Venturia inaequalis is the most common disease of cultivated apple (Malus x domestica Borkh.). Monogenic resistance against scab is found in some small-fruited wild Malus species and has been used in apple breeding for scab resistance. Vf resistance of Malus floribunda 821 is the most widely used scab resistance source. Because breeding a high-quality cultivar in perennial fruit trees takes dozens of years, cloning disease resistance genes and using them in the transformation of high-quality apple varieties would be advantageous. We report the identification of a cluster of receptor-like genes with homology to the Cladosporium fulvum (Cf) resistance gene family of tomato on bacterial artificial chromosome clones derived from the Vf scab resistance locus. Three members of the cluster were sequenced completely. Similar to the Cf gene family of tomato, the deduced amino acid sequences coded by these genes contain an extracellular leucine-rich repeat domain and a transmembrane domain. The transcription of three members of the cluster was determined by reverse transcriptionpolymerase chain reaction to be constitutive, and the transcription and translation start of one member was verified by 5' rapid amplification of cDNA ends. We discuss the parallels between Cf resistance of tomato and Vf resistance of apple and the possibility that one of the members of the gene cluster is the Vf gene. Cf homologs from other regions of the apple genome also were identified and are likely to present other scab resistance genes.

  8. Occurrence and reservoirs of antibiotic resistance genes in the environment

    NARCIS (Netherlands)

    Seveno, N.; Kallifidas, D.; Smalla, K.; Elsas, van J.D.; Collard, J.M.; Karagouni, A.; Wellington, E.M.H.

    2002-01-01

    Antibiotic resistance genes have become highly mobile since the development of antibiotic chemotherapy. A considerable body of evidence exists proving the link between antibiotic use and the significant increase in drug-resistant human bacterial pathogens. The application of molecular detection and

  9. Occurrence and reservoirs of antibiotic resistance genes in the environment

    NARCIS (Netherlands)

    Seveno, N.; Kallifidas, D.; Smalla, K.; Elsas, van J.D.; Collard, J.M.; Karagouni, A.; Wellington, E.M.H.

    2002-01-01

    Antibiotic resistance genes have become highly mobile since the development of antibiotic chemotherapy. A considerable body of evidence exists proving the link between antibiotic use and the significant increase in drug-resistant human bacterial pathogens. The application of molecular detection and