Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery.

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Salsano, Antonio; Giacobbe, Daniele Roberto; Sportelli, Elena; Olivieri, Guido Maria; Brega, Carlotta; Di Biase, Carlo; Coppo, Erika; Marchese, Anna; Del Bono, Valerio; Viscoli, Claudio; Santini, Francesco

2016-11-01

Patients undergoing major surgery are at increased risk of developing infections due to resistant organisms, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp). In this study, we assessed risk factors for CR-Kp infections after open heart surgery in a teaching hospital in northern Italy. A retrospective study was conducted from January to December 2014. The primary outcome measure was postoperative CR-Kp infection, defined as a time-to-event end-point. The effect of potentially related variables was assessed by univariable and multivariable analyses. Secondary end-points were in-hospital mortality and 180-day postoperative mortality. Among 553 patients undergoing open heart surgery, 32 developed CR-Kp infections (6%). In the final multivariable model, CR-Kp colonization [hazard ratio (HR) 227.45, 95% confidence intervals (CI) 67.13-1225.20, P open heart surgery. CR-Kp infection after surgery significantly affected survival. Preventing colonization is conceivably the most effective current strategy to reduce the impact of CR-Kp. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Outbreak by Hypermucoviscous Klebsiella pneumoniae ST11 Isolates with Carbapenem Resistance in a Tertiary Hospital in China

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Lingling Zhan

2017-05-01

Full Text Available Hypervirulent and multidrug resistant Klebsiella pneumoniae strains pose a significant threat to the public health. In the present study, 21 carbapenem-resistant K. pneumoniae isolates (CRKP were determined by the string test as hypermucoviscous K. pneumoniae (HMKP, with the prevalence of 15.0% (21/140 among CRKP, and 1.1% (21/1838 among all K. pneumoniae isolates. Among them, 7 (33.3%, and 1 (4.76% isolate belonged to capsular serotype K20 and K2 respectively, while 13 (61.9%, 13/21 weren't successfully typed by capsular serotyping. All the 21 isolates were carbapenemase-producers and were positive for blaKPC-2. In addition to blaKPC-2, all the 21 isolates except one harbor blaSHV-11, and 15 carry extended-spectrum β-lactamase gene blaCTX-M-65. The virulence-associated genes with more than 90% of positive rates among 21 isolates included ureA (100%, 21/21, wabG (100%, 21/21, fimH (95.2%, 20/21, entB (95.2%, 20/21, ycf (95.2%, 20/21, ybtS (95.2%, 20/21, and iutA (90.5%, 19/21. rmpA and aerobactin were found in 57.1% (12/21 isolates. Five sequence types (STs were identified by multilocus sequence typing (MLST, including ST11 (11 K-non capsule typable and 5 K20 isolates, ST268 (1 K20 isolate and 1 K-non capsule typable isolate, ST65 (1 K2 isolate, ST692 (1 K-non capsule typable isolate, and ST595, a novel sequence type (1 K-non capsule typable isolate. Pulsed-field gel electrophoresis (PFGE results showed two major PFGE clusters, of which cluster A accounts for 6 ST11 isolates (28.6% and cluster B includes 8 ST11 isolates (38.1%, 8/21. Ten and six ST11 isolates were isolated from 2014 and 2015, respectively, while 8 were isolated from the same month of December in 2014. Ten isolates were collected from the intensive care unit (ICU, and all except one belonged to ST11. Additional 4 ST11 isolates were collected from patients in non-ICU wards, who had more than 10 days of ICU stay history in 2014 prior to transfer to their current wards where the

Three Dimensional Checkerboard Synergy Analysis of Colistin, Meropenem, Tigecycline against Multidrug-Resistant Clinical Klebsiella pneumonia Isolates.

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Claudia Stein

Full Text Available The spread of carbapenem-non-susceptible Klebsiella pneumoniae strains bearing different resistance determinants is a rising problem worldwide. Especially infections with KPC (Klebsiella pneumoniae carbapenemase - producers are associated with high mortality rates due to limited treatment options. Recent clinical studies of KPC-blood stream infections revealed that colistin-based combination therapy with a carbapenem and/or tigecycline was associated with significantly decreased mortality rates when compared to colistin monotherapy. However, it remains unclear if these observations can be transferred to K. pneumoniae harboring other mechanisms of carbapenem resistance. A three-dimensional synergy analysis was performed to evaluate the benefits of a triple combination with meropenem, tigecycline and colistin against 20 K. pneumoniae isolates harboring different β-lactamases. To examine the mechanism behind the clinically observed synergistic effect, efflux properties and outer membrane porin (Omp genes (ompK35 and ompK36 were also analyzed. Synergism was found for colistin-based double combinations for strains exhibiting high minimal inhibition concentrations against all of the three antibiotics. Adding a third antibiotic did not result in further increased synergistic effect in these strains. Antagonism did not occur. These results support the idea that colistin-based double combinations might be sufficient and the most effective combination partner for colistin should be chosen according to its MIC.

Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms

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Chang-Ro Lee

2017-11-01

Full Text Available Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.

Mapping the resistance-associated mobilome of a carbapenem-resistant Klebsiella pneumoniae strain reveals insights into factors shaping these regions and facilitates generation of a 'resistance-disarmed' model organism.

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Bi, Dexi; Jiang, Xiaofei; Sheng, Zi-Ke; Ngmenterebo, David; Tai, Cui; Wang, Minggui; Deng, Zixin; Rajakumar, Kumar; Ou, Hong-Yu

2015-10-01

This study aims to investigate the landscape of the mobile genome, with a focus on antibiotic resistance-associated factors in carbapenem-resistant Klebsiella pneumoniae. The mobile genome of the completely sequenced K. pneumoniae HS11286 strain (an ST11, carbapenem-resistant, near-pan-resistant, clinical isolate) was annotated in fine detail. The identified mobile genetic elements were mapped to the genetic contexts of resistance genes. The blaKPC-2 gene and a 26 kb region containing 12 clustered antibiotic resistance genes and one biocide resistance gene were deleted, and the MICs were determined again to ensure that antibiotic resistance had been lost. HS11286 contains six plasmids, 49 ISs, nine transposons, two separate In2-related integron remnants, two integrative and conjugative elements (ICEs) and seven prophages. Sixteen plasmid-borne resistance genes were identified, 14 of which were found to be directly associated with Tn1721-, Tn3-, Tn5393-, In2-, ISCR2- and ISCR3-derived elements. IS26 appears to have actively moulded several of these genetic regions. The deletion of blaKPC-2, followed by the deletion of a 26 kb region containing 12 clustered antibiotic resistance genes, progressively decreased the spectrum and level of resistance exhibited by the resultant mutant strains. This study has reiterated the role of plasmids as bearers of the vast majority of resistance genes in this species and has provided valuable insights into the vital role played by ISs, transposons and integrons in shaping the resistance-coding regions in this important strain. The 'resistance-disarmed' K. pneumoniae ST11 strain generated in this study will offer a more benign and readily genetically modifiable model organism for future extensive functional studies. © 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.

Resistance to K. pneumoniae in young children with congenital heart defects

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V. N. Ilina

2015-10-01

Full Text Available Klebsiella pneumoniae is one of the leading agents of nosocomial infections (NI. In Russia, Klebsiella pneumoniae is the third in frequency of gram-negative pathogen NI. For a long time one of the major clinically relevant mechanisms of acquired resistance to K. pneumoniae is multidrug resistance caused by extended spectrum -lactamase production (ESBL. Carbapenems show the greatest resistance to the action of ESB. However, now there exist registered strains of K.pneumoniae resistant to carbapenems. In connection with this in 2008 we conducted a prospective study on resistance to K. pneumoniae in young children being treated at ICU. It was found out that resistance to III-IV-generation cephalosporines, fluoroquinolones, aminoglycosides is determined by production of ESBL, while resistance to carbapenems occurs due to reduction of permeability of cell membranes, in combination with production of ESBL. Some features of patients colonized with multidrug-resistant strains of K. pneumoniae are described.

Characterization of carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream isolates at a Taiwanese hospital: clinical impacts of lowered breakpoints for carbapenems.

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Lee, N Y; Wu, J J; Lin, S H; Ko, W C; Tsai, L H; Yan, J J

2012-08-01

This study was conducted in order to characterize carbapenem-nonsusceptible Klebsiella pneumoniae isolates and to evaluate the impacts of recently lowered interpretative breakpoints for carbapenems for Enterobacteriaceae. Among 152 K. pneumoniae bloodstream isolates suspected as AmpC or extended-spectrum β-lactamase (ESBL) producers, 58 (38.2%) isolates were currently interpreted as nonsusceptible to ertapenem, imipenem, or meropenem, and 42 (72.4%) of them were categorized as carbapenem-susceptible by the previous criteria. The high revision rate was associated with the predominance (79.3%) of DHA-1 among the carbapenem-nonsusceptible isolates due to both polyclonal and clonal spread. ESBLs were common (~57%) in both ertapenem-susceptible and -nonsusceptible isolates; however, 84.8% of the carbapenem-nonsusceptible isolates were also AmpC producers. The IMP-8 metallo-β-lactamase was detected in three isolates. Polyacrylamide gel electrophoresis suggested decreased OmpK35 expression in all but one ertapenem-nonsusceptible isolate, and genetic disruptions of ompK35 and ompK36 were detected in 30 and six ertapenem-nonsusceptible isolates, respectively. A comparison between patients infected by AmpC- or ESBL-producing ertapenem-susceptible (n=62) isolates and those with isolates revised as ertapenem-nonsusceptible (n=41) revealed more cases of malignancies (36.6% versus 14.5%; p=0.01) and higher Charlson score (p=0.033) among the patients with ertapenem-nonsusceptible isolates; however, the acquisition of an isolate revised as carbapenem-nonsusceptible was not identified as an independent mortality risk factor.

First identification of class A carbapenemase-producing Klebsiella pneumoniae in the Republic of Ireland.

LENUS (Irish Health Repository)

Roche, C

2009-04-02

The Klebsiella pneumoniae carbapenemase (KPC) was detected in a carbapenem-resistant respiratory isolate of Klebsiella pneumoniae in an Irish hospital. This is the first report of a KPC-producing isolate in the Republic of Ireland. The isolate was resistant to all beta-lactams. Furthermore, it had reduced susceptibility to three other classes of non-beta-lactam antibiotics. The isolate was not associated with travel abroad. Detection of KPC-producing bacteria has important infection control and public health implications.

Comparison of synergism between colistin, fosfomycin and tigecycline against extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates or with carbapenem resistance

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Yee-Huang Ku

2017-12-01

Full Text Available Purpose: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL-producing Klebsiella pneumoniae (KP clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. Methods: In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 × 105 CFU/mL by using 1/2× MIC for each alone, and both 1/2× and 1/4× MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. Results: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively. Conclusions: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance. Keywords: Carbapenem resistance, Colistin, ESBL, Fosfomycin, Tigecycline

Community-onset carbapenem-resistant Klebsiella pneumoniae urinary tract infections in infancy following NICU hospitalisation.

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Vergadi, Eleni; Bitsori, Maria; Maraki, Sofia; Galanakis, Emmanouil

2017-10-01

Urinary tract infection (UTI) is a common bacterial infection in childhood with favourable outcome. However, the recent emergence of UTI caused by multidrug-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae (CRE), has become a great concern worldwide. CRE are mainly responsible for nosocomial infections and community-onset CRE infections in healthy individuals are rare. In this study, we report a series of infants without substantial genitourinary abnormalities that were admitted with community-onset urinary tract infections (UTIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and we discuss their aetiology. We retrospectively reviewed the medical records of nine infants who presented from community to the paediatric ward with CRKP urinary tract infections, as well as all affected neonates of a concomitant CRKP outbreak that occurred in the neonatal intensive care unit (NICU) in a tertiary hospital (period from April 2009 to July 2012). We further retrieved all culture-proven CRKP infections of any site from 2007 to 2015 in our paediatric department. Over a 33-month period, nine infants, all males, aged 0.9-19.3 (median 4.0) months, were admitted to the Department of Paediatrics with UTI caused by CRKP. Three of them were diagnosed with urinary tract abnormalities but only one had vesicoureteral reflux (VUR), which was a UTI-associated one. History revealed that they had all been hospitalised in the same NICU during a concurrent long-lasting CRKP outbreak for a median of 17 (2-275) days and thereafter presented with CRKP UTI 15 to 207 (median 41) days after NICU discharge. The antibiotic susceptibility and phenotypic characteristics were identical among all isolates in NICU and the paediatric ward. The summary Figure shows a timeline of NICU hospitalisation indicative of its duration and subsequent CRKP UTI of study participants is presented. These cases illustrate that UTI caused by multidrug-resistant pathogens does not

Molecular epidemiology and drug resistant mechanism in carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China.

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Zhang, Xingyu; Chen, Di; Xu, Guifeng; Huang, Weichun; Wang, Xing

2018-01-01

Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center. Multilocus sequence typing (MLST), antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance associated genes were applied to all these isolates. MLST analysis revealed 16 distinct STs identified within the 41 isolates, among which the most frequently represented were ST11(19.5%),ST25(14.6%),ST76(14.6%),ST37(9.8%).One new ST was first identified. All CR-KP isolates showed MDR phenotypes and were resistance to ceftazidime, imipenem, piperacillin / tazobactam, ceftriaxone, ampicillin /sulbactam, aztreonam. They were confirmed as carbapenemase producer, NDM-1 (56.1%, 23/41), IMP (26.8%, 11/41), KPC-2 (22.0%, 9/41) were detected. Of note, two isolates carried simultaneously both NDM-1 and IMP-4. All CR-KP strains contained at least one of extended spectrum β-lactamase genes tested(TEM, SHV, OXA-1, CTX-M group) and six isolates carried both ESBL and AmpC genes(DHA-1). Among the penicllinase and β-lactamase genes, the most frequently one is SHV(92.7%,38/41), followed by TEM-1(68.3%,28/41), CTX-M-14(43.9%,18/41), CTX-M-15(43.9%,14/41), OXA-1(14.6%,6/41). In the present study, NDM-1-producing isolates was the predominant CR-KP strains in children, follow by IMP and KPC-producing strains. NDM-1and IMP-4 were more frequent than KPC-2 and showed a multiclonal background. Those suggested carbapenem-resistant in children is diverse, and certain resistance mechanisms differ from prevalent

Molecular characterization of multidrug-resistant Klebsiella pneumoniae isolates

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Xiang-hua Hou

2015-09-01

Full Text Available Klebsiella pneumoniae is an important cause of healthcare-associated infections worldwide. Selective pressure, the extensive use of antibiotics, and the conjugational transmission of antibiotic resistance genes across bacterial species and genera facilitate the emergence of multidrug-resistant (MDR K. pneumoniae. Here, we examined the occurrence, phenotypes and genetic features of MDR K. pneumoniae isolated from patients in intensive care units (ICUs at the First Affiliated Hospital of Xiamen University in Xiamen, China, from January to December 2011. Thirty-eight MDR K. pneumoniae strains were collected. These MDR K. pneumoniae isolates possessed at least seven antibiotic resistance determinants, which contribute to the high-level resistance of these bacteria to aminoglycosides, macrolides, quinolones and β-lactams. Among these isolates, 24 strains were extended-spectrum β-lactamase (ESBL producers, 2 strains were AmpC producers, and 12 strains were both ESBL and AmpC producers. The 38 MDR isolates also contained class I (28/38 and class II integrons (10/38. All 28 class I-positive isolates contained aacC1, aacC4, orfX, orfX’ and aadA1 genes. β-lactam resistance was conferred through blaSHV (22/38, blaTEM (10/38, and blaCTX-M (7/38. The highly conserved blaKPC-2 (37/38 and blaOXA-23(1/38 alleles were responsible for carbapenem resistance, and a gyrAsite mutation (27/38 and the plasmid-mediated qnrB gene (13/38 were responsible for quinolone resistance. Repetitive-sequence-based PCR (REP-PCR fingerprinting of these MDR strains revealed the presence of five groups and sixteen patterns. The MDR strains from unrelated groups showed different drug resistance patterns; however, some homologous strains also showed different drug resistance profiles. Therefore, REP-PCR-based analyses can provide information to evaluate the epidemic status of nosocomial infection caused by MDR K. pneumoniae; however, this test lacks the power to discriminate some

Detection of an Ambler class D OXA-48-type β-lactamase in a Klebsiella pneumoniae strain in The Netherlands.

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Kalpoe, Jayant S; Al Naiemi, Nashwan; Poirel, Laurent; Nordmann, Patrice

2011-05-01

Traditionally, bacteria in The Netherlands have low levels of resistance to antibiotics. This report describes what is believed to be the first carbapenem-resistant Klebsiella pneumoniae producing an OXA-48 type β-lactamase in The Netherlands. The isolate co-produced a CTX-M-15 type β-lactamase and was recovered from a patient who was transferred from a hospital in India to an intensive care unit in The Netherlands. His recovery in The Netherlands was complicated by pneumonia due to the carbapenem-resistant K. pneumoniae to which he eventually succumbed. Pre-emptive screening for carbapenem-resistant Enterobacteriaceae in selected patients could be imperative to maintain the low prevalence of these highly resistant bacteria in Dutch hospitals.

Characterization of carbapenem-resistant Gram-negative bacteria from Tamil Nadu.

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Nachimuthu, Ramesh; Subramani, Ramkumar; Maray, Suresh; Gothandam, K M; Sivamangala, Karthikeyan; Manohar, Prasanth; Bozdogan, Bülent

2016-10-01

Carbapenem resistance is disseminating worldwide among Gram-negative bacteria. The aim of this study was to identify carbapenem-resistance level and to determine the mechanism of carbapenem resistance among clinical isolates from two centres in Tamil Nadu. In the present study, a total of 93 Gram-negative isolates, which is found to be resistant to carbapenem by disk diffusion test in two centres, were included. All isolates are identified at species level by 16S rRNA sequencing. Minimal inhibitory concentrations (MICs) of isolates for Meropenem were tested by agar dilution method. Presence of blaOXA, blaNDM, blaVIM, blaIMP and blaKPC genes was tested by PCR in all isolates. Amplicons were sequenced for confirmation of the genes. Among 93 isolates, 48 (%52) were Escherichia coli, 10 (%11) Klebsiella pneumoniae, nine (%10) Pseudomonas aeruginosa. Minimal inhibitory concentration results showed that of 93 suspected carbapenem-resistant isolates, 27 had meropenem MICs ≥ 2 μg/ml. The MIC range, MIC50 and MIC90 were 128 μg/ml, 0.12 and 16 μg/ml, respectively. Fig. 1 . Among meropenem-resistant isolates, E. coli were the most common (9/48, 22%), followed by K. pneumoniae (7/9, 77%), P. aeruginosa (6/10, 60%), Acinetobacter baumannii (2/2, 100%), Enterobacter hormaechei (2/3, 67%) and one Providencia rettgeri (1/1, 100%). PCR results showed that 16 of 93 carried blaNDM, three oxa181, and one imp4. Among blaNDM carriers, nine were E. coli, four Klebsiella pneumoniae, two E. hormaechei and one P. rettgeri. Three K. pneumoniae were OXA-181 carriers. The only imp4 carrier was P. aeruginosa. A total of seven carbapenem-resistant isolates were negatives by PCR for the genes studied. All carbapenem-resistance gene-positive isolates had meropenem MICs >2 μg/ml. Our results confirm the dissemination of NDM and emergence of OXA-181 beta-lactamase among Gram-negative bacteria in South India. This study showed the emergence of NDM producer in clinical isolates of E

Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China.

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Li, Yi; Sun, Qiao-Ling; Shen, Yingbo; Zhang, Yangjunna; Yang, Jun-Wen; Shu, Ling-Bin; Zhou, Hong-Wei; Wang, Yang; Wang, Bing; Zhang, Rong; Wang, Shaolin; Shen, Zhangqi

2018-04-01

The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% ( n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, bla NDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital. Copyright © 2018 American Society for Microbiology.

Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy.

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Girmenia, C; Rossolini, G M; Piciocchi, A; Bertaina, A; Pisapia, G; Pastore, D; Sica, S; Severino, A; Cudillo, L; Ciceri, F; Scimè, R; Lombardini, L; Viscoli, C; Rambaldi, A

2015-02-01

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) represent a challenging problem after SCT. A retrospective survey (January 2010 to July 2013) involving 52 Italian centers was performed to assess the epidemiology and the prognostic factors of CRKp infections in auto- and allo-SCT. Cases of CRKp infection were reported in 53.4% of centers. CRKp infections were documented in 25 auto-SCTs and 87 allo-SCTs, with an incidence of 0.4% (from 0.1% in 2010 to 0.7% in 2013) and 2% (from 0.4% in 2010 to 2.9% in 2013), respectively. A CRKp colonization documented before or after transplant was followed by an infection in 25.8% of auto-SCT and 39.2% of allo-SCT patients. The infection-related mortality rates were 16% and 64.4%, respectively. A pre-transplant CRKp infection (hazard ratio (HR) 0.33, 95% confidence intervals (CIs) 0.15-0.74; P=0.007) and a not CRKp-targeted first-line treatment (HR 2.67, 95% CI 1.43-4.99; P=0.002) were independent factors associated with an increased mortality in allo-SCT patients who developed a CRKp infection. Our study shows challenging findings of CRKp infections in SCT patients in Italy particularly after allo-SCT. The detection of carriers and the definition of early therapeutic strategies represent critical aspects of the management of CRKp infections after SCT.

Identification of KPC-producing Klebsiella pneumoniae in clinical samples in Iran

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fereshte sadat Hashemizadeh

2013-05-01

Results: In this study of 202 isolates of Klebsiella, 180 isolates (89.1% of K. pneumoniae and 22 isolates (10.9% of Klebsiella oxytoca were isolated from patients. More than 55% of isolates showed multiple-drug resistance and also above 40% resistance to imipeneme and meropeneme was recorded. The MIC of isolates which were resistant to carbapenemes was above 32µg/ml.The PCR results showed that 22 cases (11.9% of isolates had blakpc gene which most of them had been isolated from urine and blood samples of patients who were hospitalized in the ICU and pediatrics. Conclusion: Regarding the existence of blakpc gene in K. pneumoniae and possibility of transformation of these genes to the other bacteria, reconsideration in antibiotics consumption patterns and more attention to nosocomial infections control criteria are inevitable.

High minimum inhibitory concentration of imipenem as a predictor of fatal outcome in patients with carbapenem non-susceptible Klebsiella pneumoniae.

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Wu, Ping-Feng; Chuang, Chien; Su, Chin-Fang; Lin, Yi-Tsung; Chan, Yu-Jiun; Wang, Fu-Der; Chuang, Yin-Ching; Siu, L Kristopher; Fung, Chang-Phone

2016-09-02

Carbapenem resistance in Klebsiella pneumoniae is important because of its increasing prevalence and limited therapeutic options. To investigate the clinical and microbiological characteristics of patients infected or colonized with carbapenem non-susceptible K. pneumoniae (CnsKP) in Taiwan, we conducted a retrospective study at Taipei Veterans General Hospital from January 2012 to November 2013. Carbapenem non-susceptibility was defined as a minimum inhibitory concentration (MIC) of ≥2 mg/L for imipenem or meropenem. A total of 105 cases with CnsKP were identified: 49 patients with infection and 56 patients with colonization. Thirty-one isolates had genes that encoded carbapenemases (29.5%), including K. pneumoniae carbapenemase (KPC)-2 (n = 27), KPC-3 (n = 1), VIM-1 (n = 1) and IMP-8 (n = 2). The in-hospital mortality among patients with CnsKP was 43.8%. A MIC for imipenem ≥16 μg/mL, nasogastric intubation and Acute Physiology and Chronic Health Evaluation II score were independent risk factors for in-hospital mortality for all patients with CnsKP. A MIC for imipenem ≥16 μg/mL was also an independent risk factor for 14-day mortality in patients with CnsKP. In conclusion, a positive culture for CnsKP was associated with high in-hospital mortality. A high imipenem MIC of CnsKP can predispose a patient to a poor prognosis.

[Aspects of the antimicrobial resistence profile in infections with Escherichia coli and Klebsiella pneumoniae in diabetic patients].

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Petrovici, Cristina G; Dorobăţ, Carmen; Matei, Mioara; Teodor, Andra; Luca, V; Miftode, Egidia

2011-01-01

Infections in diabetic patient remains an important cause of morbidity and mortality, triggering and maintaining a prolonged metabolic imbalance. Emergence of extented spectrum beta-lactmase (ESBL) in Escherichia coli and Klebsiella pneumoniae is a major concern, because of the atypical manner infection acts in this group of imunodepressed patients and also for the limited therapeutic solutions. For this reason we have evaluated the profile of antimicrobial resistance of these pathogens in both diabetic and non diabetic patients. The aim of this study was to evaluate, in a retrospective case control study, the antibiotic susceptibility pattern in isolates of E. coli and Klebsiella spp. from different biological products in 49 diabetics and 150 non-diabetics admitted in The Clinical Hospital of Infectious Diseases Iaşi over a period of two years. Most of strains of E. coli and Klebsiella spp. ESBL positive were found in uroculture. Significant differences in E. coli resistance rate between diabetics and nondiabetics were noted for amoxicillin-clavulanic acid and ciprofloxacin (31,4% vs.13,98%, p=0,04, respectively 52,9% vs. 24,46%, p=0,004). More isolates of ESBL positive K. pneumoniae were found in diabetic patients (50% vs. 24%). Ciprofloxacin resistance of K. pneumoniae was significantly higher in diabetics (75% vs 39%; p=0,05). There was no resistance in E. coli and K. pneumoniae isolates to imipenem in the diabetic group. The high resistance rate to quinolones and 3rd generation cefalosporins limits their use for the treatment of Escherichia coli and K. pneumoniae infections. Other alternatives for empiric therapy in community and nosocomial-acquired infections in diabetic patient remains carbapenems, aminoglycosides and colimycin.

Whole genome sequencing for the molecular characterization of carbapenem-resistant Klebsiella pneumoniae strains isolated at the Italian ASST Fatebenefratelli Sacco Hospital, 2012-2014.

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Rimoldi, Sara Giordana; Gentile, Bernardina; Pagani, Cristina; Di Gregorio, Annamaria; Anselmo, Anna; Palozzi, Anna Maria; Fortunato, Antonella; Pittiglio, Valentina; Ridolfo, Anna Lisa; Gismondo, Maria Rita; Rizzardini, Giuliano; Lista, Florigio

2017-10-10

The emergence of carbapenem-resistant Klebsiella pneumoniae strains is threatening antimicrobial treatment. Sixty-eight carbapenemase-producing K. pneumoniae strains isolated at Luigi Sacco University Hospital-ASST Fatebenefratelli Sacco (Milan, Italy) between 2012 and 2014 were characterised microbiologically and molecularly. They were tested for drug susceptibility and carbapenemase phenotypes, investigated by means of repetitive extra-genic palindromic polymerase chain reaction (REP-PCR), and fully sequenced by means of next-generation sequencing for the in silico analysis of multi-locus sequence typing (MLST), their resistome, virulome and plasmid content, and their core single nucleotide polymorphism (SNP) genotypes. All of the samples were resistant to carbapenems, other β-lactams and ciprofloxacin; many were resistant to aminoglycosides and tigecycline; and seven were resistant to colistin. Resistome analysis revealed the presence of blaKPC genes and, less frequently blaSHV, blaTEM, blaCTX-M and blaOXA, which are related to resistance to carbapenem and other β-lactams. Other genes conferring resistance to aminoglycoside, fluoroquinolone, phenicol, sulphonamide, tetracycline, trimethoprim and macrolide-lincosamide-streptogramin were also detected. Genes related to AcrAB-TolC efflux pump-dependent and pump-independent tigecycline resistance mechanisms were investigated, but it was not possible to clearly correlate the genomic features with tigecycline resistance because of the presence of a common mutation in susceptible, intermediate and resistant strains. Concerning colistin resistance, the mgrB gene was disrupted by an IS5-like element, and the mobile mcr-1 and mcr-2 genes were not detected in two cases. The virulome profile revealed type-3 fimbriae and iron uptake system genes, which are important during the colonisation stage in the mammalian host environment. The in silico detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), Col

Erster Bericht über Klebsiella pneumoniae Carbapenemase-bildende Pseudomonas aeruginosa-Stämme, isoliert von Verbrennungspatienten im Iran: phenotypische und genotypische Methoden

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Lari, AR; Azimi, L; Rahbar, M; Alaghehbandan, R; Sattarzadeh-Tabrizi, M

2014-01-01

Wound infection associated with carbapenem-resistant Pseudomonas aeruginosa in burn patients is a growing problem. One of the main mechanisms of resistance to carbapenem antibiotics is the ability of P. aeruginosa to produce carbapenemase enzymes. Klebsiella pneumonia carbapemenase (KPC) is an important type of carbapenemase which can hydrolyze carbapenem antibiotics. The Modified Hodge Test (MHT) and boronic acid as a KPC inhibitor are two phenotypic methods used for detection of carbapen...

Risk factors for KPC-producing Klebsiella pneumoniae: watch out for surgery.

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da Silva, Kesia Esther; Maciel, Wirlaine Glauce; Sacchi, Flávia Patussi Correia; Carvalhaes, Cecilia Godoy; Rodrigues-Costa, Fernanda; da Silva, Ana Carolina Ramos; Croda, Mariana Garcia; Negrão, Fábio Juliano; Croda, Julio; Gales, Ana Cristina; Simionatto, Simone

2016-06-01

This study describes the molecular characteristics and risk factors associated with carbapenem-resistant Klebsiella pneumoniae strains. Risk factors associated with KPC-producing K. pneumoniae strains were investigated in this case-control study from May 2011 to May 2013. Bacterial identification was performed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined by broth microdilution. Carbapenemase production was assessed by both modified Hodge test (MHT) and ertapenem hydrolysis using MALDI-TOF MS. The presence of β-lactamase-encoding genes was evaluated by PCR and DNA sequencing. Alterations in genes encoding K. pneumoniae outer membrane proteins were analysed by PCR and DNA sequencing as well as SDS-PAGE. Genetic relatedness among strains was determined by pulsed-field gel electrophoresis. This study included 94 patients. Longer hospitalisation, mechanical ventilation, catheters, and previous surgery were associated with KPC-producing K. pneumoniae. Sixty-eight strains showed resistance to carbapenems. Carbapenemase production was detected by MHT in 67 K. pneumoniae strains and by MALDI-TOF MS in 57. The presence of the blaKPC-2 gene was identified in 57 strains. The blaKPC-2 gene was not found in 11 carbapenem-resistant K. pneumoniae; instead, the blaCTX-M-1-like, blaCTX-M-2-like, blaCTX-M-8 like, blaCTX-M-14-like and blaSHV- like genes associated with OmpK35 and OmpK36 alterations were observed. Thirty-three KPC-producing K. pneumoniae strains were clonally related, and patients infected with these strains had a higher mortality rate (78.78 %). Our results show that KPC-producing K. pneumoniae was associated with several healthcare-related risk factors, including recent surgery.

A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae.

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Seeberger, Peter H; Pereira, Claney L; Khan, Naeem; Xiao, Guozhi; Diago-Navarro, Elizabeth; Reppe, Katrin; Opitz, Bastian; Fries, Bettina C; Witzenrath, Martin

2017-11-06

Hospital-acquired infections are an increasingly serious health concern. Infections caused by carpabenem-resistant Klebsiella pneumoniae (CR-Kp) are especially problematic, with a 50 % average survival rate. CR-Kp are isolated from patients with ever greater frequency, 7 % within the EU but 62 % in Greece. At a time when antibiotics are becoming less effective, no vaccines to protect from this severe bacterial infection exist. Herein, we describe the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences. Immunization with the synthetic hexasaccharide 1 glycoconjugate resulted in high titers of cross-reactive antibodies against CR-Kp CPS in mice and rabbits. Whole-cell ELISA was used to establish the surface staining of CR-Kp strains. The antibodies raised were found to promote phagocytosis. Thus, this semi-synthetic glycoconjugate is a lead for the development of a vaccine against a rapidly progressing, deadly bacterium. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Emergence and nosocomial spread of carbapenem-resistant OXA-232-producing Klebsiella pneumoniae in Brunei Darussalam

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Abdul Momin, Muhd Haziq Fikry; Liakopoulos, Apostolos; Phee, Lynette M.; Wareham, David W.

2017-01-01

Objectives Carbapenem-resistant Enterobacteriaceae (CRE) are identified as a major global health concern. The success of CRE is facilitated by the emergence, acquisition and spread of successful clones carrying plasmid-encoded resistance genes. In this study, an outbreak of carbapenem-resistant

Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae.

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Siu, Leung-Kei Kristopher; Huang, David B; Chiang, Tom

2014-03-31

KPC-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality; however, their virulence determinants are not well defined. We investigated the virulence and plasmid transferability among KPC-containing K. pneumoniae isolates. KPC-2 and -3 were successfully conjugated and retained by a virulent K2 K. pneumoniae recipient isolate. Antimicrobial susceptibility testing showed KPC-2 and -3 donor strains were resistant to more than four classes of antibiotics while the K2 isolate was only initially resistant to ampicillin. After conjugation of KPC-2 and -3, the K2 K. pneumoniae transconjugants became resistant to all beta-lactams. Additionally, the KPC K2 K. pneumoniae transconjugants continued to retain its high serum resistance and murine lethality. Conjugation and retainment of KPC by virulent K2 K. pneumoniae and the ability of the tranconjugants to maintain its high serum resistance and murine lethality after conjugation was demonstrated in this study. These findings are concerning for the potential of KPC-like genes to disseminate among virulent K. pneumoniae isolates.

Whole-Genome Sequencing of Human Clinical Klebsiella pneumoniae Isolates Reveals Misidentification and Misunderstandings of Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae

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Linson, Sarah E.; Ojeda Saavedra, Matthew; Cantu, Concepcion; Davis, James J.; Brettin, Thomas; Olsen, Randall J.

2017-01-01

ABSTRACT Klebsiella pneumoniae is a major threat to public health, causing significant morbidity and mortality worldwide. The emergence of highly drug-resistant strains is particularly concerning. There has been a recognition and division of Klebsiella pneumoniae into three distinct phylogenetic groups: Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. K. variicola and K. quasipneumoniae have often been described as opportunistic pathogens that have less virulence in humans than K. pneumoniae does. We recently sequenced the genomes of 1,777 extended-spectrum-beta-lactamase (ESBL)-producing K. pneumoniae isolates recovered from human infections and discovered that 28 strains were phylogenetically related to K. variicola and K. quasipneumoniae. Whole-genome sequencing of 95 additional non-ESBL-producing K. pneumoniae isolates recovered from patients found 12 K. quasipneumoniae strains. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis initially identified all patient isolates as K. pneumoniae, suggesting a potential pitfall in conventional clinical microbiology laboratory identification methods. Whole-genome sequence analysis revealed extensive sharing of core gene content and plasmid replicons among the Klebsiella species. For the first time, strains of both K. variicola and K. quasipneumoniae were found to carry the Klebsiella pneumoniae carbapenemase (KPC) gene, while another K. variicola strain was found to carry the New Delhi metallo-beta-lactamase 1 (NDM-1) gene. K. variicola and K. quasipneumoniae infections were not less virulent than K. pneumoniae infections, as assessed by in-hospital mortality and infection type. We also discovered evidence of homologous recombination in one K. variicola strain, as well as one strain from a novel Klebsiella species, which challenge the current understanding of interrelationships between clades of Klebsiella. IMPORTANCE Klebsiella

Factors associated with acquisition of carbapenem-resistant Enterobacteriaceae

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Lilian Silva Lavagnoli

2017-10-01

Full Text Available ABSTRACT Objective: to identify possible risk factors for acquisition of Enterobacterial strains with a marker for resistance to carbapenems. Methods: exploratory case-control study performed in hospital settings. The study sample consisted of patients with biological specimens that tested positive for carbapenem-resistant Enterobacteriaceae (cases, with the disk diffusion test and Etest, and controls with biological samples testing negative for carbapenem-resistant Enterobacteriaceae. In all, 65 patients were included: 13 (20% cases and 52 (80% controls. Results: the microorganisms isolated were Serratia marcescens (6, Klebsiella pneumoniae (4, and Enterobacter cloacae (3. Univariate analysis revealed that length of hospitalization prior to sample collection (p=0.002 and having a surgical procedure (p=0.006 were statistically significant. In the multivariable logistic regression model, both were still significant, with odds ratios of 0.93 (p = 0.009; 95% CI: 0.89 to 0.98 for length of hospitalization prior to sample collection, and 9.28 (p = 0.05; 95% CI: 1.01 to 85.14 for having a surgical procedure. Conclusion: shorter hospitalization times and increased surveillance of patients undergoing surgery could play a decisive role in reducing the spread of carbapenem-resistant microorganisms in hospital settings.

Molecular epidemiology of Klebsiella pneumoniae invasive infections over a decade at Kilifi County Hospital in Kenya.

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Henson, Sonal P; Boinett, Christine J; Ellington, Matthew J; Kagia, Ngure; Mwarumba, Salim; Nyongesa, Sammy; Mturi, Neema; Kariuki, Samuel; Scott, J Anthony G; Thomson, Nicholas R; Morpeth, Susan C

2017-10-01

Multidrug resistant (MDR) Klebsiella pneumoniae is a common cause of nosocomial infections worldwide. Recent years have seen an explosion of resistance to extended-spectrum β-lactamases (ESBLs) and emergence of carbapenem resistance. Here, we examine 198 invasive K. pneumoniae isolates collected from over a decade in Kilifi County Hospital (KCH) in Kenya. We observe a significant increase in MDR K. pneumoniae isolates, particularly to third generation cephalosporins conferred by ESBLs. Using whole-genome sequences, we describe the population structure and the distribution of antimicrobial resistance genes within it. More than half of the isolates examined in this study were ESBL-positive, encoding CTX-M-15, SHV-2, SHV-12 and SHV-27, and 79% were MDR conferring resistance to at least three antimicrobial classes. Although no isolates in our dataset were found to be resistant to carbapenems we did find a plasmid with the genetic architecture of a known New Delhi metallo-β-lactamase-1 (NDM)-carrying plasmid in 25 isolates. In the absence of carbapenem use in KCH and because of the instability of the NDM-1 gene in the plasmid, the NDM-1 gene has been lost in these isolates. Our data suggests that isolates that encode NDM-1 could be present in the population; should carbapenems be introduced as treatment in public hospitals in Kenya, resistance is likely to ensue rapidly. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from Humans, Animals and Food

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Javier Fernández

2018-04-01

Full Text Available Non-typhoidal serovars of Salmonella enterica (NTS are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical “last resort” antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli, and Enterobacter, which are major nosocomial pathogens affecting debilitated and immunocompromised patients, carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance—namely KPC (Klebsiella pneumoniae carbapenemase (class A, IMP (imipenemase, NDM (New Delhi metallo-β-lactamase, VIM (Verona integron-encoded metallo-β-lactamase (class B, and OXA-48 (oxacillinase, class D—have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids, together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these “last resort” antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria.

Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from Humans, Animals and Food.

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Fernández, Javier; Guerra, Beatriz; Rodicio, M Rosario

2018-04-08

Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical "last resort" antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae , Escherichia coli , and Enterobacter , which are major nosocomial pathogens affecting debilitated and immunocompromised patients), carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance-namely KPC ( Klebsiella pneumoniae carbapenemase) (class A), IMP (imipenemase), NDM (New Delhi metallo-β-lactamase), VIM (Verona integron-encoded metallo-β-lactamase) (class B), and OXA-48 (oxacillinase, class D)-have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids), together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these "last resort" antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria.

The Growing Resistance of Klebsiella pneumonia ; the Need to ...

African Journals Online (AJOL)

During the course of her treatment she acquired various infections that led to her exposure to antimicrobials from almost all classes at various times; including bacteremia due to a pan-drug resistant Klebsiella pneumoniae and multi-drug resistant Acinetobacter baumannii. She was successfully treated with a combination of ...

EFFECT OF TOBRACEF IN CARBAPENEM RESISTANT PNEUMONIA INFECTION

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A. Ahmad, V.K. Dwivedi * , and M. Chaudhary

2010-01-01

To determine ef ect of Tobracef and imipenem drug on antioxidant enzyme actvity and lipid peroxidation leveland some biochemical parametrs in carbapenem resistant pneumonia infection rat model. Total 40 rats wereselected and diveded into 4 groups of 10 rats each. Group I was control group; group II was infected via A.baumanni bacterial strain. Group III and IV were infected plus treated group with tobracef and imipenemdrugs.Our results showed that a significant (p

Treatment of ESBL-producing Klebsiella pneumoniae bacteraemia with carbapenems or flomoxef: a retrospective study and laboratory analysis of the isolates.

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Lee, Chen-Hsiang; Su, Lin-Hui; Tang, Ya-Fen; Liu, Jien-Wei

2006-11-01

To better understand the clinical outcomes of patients with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia treated with either flomoxef or a carbapenem, and to evaluate the in vitro activities of these antibiotics against ESBL-KP. Retrospective analyses to identify risk factors for mortality in patients with flomoxef-susceptible ESBL-KP, especially addressing the therapeutic roles of flomoxef and carbapenem. In vitro activities of flomoxef and carbapenem against flomoxef-susceptible ESBL-KP isolates were evaluated by susceptibility testing and time-kill study. Twenty-seven patients (flomoxef group, n=7; carbapenem group, n=20) were included. Clinical severity reflected by high Pitt bacteraemia score (>or=6) was an independent risk factor for mortality (OR 13.43; 95% CI, 1.08-166.73; P=0.043), while use of flomoxef or a carbapenem was not. The MICs of flomoxef and carbapenem indicated that the tested ESBL-KP were susceptible to these antibiotics regardless of the inoculum size of 10(5) or 10(7) cfu/mL. Time-kill study showed that these antibiotics (flomoxef 8 mg/L and meropenem 4 mg/L) each acted actively against and inhibited the regrowth of the tested ESBL-KP for at least 24 h. Flomoxef might be as clinically effective as a carbapenem in treating flomoxef-susceptible ESBL-KP bacteraemia.

The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace

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Weinstein, Robert A.

2017-01-01

Abstract Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase–producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens. PMID:28375512

Anti-Restriction Protein, KlcAHS, Promotes Dissemination of Carbapenem Resistance

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Xiaofei Jiang

2017-05-01

Full Text Available Carbapenemase-producing Klebsiella pneumoniae (KPC has emerged and spread throughout the world. A retrospective analysis was performed on carbapenem-resistant K. pneumoniae isolated at our teaching hospital during the period 2009–2010, when the initial outbreak occurred. To determine the mechanism(s that underlies the increased infectivity exhibited by KPC, Multilocus Sequence Typing (MLST was conducted. A series of plasmids was also extracted, sequenced and analyzed. Concurrently, the complete sequences of blaKPC−2-harboring plasmids deposited in GenBank were summarized and aligned. The blaKPC−2 and KlcAHS genes in the carbapenem-resistant K. pneumoniae isolates were examined. E. coli strains, carrying different Type I Restriction and Modification (RM systems, were selected to study the interaction between RM systems, anti-RM systems and horizontal gene transfer (HGT. The ST11 clone predominated among 102 carbapenem-resistant K. pneumoniae isolates, all harbored the blaKPC−2 gene; 98% contained the KlcAHS gene. KlcAHS was one of the core genes in the backbone region of most blaKPC−2 carrying plasmids. Type I RM systems in the host bacteria reduced the rate of pHS10842 plasmid transformation by 30- to 40-fold. Presence of the anti-restriction protein, KlcAHS, on the other hand, increased transformation efficiency by 3- to 6-fold. These results indicate that RM systems can significantly restrict HGT. In contrast, KlcAHS can disrupt the RM systems and promote HGT by transformation. These findings suggest that the anti-restriction protein, KlcAHS, represents a novel mechanism that facilitates the increased transfer of blaKPC-2 and KlcAHS-carrying plasmids among K. pneumoniae strains.

Act Fast as Time Is Less: High Faecal Carriage of Carbapenem-Resistant Enterobacteriaceae in Critical Care Patients.

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Saseedharan, Sanjith; Sahu, Manisa; Pathrose, Edwin Joseph; Shivdas, Sarita

2016-09-01

Carbapenem-resistant Enterobacteriaceae (CRE) are drug-resistant Gram-negative bacteria that are present in the community as well as in hospitals. Their infection and colonisation puts critically ill patients at high risk due to the drug-resistant nature of the strains and possible spreading of these organisms, even in a hospital environment. To examine the presence and types of Enterobacteriaceae species in patients admitted directly from the community. The present study was a one-month pilot conducted in the ICU of a tertiary care hospital in Mumbai, India in 2015. Faecal samples of patients admitted from the community directly to the ICU were analysed using tests like MHT (Modified Hodge) and EDTA for the presence of IMP (action on Imipenem) and KPC ( Klebsiella Test Pneumoniae Carbapenemase) producing strains of Enterobacteriaceae . Polymerase Chain Reaction (PCR) was performed to look for VIM , IMP , NDM 1, OXA , and KPC genes. Antibiotic Sensitivity Test was carried out as per CLSI guidelines. The results showed an alarming level of faecal carriage rates in adult ICU patients. Klebsiella pneumonia was the most common carbapenem-resistant isolate, closely followed by Escherichia coli . PCR results revealed nine strains were positive for bla (KPC) gene, from which 7 were Klebsiella pneumoniae and one each of Escherichia coli and Klebsiella oxytoca was observed. Antibiotic Sensitivity Test results showed that the isolates had maximum sensitivity to Colistin (100%) and Tigecycline (95%). These levels indicate that in the absence of CRE screenings, proper isolation of carrier patients is not possible, leading to possible spreading of these resistant bacteria strains in ICUs. A longer period of study is required to obtain more substantial data to validate the results of this pilot.

The distribution of carbapenem- and colistin-resistance in Gram-negative bacteria from the Tamil Nadu region in India.

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Manohar, Prasanth; Shanthini, Thamaraiselvan; Ayyanar, Ramankannan; Bozdogan, Bulent; Wilson, Aruni; Tamhankar, Ashok J; Nachimuthu, Ramesh; Lopes, Bruno S

2017-07-01

The occurrence of carbapenem- and colistin-resistance among Gram-negative bacteria is increasing worldwide. The aim of this study was to understand the distribution of carbapenem- and colistin-resistance in two areas in Tamil Nadu, India. The clinical isolates (n=89) used in this study were collected from two diagnostic centres in Tamil Nadu, India. The bacterial isolates were screened for meropenem- and colistin-resistance. Further, resistance genes blaNDM-1, blaOXA-48-like, blaIMP, blaVIM, blaKPC, mcr-1 and mcr-2 and integrons were studied. The synergistic effect of meropenem in combination with colistin was assessed. A total of 89 bacterial isolates were studied which included Escherichia coli (n=43), Klebsiella pneumoniae (n=18), Pseudomonas aeruginosa (n=10), Enterobacter cloacae (n=6), Acinetobacter baumannii (n=5), Klebsiella oxytoca (n=4), Proteus mirabilis (n=2) and Salmonella paratyphi (n=1). MIC testing showed that 58/89 (65 %) and 29/89 (32 %) isolates were resistant to meropenem and colistin, respectively, whereas 27/89 (30 %) isolates were resistant to both antibiotics. Escherichia coli, K. pneumoniae, K. oxytoca, Pseudomonas aeruginosa, and Enterobacter cloacae isolates were blaNDM-1-positive (n=20). Some strains of Escherichia coli, K. pneumoniae and K. oxytoca were blaOXA-181-positive (n=4). Class 1, 2 and 3 integrons were found in 24, 20 and 3 isolates, respectively. Nine NDM-1-positive Escherichia coli strains could transfer carbapenem resistance via plasmids to susceptible Escherichia coli AB1157. Meropenem and colistin showed synergy in 10/20 (50 %) isolates by 24 h time-kill studies. Our results highlight the distribution of carbapenem- and colistin-resistance in Gram-negative bacteria isolated from the Tamil Nadu region in South India.

Avaliação fenotípica da enzima Klebsiella pneumoniae carbapenemase (KPC em Enterobacteriaceae de ambiente hospitalar Phenotypic research on Klebsiella pneumoniae carbapenemase (KPC enzyme in Enterobacteriaceae from hospitals

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Rosabel Dienstmann

2010-02-01

Full Text Available INTRODUÇÃO E OBJETIVO: A resistência bacteriana é problema frequente e importante no ambiente nosocomial. Nesse contexto, várias bactérias apresentam habilidade de desenvolver mecanismos de resistência enzimáticos, destacando-se as Enterobacteriaceae. Nesta família de microrganismos, a produção de Klebsiella pneumoniae carbapenemase (KPC é um mecanismo emergente, o que justifica sua vigilância constante. MATERIAL E MÉTODO: Este trabalho pesquisou o fenótipo de KPC em 30 isolados clínicos de enterobactérias resistentes a cefalosporinas de terceira geração e sensibilidade diminuída a carbapenem oriundas de dois hospitais (em Porto Alegre e na Grande Porto Alegre, RS. Realizou-se discodifusão com imipenem, meropenem e ertapenem, e 14 cepas com halo INTRODUCTION AND OBJECTIVE: Bacterial resistance is a frequent and important problem in the nosocomial environment. In this context, several bacteria have the ability to develop mechanisms of enzymatic resistance, mainly Enterobacteriaceae. In this family of microorganisms, the production of Klebsiella pneumoniae carbapenemase (KPC is an emerging mechanism, which should be under constant observation. MATERIAL AND METHOD: This study investigated the phenotype of KPC in 30 clinical isolates of Enterobacteriaceae resistant to third generation cephalosporin and carbapenem from two hospitals (Porto Alegre city and Porto Alegre, RS. It was performed disk diffusion method with imipenem, meropenem and ertapenem. Additionally, 14 strains with halo < 22 mm for the last antimicrobial agent underwent modified Hodge test. RESULTS: No sample showed carbapenemase (Hodge negative. DISCUSSION: Despite the fact there was no carbapenemase, resistance to carbapenems is possibly attributed to the presence of beta-lactamases AmpC and/or ESBL associated with changes in the permeability of porin channels. CONCLUSION: Given the emerging nature of KPC, it is important to trace it in Enterobacteriaceae

Tigecycline Resistant Klebsiella pneumoniae Isolated from Austrian River Water

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Alexander Hladicz

2017-10-01

Full Text Available Abstract: Antibiotic-resistant bacteria are spreading worldwide in medical settings but also in the environment. These resistant bacteria illustrate a major health problem in our times, and last-line antibiotics such as tigecycline represent an ultimate therapy option. Reports on tigecycline non-susceptible Enterobacteriaceae are presented with regard to medical settings but are rare with that for the environment. The aim of this study was to characterize two tigecycline non-susceptible Klebsiella pneumoniae isolates from the river Mur, and to question the resistance mechanism. The screening for chromosomal mutations revealed a deletion and a silent point mutation in one isolate and a point mutation in the other isolate all within the ramR allele. RamR acts as repressor and prevents overexpression of ramA. These mutations are likely to cause a resistant phenotype due to the overexpression of AcrAB-TolC. MLST revealed that the isolates belonged to two unrelated MLST types (ST2392 and ST2394. Both isolates only revealed resistance to tigecycline and tetracycline. This is one of the rare reports of tigecycline-resistant Klebsiella pneumoniae from surface water. The presence of two genetically different isolates suggests that the river water may bear substances that favor mutations that can lead to this efflux pump-driven resistance.

Prevalence of Acquired Carbapenemase Genes in Klebsiella Pneumoniae by Multiplex PCR in Isfahan

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Farzin Khorvash

2017-01-01

Full Text Available Background: Multi-drug resistant Klebsiella pneumoniae has been considered as a serious global threat. This study was done to investigate carbapenemase producing genomes among K. pneumoniae isolates in Isfahan, Central Iran. Materials and Methods: In a cross-sectional study from 2011 to 2012, 29 carbapenem resistant (according to disc diffusion method carbapenemase producing (according to modified Hodge test K. pneumoniae strains were collected from Intensive Care Unit (ICUs of Al-Zahra referral Hospital. In the strains with the lack of sensitivity to one or several carbapenems, beta-lactams, or beta-lactamases, there has been performed modified Hodge test to investigate carbapenmase and then only strains producing carbapenmases were selected for molecular methods. Results: In this study, there have been 29 cases of K. pneumoniae isolated from hospitalized patients in the (ICU. Three cases (10.3% contained blaVIM, 1 case (3.4% contained blaIMP, and 1 case (3.4% contained blaOXA. The genes blaNDM and blaKPC were not detected. Then, 16 cases (55.2% from positive cases of K. pneumoniae were related to the chip, 4 cases (13.8% to catheter, 6 cases (20.7% to urine, and 3 cases (10.3% to wound. Conclusion: It is necessary to monitor the epidemiologic changes of these carbapenemase genes in K. pneumoniae in our Hospital. More attention should be paid to nosocomial infection control measures. Other carbapenemase producing genes should be investigated.

[Investigation of antimicrobial resistance of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates from rat-like animals around a hospital in Guangzhou].

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Zhong, Xue-Shan; Ge, Jing; Chen, Shao-Wei; Xiong, Yi-Quan; Zheng, Xue-Yan; Qiu, Min; Huo, Shu-Ting; Chen, Qing

2016-05-01

To investigate antimicrobial resistance of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates in fecal samples from rat-like animals. Rat-like animals were captured using cages around a hospital and the neighboring residential area between March and October, 2015. K. pneumoniae and P. aeruginosa were isolated from the fecal samples of the captured animals. Antimicrobial susceptibility test was performed according to the guidelines of Clinical and Laboratory Standards Institute (2014). A total of 329 rat-like animals were captured, including 205 Suncus murinus, 111 Rattus norvegicus, 5 Rattus flavipectus and 8 Mus musculus. The positivity rates of K. pneumoniae and P. aeruginosa were 78.4% and 34.7% in the fecal samples from the captured animals, respectively. K. pneumoniae isolates from Suncus murinus showed a high resistance to ampicillin, cephazolin, nitrofurantoin, piperacillin and cefotaxime (with resistance rates of 100%, 51.2%, 44.2%, 37.2%, and 23.3%, respectively), and K. pneumoniae isolates from Rattus spp. showed a similar drug-resistance profile. The prevalence rates of multidrug resistance and ESBLs were 40.9% and 10.7%, respectively. P. aeruginosa from both Suncus murinus and Rattus spp. exhibited the highest resistance rates to aztreonam (12.4% and 16.0%, respectively), followed by penicillins and fluoroquinolones. P. aeruginosa isolates were susceptible to cephems, aminoglycosides and carbapenems (with resistance rates below 5%). K. pneumoniae and P. aeruginosa isolated from rat-like animals showed drug-resistance profiles similar to those of the strains isolated from clinical patients, suggesting that the possible transmission of K. pneumoniae and P. aeruginosa between rat-like animals and human beings.

Emergence of KPC-producing Klebsiella pneumoniae in Italy

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Bossa Maria C

2010-02-01

Full Text Available Abstract Background The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC beta-lactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs, can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed. Findings Klebsiella pneumoniae carbapenemase (KPC was detected in two isolates of carbapenem-resistant K. pneumoniae obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC in a patient with Crohn's disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all β-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-β-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin, trimethoprim-sulfamethoxazole (TMP-SMX and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene bla-KPC and were also positive in the Hodge test. Conclusions This is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.

A Novel IncA/C1 Group Conjugative Plasmid, Encoding VIM-1 Metallo-Beta-Lactamase, Mediates the Acquisition of Carbapenem Resistance in ST104 Klebsiella pneumoniae Isolates from Neonates in the Intensive Care Unit of V. Monaldi Hospital in Naples.

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Esposito, Eliana P; Gaiarsa, Stefano; Del Franco, Mariateresa; Crivaro, Valeria; Bernardo, Mariano; Cuccurullo, Susanna; Pennino, Francesca; Triassi, Maria; Marone, Piero; Sassera, Davide; Zarrilli, Raffaele

2017-01-01

The emergence of carbapenemase producing Enterobacteriaceae has raised major public health concern. The aim of this study was to investigate the molecular epidemiology and the mechanism of carbapenem resistance acquisition of multidrug-resistant Klebsiella pneumoniae isolates from 20 neonates in the neonatal intensive care unit (NICU) of the V. Monaldi Hospital in Naples, Italy, from April 2015 to March 2016. Genotype analysis by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) identified PFGE type A and subtypes A1 and A2 in 17, 2, and 1 isolates, respectively, and assigned all isolates to sequence type (ST) 104. K. pneumoniae isolates were resistant to all classes of β-lactams including carbapenems, fosfomycin, gentamicin, and trimethoprim-sulfamethoxazole, but susceptible to quinolones, amikacin, and colistin. Conjugation experiments demonstrated that resistance to third-generation cephems and imipenem could be transferred along with an IncA/C plasmid containing the extended spectrum β-lactamase bla SHV -12 and carbapenem-hydrolyzing metallo-β-lactamase bla V IM-1 genes. The plasmid that we called pIncAC_KP4898 was 156,252 bp in size and included a typical IncA/C backbone, which was assigned to ST12 and core genome (cg) ST12.1 using the IncA/C plasmid MLST (PMLST) scheme. pIncAC_KP4898 showed a mosaic structure with bla V IM-1 into a class I integron, bla SHV -12 flanked by IS6 elements, a mercury resistance and a macrolide 2'-phosphotransferase clusters, ant(3″), aph(3″), aacA4, qnrA1, sul1 , and dfrA14 conferring resistance to aminoglycosides, quinolones, sulfonamides, and trimethoprim, respectively, several genes predicted to encode transfer functions and proteins involved in DNA transposition. The acquisition of pIncAC_KP4898 carrying bla V IM-1 and bla SHV -12 contributed to the spread of ST104 K. pneumoniae in the NICU of V. Monaldi Hospital in Naples.

A Novel IncA/C1 Group Conjugative Plasmid, Encoding VIM-1 Metallo-Beta-Lactamase, Mediates the Acquisition of Carbapenem Resistance in ST104 Klebsiella pneumoniae Isolates from Neonates in the Intensive Care Unit of V. Monaldi Hospital in Naples

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Eliana P. Esposito

2017-11-01

Full Text Available The emergence of carbapenemase producing Enterobacteriaceae has raised major public health concern. The aim of this study was to investigate the molecular epidemiology and the mechanism of carbapenem resistance acquisition of multidrug-resistant Klebsiella pneumoniae isolates from 20 neonates in the neonatal intensive care unit (NICU of the V. Monaldi Hospital in Naples, Italy, from April 2015 to March 2016. Genotype analysis by pulsed-field gel electrophoresis (PFGE and multi-locus sequence typing (MLST identified PFGE type A and subtypes A1 and A2 in 17, 2, and 1 isolates, respectively, and assigned all isolates to sequence type (ST 104. K. pneumoniae isolates were resistant to all classes of β-lactams including carbapenems, fosfomycin, gentamicin, and trimethoprim–sulfamethoxazole, but susceptible to quinolones, amikacin, and colistin. Conjugation experiments demonstrated that resistance to third-generation cephems and imipenem could be transferred along with an IncA/C plasmid containing the extended spectrum β-lactamase blaSHV -12 and carbapenem-hydrolyzing metallo-β-lactamase blaV IM-1 genes. The plasmid that we called pIncAC_KP4898 was 156,252 bp in size and included a typical IncA/C backbone, which was assigned to ST12 and core genome (cg ST12.1 using the IncA/C plasmid MLST (PMLST scheme. pIncAC_KP4898 showed a mosaic structure with blaV IM-1 into a class I integron, blaSHV -12 flanked by IS6 elements, a mercury resistance and a macrolide 2′-phosphotransferase clusters, ant(3″, aph(3″, aacA4, qnrA1, sul1, and dfrA14 conferring resistance to aminoglycosides, quinolones, sulfonamides, and trimethoprim, respectively, several genes predicted to encode transfer functions and proteins involved in DNA transposition. The acquisition of pIncAC_KP4898 carrying blaV IM-1 and blaSHV -12 contributed to the spread of ST104 K. pneumoniae in the NICU of V. Monaldi Hospital in Naples.

First case of New Delhi metallo-β-lactamase in Klebsiella pneumoniae from Ecuador: An update for South America

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Daniel Romero-Alvarez; Jorge Reyes; Viviana Quezada; Carolina Satán; Nelson Cevallos; Sofía Barrera; Gabriel Trueba; Luis E. Escobar; José E. Villacís

2017-01-01

Objectives: To describe a clinical case of Klebsiella pneumoniae harboring a New Delhi metallo-β-lactamase (NDM) plasmid in Ecuador and to present a map of reports of NDM isolates in South America. Methods: The modified Hodge test, carbapenem inactivation method, imipenemâEDTA disk method (synergy), and Rapidec Carba NP test were used to identify antibiotic resistance mechanisms. The presence of resistance genes was explored with a conjugation assay, and molecular confirmation of NDM was per...

The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace.

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Logan, Latania K; Weinstein, Robert A

2017-02-15

Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase-producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains.

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Morici, P; Florio, W; Rizzato, C; Ghelardi, E; Tavanti, A; Rossolini, G M; Lupetti, A

2017-10-01

The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1-11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1-11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1-11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1-11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1-11 and colistin are not strictly associated, and suggest an hLF1-11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1-11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.

Genomically Informed Surveillance for Carbapenem-Resistant Enterobacteriaceae in a Health Care System.

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Pecora, Nicole D; Li, Ning; Allard, Marc; Li, Cong; Albano, Esperanza; Delaney, Mary; Dubois, Andrea; Onderdonk, Andrew B; Bry, Lynn

2015-07-28

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health concern. Rapid identification of the resistance genes, their mobilization capacity, and strains carrying them is essential to direct hospital resources to prevent spread and improve patient outcomes. Whole-genome sequencing allows refined tracking of both chromosomal traits and associated mobile genetic elements that harbor resistance genes. To enhance surveillance of CREs, clinical isolates with phenotypic resistance to carbapenem antibiotics underwent whole-genome sequencing. Analysis of 41 isolates of Klebsiella pneumoniae and Enterobacter cloacae, collected over a 3-year period, identified K. pneumoniae carbapenemase (KPC) genes encoding KPC-2, -3, and -4 and OXA-48 carbapenemases. All occurred within transposons, including multiple Tn4401 transposon isoforms, embedded within more than 10 distinct plasmids representing incompatibility (Inc) groups IncR, -N, -A/C, -H, and -X. Using short-read sequencing, draft maps were generated of new KPC-carrying vectors, several of which were derivatives of the IncN plasmid pBK31551. Two strains also had Tn4401 chromosomal insertions. Integrated analyses of plasmid profiles and chromosomal single-nucleotide polymorphism (SNP) profiles refined the strain patterns and provided a baseline hospital mobilome to facilitate analysis of new isolates. When incorporated with patient epidemiological data, the findings identified limited outbreaks against a broader 3-year period of sporadic external entry of many different strains and resistance vectors into the hospital. These findings highlight the utility of genomic analyses in internal and external surveillance efforts to stem the transmission of drug-resistant strains within and across health care institutions. We demonstrate how detection of resistance genes within mobile elements and resistance-carrying strains furthers active surveillance efforts for drug resistance. Whole-genome sequencing is increasingly

Polysaccharide capsule-mediated resistance to opsonophagocytosis in Klebsiella pneumoniae.

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Domenico, P; Salo, R J; Cross, A S; Cunha, B A

1994-01-01

The polysaccharide capsule of Klebsiella pneumoniae is an important virulence factor that confers resistance to phagocytosis. The treatment of encapsulated bacteria with salicylate to inhibit capsule expression was found to enhance the phagocytosis of encapsulated bacteria by human neutrophils only in the presence of cell surface-specific antibodies. Both type-specific rabbit antisera and anticapsular human hyperimmune globulin were employed as opsonins. Salicylate significantly enhanced phag...

Add-On Therapy with Ertapenem in Infections with Multidrug Resistant Gram-Negative Bacteria: Pediatric Experience

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Sevgen Tanır Basaranoglu

2017-01-01

Full Text Available Optimal therapy for infections with carbapenem resistant GNB is not well established due to the weakness of data. Patients presenting with bloodstream infections caused by multidrug resistant Klebsiella pneumoniae were treated with a combination treatment. Optimal therapy for infections with carbapenem resistant Gram-negative bacteria is a serious problem in pediatric patients. We presented three cases who were successfully treated with addition of ertapenem to the combination treatment for bacteremia with multidrug resistant Klebsiella pneumoniae. Dual carbapenem treatment approach is a new approach for these infections and requires more data in children.

Whole-Genome Sequences of Two Carbapenem-Resistant Klebsiella quasipneumoniae Strains Isolated from a Tertiary Hospital in Johor, Malaysia.

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Gan, Han Ming; Rajasekaram, Ganeswrie; Eng, Wilhelm Wei Han; Kaniappan, Priyatharisni; Dhanoa, Amreeta

2017-08-10

We report the whole-genome sequences of two carbapenem-resistant clinical isolates of Klebsiella quasipneumoniae subsp. similipneumoniae obtained from two different patients. Both strains contained three different extended-spectrum β-lactamase genes and showed strikingly high pairwise average nucleotide identity of 99.99% despite being isolated 3 years apart from the same hospital. Copyright © 2017 Gan et al.

Resistencia a los antibióticos beta-lactámicos Carbapenems mediada por el gen blaKPC en Klebsiella pneumoniae

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Aura Dayana del Carmen Falco Restrepo

2015-12-01

Full Text Available  Los carbapenems son antibióticos â-lactamicos de amplio espectro que se utilizan como terapia de primera línea para tratar pacientes con infecciones graves. Actualmente, la resistencia a carbapenems se asocia con la presencia de â-lactamasas capaces de hidrolizar estos antibióticos. La carbapenemasa de clase A más común es KPC, la cual es codificada por el gen blaKPC que generalmente, se encuentra ubicado en plásmidos. La selección y la rápida propagación de aislados de Klebsiella pneumoniae portadores de estas carbapenemasas se ha convertido en un problema de salud pública a nivel mundial. Esta mini-revision describe uno de los mecanismos más frecuentes de resistencia a carbapenems como lo son las enzimas carbapenemasas tipo KPC. Además se describen las variantes del gen blaKPC asi como el elemento genético móvil, el transposon Tn4401, el principal responsable de su diseminación entre géneros y especies bacterianas diferentes. Finalmente se hace una pequeña revisión cronológica de los reportes de la enzima KPC a nivel mundial.

In Vitro Activity of Imipenem and Colistin against a Carbapenem-Resistant Klebsiella pneumoniae Isolate Coproducing SHV-31, CMY-2, and DHA-1

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Hung-Jen Tang

2015-01-01

Full Text Available We investigated the synergism of colistin and imipenem against a multidrug-resistant K. pneumoniae isolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the common β-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. The blaSHV-31, blaCMY-2, and blaDHA-1 were detected. Outer membrane porin genes analysis revealed loss of ompK36 and frame-shift mutation of ompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L and 1x MIC of imipenem (8 mg/L was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistant K. pneumoniae infections.

First Identification of a Patient Colonized With Klebsiella pneumoniae Carrying blaNDM-1 in Taiwan

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Hua-Shin Wu

2010-11-01

Full Text Available New Delhi metallo-β-lactamase 1 (NDM-1 is a novel type of metallo-β-lactamase (MBL. Enterobacteriaceae carrying this NDM-1 encoding gene, blaNDM-1, have been identified worldwide. Bacteria carrying blaNDM-1 are not only resistant to carbapenem, but also highly resistant to many classes of antibiotics, which indicate the importance of prompt identification of these bacteria and implementation of strict infection control measures to prevent their transmission. Here, we report the first identification and management of a patient colonized with Klebsiella pneumoniae carrying blaNDM-1 in Taiwan, who returned from New Delhi where he had been hospitalized for a gun-shot injury.

Could Frequent Carbapenem Use Be a Risk Factor for Colistin Resistance?

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Gundogdu, Aycan; Ulu-Kilic, Aysegul; Kilic, Huseyin; Ozhan, Esra; Altun, Dilek; Cakir, Ozlem; Alp, Emine

2017-10-13

The antibiotic colistin, which had been previously abandoned, is being brought back as a last line of defense against bacterial infection. However, colistin resistance was reported shortly after its reintroduction. This study evaluated the risk factors for colonization/infections due to colistin-resistant Acinetobacter baumannii (ColR-Ab) and Klebsiella pneumoniae (ColR-Kp) strains and characterized the molecular epidemiology of these two strains. Age, previous hospitalization duration, and previous use of carbapenem and colistin were risk factors for ColR-Kp, whereas previous use of carbapenem and colistin was a risk factor for ColR-Ab. According to pulsed-field gel electrophoresis analysis, most ColR-Kp strains could be grouped into two major pulsotypes. This appears to be an indicator of cross contamination of ColR-Kp strain, since different isolates appeared to be belonging to the same clones. The existence of colistin-susceptible (ColS) and colistin-resistant (ColR) strains in the same pulsotypes might also be an indicator of the recent emergence of resistance mechanisms. The results highlight the emergence of ColR pathogens in Turkey, which is considered to be developing country, and that carbapenem use coupled with insufficient infection control measures might increase the risk of ColR outbreaks.

Nonclonal Emergence of Colistin-Resistant Klebsiella pneumoniae Isolates from Blood Samples in South Korea ▿

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Suh, Ji-Yoeun; Son, Jun Seong; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Song, Jae-Hoon

2010-01-01

In vitro activities of colistin and other drugs were tested against 221 Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in K. pneumoniae occurring independently and not by clonal spreading. PMID:19752282

Exploring the Genome and Phenotype of Multi-Drug Resistant Klebsiella pneumoniae of Clinical Origin

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João Anes; Daniel Hurley; Marta Martins; Séamus Fanning; Séamus Fanning

2017-01-01

Klebsiella pneumoniae is an important nosocomial pathogen with an extraordinary resistant phenotype due to a combination of acquired resistant-elements and efflux mechanisms. In this study a detailed molecular characterization of 11 K. pneumoniae isolates of clinical origin was carried out. Eleven clinical isolates were tested for their susceptibilities, by disk diffusion and broth microdilution and interpreted according to CLSI guidelines. Efflux activity was determined by measuring the extr...

The secondary resistome of multidrug-resistant Klebsiella pneumoniae.

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Jana, Bimal; Cain, Amy K; Doerrler, William T; Boinett, Christine J; Fookes, Maria C; Parkhill, Julian; Guardabassi, Luca

2017-02-15

Klebsiella pneumoniae causes severe lung and bloodstream infections that are difficult to treat due to multidrug resistance. We hypothesized that antimicrobial resistance can be reversed by targeting chromosomal non-essential genes that are not responsible for acquired resistance but essential for resistant bacteria under therapeutic concentrations of antimicrobials. Conditional essentiality of individual genes to antimicrobial resistance was evaluated in an epidemic multidrug-resistant clone of K. pneumoniae (ST258). We constructed a high-density transposon mutant library of >430,000 unique Tn5 insertions and measured mutant depletion upon exposure to three clinically relevant antimicrobials (colistin, imipenem or ciprofloxacin) by Transposon Directed Insertion-site Sequencing (TraDIS). Using this high-throughput approach, we defined three sets of chromosomal non-essential genes essential for growth during exposure to colistin (n = 35), imipenem (n = 1) or ciprofloxacin (n = 1) in addition to known resistance determinants, collectively termed the "secondary resistome". As proof of principle, we demonstrated that inactivation of a non-essential gene not previously found linked to colistin resistance (dedA) restored colistin susceptibility by reducing the minimum inhibitory concentration from 8 to 0.5 μg/ml, 4-fold below the susceptibility breakpoint (S ≤ 2 μg/ml). This finding suggests that the secondary resistome is a potential target for developing antimicrobial "helper" drugs that restore the efficacy of existing antimicrobials.

KPC-mediated resistance in Klebsiella pneumoniae in two hospitals in Padua, Italy, June 2009-December 2011: massive spreading of a KPC-3-encoding plasmid and involvement of non-intensive care units

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Richter Sara N

2012-07-01

Full Text Available Abstract Background Klebsiella pneumoniae carbapenemases (KPCs producing bacteria have emerged as a cause of multidrug-resistant nosocomial infections worldwide. KPCs are plasmid-encoded enzymes capable of hydrolysing a broad spectrum of beta-lactams, including carbapenems and monobactams, therefore worryingly limiting antimicrobial treatment options. Analysis of circulating bacterial strains and KPC alleles may help understanding the route of KPC dissemination and therefore help containing the infection. Methods KPC-producing Klebsiella pneumoniae dissemination in two 1580- and 300- bed hospitals in Padua, Italy, from initial outbreak in 2009 to late 2011 was analysed. Molecular and clinical epidemiology, including bacterial strains, KPC-encoding plasmid sequences and associated resistance genes, involved hospital wards and relocation of patients were described. Routine antimicrobial susceptibility testing and MIC of carbapenems on clinical isolates were performed. Detection of resistance genes was obtained by PCR and sequencing. MLST, PFGE and ERIC were used for molecular genotyping. Plasmid analysis was obtained by digestion with restriction enzymes and deep sequencing. Results KPC-positive clinical samples were isolated from nearly 200 patients. In the initial outbreak intensive care units were almost exclusively involved, while medical, surgical and long-term wards were successively massively concerned. Analysis of KPC alleles, plasmids and bacterial sequence types (STs indicated that during the initial outbreak KPC-3 in ST258 and KPC-2 in ST147 were each confined in one of the two surveilled hospitals. While KPC-2 dissemination was effectively contained, KPC-3 in ST258 cross-spreading was observed. The simultaneous presence of two carbapenemases, VIM-1 and KPC-2, in the same isolate was also observed in three patients. Total sequencing of plasmid content of two KPC-3 strains showed novel association of resistance plasmids. Conclusions The

First case of New Delhi metallo-β-lactamase in Klebsiella pneumoniae from Ecuador: An update for South America

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Daniel Romero-Alvarez

2017-12-01

Full Text Available Objectives: To describe a clinical case of Klebsiella pneumoniae harboring a New Delhi metallo-β-lactamase (NDM plasmid in Ecuador and to present a map of reports of NDM isolates in South America. Methods: The modified Hodge test, carbapenem inactivation method, imipenem–EDTA disk method (synergy, and Rapidec Carba NP test were used to identify antibiotic resistance mechanisms. The presence of resistance genes was explored with a conjugation assay, and molecular confirmation of NDM was performed by PCR and DNA sequencing. Plasmid characterization was conducted by PCR-based replicon typing. A literature review was performed in Google Scholar and PubMed to identify reports from South America. Results: An HIV-infected patient, who had never traveled abroad, developed a bloodstream infection caused by K. pneumoniae ST147 harboring the NDM-1 resistance gene in a plasmid from the IncA/C group. Local circulation of NDM has also been described in other South American countries, in particular in Colombia and Brazil, although published scientific records were not found for other countries. Conclusions: This report presents the first evidence of autochthonous circulation of the NDM-1 resistance gene harbored by an IncA/C plasmid isolated from a K. pneumoniae ST147 in Ecuador. Efforts should be implemented to monitor and characterize the spatial and temporal distribution of NDM in Ecuador and other countries of South America. Keywords: NDM, South America, Klebsiella pneumoniae, Antibiotic resistance, Plasmid

The Complex Epidemiology of Carbapenem-Resistant Enterobacter Infections: A Multicenter Descriptive Analysis.

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Lazarovitch, Tsilia; Amity, Keren; Coyle, Joseph R; Ackerman, Benjamin; Tal-Jasper, Ruthy; Ofer-Friedman, Hadas; Hayakawa, Kayoko; Bogan, Christopher; Lephart, Paul R; Kaplansky, Tamir; Maskit, Moran; Azouri, Tal; Zaidenstein, Ronit; Perez, Federico; Bonomo, Robert A; Kaye, Keith S; Marchaim, Dror

2015-11-01

The pandemic of carbapenem-resistant Enterobacteriaceae (CRE) was primarily due to clonal spread of bla KPC producing Klebsiella pneumoniae. Thus, thoroughly studied CRE cohorts have consisted mostly of K. pneumoniae. To conduct an extensive epidemiologic analysis of carbapenem-resistant Enterobacter spp. (CREn) from 2 endemic and geographically distinct centers. CREn were investigated at an Israeli center (Assaf Harofeh Medical Center, January 2007 to July 2012) and at a US center (Detroit Medical Center, September 2008 to September 2009). bla KPC genes were queried by polymerase chain reaction. Repetitive extragenic palindromic polymerase chain reaction and pulsed-field gel electrophoresis were used to determine genetic relatedness. In this analysis, 68 unique patients with CREn were enrolled. Sixteen isolates (24%) were from wounds, and 33 (48%) represented colonization only. All isolates exhibited a positive Modified Hodge Test, but only 93% (27 of 29) contained bla KPC. Forty-three isolates (63%) were from elderly adults, and 5 (7.4%) were from neonates. Twenty-seven patients died in hospital (40.3% of infected patients). Enterobacter strains consisted of 4 separate clones from Assaf Harofeh Medical Center and of 4 distinct clones from Detroit Medical Center. In this study conducted at 2 distinct CRE endemic regions, there were unique epidemiologic features to CREn: (i) polyclonality, (ii) neonates accounting for more than 7% of cohort, and (iii) high rate of colonization (almost one-half of all cases represented colonization). Since false-positive Modified Hodge Tests in Enterobacter spp. are common, close monitoring of carbapenem resistance mechanisms (particularly carbapenemase production) among Enterobacter spp. is important.

Screening of nursing home residents for colonization with carbapenem-resistant Enterobacteriaceae admitted to acute care hospitals: Incidence and risk factors.

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Cunha, Cheston B; Kassakian, Steven Z; Chan, Ryan; Tenover, Fred C; Ziakas, Panos; Chapin, Kimberle C; Mermel, Leonard A

2016-02-01

There are increasing reports of multidrug-resistant gram-negative bacilli in nursing homes and acute care hospitals. We performed a point prevalence survey to detect fecal carriage of gram-negative bacteria carrying carbapenem resistance genes or which were otherwise resistant to carbapenem antibiotics among 500 consecutive admissions from local nursing homes to 2 hospitals in Providence, Rhode Island. We performed a case-control study to identify risk factors associated with carriage of carbapenem-resistant Enterobacteriaceae (CRE). There were 404 patients with 500 hospital admissions during which they had rectal swab samples cultured. Fecal carriage of any carbapenem-resistant or carbapenemase- producing gram-negative bacteria was found in 23 (4.6%) of the 500 hospital admissions, including 7 CRE (1.4%), 2 (0.4%) of which were Klebsiella pneumoniae carbapenemase (ie, blaKPC) producing (CPE) Citrobacter freundii, 1 of which was carbapenem susceptible by standard testing methods. Use of a gastrostomy tube was associated with CRE carriage (P = .04). We demonstrated fecal carriage of carbapenem-resistant or carbapenemase-producing gram-negative bacteria in 4.6% of nursing home patients admitted to 2 acute care hospitals, but only 0.4% of such admissions were patients with fecal carriage of CPE. Use of gastrostomy tubes was associated with fecal carriage of gram-negative bacteria with detectable carbapenem resistance. CRE fecal carriage is uncommon in our hospital admissions from nursing homes. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Intermingled Klebsiella pneumoniae Populations Between Retail Meats and Human Urinary Tract Infections

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Davis, Gregg S.; Waits, Kara; Nordstrom, Lora; Weaver, Brett; Aziz, Maliha; Gauld, Lori; Grande, Heidi; Bigler, Rick; Horwinski, Joseph; Porter, Stephen; Stegger, Marc; Johnson, James R.; Liu, Cindy M.; Price, Lance B.

2015-01-01

Background. ?Klebsiella pneumoniae is a common colonizer of the gastrointestinal tract of humans, companion animals, and livestock. To better understand potential contributions of foodborne K. pneumoniae to human clinical infections, we compared K. pneumoniae isolates from retail meat products and human clinical specimens to assess their similarity based on antibiotic resistance, genetic relatedness, and virulence. Methods. ?Klebsiella pneumoniae was isolated from retail meats from Flagstaff ...

Trends in Resistance to Extended-Spectrum Cephalosporins and Carbapenems among Escherichia coli and Klebsiella spp. Isolates in a District in Western India during 2004–2014

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Ingvild Odsbu

2018-01-01

Full Text Available Surveillance data on the level of resistant bacteria is needed to inform strategies to reduce the development and spread of antibiotic resistance. The aim of this study was to determine the non-susceptibility trends to extended-spectrum cephalosporins and carbapenems among Escherichia coli and Klebsiella spp. isolates from the district of Nashik in Western India during the period 2004–2014. Antibacterial susceptibility testing of clinical isolates was performed using Kirby-Bauer disc diffusion method to determine inhibitory zone diameters. The change in proportions of non-susceptible bacteria over calendar time was investigated with spline transformations in a logistic regression model. For the extended-spectrum cephalosporins, the proportions of non-susceptible E. coli and Klebsiella spp. isolates were above 78.4% and 84.9% throughout the study period, respectively. E. coli and Klebsiella spp. isolates exhibited carbapenem non-susceptibility levels as high as 76.9% and 84.1% respectively. The proportions of extended-spectrum betalactamase (ESBL-producing isolates ranged from 38.3–85.9% in E. coli and from 45.1–93.1% in Klebsiella spp. Significantly higher proportions of non-susceptible and ESBL-producing isolates were found among isolates from inpatients compared to isolates from outpatients for both E. coli and Klebsiella spp. (p < 0.050. The high proportions of non-susceptible isolates observed show that there is great need to focus on optimal use of antibiotics to reduce the development of antibiotic resistance.

An outbreak of colistin-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in the Netherlands (July to December 2013), with inter-institutional spread.

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Weterings, V; Zhou, K; Rossen, J W; van Stenis, D; Thewessen, E; Kluytmans, J; Veenemans, J

2015-08-01

We describe an outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-KP) ST258 that occurred in two institutions (a hospital and a nursing home) in the Netherlands between July and December 2013. In total, six patients were found to be positive for KPC-KP. All isolates were resistant to colistin and exhibited reduced susceptibility to gentamicin and tigecycline. In all settings, extensive environmental contamination was found. Whole genome sequencing revealed the presence of bla KPC-2 and bla SHV-12 genes, as well as the close relatedness of patient and environmental isolates. In the hospital setting, one transmission was detected, despite contact precautions. After upgrading to strict isolation, no further spread was found. After the transfer of the index patient to a nursing home in the same region, four further transmissions occurred. The outbreak in the nursing home was controlled by transferring all KPC-KP-positive residents to a separate location outside the nursing home, where a dedicated nursing team cared for patients. This outbreak illustrates that the spread of pan-resistant Enterobacteriaceae can be controlled, but may be difficult, particularly in long-term care facilities. It, therefore, poses a major threat to patient safety. Clear guidelines to control reservoirs in and outside the hospitals are urgently needed.

Outbreak of Imipenemase-1-Producing Carbapenem-Resistant in an Intensive Care Unit

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Jin Young Lee

2017-02-01

Full Text Available Background Carbapenem-resistant Enterobacteriaceae (CRE with acquired metallo β-lactamase (MBL resistance have been increasingly reported worldwide and associated with significant mortality and morbidity. Here, an outbreak of genetically related strains of Klebsiella pneumoniae producing the imipenemase (IMP-1 MBL in a medical intensive care unit (MICU in Korea is reported. Methods Since isolating carbapenem-resistant K. pneumoniae (CRKP at the MICU of the hospital on August 10, 2011, surveillance cultures for CRE in 31 hospitalized patients were performed from August to September 2011. Carbapenem resistance was determined based on the disk diffusion method outlined in the Clinical and Laboratory Standards Institute guidelines. Polymerase chain reaction (PCR was performed for genes coding for β-lactamase. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE. In addition, a surveillance study of environmental cultures and health-care workers (HCWs was conducted in the MICU during the same time frame. Results During the study period, non-duplicated CRKP specimens were discovered in four patients in the MICU, suggestive of an outbreak. On August 10, 2011, CRKP was isolated from the sputum of a 79-year-old male patient who was admitted to the MICU. A surveillance study to detect additional CRE carriers by rectal swab revealed an additional three CRKP isolates. PCR and sequencing of the four isolates identified the presence of the IMP-1 gene. In addition, PFGE showed that the four isolated strains were genetically related. CRE was not identified in specimens taken from the hands of HCWs or other environmental sources during surveillance following the outbreak. Transmission of the carbapenemase-producing Enterobacteriaceae strain was controlled by isolation of the patients and strict contact precautions. Conclusions This study shows that rapid and systemic detection of CRE and strict infection controls are important

Carbapenem MICs in Escherichia coli and Klebsiella Species Producing Extended-Spectrum β-Lactamases in Critical Care Patients from 2001 to 2009.

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Johnson, J Kristie; Robinson, Gwen L; Pineles, Lisa L; Ajao, Adebola O; Zhao, LiCheng; Albrecht, Jennifer S; Harris, Anthony D; Thom, Kerri A; Furuno, Jon P

2017-04-01

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae strains are increasing in prevalence worldwide. Carbapenem antibiotics are used as a first line of therapy against ESBL-producing Enterobacteriaceae We examined a cohort of critical care patients for gastrointestinal colonization with carbapenem-resistant ESBL-producing strains (CR-ESBL strains). We cultured samples from this cohort of patients for ESBL-producing Klebsiella spp. and Escherichia coli and then tested the first isolate from each patient for susceptibility to imipenem, doripenem, meropenem, and ertapenem. Multilocus sequence typing was performed on isolates that produced an ESBL and that were carbapenem resistant. Among all patients admitted to an intensive care unit (ICU), 4% were positive for an ESBL-producing isolate and 0.64% were positive for a CR-ESBL strain on surveillance culture. Among the first ESBL-producing E. coli and Klebsiella isolates from the patients' surveillance cultures, 11.2% were carbapenem resistant. Sequence type 14 (ST14), ST15, ST42, and ST258 were the dominant sequence types detected in this cohort of patients, with ST15 and ST258 steadily increasing in prevalence from 2006 to 2009. Patients colonized by a CR-ESBL strain were significantly more likely to receive antipseudomonal and anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) therapy prior to ICU admission than patients colonized by carbapenem-susceptible ESBL-producing strains. They were also significantly more likely to have received a cephalosporin or a carbapenem antibiotic than patients colonized by carbapenem-susceptible ESBL-producing strains. In conclusion, in a cohort of patients residing in intensive care units within the United States, we found that 10% of the isolates were resistant to at least one carbapenem antibiotic. The continued emergence of carbapenem-resistant ESBL-producing strains is of significant concern, as infections due to these organisms are notoriously difficult to

Cefoxitin resistance mediated by loss of a porin in clinical strains of Klebsiella pneumoniae and Escherichia coli

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Ananthan S

2005-01-01

Full Text Available PURPOSE: Porins are outer membrane protein (OMP that form water filled channels that permit the diffusion of small hydrophilic solutes like -lactam antibiotics across the outer membrane. Two major porins that facilitate diffusion of antimicrobials have been described in Klebsiella spp. and Escherichia coli. The present study was carried out to examine the role of porins among Extended Spectrum -Lactamase (ESBL and AmpC -Lactamase positive strains of Klebsiella spp. and E.coli. METHODS: Preparation of OMP from phenotypically characterized clinical isolates K.pneumoniae and E.coli and the separation of the proteins by sodium dodecyl sulfate - polyacrylamide gel electrophoresis were performed as per a previously described procedure. RESULTS: OMP analysis revealed that cefoxitin and ceftazidime resistance was mediated by loss of a porin Omp K35 in the isolates of K.pneumoniae and E.coli. CONCLUSIONS: Loss of porin mediated resistance mechanism against cefoxitin was observed among the multidrug resistant K.pneumoniae and E.coli.

Carbapenem-resistant Klebsiella pneumoniae infections in a Greek intensive care unit: Molecular characterisation and treatment challenges.

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Katsiari, Maria; Panagiota, Giakkoupi; Likousi, Sophia; Roussou, Zoi; Polemis, Michalis; Alkiviadis Vatopoulos, C; Evangelia Platsouka, D; Maguina, Asimina

2015-06-01

Acquisition of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) strains poses a major threat to critically ill patients. The objectives of this study were to describe the epidemiology of CP-Kp isolates as well as the clinical outcome associated with the corresponding infections and to identify risk factors for mortality of intensive care unit (ICU) patients in a Greek hospital. A prospective, observational study was conducted in a nine-bed general ICU over a 2-year period (April 2010-March 2012). Imipenem-resistant K. pneumoniae isolates recovered from clinical samples of ICU patients were prospectively collected and studied for the presence of carbapenemases. Isolates were submitted to molecular typing using pulsed-field gel electrophoresis (PFGE). In total, 61 CP-Kp isolates (48 KPC-producers and 13 VIM-producers) were recovered from 58 ICU patients. The majority of KPC-producers were classified into a single PFGE type, indicating potent clonal dissemination. Among the 32 infected patients, bacteraemia was diagnosed in 16. Tigecycline+colistin was the most common combination antimicrobial regimen. Infection-attributable mortality was 43.8%. Regarding mortality risk factors, non-survivors were older (P=0.080), all of them presented with septic shock (P=0.010) and they had higher Sepsis-related Organ Failure Assessment (SOFA) scores at infection onset (P=0.004) compared with survivors. Appropriate definitive treatment and combination regimens were not associated with patient survival. In conclusion, CP-Kp infections are associated with limited treatment options and high in-hospital mortality. Effective measures for preventing dissemination of respective isolates in the hospital setting are required. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis.

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Righi, Elda; Peri, Anna Maria; Harris, Patrick N A; Wailan, Alexander M; Liborio, Mariana; Lane, Steven W; Paterson, David L

2017-03-01

Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infections associated with high mortality. To perform a systematic review of currently available data on distribution, characteristics and outcome associated with carbapenem-resistant bloodstream infections in adult neutropenic patients. Included studies were identified through Medline, Embase and Cochrane databases between January 1995 and April 2016. Random effect meta-analysis was used to quantify the association between carbapenem resistance and mortality and between carbapenem exposure and resistance. A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to 53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp . were reported in 18 (60%) studies showing high median resistance rates (44% of all carbapenem-resistant Gram-negatives and 19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream infections due to carbapenem-resistant Klebsiella spp. were mainly documented from endemic areas (Greece, Italy, Israel). Carbapenem resistance in Acinetobacter spp. was reported in 9 (30%) studies (median resistance 58% of Acinetobacter isolates). Mortality rates ranged from 33% to 71% (median 50%) in patients with carbapenem-resistant infections. Carbapenem resistance appeared to correlate with mortality (OR 4.89, 95% CI 3.30-7.26) and previous exposure to carbapenems (OR 4.63, 95% CI 3.08-6.96). Carbapenem resistance represents a threat to neutropenic patients. In this group, resistance is likely promoted by previous carbapenem use and leads to high mortality rates. The knowledge of resistance patterns is crucial and can direct clinicians in the use of alternatives to carbapenem-based regimens. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please

Klebsiella pneumoniae KPC: first isolations in Italy

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Carla Fontana

2009-12-01

Full Text Available Klebsiella pneumoniae carbapenemase (KPC was detected in two isolates of carbapenem-resistant K. pneumoniae in an italian teaching hospital. This is the first report of a KPC-producing isolates in our country. The first strain was isolated from a urine sample collected from a indwelling urinary catheter in a ICU-patient with subdural haematoma, while the second was from the culture of the central venous catheter (CVC in a patient affected by Crohn’s disease admitted in gastroenterology ward. Both were resistant to all ß-lactams, susceptible to imipenem and meropenem and resistant to ertapenem.They were resistant to other classes of non-ß-lactams antibiotics such as quinolones, aminoglycosides (with the exception of amikacin, trimethoprim-sulfamethoxazole (TMP-SMX as well as to nitrofurantoin.The isolates were not associated with travel abroad.They were found to contain the plasmid encoded carbapenemase gene blaKPC and were also positive to the Hodge’s test.The detection of KPC-producing bacteria has important implications in infection control and public health. The K. pneumoniae carbapenemase (KPC belong to class A ß-lactamases of the functional group 2f. Reported for the first time in U.S. in 2001, these agents were subsequently identified in Europe. KPC strains are typically resistant to penicillins, extended-spectrum cephalosporin and aztreonam and present a peculiar behavior against carbapenems in that MIC is close to the susceptibility value or is borderline (except for ertapenem.This pattern is often associated with resistance to quinolones.The information is conveyed by the resistance plasmids, thus explaining their diffusion and implication in outbreaks of KPC. Despite this, to date there are few reports concerning the isolation of this phenotype in Italy.The purpose of this paper is to present two clinical cases related to the isolation of KPC in our hospital. The KPC-producing strains have been respectively isolated: the first

Global survey of Klebsiella pneumoniae major porins from ertapenem non-susceptible isolates lacking carbapenemases.

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Wise, Mark G; Horvath, Elizabeth; Young, Katherine; Sahm, Daniel F; Kazmierczak, Krystyna M

2018-03-01

To understand the diversity of porin disruption in Klebsiella pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36, were examined in a set of isolates that did not harbour traditional carbapenem-hydrolysing enzymes, but nevertheless tested non-susceptible to ertapenem. A world-wide collection of Klebsiella pneumoniae isolates that were part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance project over the years 2008-2014 were characterised with regard to their β-lactamase gene carriage and potential permeability defects. Four hundred and eighty-seven isolates that did not carry carbapenemase genes, but were non-susceptible to ertapenem, were investigated by sequence analysis of the genes encoding OmpK35 and OmpK36. Isolates without obvious genetic lesions in either major porin gene were further examined by outer membrane protein SDS-PAGE. The majority of isolates, 83.0 % (404/487), exhibited clear genetic disruption in either or both of the ompK35 and ompK36 genes. Among the proportion of the collection with the highest ertapenem MIC value (>4 mg l -1 ), 60.5 % (115/190) showed mutation in both porin genes. Isolates without obvious genetic mutations were examined by SDS-PAGE, and 90.4 % (75/83) were found to lack or show altered expression of at least one of the major OMPs when compared to an ertapenem sensitive control strain. This study illustrates that porin deficiency in Klebsiella pneumoniae is a widespread phenomenon, and in combination with ESBLs and/or AmpC enzymes, likely accounts for the elevated ertapenem MICs observed in this study.

A Five-Year Experience of Carbapenem Resistance in Enterobacteriaceae Causing Neonatal Septicaemia: Predominance of NDM-1

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Datta, Saswati; Roy, Subhasree; Chatterjee, Somdatta; Saha, Anindya; Sen, Barsha; Pal, Titir; Som, Tapas; Basu, Sulagna

2014-01-01

Treatment of neonatal sepsis has become a challenge with the emergence of carbapenemase-producing bacteria. This study documents the trend of carbapenem susceptibility in Enterobacteriaceae that caused septicaemia in neonates over a five year period (2007–2011) and the molecular characterisation of Enterobacteriaceae resistant to carbapenems and cephalosporins. Hundred and five Enterobacteriaceae including Escherichia coli (n = 27), Klebsiella pneumoniae (n = 68) and Enterobacter spp. (n = 10) were isolated from blood of septicaemic neonates followed by antibiotic susceptibility tests, determination of MIC values, phenotypic and genotypic detection of β-lactamases. Carbapenem was the most active antimicrobial tested after tigecycline. CTX-M type was the most prevalent ESBL throughout the period (82%). New Delhi Metallo-β-lactamase-1 (NDM-1), which is a recent addition to the carbapenemase list, was the only carbapenemase identified in our setting. Fourteen percent of the isolates possessed bla NDM-1. Carbapenem non-susceptibility was first observed in 2007 and it was due to loss of Omp F/Ompk36 in combination with the presence of ESBLs/AmpCs. NDM-1 first emerged in E. coli during 2008; later in 2010, the resistance was detected in K. pneumoniae and E. cloacae isolates. NDM-1-producing isolates were resistant to other broad-spectrum antibiotics and possessed ESBLs, AmpCs, 16S-rRNA methylases, AAC(6′)-Ib-cr, bleomycin resistant gene and class 1 integron. Pulsed field gel electrophoresis of the NDM-1-producing isolates indicated that the isolates were clonally diverse. The study also showed that there was a significantly higher incidence of sepsis caused by NDM-1-harbouring isolates in the male sex, in neonates with low birth weight and neonates born at an extramural centre. However, sepsis with NDM-1-harbouring isolates did not result in a higher mortality rate. The study is the first to review the carbapenem resistance patterns in neonatal sepsis

Double Copies of bla(KPC-3)::Tn4401a on an IncX3 Plasmid in Klebsiella pneumoniae Successful Clone ST512 from Italy.

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Fortini, Daniela; Villa, Laura; Feudi, Claudia; Pires, João; Bonura, Celestino; Mammina, Caterina; Endimiani, Andrea; Carattoli, Alessandra

2016-01-01

A carbapenem-resistant sequence type 512 (ST512) Klebsiella pneumoniae carbapenemase 3 (KPC-3)-producing K. pneumoniae strain showing a novel variant plasmid content was isolated in Palermo, Italy, in 2014. ST512 is a worldwide successful clone associated with the spread of bla(KPC) genes located on the IncFIIk pKpQIL plasmid. In our ST512 strain, the bla(KPC-3) gene was unusually located on an IncX3 plasmid, whose complete sequence was determined. Two copies of bla(KPC-3)::Tn4401a caused by intramolecular transposition events were detected in the plasmid. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals.

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Fujimoto, Koichi; Takemoto, Koji; Hatano, Kazuo; Nakai, Toru; Terashita, Shigeyuki; Matsumoto, Masahiro; Eriguchi, Yoshiro; Eguchi, Ken; Shimizudani, Takeshi; Sato, Kimihiko; Kanazawa, Katsunori; Sunagawa, Makoto; Ueda, Yutaka

2013-02-01

SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae (including β-lactamase-negative ampicillin-resistant strains), and Neisseria gonorrhoeae (including ciprofloxacin-resistant strains), with MIC(90)s of ≤ 1 μg/ml. Unlike tebipenem (MIC(50), 8 μg/ml), SM-295291 and SM-369926 had no activity against hospital pathogens such as Pseudomonas aeruginosa (MIC(50), ≥ 128 μg/ml). The bactericidal activities of SM-295291 and SM-369926 against penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren. The therapeutic efficacies of intravenous administrations of SM-295291 and SM-369926 against experimentally induced infections in mice caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren, respectively, reflecting their in vitro activities. SM-295291 and SM-369926 showed intravenous pharmacokinetics similar to those of meropenem in terms of half-life in monkeys (0.4 h) and were stable against human dehydropeptidase I. SM-368589 and SM-375769, which are medoxomil esters of SM-295291 and SM-369926, respectively, showed good oral bioavailability in rats, dogs, and monkeys (4.2 to 62.3%). Thus, 2-aryl carbapenems are promising candidates that show an ideal broad spectrum for the treatment of community-acquired infections, including infections caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae, have low selective pressure on antipseudomonal

Transposons and integrons in colistin-resistant clones of Klebsiella pneumoniae and Acinetobacter baumannii with epidemic or sporadic behaviour.

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Arduino, Sonia M; Quiroga, María Paula; Ramírez, María Soledad; Merkier, Andrea Karina; Errecalde, Laura; Di Martino, Ana; Smayevsky, Jorgelina; Kaufman, Sara; Centrón, Daniela

2012-10-01

Multiple transposons, integrons and carbapenemases were found in Klebsiella pneumoniae colistin-resistant isolates as well as a genomic resistance island of the AbaR type in Acinetobacter baumannii colistin-resistant isolates from different hospitals from Buenos Aires City. PFGE analysis showed a polyclonal dissemination of antimicrobial resistance mechanisms among K. pneumoniae isolates, while in A. baumannii isolates the epidemic clone 1 from South America was found. Resistance determinants associated with horizontal gene transfer are contributing to the evolution to pandrug resistance in both epidemic and sporadic clones.

Extended spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae: critical tools for antibiotic resistance pattern.

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Padmini, Nagarajan; Ajilda, Antony Alex Kennedy; Sivakumar, Natesan; Selvakumar, Gopal

2017-06-01

Drug resistance is a phenomenon where by an organism becomes fully or partially resistant to drugs or antibiotics being used against it. Antibiotic resistance poses an exacting intimidation for people with underlying medical immune conditions or weakened immune systems. Infections caused by the enzyme extended spectrum β-lactamase (ESBL) producing multi drug resistance (MDR) Enterobacteriaceae especially Escherichia coli and Klebsiella pneumoniae are resistant to a broad range of beta lactams, including third generation cephalosporins. Among all the pathogens, these two MDR E. coli and K. pneumoniae have emerged as one of the world's greatest health threats in past two decades. The nosocomial infections caused by these ESBL producing MDR E. coli and K. pneumoniae complicated the therapy and limit treatment options. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trends in Expanded-Spectrum Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae among Dutch Clinical Isolates, from 2008 to 2012

NARCIS (Netherlands)

van der Steen, Matthijs; Leenstra, Tjalling; Kluytmans, Jan A J W; van der Bij, Akke K

2015-01-01

We investigated time trends in extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates from different patient settings in The Netherlands from 2008-2012. E. coli and K. pneumoniae isolates from blood and urine samples of patients > = 18 years were selected from

A managed multidisciplinary programme on multi-resistant Klebsiella pneumoniae in a Danish university hospital

DEFF Research Database (Denmark)

Andersen, Stig Ejdrup; Knudsen, Inge Jenny Dahl

2013-01-01

BACKGROUND: Bacteria-producing extended spectrum β-lactamase (ESBL) enzymes are resistant to commonly used antimicrobials. In 2008, routine monitoring revealed a clonal hospital outbreak of ESBL-producing Klebsiella pneumoniae (ESBL-KP). METHODS: At a 510-bed Danish university hospital...... the application of a managed, multi-faceted intervention that does not require ongoing antibiotic stewardship....

Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae, United States 2016.

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de Man, Tom J B; Lutgring, Joseph D; Lonsway, David R; Anderson, Karen F; Kiehlbauch, Julia A; Chen, Lei; Walters, Maroya Spalding; Sjölund-Karlsson, Maria; Rasheed, J Kamile; Kallen, Alexander; Halpin, Alison Laufer

2018-04-03

Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae , nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. The isolate harbored four known beta-lactamase genes, including plasmid-mediated bla NDM-1 and bla CMY-6 , as well as chromosomal bla CTX-M-15 and bla SHV-28 , which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline. IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide

Radiologic discussion on Klebsiella pneumonia in 89 cases

International Nuclear Information System (INIS)

Zhang Chunsheng; Li Xuejun; Tai Hanzhen; Wang Guohua; Qi Shi

2007-01-01

Objective: To evaluate the diagnostic value of radiology and CT scanning in Klebsiella pneumoniae. Methods: The clinical, radiologic data and CT films of 89 patients with Klebsiella pneumoniae were retrospectively analyzed. Results: Three types of chest X-ray and computed tomography (CT) findings for Klebsiella pneumonia were found. (1)Increased pulmonary markings occured in 31 cases. (2)35 cases with single lesions showed frequently involvement in the upper or lower lobe of right lung. When lesion was involved in the upper lobe, it developed oblique fissure shift down in radiology films and represent stalactitic symptom in CT imagining. (3)In 23 cases with Klebsiella pneumonia showed typical cavitary lung abscesses. Conclusion: The radiologic findings of Klebsiella pneumoniae were complicated and hard to make a good diagnosis. Combined the imaging features with the clinic data, sometimes, we can get the right diagnosis in some cases with typical Klebsiella pneumoniae. (authors)

(ESBL) producing Escherichia coli and Klebsiella pneumoniae

African Journals Online (AJOL)

Emerging antibiotic resistance due to extended spectrum β-lactamase (ESBL) production limited the use of β-lactam antibiotics against Escherichia coli and Klebsiella pneumoniae. This observational study was conducted at the Microbiology department of the Children's Hospital, Lahore Pakistan, from June, 2009 to ...

The Impact of a Carbapenem-Resistant Enterobacteriaceae Outbreak on Facilitating Development of a National Infrastructure for Infection Control in Israel.

Science.gov (United States)

Schwaber, Mitchell J; Carmeli, Yehuda

2017-11-29

In 2006 the Israeli healthcare system faced an unprecedented outbreak of carbapenem-resistant Enterobacteriaceae, primarily involving KPC-producing Klebsiella pneumoniae clonal complex CC258. This public health crisis exposed major gaps in infection control. In response, Israel established a national infection control infrastructure. The steps taken to build this infrastructure and benefits realized from its creation are described here. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Klebsiella pneumoniae inoculants for enhancing plant growth

Science.gov (United States)

Triplett, Eric W [Middleton, WI; Kaeppler, Shawn M [Oregon, WI; Chelius, Marisa K [Greeley, CO

2008-07-01

A biological inoculant for enhancing the growth of plants is disclosed. The inoculant includes the bacterial strains Herbaspirillum seropedicae 2A, Pantoea agglomerans P101, Pantoea agglomerans P102, Klebsiella pneumoniae 342, Klebsiella pneumoniae zmvsy, Herbaspirillum seropedicae Z152, Gluconacetobacter diazotrophicus PA15, with or without a carrier. The inoculant also includes strains of the bacterium Pantoea agglomerans and K. pneumoniae which are able to enhance the growth of cereal grasses. Also disclosed are the novel bacterial strains Herbaspirillum seropedicae 2A, Pantoea agglomerans P101 and P102, and Klebsiella pneumoniae 342 and zmvsy.

Clinical and pulmonary thin-section CT findings in acute Klebsiella Pneumoniae pneumonia

International Nuclear Information System (INIS)

Okada, Fumito; Ando, Yumiko; Honda, Koichi; Nakayama, Tomoko; Kiyonaga, Maki; Ono, Asami; Tanoue, Shuichi; Maeda, Toru; Mori, Hiromu

2009-01-01

The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded. Thus, our study group comprised 198 patients (118 male, 80 female; age range 18-97 years, mean age 61.5). Underlying diseases and clinical findings were assessed. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusion. CT findings in patients with acute Klebsiella pneumoniae pneumonia consisted mainly of ground-glass attenuation (100%), consolidation (91.4%), and intralobular reticular opacity (85.9%), which were found in the periphery (96%) of both sides of the lungs (72.2%) and were often associated with pleural effusion (53%). The underlying conditions in patients with Klebsiella pneumoniae pneumonia were alcoholism or smoking habit. (orig.)

Clinical and pulmonary thin-section CT findings in acute Klebsiella Pneumoniae pneumonia

Energy Technology Data Exchange (ETDEWEB)

Okada, Fumito [Oita University Faculty of Medicine, Department of Diagnostic and Interventional Radiology, Oita (Japan); Oita University Faculty of Medicine, Department of Radiology, Oita (Japan); Ando, Yumiko; Honda, Koichi; Nakayama, Tomoko; Kiyonaga, Maki; Ono, Asami; Tanoue, Shuichi; Maeda, Toru; Mori, Hiromu [Oita University Faculty of Medicine, Department of Diagnostic and Interventional Radiology, Oita (Japan)

2009-04-15

The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded. Thus, our study group comprised 198 patients (118 male, 80 female; age range 18-97 years, mean age 61.5). Underlying diseases and clinical findings were assessed. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusion. CT findings in patients with acute Klebsiella pneumoniae pneumonia consisted mainly of ground-glass attenuation (100%), consolidation (91.4%), and intralobular reticular opacity (85.9%), which were found in the periphery (96%) of both sides of the lungs (72.2%) and were often associated with pleural effusion (53%). The underlying conditions in patients with Klebsiella pneumoniae pneumonia were alcoholism or smoking habit. (orig.)

Clinical evaluation of the need for carbapenems to treat community-acquired and healthcare-associated pneumonia.

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Kamata, Kazuhiro; Suzuki, Hiromichi; Kanemoto, Koji; Tokuda, Yasuharu; Shiotani, Seiji; Hirose, Yumi; Suzuki, Masatsune; Ishikawa, Hiroichi

2015-08-01

Carbapenems have an overall broad antibacterial spectrum and should be protected against from the acquisition of drug resistance. The clinical advantages of carbapenem in cases of pneumonia have not been certified and the need for antipseudomonal antimicrobial agents to treat healthcare-associated pneumonia (HCAP) remains controversial. We introduced an antimicrobial stewardship program for carbapenem and tazobactam/piperacillin use and investigated the effects of this program on the clinical outcomes of 591 pneumonia cases that did not require intensive care unit management, mechanical ventilation or treatment with vasopressor agents [221 patients with community-acquired pneumonia (CAP) and 370 patients with HCAP]. Compared with the pre-intervention period, age, comorbidities and the severity and etiology of pneumonia did not differ during the intervention period. Carbapenems were rarely used during the intervention period in cases of pneumonia (CAP: 12% vs. 1%, HCAP: 13% vs. 1%), while antipseudomonal beta-lactam use was reduced from 33% to 8% among cases with HCAP. This reduction in the rate of carbapenem administration did not have an impact on the prognosis in the cases of CAP, and the in-hospital mortality was lower among the patients with HCAP during the intervention period (15% vs. 5%, p = 0.013). The causes of death in the cases of HCAP were not directly related to pneumonia during the intervention period. The current study shows that carbapenem use can be avoided in cases of CAP or HCAP that are not in a critical condition. The frequent use of antipseudomonal beta-lactams does not improve the clinical outcomes of HCAP. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

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Chen, Liang; Patel, Gopi; Gomez-Simmonds, Angela; Weston, Gregory; Kim, Angela C.; Seo, Susan K.; Rosenthal, Marnie E.; Sperber, Steven J.; Jenkins, Stephen G.; Hamula, Camille L.; Uhlemann, Anne-Catrin; Levi, Michael H.; Fries, Bettina C.; Juretschko, Stefan; Rojtman, Albert D.; Hong, Tao; Mathema, Barun; Jacobs, Michael R.; Walsh, Thomas J.; Bonomo, Robert A.; Kreiswirth, Barry N.

2017-01-01

ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics. PMID:28167547

Enhanced Peroxide Resistance of In Vitro Mutagenized Fluorideresistant Klebsiella pneumoniae Ureases for Catalytic Buffering of Agent Decontamination Reactions

National Research Council Canada - National Science Library

Fry, Ilona J; DeFrank, Joseph J

2004-01-01

.... Fluoride-resistant (FR) ureases developed previously in our laboratory were >95% inhibited by 1% hydrogen peroxide. To overcome this problem, the FR mutant urease structural genes of Klebsiella pneumoniae were mutagenized in vitro in an E...

Imipenem represses CRISPR-Cas interference of DNA acquisition through H-NS stimulation in Klebsiella pneumoniae

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Lin, Tzu-Lung; Pan, Yi-Jiun; Hsieh, Pei-Fang; Hsu, Chun-Ru; Wu, Meng-Chuan; Wang, Jin-Town

2016-01-01

Analysis of the genome of Klebsiella pneumoniae NTUH-K2044 strain revealed the presence of two clustered regularly interspaced short palindromic repeats (CRISPR) arrays separated with CRISPR-associated (cas) genes. Carbapenem-resistant K. pneumoniae isolates were observed to be less likely to have CRISPR-Cas than sensitive strains (5/85 vs. 22/132). Removal of the transcriptional repressor, H-NS, was shown to prevent the transformation of plasmids carrying a spacer and putative proto-spacer adjacent motif (PAM). The CRISPR-Cas system also decreased pUC-4K plasmid stability, resulting in plasmid loss from the bacteria with acquisition of new spacers. Analysis of the acquired proto-spacers in pUC-4K indicated that 5′-TTN-3′ was the preferred PAM in K. pneumoniae. Treatment of cells by imipenem induced hns expression, thereby decreasing cas3 expression and consequently repressed CRISPR-Cas activity resulted in increase of plasmid stability. In conclusion, NTUH-K2044 CRISPR-Cas contributes to decrease of plasmid transformation and stability. Through repression of CRISPR-Cas activity by induced H-NS, bacteria might be more able to acquire DNA to confront the challenge of imipenem. PMID:27531594

Imipenem represses CRISPR-Cas interference of DNA acquisition through H-NS stimulation in Klebsiella pneumoniae.

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Lin, Tzu-Lung; Pan, Yi-Jiun; Hsieh, Pei-Fang; Hsu, Chun-Ru; Wu, Meng-Chuan; Wang, Jin-Town

2016-08-17

Analysis of the genome of Klebsiella pneumoniae NTUH-K2044 strain revealed the presence of two clustered regularly interspaced short palindromic repeats (CRISPR) arrays separated with CRISPR-associated (cas) genes. Carbapenem-resistant K. pneumoniae isolates were observed to be less likely to have CRISPR-Cas than sensitive strains (5/85 vs. 22/132). Removal of the transcriptional repressor, H-NS, was shown to prevent the transformation of plasmids carrying a spacer and putative proto-spacer adjacent motif (PAM). The CRISPR-Cas system also decreased pUC-4K plasmid stability, resulting in plasmid loss from the bacteria with acquisition of new spacers. Analysis of the acquired proto-spacers in pUC-4K indicated that 5'-TTN-3' was the preferred PAM in K. pneumoniae. Treatment of cells by imipenem induced hns expression, thereby decreasing cas3 expression and consequently repressed CRISPR-Cas activity resulted in increase of plasmid stability. In conclusion, NTUH-K2044 CRISPR-Cas contributes to decrease of plasmid transformation and stability. Through repression of CRISPR-Cas activity by induced H-NS, bacteria might be more able to acquire DNA to confront the challenge of imipenem.

Phylogenetic groups among Klebsiella pneumoniae isolates from Brazil: relationship with antimicrobial resistance and origin.

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de Melo, Maíra Espíndola Silva; Cabral, Adriane Borges; Maciel, Maria Amélia Vieira; da Silveira, Vera Magalhães; de Souza Lopes, Ana Catarina

2011-05-01

The objectives of this study were to determine the distribution of phylogenetic groups among Klebsiella pneumoniae isolates from Recife, Brazil and to assess the relationship between the groups and the isolation sites and resistance profile. Ninety four isolates of K. pneumoniae from hospital or community infections and from normal microbiota were analyzed by gyrA PCR-RFLP, antibiotic susceptibility, and adonitol fermentation. The results revealed the distinction of three phylogenetic groups, as it has also been reported in Europe, showing that these clusters are highly conserved within K. pneumoniae. Group KpI was dominantly represented by hospital and community isolates while groups KpII and KpIII displayed mainly normal microbiota isolates. The resistance to third generation cephalosporins, aztreonam, imipenem, amoxicillin/clavulanic acid, and streptomycin was only observed in KpI. The percentage of resistance was higher in KpI, followed by KpII and KpIII. The differences in the distribution of K. pneumoniae phylogenetic groups observed in this study suggest distinctive clinical and epidemiological characteristics among the three groups, which is important to understand the epidemiology of infections caused by this organism. This is the first study in Brazil on K. pneumoniae isolates from normal microbiota and community infections regarding the distribution of phylogenetic groups based on the gyrA gene.

Mutant prevention concentrations of four carbapenems against gram-negative rods.

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Credito, Kim; Kosowska-Shick, Klaudia; Appelbaum, Peter C

2010-06-01

We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ss-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains.

Characterization of ST258 Colistin-Resistant, blaKPC-Producing Klebsiella pneumoniae in a Greek Hospital.

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Mavroidi, Angeliki; Katsiari, Maria; Likousi, Sofia; Palla, Eleftheria; Roussou, Zoi; Nikolaou, Charikleia; Maguina, Asimina; Platsouka, Evangelia D

2016-07-01

The emergence of colistin resistance may further contribute to treatment failure of infection caused by multidrug-resistant (MDR) Klebsiella pneumoniae. The colistin resistance rates were determined and colistin-resistant carbapenemase-producing K. pneumoniae (COL-R CP-Kp) were characterized over an 18-month period in a Greek hospital. Out of 135 carbapenemase producers, 19 isolates (14%) were categorized as resistant to colistin. Phenotypic and molecular characterization of the COL-R CP-Kp isolates revealed that all were MDR blaKPC producers and, excluding one isolate of MLST ST383, belonged to the international clonal lineage ST258. Furthermore, PCR amplification and sequencing of the mgrB locus revealed nucleotide sequences of different sizes and insertions of IS1- and IS5-like mobile elements. The majority (63%) of the COL-R blaKPC producers was recovered from patients in the intensive care unit (ICU) and clinical data indicated that all patients should have acquired these isolates in the ICU. The findings of the present study underscore a concerning evolution of colistin resistance in a setting of high K. pneumoniae carbapenemase (KPC)-Kp endemicity, such as Greece. Thus, continuous surveillance, molecular characterization, prudent use of antibiotics, and implementation of infection control measures for K. pneumoniae are urgent.

Comparison of Molecular and Phenotypic Methods for the Detection and Characterization of Carbapenem Resistant Enterobacteriaceae.

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Somily, Ali M; Garaween, Ghada A; Abukhalid, Norah; Absar, Muhammad M; Senok, Abiola C

2016-03-01

In recent years, there has been a rapid dissemination of carbapenem resistant Enterobacteriaceae (CRE). This study aimed to compare phenotypic and molecular methods for detection and characterization of CRE isolates at a large tertiary care hospital in Saudi Arabia. This study was carried out between January 2011 and November 2013 at the King Khalid University Hospital (KKUH) in Saudi Arabia. Determination of presence of extended-spectrum beta-lactamases (ESBL) and carbapenem resistance was in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. Phenotypic classification was done by the MASTDISCS(TM) ID inhibitor combination disk method. Genotypic characterization of ESBL and carbapenemase genes was performed by the Check-MDR CT102. Diversilab rep-PCR was used for the determination of clonal relationship. Of the 883 ESBL-positive Enterobacteriaceae detected during the study period, 14 (1.6%) isolates were carbapenem resistant. Both the molecular genotypic characterization and phenotypic testing were in agreement in the detection of all 8 metalo-beta-lactamases (MBL) producing isolates. Of these 8 MBL-producers, 5 were positive for blaNDM gene and 3 were positive for blaVIM gene. Molecular method identified additional blaOXA gene isolates while MASTDISCS(TM) ID detected one AmpC producer isolate. Both methods agreed in identifying 2 carbapenem resistant isolates which were negative for carbapenemase genes. Diversilab rep-PCR analysis of the 9 Klebsiella pneumoniae isolates revealed polyclonal distribution into eight clusters. MASTDISCS(TM) ID is a reliable simple cheap phenotypic method for detection of majority of carbapenemase genes with the exception of the blaOXA gene. We recommend to use such method in the clinical laboratory.

Colistin resistance associated with outer membrane protein change in Klebsiella pneumoniae and Enterobacter asburiae.

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Kádár, Béla; Kocsis, Béla; Tóth, Ákos; Kristóf, Katalin; Felső, Péter; Kocsis, Béla; Böddi, Katalin; Szabó, Dóra

2017-06-01

In this study, outer membrane proteins (OMPs) of colistin-resistant Klebsiella pneumoniae and Enterobacter asburiae were analyzed. One colistin-susceptible and three colistin-resistant K. pneumoniae sequence type 258 strains as well as one colistin-susceptible E. asburiae and its colistin-heteroresistant counterpart strain were involved in the study. OMP analysis of each strain was performed by microchip method. Matrix-assisted laser desorption ionization time of flight/mass spectrometry (MALDI-TOF/MS) investigation was carried out after separation of OMPs by two-dimensional gel electrophoresis and in-gel digestion. The MALDI-TOF/MS analysis of OMPs in the colistin-susceptible K. pneumoniae found 16 kDa proteins belonging to the LysM domain/BON superfamily, as well as DNA starvation proteins, whereas OmpX and OmpW were detected in the colistin-resistant counterpart strains. OmpC and OmpW were detected in the colistin-susceptible E. asburiae, whereas OmpA and OmpX were identified in the colistin-resistant counterpart. This study demonstrated that OMP differences were between colistin-susceptible and -resistant counterpart strains. The altered Gram-negative cell wall may contribute to acquired colistin resistance in Enterobacteriaceae.

Frequency, Antimicrobial Resistance and Genetic Diversity of Klebsiella pneumoniae in Food Samples.

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Yumei Guo

Full Text Available This study aimed to assess the frequency of Klebsiella pneumoniae in food samples and to detect antibiotic resistance phenotypes, antimicrobial resistance genes and the molecular subtypes of the recovered isolates. A total of 998 food samples were collected, and 99 (9.9% K. pneumoniae strains were isolated; the frequencies were 8.2% (4/49 in fresh raw seafood, 13.8% (26/188 in fresh raw chicken, 11.4% (34/297 in frozen raw food and 7.5% (35/464 in cooked food samples. Antimicrobial resistance was observed against 16 antimicrobials. The highest resistance rate was observed for ampicillin (92.3%, followed by tetracycline (31.3%, trimethoprim-sulfamethoxazole (18.2%, and chloramphenicol (10.1%. Two K. pneumoniae strains were identified as extended-spectrum β-lactamase (ESBL-one strain had three beta-lactamases genes (blaSHV, blaCTX-M-1, and blaCTX-M-10 and one had only the blaSHV gene. Nineteen multidrug-resistant (MDR strains were detected; the percentage of MDR strains in fresh raw chicken samples was significantly higher than in other sample types (P<0.05. Six of the 18 trimethoprim-sulfamethoxazole-resistant strains carried the folate pathway inhibitor gene (dhfr. Four isolates were screened by PCR for quinolone resistance genes; aac(6'-Ib-cr, qnrB, qnrA and qnrS were detected. In addition, gyrA gene mutations such as T247A (Ser83Ile, C248T (Ser83Phe, and A260C (Asp87Ala and a parC C240T (Ser80Ile mutation were identified. Five isolates were screened for aminoglycosides resistance genes; aacA4, aacC2, and aadA1 were detected. Pulsed-field gel electrophoresis-based subtyping identified 91 different patterns. Our results indicate that food, especially fresh raw chicken, is a reservoir of antimicrobial-resistant K. pneumoniae, and the potential health risks posed by such strains should not be underestimated. Our results demonstrated high prevalence, antibiotic resistance rate and genetic diversity of K. pneumoniae in food in China. Improved

In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam.

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Le Minh, Vien; Thi Khanh Nhu, Nguyen; Vinh Phat, Voong; Thompson, Corinne; Huong Lan, Nguyen Phu; Thieu Nga, Tran Vu; Thanh Tam, Pham Thi; Tuyen, Ha Thanh; Hoang Nhu, Tran Do; Van Hao, Nguyen; Thi Loan, Huynh; Minh Yen, Lam; Parry, Christopher M; Trung Nghia, Ho Dang; Campbell, James I; Hien, Tran Tinh; Thwaites, Louise; Thwaites, Guy; Van Vinh Chau, Nguyen; Baker, Stephen

2015-10-01

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

Emergence of Serratia marcescens isolates possessing carbapenem-hydrolysing β-lactamase KPC-2 from China.

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Lin, X; Hu, Q; Zhang, R; Hu, Y; Xu, X; Lv, H

2016-09-01

Eighty-three carbapenem-resistant Serratia marcescens isolates were recovered from Zhejiang Provincial People's Hospital, China. The minimum inhibitory concentrations of imipenem, meropenem, and ertapenem for all isolates were 2 to >128 μg/mL. Polymerase chain reaction indicated that 63 S. marcescens isolates produced Klebsiella pneumoniae carbapenemase (KPC)-2. Clone A (15 isolates) and clone B (41 isolates) were the two dominant clones and clone A strains were gradually replaced by clone B strains between 2011 and 2014. The results indicate that blaKPC-2-positive S. marcescens emerged in our hospital as the major mechanism of carbapenem resistance. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Plasmid-Mediated Antibiotic Resistance and Virulence in Gram-negatives: the Klebsiella pneumoniae Paradigm.

Science.gov (United States)

Ramirez, Maria S; Traglia, German M; Lin, David L; Tran, Tung; Tolmasky, Marcelo E

Plasmids harbor genes coding for specific functions including virulence factors and antibiotic resistance that permit bacteria to survive the hostile environment found in the host and resist treatment. Together with other genetic elements such as integrons and transposons, and using a variety of mechanisms, plasmids participate in the dissemination of these traits resulting in the virtual elimination of barriers among different kinds of bacteria. In this article we review the current information about physiology and role in virulence and antibiotic resistance of plasmids from the gram-negative opportunistic pathogen Klebsiella pneumoniae . This bacterium has acquired multidrug resistance and is the causative agent of serious communityand hospital-acquired infections. It is also included in the recently defined ESKAPE group of bacteria that cause most of US hospital infections.

Klebsiella pneumoniae Invasive Syndrome

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Vasco Evangelista

2018-01-01

Full Text Available Klebsiella pneumoniae invasive syndrome (KPIS is a rare clinical condition characterized by primary liver abscess associated with metastatic infection. Most case reports are from Southeast Asia, with only one case described in Portugal. The Authors present the case of a 44-year-old man with a history of fever, dry cough and cervicalgia. A thoracic computed tomography (CT scan showed multiple pulmonary and hepatic nodules, suggestive of metastatic malignancy. Both blood cultures and bronchoalveolar lavage were positive for Klebsiella pneumoniae. Imaging studies were repeated during his hospital stay, showing a reduction in both number and volume of identified lesions, thus revealing their infectious nature. This case illustrates how much this entity can mimic other illnesses.

Cross-class resistance to non-beta-lactam antimicrobials in extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

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Procop, Gary W; Tuohy, Marion J; Wilson, Deborah A; Williams, Delisa; Hadziyannis, Emilia; Hall, Gerri S

2003-08-01

Extended spectrum beta-lactamases are modified beta-lactamase enzymes that impart resistance to third-generation cephalosporins and make all beta-lactam antibiotics and cephalosporins useless for therapy. We compared the antimicrobial susceptibility profiles of extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing isolates of Klebsiella pneumoniae. The ESBL producers had significantly diminished susceptibility compared with the non-ESBL producers for gentamicin (P < .001), tobramycin (P < .001), amikacin (P < .005), trimethoprim-sulfamethoxazole (P < .01), ciprofloxacin (P < .001), and nitrofurantoin (P < .001). All isolates were susceptible to imipenem. ESBL-producing K pneumoniae may also be resistant to non-beta-lactam antibiotics. Therefore, susceptibility testing of these isolates is critical for guiding therapy.

Molecular epidemiology of carbapenem resistant gram-negative bacilli from infected pediatric population in tertiary - care hospitals in Medellín, Colombia: an increasing problem.

Science.gov (United States)

Vanegas, Johanna M; Parra, O Lorena; Jiménez, J Natalia

2016-09-01

Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia. A cross-sectional study was conducted in five tertiary-care hospitals from June 2012 to June 2014. All pediatric patients infected by carbapenem-resistant Gram-negative bacilli were included. Clinical information for each patient was obtained from medical records. Molecular analyses included PCR for detection of bla VIM, bla IMP bla NDM, bla OXA-48 and bla KPC genes and PFGE and MLST for molecular typing. A total of 59 patients were enrolled, most of them less than 1 year old (40.7 % n = 24), with a previous history of antibiotic use (94.9 %; n = 56) and healthcare-associated infections - predominately urinary tract infections (31.0 %; n = 18). Klebsiella pneumoniae was the most frequent bacteria (47.4 %), followed by Enterobacter cloacae (40.7 %) and Pseudomonas aeruginosa (11.9 %). For K. pneumoniae, KPC was the predominant resistance mechanism (85.7 %; n = 24) and ST14 was the most common clone (39.3 % n = 11), which included strains closely related by PFGE. In contrast, E. cloacae and P. aeruginosa were prevailing non-carbapenemase-producing isolates (only KPC and VIM were detected in 1 and 3 isolates, respectively) and high genetic diversity according to PFGE and MLST was found in the majority of the cases. In recent years, increasing carbapenem-resistant bacilli in children has become in a matter

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

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Paczosa, Michelle K.

2016-01-01

SUMMARY Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae has caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore, K. pneumoniae strains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity in K. pneumoniae strains, and not every factor plays the same critical role in all virulent Klebsiella strains. Recent studies have identified additional K. pneumoniae virulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections. PMID:27307579

The Rapid Emergence of Tigecycline Resistance in blaKPC–2 Harboring Klebsiella pneumoniae, as Mediated in Vivo by Mutation in tetA During Tigecycline Treatment

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Xiaoxing Du

2018-04-01

Full Text Available Tigecycline is one of the last resort treatments for carbapenem-resistant Klebsiella pneumoniae (CRKP infections. Tigecycline resistance often occurs during the clinical treatment of CRKP, yet its mechanism has still not been clearly elucidated. This study presents an analysis of a tigecycline resistance mechanism that developed in clinical isolates from a 56-year-old female patient infected with CRKP during tigecycline treatment. Consecutive clonal consistent K. pneumoniae isolates were obtained during tigecycline treatment. Whole genome sequencing of the isolates was performed, and putative single nucleotide polymorphisms and insertion and deletion mutations were analyzed in susceptible and resistant isolates. The identified gene of interest was examined through experiments involving transformations and conjugations. Four isolates, two of which were susceptible and two resistant, were collected from the patient. All of the isolates belonged to Sequence Type 11 (ST11 and were classified as extensively drug resistant (XDR. One amino acid substitution S251A in TetA was identified in the tigecycline-resistant isolates. Subsequent transformation experiments confirmed the contribution of the TetA variant (S251A to tigecycline resistance. The transfer capacity of tigecycline resistance via this mutation was confirmed by conjugation experiments. Using southern blot hybridization and PCR assays, we further proved that the tetA gene was located on a transferable plasmid of ca. 65 kb in an Escherichia coli EC600 transconjugant. Our results provide direct in vivo evidence that evolution in the tetA gene can lead to tigecycline treatment failure in CRKP clinical strains that carry tetA. Moreover, the transfer capacity of tigecycline resistance mediated by mutated tetA is a threat.

Comparative effectiveness of flomoxef versus carbapenems in the treatment of bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae with emphasis on minimum inhibitory concentration of flomoxef: a retrospective study.

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Lee, Chen-Hsiang; Su, Lin-Hui; Chen, Fang-Ju; Tang, Ya-Feng; Li, Chia-Chin; Chien, Chun-Chih; Liu, Jien-Wei

2015-12-01

This study compared treatment outcomes of adult patients with bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae (ESBL-EK) receiving flomoxef versus those receiving a carbapenem as definitive therapy. In propensity score matching (PSM) analysis, case patients receiving flomoxef shown to be active in vitro against ESBL-EK were matched with controls who received a carbapenem. The primary endpoint was 30-day crude mortality. The flomoxef group had statistically significantly higher sepsis-related mortality (27.3% vs. 10.5%) and 30-day mortality (28.8% vs. 12.8%) than the carbapenem group. Of the bacteraemic episodes caused by isolates with a MICflomoxef of ≤1 mg/L, sepsis-related mortality rates were similar between the two treatment groups (8.7% vs. 6.4%; P=0.73). The sepsis-related mortality rate of the flomoxef group increased to 29.6% and 50.0% of episodes caused by isolates with a MICflomoxef of 2-4 mg/L and 8 mg/L, respectively, which was significantly higher than the carbapenem group (12.3%). In the PSM analysis of 86 case-control pairs infected with strains with a MICflomoxef of 2-8 mg/L, case patients had a significantly higher 30-day mortality rate (38.4% vs. 18.6%). Multivariate regression analysis revealed that flomoxef therapy for isolates with a MICflomoxef of 2-8 mg/L, concurrent pneumonia or urosepsis, and a Pitt bacteraemia score ≥4 were independently associated with 30-day mortality. Definitive flomoxef therapy appears to be inferior to carbapenems in treating ESBL-EK bacteraemia, particularly for isolates with a MICflomoxef of 2-8 mg/L, even though the currently suggested MIC breakpoint of flomoxef is ≤8 mg/L. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Mutant Prevention Concentrations of Four Carbapenems against Gram-Negative Rods▿ †

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Credito, Kim; Kosowska-Shick, Klaudia; Appelbaum, Peter C.

2010-01-01

We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ß-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to ≥16. The MPC/MIC ratios for β-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 μg/ml) than those for ß-lactamase-negative strains. PMID:20308376

Nitrofurantoin and Fosfomycin for Extended Spectrum Beta-lactamases Producing Escherichia coli and Klebsiella pneumoniae

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Neeraj Kumar Tulara

2018-01-01

Full Text Available Urinary tract infection (UTI is a common and painful human illness that, unfortunately not responsive to commonly used antibiotics in current practice. The role of fosfomycin and nitrofurantoin in the era of growing bacteria resistance has been widely discussed. In this study, we aimed to know the local antimicrobial susceptibilities, fosfomycin and nitrofurantoin susceptibility in particular, for urinary extended-spectrum-beta-lactamase-producing Escherichia coli and Escherichia pneumoniae (ESBL-EC and ESBL-KP isolates in our hospital. We collected 464 urine isolates, including 384 ESBL-EC and 80 ESBL-KP isolates. Of 464 urine isolates culture positive ESBL-UTIs, EC caused 384 (82.75%, followed by Klebsiella in 80 (17.24%. Carbapenems and Colistin seems to remain as the first line therapy for the majority of ESBL-UTIs in the local setting. Colistin and fosfomycin remains the most sensitive antibiotic while nitrofurantoin still preserves the good sensitivity against ESBL and found to be an only oral sensitive antibiotic.

First case of New Delhi metallo-β-lactamase in Klebsiella pneumoniae from Ecuador: An update for South America.

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Romero-Alvarez, Daniel; Reyes, Jorge; Quezada, Viviana; Satán, Carolina; Cevallos, Nelson; Barrera, Sofía; Trueba, Gabriel; Escobar, Luis E; Villacís, José E

2017-12-01

To describe a clinical case of Klebsiella pneumoniae harboring a New Delhi metallo-β-lactamase (NDM) plasmid in Ecuador and to present a map of reports of NDM isolates in South America. The modified Hodge test, carbapenem inactivation method, imipenem-EDTA disk method (synergy), and Rapidec Carba NP test were used to identify antibiotic resistance mechanisms. The presence of resistance genes was explored with a conjugation assay, and molecular confirmation of NDM was performed by PCR and DNA sequencing. Plasmid characterization was conducted by PCR-based replicon typing. A literature review was performed in Google Scholar and PubMed to identify reports from South America. An HIV-infected patient, who had never traveled abroad, developed a bloodstream infection caused by K. pneumoniae ST147 harboring the NDM-1 resistance gene in a plasmid from the IncA/C group. Local circulation of NDM has also been described in other South American countries, in particular in Colombia and Brazil, although published scientific records were not found for other countries. This report presents the first evidence of autochthonous circulation of the NDM-1 resistance gene harbored by an IncA/C plasmid isolated from a K. pneumoniae ST147 in Ecuador. Efforts should be implemented to monitor and characterize the spatial and temporal distribution of NDM in Ecuador and other countries of South America. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States.

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Satlin, Michael J; Chen, Liang; Patel, Gopi; Gomez-Simmonds, Angela; Weston, Gregory; Kim, Angela C; Seo, Susan K; Rosenthal, Marnie E; Sperber, Steven J; Jenkins, Stephen G; Hamula, Camille L; Uhlemann, Anne-Catrin; Levi, Michael H; Fries, Bettina C; Tang, Yi-Wei; Juretschko, Stefan; Rojtman, Albert D; Hong, Tao; Mathema, Barun; Jacobs, Michael R; Walsh, Thomas J; Bonomo, Robert A; Kreiswirth, Barry N

2017-04-01

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types ( cps ), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae , Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC- Kp ). The wzi154 allele, corresponding to cps-2 , was present in 93% of KPC-3- Kp , whereas KPC-2- Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3- Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3- Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics. Copyright © 2017 American Society for Microbiology.

Outbreak of Ampicillin/Piperacillin-Resistant Klebsiella Pneumoniae in a Neonatal Intensive Care Unit (NICU: Investigation and Control Measures

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Patrizia Farruggia

2013-02-01

Full Text Available Klebsiella pneumoniae is a frequent cause of infectious outbreaks in Neonatal Intensive Care Units (NICUs. The aim of this paper is to describe an outbreak occurred in a 13-bed NICU and the control measures adopted in order to interrupt the chain of transmission. We described the microbiological investigations, the NICU staff compliance to the infection control measures by means of a specifically designed check-list and the control measures adopted. Six cases of primary bloodstream infections sustained by ampicillin/piperacillin-resistant Klebsiella pneumoniae were observed over a two-month period. One culture obtained from a 12% saccarose multiple-dose solution allowed the growth of Klebsiella pneumoniae. During the inspections performed by the Hospital Infection Control Team, using the check-list for the evaluation of the NICU staff compliance to the infection control measures, several breaches in the infection control policy were identified and control measures were adopted. In our case the definition of a specific check-list led to the adoption of the correct control measures. Further studies would be helpful in order to develop a standard check-list able to identify critical flows in the adhesion to the guidelines. It could be used in different NICUs and allow to obtain reproducible levels of infection control.

Outbreak of ampicillin/piperacillin-resistant Klebsiella pneumoniae in a neonatal intensive care unit (NICU): investigation and control measures.

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Fabbri, Giuliana; Panico, Manuela; Dallolio, Laura; Suzzi, Roberta; Ciccia, Matilde; Sandri, Fabrizio; Farruggia, Patrizia

2013-02-26

Klebsiella pneumoniae is a frequent cause of infectious outbreaks in Neonatal Intensive Care Units (NICUs). The aim of this paper is to describe an outbreak occurred in a 13-bed NICU and the control measures adopted in order to interrupt the chain of transmission. We described the microbiological investigations, the NICU staff compliance to the infection control measures by means of a specifically designed check-list and the control measures adopted. Six cases of primary bloodstream infections sustained by ampicillin/piperacillin-resistant Klebsiella pneumoniae were observed over a two-month period. One culture obtained from a 12% saccarose multiple-dose solution allowed the growth of Klebsiella pneumoniae. During the inspections performed by the Hospital Infection Control Team, using the check-list for the evaluation of the NICU staff compliance to the infection control measures, several breaches in the infection control policy were identified and control measures were adopted. In our case the definition of a specific check-list led to the adoption of the correct control measures. Further studies would be helpful in order to develop a standard check-list able to identify critical flows in the adhesion to the guidelines. It could be used in different NICUs and allow to obtain reproducible levels of infection control.

Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome

OpenAIRE

Huang, Weihua; Wang, Guiqing; Sebra, Robert; Zhuge, Jian; Yin, Changhong; Aguero-Rosenfeld, Maria E.; Schuetz, Audrey N.; Dimitrova, Nevenka; Fallon, John T.

2017-01-01

The extended-spectrum-β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying both blaCTX-M and blaKPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, bla...

Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates.

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Shaaban, Mona I; Shaker, Mohamed A; Mady, Fatma M

2017-04-11

Carbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains easily develop a multi-resistance action to other potent antimicrobial agents. Nonetheless, the protective delivery of current antibiotics using nano-carriers opens a tremendous approach in the antimicrobial therapy, allowing the nano-formulated antibiotics to beat these health threat pathogens. Herein, we encapsulated imipenem into biodegradable polymeric nanoparticles to destroy the imipenem-resistant bacteria and overcome the microbial adhesion and dissemination. Imipenem loaded poly Ɛ-caprolactone (PCL) and polylactide-co-glycolide (PLGA) nanocapsules were formulated using double emulsion evaporation method. The obtained nanocapsules were characterized for mean particle diameter, morphology, loading efficiency, and in vitro release. The in vitro antimicrobial and anti adhesion activities were evaluated against selected imipenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates. The obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2-3 h compared to the imipenem loaded PLGA and free drug. Successfully, PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. Moreover, the imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively. These promising results indicate that polymeric nanoparticles recover the efficacy of imipenem and can be considered as a new paradigm shift against multidrug-resistant isolates in treating severe bacterial infections.

Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in an In Vitro Hollow-Fiber Model.

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Sabet, Mojgan; Tarazi, Ziad; Rubio-Aparicio, Debora; Nolan, Thomas G; Parkinson, Jonathan; Lomovskaya, Olga; Dudley, Michael N; Griffith, David C

2018-02-01

The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains when tested at an inoculum of 10 8 CFU/ml. Thirteen K. pneumoniae isolates, three Enterobacter cloacae isolates, and one Escherichia coli isolate were examined in an in vitro hollow-fiber model over 32 h. Simulated dosage regimens of 1 to 2 g of meropenem with 1 to 2 g of vaborbactam, with meropenem administered every 8 h by a 3-h infusion based on phase 1 or phase 3 patient pharmacokinetic data, were studied in the model. A dosage of 2 g of meropenem in combination with 2 g of vaborbactam was bactericidal against K. pneumoniae , E. cloacae , and E. coli strains, with meropenem-vaborbactam MICs of up to 8 mg/liter. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in phase 3 trials (24-h free AUC, ∼550 mg · h/liter, versus 320 mg · h/liter in the phase 1 studies), 2 g of meropenem with 2 g of vaborbactam was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/liter. In addition, this level of vaborbactam also suppressed the development of resistance observed using phase 1 exposures. In this pharmacodynamic model, exposures similar to 2 g of meropenem in combination with 2 g of vaborbactam administered every 8 h by a 3-h infusion in phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem-resistant KPC-producing strains of Enterobacteriaceae . Copyright © 2018 American Society for Microbiology.

Klebsiella pneumonia strains moderately resistant to ampicillin and carbenicillin: characterization of a new β-lactamase

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Labia, Roger; Fabre, Christian; Masson, Jean-Michel; Barthelemy, Michel; Heitz, Madeleine; Pitton, Jean-S

2017-01-01

Klebsiella pneumoniae strain 11-03, moderately resistant to ampicillin and carbenicillin, produces one constitutive β-lactamase with an isoelectric point of 7.10 and a molecular weight of 20,000±500. The enzymatic activity is directed primarily against the penicillins, ampicillin being the best substrate. Some cephalosporins are also hydrolyzed to some extent but the affinity of the enzyme for these antibiotics is low (high Km values). It has not been possible to determine whether the biogene...

High prevalence of multi-drug resistant Klebsiella pneumoniae in a ...

African Journals Online (AJOL)

The lowest resistance rates were documented for Carbapenems (23.2%). For specific antibiotics, there was high resistance to commonly used antibiotics (over 80% for Ceftriaxone, Cefipime, Gentamycin and Ceftazidime). The antibiotics with least resistance were Amikacin and Meropenem (21% and 7 % respectively).

Correlation between carbapenem consumption and resistance to carbapenems among Enterobacteriaceae isolates collected from patients with intra-abdominal infections at five medical centers in Taiwan, 2006-2010.

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Ho, Cheng-Mao; Ho, Mao-Wang; Liu, Yung-Ching; Toh, Han-Siong; Lee, Yu-Lin; Liu, Yuag-Meng; Huang, Chi-Chang; Lu, Po-Liang; Liu, Chun-Eng; Chen, Yen-Hsu; Ko, Wen-Chien; Tang, Hung-Jen; Yu, Kwok-Woon; Chen, Yao-Shen; Chuang, Yin-Ching; Wang, Jen-Hsien; Hsueh, Po-Ren

2012-06-01

We investigated the trend in resistance to carbapenems among isolates of Enterobacteriaceae that had been collected from patients with intra-abdominal infections at five medical centers in Taiwan from 2006 to 2010 and evaluated the correlation between resistance to carbapenems and consumption of said agents as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, the usage of ertapenem and that of total carbapenems (ertapenem, imipenem, and meropenem) increased significantly from 6.13 to 13.38 defined daily doses per 1000 patient-days for ertapenem and from 20.43 to 34.25 defined daily doses per 1000 patient-days for total carbapenems. The most common species were Escherichia coli (n = 1095), Klebsiella spp. (n = 663), and Enterobacter spp. (n = 202). The susceptibility of all isolates to ertapenem and to imipenem varied during the study period. For ertapenem, the rates of nonsusceptibility ranged from 3.5% to 10.3% and those for imipenem ranged from 3.5% to 10.7%. Although the use of carbapenems increased during the study period, there was no marked increase in resistance to carbapenems. Continuous monitoring of resistance trends is necessary so that antimicrobial prescription policies can be adjusted and infection control intervention programs can be implemented. Copyright © 2012 Elsevier B.V. All rights reserved.

Trends in Expanded-Spectrum Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae among Dutch Clinical Isolates, from 2008 to 2012.

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Matthijs van der Steen

Full Text Available We investigated time trends in extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates from different patient settings in The Netherlands from 2008-2012. E. coli and K. pneumoniae isolates from blood and urine samples of patients > = 18 years were selected from the Dutch Infectious Disease Surveillance System-Antimicrobial Resistance (ISIS-AR database. We used multivariable Poisson regression to study the rate per year of blood stream infections by susceptible and resistant isolates, and generalized estimating equation (GEE log-binomial regression for trends in the proportion of extended-spectrum cephalosporin-resistant isolates. Susceptibility data of 197,513 E. coli and 38,244 K. pneumoniae isolates were included. The proportion of extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates from urine and blood samples increased in all patient settings, except for K. pneumoniae isolates from patients admitted to intensive care units. For K. pneumoniae, there was a different time trend between various patient groups (p<0.01, with a significantly higher increase in extended-spectrum cephalosporin-resistant isolates from patients attending a general practitioner than in isolates from hospitalized patients. For E. coli, the increasing time trends did not differ among different patient groups. This nationwide study shows a general increase in extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates. However, differences in trends between E. coli en K. pneumoniae underline the importance of E. coli as a community-pathogen and its subsequent influence on hospital resistance level, while for K. pneumoniae the level of resistance within the hospital seems less influenced by the resistance trends in the community.

Multihospital Occurrence of Pan-Resistant Klebsiella pneumoniae Sequence Type 147 with an ISEcp1-Directed blaOXA-181 Insertion in the mgrB Gene in the United Arab Emirates.

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Sonnevend, Ágnes; Ghazawi, Akela; Hashmey, Rayhan; Haidermota, Aliasgher; Girgis, Safinaz; Alfaresi, Mubarak; Omar, Mohammed; Paterson, David L; Zowawi, Hosam M; Pál, Tibor

2017-07-01

The emergence of pan-resistant Klebsiella pneumoniae strains is an increasing concern. In the present study, we describe a cluster of 9 pan-resistant K. pneumoniae sequence type 147 (ST147) isolates encountered in 4 patients over nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181, and the majority also produced the NDM-5 carbapenemase. As with the previously described single isolate from the UAE, MS6671, the mgrB was disrupted by a functional, IS Ecp1 -driven bla OXA-181 insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact mgrB gene, indicating that it was responsible for colistin resistance. bla NDM-5 was located within a resistance island of an approximately 100-kb IncFII plasmid carrying ermB , mph (A), bla TEM-1B , rmtB , bla NDM-5 , sul1 , aadA2 , and dfrA12 resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including bla NDM-5 , had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the bla NDM-5 -carrying IncFII plasmids of two K. pneumoniae ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably, one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time and is even likely to be transmitted internationally. Copyright © 2017 American Society for Microbiology.

Klebsiella pneumoniae as a nosocomial pathogen: epidemiology and drug resistance Klebsiella pneumoniae como patógeno intrahospitalario: epidemiología y resistencia

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Juan Carlos Cataño Correa

2010-08-01

Full Text Available

Worldwide, bacterial resistance is an increasingly serious problem, especially in hospital environments. Staphylococcus aureus and Escherichia coli are the most frequently isolated microorganisms in patients with nosocomial infections. In Medellín, Colombia, however, Klebsiella pneumoniae has become increasingly important in this kind of infection, for which reason this review was carried out.

It includes the following aspects: microbiology, epidemiology, dissemination, resistance to betalactamic antibiotics and its mechanisms, clinical impact and importance of the problem in this city.

La resistencia bacteriana es un problema serio, de magnitud creciente y presentación universal, que reviste gran importancia, especialmente en los ambientes hospitalarios; los microorganismos más frecuentemente aislados de pacientes con infecciones intrahospitalarias son Staphylococcus aureus y Escherichia coli. En Medellín, sin embargo, Klebsiella pneumoniae ha cobrado gran importancia en años recientes debido a su gran incremento como agente causal de ese tipo de infecciones, lo que motiva esta revisión. Se incluyen los siguientes aspectos: microbiología, epidemiología, diseminación, resistencia a los beta-lactámicos y sus mecanismos, impacto clínico e importancia del problema

Intermingled Klebsiella pneumoniae Populations Between Retail Meats and Human Urinary Tract Infections

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Davis, Gregg S.; Waits, Kara; Nordstrom, Lora; Weaver, Brett; Aziz, Maliha; Gauld, Lori; Grande, Heidi; Bigler, Rick; Horwinski, Joseph; Porter, Stephen; Stegger, Marc; Johnson, James R.; Liu, Cindy M.; Price, Lance B.

2015-01-01

Background. Klebsiella pneumoniae is a common colonizer of the gastrointestinal tract of humans, companion animals, and livestock. To better understand potential contributions of foodborne K. pneumoniae to human clinical infections, we compared K. pneumoniae isolates from retail meat products and human clinical specimens to assess their similarity based on antibiotic resistance, genetic relatedness, and virulence. Methods. Klebsiella pneumoniae was isolated from retail meats from Flagstaff grocery stores in 2012 and from urine and blood specimens from Flagstaff Medical Center in 2011–2012. Isolates underwent antibiotic susceptibility testing and whole-genome sequencing. Genetic relatedness of the isolates was assessed using multilocus sequence typing and phylogenetic analyses. Extraintestinal virulence of several closely related meat-source and urine isolates was assessed using a murine sepsis model. Results. Meat-source isolates were significantly more likely to be multidrug resistant and resistant to tetracycline and gentamicin than clinical isolates. Four sequence types occurred among both meat-source and clinical isolates. Phylogenetic analyses confirmed close relationships among meat-source and clinical isolates. Isolates from both sources showed similar virulence in the mouse sepsis model. Conclusions. Meat-source K. pneumoniae isolates were more likely than clinical isolates to be antibiotic resistant, which could reflect selective pressures from antibiotic use in food-animal production. The close genetic relatedness of meat-source and clinical isolates, coupled with similarities in virulence, suggest that the barriers to transmission between these 2 sources are low. Taken together, our results suggest that retail meat is a potential vehicle for transmitting virulent, antibiotic-resistant K. pneumoniae from food animals to humans. PMID:26206847

Metabolic Characterization of Peripheral Host Responses to Drainage-Resistant Klebsiella pneumoniae Liver Abscesses by Serum 1H-NMR Spectroscopy

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Zhihui Chang

2018-06-01

Full Text Available Purpose: To explore the metabolic characterization of host responses to drainage-resistant Klebsiella pneumoniae liver abscesses (DRKPLAs with serum 1H-nuclear magnetic resonance (NMR spectroscopy.Materials and Methods: The hospital records of all patients with a diagnosis of a liver abscess between June 2015 and December 2016 were retrieved from an electronic hospital database. Eighty-six patients with Klebsiella pneumoniae (K. pneumoniae liver abscesses who underwent percutaneous drainage were identified. Twenty patients with confirmed DRKPLAs were studied. Moreover, we identified 20 consecutive patients with drainage-sensitive Klebsiella pneumoniae liver abscesses (DSKPLAs as controls. Serum samples from the two groups were analyzed with 1H NMR spectroscopy. Partial least squares discriminant analysis (PLS-DA was used to perform 1H NMR metabolic profiling. Metabolites were identified using the Human Metabolome Database, and pathway analysis was performed with MetaboAnalyst 3.0.Results: The PLS-DA test was able to discriminate between the two groups. Five key metabolites that contributed to their discrimination were identified. Glucose, lactate, and 3-hydroxybutyrate were found to be upregulated in DRKPLAs, whereas glutamine and alanine were downregulated compared with the DSKPLAs. Pathway analysis indicated that amino acid metabolisms were significantly different between the DRKPLAs and the DSKPLAs. The D-glutamine and D-glutamate metabolisms exhibited the greatest influences.Conclusions: The five key metabolites identified in our study may be potential targets for guiding novel therapeutics of DRKPLAs and are worthy of additional investigation.

Whole-genome typing and characterization of blaVIM19-harbouring ST383 Klebsiella pneumoniae by PFGE, whole-genome mapping and WGS.

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Sabirova, Julia S; Xavier, Basil Britto; Coppens, Jasmine; Zarkotou, Olympia; Lammens, Christine; Janssens, Lore; Burggrave, Ronald; Wagner, Trevor; Goossens, Herman; Malhotra-Kumar, Surbhi

2016-06-01

We utilized whole-genome mapping (WGM) and WGS to characterize 12 clinical carbapenem-resistant Klebsiella pneumoniae strains (TGH1-TGH12). All strains were screened for carbapenemase genes by PCR, and typed by MLST, PFGE (XbaI) and WGM (AflII) (OpGen, USA). WGS (Illumina) was performed on TGH8 and TGH10. Reads were de novo assembled and annotated [SPAdes, Rapid Annotation Subsystem Technology (RAST)]. Contigs were aligned directly, and after in silico AflII restriction, with corresponding WGMs (MapSolver, OpGen; BioNumerics, Applied Maths). All 12 strains were ST383. Of the 12 strains, 11 were carbapenem resistant, 7 harboured blaKPC-2 and 11 harboured blaVIM-19. Varying the parameters for assigning WGM clusters showed that these were comparable to STs and to the eight PFGE types or subtypes (difference of three or more bands). A 95% similarity coefficient assigned all 12 WGMs to a single cluster, whereas a 99% similarity coefficient (or ≥10 unmatched-fragment difference) assigned the 12 WGMs to eight (sub)clusters. Based on a difference of three or more bands between PFGE profiles, the Simpson's diversity indices (SDIs) of WGM (0.94, Jackknife pseudo-values CI: 0.883-0.996) and PFGE (0.93, Jackknife pseudo-values CI: 0.828-1.000) were similar (P = 0.649). However, the discriminatory power of WGM was significantly higher (SDI: 0.94, Jackknife pseudo-values CI: 0.883-0.996) than that of PFGE profiles typed on a difference of seven or more bands (SDI: 0.53, Jackknife pseudo-values CI: 0.212-0.849) (P = 0.007). This study demonstrates the application of WGM to understanding the epidemiology of hospital-associated K. pneumoniae. Utilizing a combination of WGM and WGS, we also present here the first longitudinal genomic characterization of the highly dynamic carbapenem-resistant ST383 K. pneumoniae clone that is rapidly gaining importance in Europe. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial

Multifocal diffusion of KPC-3-producing ST512 Klebsiella pneumoniae in Italy

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Aurora Piazza

2012-03-01

Full Text Available Introduction. The dissemination of carbapenemase-producing Klebsiella pneumoniae strains is an increasing problem worldwide. KPC ß-lactamases are Ambler class A enzymes mostly plasmid-encoded; their global spread represents a threat to clinical patients care and public health. Multi locus sequence type (ST258 is currently the most spread K. pneumoniae clone associated with KPC enzymes. Here we report the first identification and multifocal spread of KPC-3 producing K. pneumoniae clinical strains belonging to ST512 in Italy. Materials and Methods. Fifty six carbapenem-resistant K. pneumoniae isolates were collected from 7 Italian hospitals during the period June 2009-May 2011. Isolates were obtained from different wards (spinal unit, medicine, hematology, etc. and biological samples (mostly rectal swabs, urine and blood. Species identification and antimicrobial susceptibilities were obtained by NBC46/NM40 Microscan panels (Siemens. MICs values were interpreted according to EUCAST 2011 breakpoints. Modified Hodge test and combined disk test with phenyl-boronic acid (BOR and EDTA were performed.The presence of blaKPC genes were confirmed by PCR and sequencing. A complete characterization of the produced ß-lactamases (BLs was obtained by IEF followed by PCR experiments using primers specific for the detection of blaCTX-M-, blaTEM- and blaSHV type genes. PFGE and multilocus sequence typing (MLST were both used to investigate clonal isolates relatedness. Results. All 56 isolates resulted positive for the presence of KPC-type carbapenemases by both phenotypical and molecular analysis. Fifteen isolates, chosen as representative, were further investigated. Ten out of 15 isolates harboring the blaKPC-2 gene clustered with the known ST258, while the remaining 5/10 belonged to the newly described ST512 and harbored the blaKPC-3 gene. ST512 isolates, from 3/7 hospitals, were collected from rectal swabs (40%, blood (20%, endotracheal aspirate (20% and

First report of a multidrug-resistant Klebsiella pneumoniae of sequence type 11 causing sepsis in a free-ranging beaver (Castor fiber).

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Pilo, Paola; Vogt, Debora; Origgi, Francesco C; Endimiani, Andrea; Peterson, Susanne; Perreten, Vincent

2015-04-01

Klebsiella pneumoniae of sequence type (ST) 11 is a hyper-epidemic nosocomial clone spreading worldwide among humans and also emerging in pets. In this report, we describe a clinical case of fatal sepsis due to this multidrug-resistant (MDR) pathogen in a Eurasian beaver. The isolate showed resistance to six different classes of antimicrobials including third generation cephalosporins and fluoroquinolones. This is the first report describing the detection of a MDR K. pneumoniae ST11 in a free-ranging animal. Our finding highlights the potential for environmental dissemination of hyper-epidemic clones of K. pneumoniae and possible spread in wildlife and cause epizootics. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Efflux pump, the masked side of beta-lactam resistance in Klebsiella pneumoniae clinical isolates.

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Jean-Marie Pages

Full Text Available BACKGROUND: Beta-lactamase production and porin decrease are the well-recognized mechanisms of acquired beta-lactam resistance in Klebsiella pneumoniae isolates. However, such mechanisms proved to be absent in K. pneumoniae isolates that are non susceptible to cefoxitin (FOX and susceptible to amoxicillin+clavulanic acid in our hospital. Assessing the role of efflux pumps in this beta-lactam phenotype was the aim of this study. METHODOLOGY/FINDINGS: MICs of 9 beta-lactams, including cloxacillin (CLX, and other antibiotic families were tested alone and with an efflux pump inhibitor (EPI, then with both CLX (subinhibitory concentrations and EPI against 11 unique bacteremia K. pneumoniae isolates displaying the unusual phenotype, and 2 ATCC strains. CLX and EPI-dose dependent effects were studied on 4 representatives strains. CLX MICs significantly decreased when tested with EPI. A similar phenomenon was observed with piperacillin+tazobactam whereas MICs of the other beta-lactams significantly decreased only in the presence of both EPI and CLX. Thus, FOX MICs decreased 128 fold in the K. pneumoniae isolates but also 16 fold in ATCC strain. Restoration of FOX activity was CLX dose-dependent suggesting a competitive relationship between CLX and the other beta-lactams with regard to their efflux. For chloramphenicol, erythromycin and nalidixic acid whose resistance was also due to efflux, adding CLX to EPI did not increase their activity suggesting differences between the efflux process of these molecules and that of beta-lactams. CONCLUSION: This is the first study demonstrating that efflux mechanism plays a key role in the beta-lactam susceptibility of clinical isolates of K. pneumoniae. Such data clearly evidence that the involvement of efflux pumps in beta-lactam resistance is specially underestimated in clinical isolates.

In vitro activity of tigecycline and comparators against carbapenem-resistant Enterobacteriaceae in Africa-Middle East countries: TEST 2007-2012.

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Renteria, M I; Biedenbach, D J; Bouchillon, S K; Hoban, D J; Raghubir, N; Sajben, P

2014-09-01

Multidrug-resistant (MDR) Enterobacteriaceae are an emerging concern for healthcare providers. Infections caused by MDR pathogens are associated with increased costs, length of hospital stay, and morbidity and mortality rates. Carbapenem-resistant Enterobacteriaceae (CRE) continue to increase, and infections with these organisms are observed worldwide not only as hospital-acquired infections but also as community-acquired infections. Increasing antimicrobial resistance dictates the need for continued surveillance studies of common and MDR pathogens. The Tigecycline Evaluation Surveillance Trial (TEST) examined the susceptibility of pathogens isolated in Africa and the Middle East from 2007 to 2012. A total of 4155 Enterobacteriaceae isolates were evaluated to determine the in vitro activity and changes in resistance patterns for tigecycline and comparators. Carbapenem resistance was found in 191 (4.6%) of the isolates tested. Klebsiella pneumoniae was the most common CRE (64.9%), followed by Enterobacter cloacae (14.1%) and Escherichia coli (9.9%). Tigecycline MIC 90 values (minimum inhibitory concentration required to inhibit 90% of the isolates) were 2μg/mL against all of these enteric species, with susceptibility rates of 96.8%, 92.6% and 100%, respectively. Tigecycline had in vitro activity against CRE, with a 95.3% susceptibility rate. Copyright © 2014 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Integrated genomic and interfacility patient-transfer data reveal the transmission pathways of multidrug-resistant Klebsiella pneumoniae in a regional outbreak.

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Snitkin, Evan S; Won, Sarah; Pirani, Ali; Lapp, Zena; Weinstein, Robert A; Lolans, Karen; Hayden, Mary K

2017-11-22

Development of effective strategies to limit the proliferation of multidrug-resistant organisms requires a thorough understanding of how such organisms spread among health care facilities. We sought to uncover the chains of transmission underlying a 2008 U.S. regional outbreak of carbapenem-resistant Klebsiella pneumoniae by performing an integrated analysis of genomic and interfacility patient-transfer data. Genomic analysis yielded a high-resolution transmission network that assigned directionality to regional transmission events and discriminated between intra- and interfacility transmission when epidemiologic data were ambiguous or misleading. Examining the genomic transmission network in the context of interfacility patient transfers (patient-sharing networks) supported the role of patient transfers in driving the outbreak, with genomic analysis revealing that a small subset of patient-transfer events was sufficient to explain regional spread. Further integration of the genomic and patient-sharing networks identified one nursing home as an important bridge facility early in the outbreak-a role that was not apparent from analysis of genomic or patient-transfer data alone. Last, we found that when simulating a real-time regional outbreak, our methodology was able to accurately infer the facility at which patients acquired their infections. This approach has the potential to identify facilities with high rates of intra- or interfacility transmission, data that will be useful for triggering targeted interventions to prevent further spread of multidrug-resistant organisms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A 12 year (1998-2009) antibiotic resistance surveillance of Klebsiella pneumoniae collected from intensive care and urology patients in 14 Dutch hospitals.

NARCIS (Netherlands)

Donk, C.F. van der; Beisser, P.S.; Hoogkamp-Korstanje, J.A.A.; Bruggeman, C.A.; Stobberingh, E.E.; Waar, K.; Vogels, W.H.; Bloembergen, P.; Beunders, A.J.; Rietra, P.; Hendrix, M.G.; Bijlmer, H.A.; Jongh, B.M. de; Hendriks, W.D.; Sturm, P.D.J.; Buiting, A.G.M.; Sabbe, L.J.; Trienekens, T.A.; Dessel, H. van

2011-01-01

OBJECTIVES: We evaluated the changes in antibiotic resistance from 1998 to 2009 of Klebsiella pneumoniae isolated from the intensive care units (ICUs) and urology services of 14 Dutch hospitals and the consequences for empirical therapy. METHODS: Quantitative antibiotic susceptibility testing of K.

Purulent pericarditis caused by Klebsiella pneumoniae in a Nigerian Child

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Igoche David Peter

2016-01-01

Full Text Available In the Western world, cases of purulent pericarditis have become almost nonexistent with progress and advent of new immunizations against many causative organisms. We report Klebsiella pneumoniae pericarditis, a rare cause of this uncommon disease, hitherto unreported in Nigeria. K. pneumoniae, which is a rod-shaped, Gram-negative, facultative anaerobe, produces extended-spectrum beta-lactamases; hence, it is usually resistant to a lot of antibiotics and is associated with a significant case fatality rate. Our 13-year-old male patient had septic arthritis of the right hip joint came with a 3 weeks complaint of difficulty with breathing. He had respiratory distress, tachypnea, and tachycardia. Although blood pressure was normal, he had pulsus paradoxus, elevated jugular venous pressure, diffuse apex beat, and heart sounds were distant. Chest radiograph revealed an increased cardiothoracic ratio (0.86 with “water bottle” appearance. Transthoracic echocardiography confirmed pericardial effusion with cardiac tamponade. Echo-guided pericardiocentesis was done, and 340 ml of foul-smelling and creamy pus with greenish tinge was aspirated and this grew K. pneumoniae sensitive to ciprofloxacin and gentamycin but resistant to other conventional antibiotics. Recovery was complete after a week of pericardial tube drainage and 3 weeks of treatment. To the best of our knowledge, this is the first case of Klebsiella - induced pyopericardium and with successful management in a Nigerian child. Pyopericardium may follow rare causes such as K. pneumoniae infection with its unique antibiogram.

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health

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Holt, Kathryn E.; Wertheim, Heiman; Zadoks, Ruth N.; Baker, Stephen; Whitehouse, Chris A.; Dance, David; Jenney, Adam; Connor, Thomas R.; Hsu, Li Yang; Severin, Juliëtte; Brisse, Sylvain; Cao, Hanwei; Wilksch, Jonathan; Gorrie, Claire; Schultz, Mark B.; Edwards, David J.; Nguyen, Kinh Van; Nguyen, Trung Vu; Dao, Trinh Tuyet; Mensink, Martijn; Minh, Vien Le; Nhu, Nguyen Thi Khanh; Schultsz, Constance; Kuntaman, Kuntaman; Newton, Paul N.; Moore, Catrin E.; Strugnell, Richard A.; Thomson, Nicholas R.

2015-01-01

Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats. PMID:26100894

Evaluation of the Clinical and Laboratory Standards Institute phenotypic confirmatory test to detect the presence of extended-spectrum β-lactamases from 4005 Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus mirabilis isolates.

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Morrissey, Ian; Bouchillon, Samuel K; Hackel, Meredith; Biedenbach, Douglas J; Hawser, Stephen; Hoban, Daryl; Badal, Robert E

2014-04-01

A subset of Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus mirabilis isolates collected for the Study for Monitoring Antimicrobial Resistance Trends that were positive for the Clinical and Laboratory Standards Institute (CLSI) extended-spectrum β-lactamase (ESBL) phenotypic confirmatory test (n = 3245) or had an ertapenem MIC of ≥0.5 µg ml(-1) (n = 293), or both (n = 467), were analysed for ESBL genes. Most ESBL phenotype E. coli or K. pneumoniae possessed an ESBL gene (95.8 and 88.4 %, respectively), and this was 93.1 % if carbapenem-non-susceptible K. pneumoniae were removed. This rate was lower for P. mirabilis (73.4 %) and K. oxytoca (62.5 %). Virtually all ESBL-positive isolates (99.5 %) were cefotaxime non-susceptible [CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints)]. Fewer isolates (82 %) were ceftazidime non-susceptible (CLSI breakpoints). In addition, 21.1 % of E. coli, 25 % of K. oxytoca and 78.7 % of P. mirabilis isolates were ceftazidime susceptible but ESBL positive. This suggests that CLSI breakpoints for ceftazidime are too high to detect ESBLs. The lower EUCAST breakpoints detected ESBLs in E. coli and K. oxytoca better, but 59.6 % of ESBL-positive isolates of P. mirabilis were ceftazidime susceptible. For isolates with ertapenem MICs ≥0.5 µg ml(-1), more accurate ESBL phenotype analysis was observed for E. coli and K. pneumoniae (sensitivity >95 % for both, specificity 94.4 and 54.1 %, respectively). If carbapenemase-positive K. pneumoniae were excluded, the specificity increased to 78 %. The positive predictive values for the ESBL phenotypic test with E. coli and K. pneumoniae were 97.6 and 81.8 %, respectively, and negative predictive values were 75.9 and 95.2 %, respectively. We therefore suggest that it would be prudent to confirm phenotypic ESBL-positive P. mirabilis, K. pneumoniae and K. oxytoca with molecular analysis.

Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan

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Wang, Jann-Tay; Wu, Un-In; Lauderdale, Tsai-Ling Yang; Chen, Mei-Chen; Li, Shu-Ying; Hsu, Le-Yin; Chang, Shan-Chwen

2015-01-01

A total of 1135 carbapenem-resistant (nonsusceptible) Enterobacteriaceae (CRE) isolates were recovered between November 2010 and July 2012 (517 from 2010-2011 and 618 from 2012) from 4 hospitals in Taiwan. Carbapenemase-producing Enterobacteriaceae (CPE) comprised 5.0% (57 isolates), including 17 KPC-2 (16 Klebsiella pneumoniae and 1 Escherichia coli), 1 NDM-1 (K. oxytoca), 37 IMP-8 (26 Enterobacter cloacae, 4 Citrobacter freundii, 4 Raoultella planticola, 1 K. pneumoniae, 1 E. coli and 1 K. oxytoca), and 2 VIM-1 (1 E. cloacae, 1 E. coli). The KPC-2-positive K. pneumoniae were highly clonal even in isolates from different hospitals, and all were ST11. IMP-8 positive E. cloacae from the same hospitals showed higher similarity in PFGE pattern than those from different hospitals. A total of 518 CRE isolates (45.6%) were positive for bla ESBL, while 704 (62.0%) isolates were bla AmpC-positive, 382 (33.6% overall) of which carried both bla ESBL and bla AmpC. CTX-M (414, 80.0%) was the most common bla ESBL, while DHA (497, 70.6%) and CMY (157, 22.3%) were the most common bla AmpC. Co-carriage of bla ESBL and bla AmpC was detected in 31 (54.4%) and 15 (26.3%) of the 57 CPE, respectively. KPC-2 was the most common carbapenemase detected in K. pneumoniae (2.8%), while IMP-8 was the most common in E. cloacae (9.7%). All KPC-2-positive CRE were resistant to all three tested carbapenems. However, fourteen of the 37 IMP-8-positive CRE were susceptible to both imipenem and meropenem in vitro. Intra- and inter-hospital spread of KPC-2-producing K. pneumoniae and IMP-8-producing E. cloacae likely occurred. Although the prevalence of CPE is still low, careful monitoring is urgently needed. Non-susceptibility to ertapenem might need to be considered as one criterion of definition for CRE in areas where IMP type carbapenemase is prevalent. PMID:25794144

Hospital-acquired Klebsiella pneumoniae infections in a paediatric ...

African Journals Online (AJOL)

is an important preventable cause of increased ... between July 2003 and December 2010, who developed a hospital-acquired Klebsiella pneumoniae infection, was undertaken to describe the trend in ..... Bacterial nosocomial pneumonia in.

Dissemination of Multidrug-Resistant, Class I and II Integrons and Molecular Typing of CTX-M-producing Klebsiella pneumoniae.

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Akya, Alisha; Elahi, Azam; Chegenelorestani, Roya; Rezaee, Mahya

2018-01-01

Klebsiella pneumoniae ( K. pneumoniae ) is an important opportunistic pathogen causes serious community and hospital-acquired infections, which is highly resistant to antibiotics. We aimed to determine the frequency of multidrug resistant (MDR) and molecular typing of clinical isolates of K. pneumoniae . One hundred isolates of K. pneumoniae were collected from clinical samples in three general hospitals in Kermanshah. The antimicrobial susceptibility and extended-spectrum beta-lactamases (ESBL) production of isolates were determined using disk diffusion and combined disk methods, respectively. The bla CTX-M gene, class I and II integrons were detected using polymerase chain reaction. The bla CTX-M positive isolates were selected for genotyping using pulsed-field gel electrophoresis (PFGE). MDR phenotype was observed in 56% of isolates. The 40% of isolates were ESBL positive and 35 isolates contained bla CTX-M . Class I and II of integrons were detected in 50 (89.2%) and 39 (69.6%) of MDR isolates, respectively. PFGE patterns of K. pneumoniae bla CTX-M positive isolates indicated 19 clusters (X 1-19 ) with different genotype patterns. The study findings highlight the concern of circulating MDR strains of K. pneumoniae with bla CTX-M and class I and II integrons in Kermanshah hospitals. The presence of integrons among isolates may facilitate the spread of new resistance genes in this bacterium. Therefore, surveillance for the spread of MDR strains of this bacterium is recommended in hospitals.

Peracute bovine mastitis caused by Klebsiella pneumoniae Mastite bovina hiperaguda causada por Klebsiella pneumoniae

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M.G. Ribeiro

2008-04-01

Full Text Available Relata-se a ocorrência de graves sintomas de mastite hiperaguda em vaca, causada por Klebsiella pneumoniae, na terceira semana de lactação. Descrevem-se aspectos epidemiológicos, sintomas clínicos, procedimentos de diagnóstico microbiológico, conduta terapêutica e medidas de controle.

K. pneumoniae: ¿The new “superbacteria”? Pathogenicity, epidemiology and resistance mechanisms K. pneumoniae: ¿la nueva

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Lina María Echeverri Toro

2010-05-01

Full Text Available The antimicrobial resistance is an increasing problem of public health. Klebsiella pneumoniae has become one of the most important pathogens because it is a frequent cause of nosocomial and community acquired infections and it has pathogenicity mechanisms like capsules, adhesive properties mediated by specialized estructures (pillis and siderophores that are capable of taking up iron, an essential factor in bacterial growth. The increase in bacterial resistance to antibiotics has evolved with the use of these in patients treatments, being increasingly wide the spectrum that they include, happening from the resistance to ampicillin by the production of betalactamase SHV-1 to carbapenems resistance by diverse mechanisms, from the production of extendedspectrum betalactamases (ESBL that are associated with hydrolysis of extended-spectrum cephalosporins and aztreonam. Microbiology laboratory should follow international recommendations to detect and confirm the presence of this resistance mechanism in bacteria and the clinicians should make a suitable interpretation of the results to make the better choice of the antibiotic therapy. ----- La resistencia de los microorganismos a los antibióticos es un problema cada vez creciente en salud pública. Entre estos, Klebsiella pneumoniae es un representante importante no sólo por su frecuencia como causa de infecciones asociadas al cuidado de la salud y de la comunidad, sino por los mecanismos patogénicos que posee, como la capacidad de producir cápsula, la presencia de estructuras especializadas que le permiten adherirse a las células del hospedero (pilis, y de sideróforos que le permiten obtener el hierro necesario para su desarrollo. La resistencia de Klebsiella pneumoniae a los antimicrobianos ha evolucionado de acuerdo con la aparición y uso de estas moléculas en el tratamiento de los pacientes, siendo cada vez más amplio el espectro que abarcan, el cual va desde la resistencia a la ampicilina

Determination of antibiotic resistance profile in Klebsiella pneumonia strains isolated from urinary tract infections of patients hospitalized in Peyambaran hospital (Tehran-Iran

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Marzieh Tavakol

2017-04-01

Full Text Available Background: Urinary tract infection (UTI is the second prevalent infection in human mostly caused by Escherichia coli and Klebsiella pneumonia. The aim of this study was to determine the antibiotic resistance profile and detect the prevalence of antibiotic resistance encoding genes in K .pneumoniae isolated from UTI. Materials and Methods: Fifty K. pneumonia strains isolated from 122 UTI samples of hospitalized patients in Payambaran Hospital (Tehran, Iran which were subjected to this study (2014 were confirmed by standard biochemical tests. Isolates were tested for susceptibility to 10 antimicrobial drugs by using disk diffusion method. Antibiotic resistance encoding genes frequently include the aadA1, aac(3-IV, sul1, blaSHV, Cat1, cmlA, tetA, tetB, dfrA1, CITM, qnr in isolates were determined by PCR. Results: The highest antibiotic resistance in K. pneumoniae isolates were for Tetracycline and the lowest resistance (2% for Gentamicin and Imipenem. To determine the frequency of antibiotic resistant genes, 64% and 4% of isolates had tetA and Gentamicin-(aac(3-IV resistant genes, respectively. Conclusion: Frequency of antibiotic resistance encoding genes may have important and basic role in the occurrence and transfer of antibiotic resistance which can be due to the indiscriminate use of antibiotics.

Extended-spectrum β-lactamase (ESBL) in Danish clinical isolates of Escherichia coli and Klebsiella pneumoniae

DEFF Research Database (Denmark)

Hansen, Dennis Schrøder; Schumacher, Helga; Hansen, Frank

2012-01-01

Most Gram-negative community-acquired and nosocomial infections are caused by Escherichia coli and Klebsiella pneumoniae, among which increasing resistance due to extended-spectrum β-lactamase (ESBL) is a major problem. We present data from the first Danish nationwide prevalence study on ESBL-pro......-producing E. coli, K. pneumoniae, and Proteus mirabilis in blood and urine cultures from hospitals and the community....

Phenotypic and molecular detection of BLACTX-M gene extended-spectrum beta-lactamases in escherichia coli and klebsiella pneumoniae of north sumatera isolates

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Hasibuan, Mirzan; Suryanto, Dwi; Lia Kusumawati, R.

2018-03-01

The application of antibiotics expanded-spectrum third-generation cephalosporin for the treatment of infectious diseases in hospitals is known contribute to increasing resistance due to the presence of the blaCTX-M gene in the bacteria producing ESBLs. This study was aimed to detect ESBLs, isolate phenotype and blaCTX-M genes on Escherichia coli and Klebsiella pneumoniae collected from H. Adam Malik Central Hospital. Phenotypes of the bacterial were detection using Vitek two compact, while the blaCTX-M genes were detection using polymerase chain reaction technique. The results showed that 85 (100%) isolates were ESBLs consisted of 41(48%) of Escherichia coli, and 44 (52%) of Klebsiella pneumoniae, respectively. blaCTX-M genes were detection in 62 (72.94%) of the isolates which 31 (36.47%) were Escherichia coli, and 31 (36.47%) of the isolates were Klebsiella pneumoniae, respectively. This study indicates the high prevalence of blaCTX-M genes in Escherichia coli and Klebsiella pneumoniea causing bacterial antibiotic resistance.

Performance evaluation of three automated identification systems in detecting carbapenem-resistant Enterobacteriaceae.

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He, Qingwen; Chen, Weiyuan; Huang, Liya; Lin, Qili; Zhang, Jingling; Liu, Rui; Li, Bin

2016-06-21

Carbapenem-resistant Enterobacteriaceae (CRE) is prevalent around the world. Rapid and accurate detection of CRE is urgently needed to provide effective treatment. Automated identification systems have been widely used in clinical microbiology laboratories for rapid and high-efficient identification of pathogenic bacteria. However, critical evaluation and comparison are needed to determine the specificity and accuracy of different systems. The aim of this study was to evaluate the performance of three commonly used automated identification systems on the detection of CRE. A total of 81 non-repetitive clinical CRE isolates were collected from August 2011 to August 2012 in a Chinese university hospital, and all the isolates were confirmed to be resistant to carbapenems by the agar dilution method. The potential presence of carbapenemase genotypes of the 81 isolates was detected by PCR and sequencing. Using 81 clinical CRE isolates, we evaluated and compared the performance of three automated identification systems, MicroScan WalkAway 96 Plus, Phoenix 100, and Vitek 2 Compact, which are commonly used in China. To identify CRE, the comparator methodology was agar dilution method, while the PCR and sequencing was the comparator one to identify CPE. PCR and sequencing analysis showed that 48 of the 81 CRE isolates carried carbapenemase genes, including 23 (28.4 %) IMP-4, 14 (17.3 %) IMP-8, 5 (6.2 %) NDM-1, and 8 (9.9 %) KPC-2. Notably, one Klebsiella pneumoniae isolate produced both IMP-4 and NDM-1. One Klebsiella oxytoca isolate produced both KPC-2 and IMP-8. Of the 81 clinical CRE isolates, 56 (69.1 %), 33 (40.7 %) and 77 (95.1 %) were identified as CRE by MicroScan WalkAway 96 Plus, Phoenix 100, and Vitek 2 Compact, respectively. The sensitivities/specificities of MicroScan WalkAway, Phoenix 100 and Vitek 2 were 93.8/42.4 %, 54.2/66.7 %, and 75.0/36.4 %, respectively. The MicroScan WalkAway and Viteck2 systems are more reliable in clinical identification of

Comparison of multilocus sequence typing, RAPD, and MALDI-TOF mass spectrometry for typing of β-lactam-resistant Klebsiella pneumoniae strains.

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Sachse, Svea; Bresan, Stephanie; Erhard, Marcel; Edel, Birgit; Pfister, Wolfgang; Saupe, Angela; Rödel, Jürgen

2014-12-01

Extended spectrum of β-lactam (ESBL) resistance of Klebsiella pneumoniae has become an increasing problem in hospital infections. Typing of isolates is important to establish the intrahospital surveillance of resistant clones. In this study, the discriminatory potential of randomly amplified polymorphic DNA and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analyses were compared with multilocus sequence typing (MLST) by using 17 β-lactam-resistant K. pneumoniae isolates of different genotypes. MLST alleles were distributed in 8 sequence types (STs). Among ESBL strains of the same ST, the presence of different β-lactamase genes was common. RAPD band patterns also revealed 8 types that corresponded to MLST-defined genotypes in 15 out of 17 cases. MALDI-TOF analysis could differentiate 5 clusters of strains. The results of this work show that RAPD may be usable as a rapid screening method for the intrahospital surveillance of K. pneumoniae, allowing a discrimination of clonally related strains. MALDI-TOF-based typing was not strongly corresponding to genotyping and warrants further investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

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Zilberberg, Marya D; Nathanson, Brian H; Sulham, Kate; Fan, Weihong; Shorr, Andrew F

2017-04-17

Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. We conducted a retrospective cohort study in Premier Perspective database (2009-2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p pneumonia or sepsis was comparable to other national estimates. Infection with CRE was associated with a four-fold increased risk of receiving IET, which in turn increased mortality, LOS and costs.

Effect of poly-hexamethylene biguanide hydrochloride (PHMB) treated non-sterile medical gloves upon the transmission of Streptococcus pyogenes, carbapenem-resistant E. coli, MRSA and Klebsiella pneumoniae from contact surfaces.

Science.gov (United States)

Ali, S; Wilson, A P R

2017-08-17

Reduction of accidental contamination of the near-patient environment has potential to reduce acquisition of healthcare-associated infection(s). Although medical gloves should be removed when soiled or touching the environment, compliance is variable. The use of antimicrobial-impregnated medical gloves could reduce the horizontal-transfer of bacterial contamination between surfaces. Determine the activity of antimicrobial-impregnated gloves against common hospital pathogens: Streptococcus pyogenes, carbapenem-resistant E.coli (CREC), MRSA and ESBL-producing Klebsiella pneumoniae. Fingerpads (~1cm 2 ) of PHMB-treated and untreated gloves were inoculated with 10 μL (~10 4 colony-forming-units [cfu]) of test-bacteria prepared in heavy-soiling (0.5%BSA), blood or distilled-water (no-soiling) and sampled after 0.25, 1, 10 or 15 min contact-time. Donor surfaces (~1cm 2 computer-keys) contaminated with wet/dry inoculum were touched with the fingerpad of treated/untreated gloves and subsequently pressed onto recipient (uncontaminated) computer-keys. Approximately 4.50log 10 cfu of all bacteria persisted after 15 min on untreated gloves regardless of soil-type. In the absence of soiling, PHMB-treated gloves reduced surface-contamination by ~4.5log 10 cfu (>99.99%) within 10 min of contact-time but only ~2.5log 10 (>99.9%) and ~1.0log 10 reduction respectively when heavy-soiling or blood was present. Gloves became highly-contaminated (~4.52log 10 -4.91log 10 cfu) when handling recently-contaminated computer-keys. Untreated gloves contaminated "recipient" surfaces (~4.5log 10 cfu) while PHMB-treated gloves transferred fewer bacteria (2.4-3.6log 10 cfu). When surface contamination was dry, PHMB gloves transferred fewer bacteria (0.3-0.6log 10 cfu) to "recipient" surfaces than untreated gloves (1.0-1.9log 10 ; P gloves may be useful in preventing dissemination of organisms in the near-patient environment during routine care. However they are not a substitute for

Changes in qnr Prevalence and Fluoroquinolone Resistance in Clinical Isolates of Klebsiella pneumoniae and Enterobacter spp. Collected from 1990 to 2005▿

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Strahilevitz, Jacob; Engelstein, Dalia; Adler, Amos; Temper, Violeta; Moses, Allon E.; Block, Colin; Robicsek, Ari

2007-01-01

Clinical isolates of Klebsiella pneumoniae and Enterobacter spp. collected from 1990 through 2005 at a tertiary care center were studied for qnr genes. Isolates bearing these genes emerged in the mid-1990s, coinciding with the time of a rapid increase in fluoroquinolone resistance. Sixty percent of these isolates were ciprofloxacin susceptible by CLSI breakpoints. PMID:17526754

A rapid diagnostic workflow for cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae detection from blood cultures by MALDI-TOF mass spectrometry.

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Elena De Carolis

Full Text Available Nowadays, the global spread of resistance to oxyimino-cephalosporins in Enterobacteriaceae implies the need for novel diagnostics that can rapidly target resistant organisms from these bacterial species.In this study, we developed and evaluated a Direct Mass Spectrometry assay for Beta-Lactamase (D-MSBL that allows direct identification of (oxyiminocephalosporin-resistant Escherichia coli or Klebsiella pneumoniae from positive blood cultures (BCs, by using the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS technology.The D-MSBL assay was performed on 93 E. coli or K. pneumoniae growing BC samples that were shortly co-incubated with cefotaxime (CTX as the indicator cephalosporin. Susceptibility and resistance defining peaks from the samples' mass spectra were analyzed by a novel algorithm for bacterial organism classification. The D-MSBL assay allowed discrimination between E. coli and K. pneumoniae that were resistant or susceptible to CTX with a sensitivity of 86.8% and a specificity of 98.2%.The proposed algorithm-based D-MSBL assay, if integrated in the routine laboratory diagnostic workflow, may be useful to enhance the establishment of appropriate antibiotic therapy and to control the threat of oxyimino-cephalosporin resistance in hospital.

A rapid diagnostic workflow for cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae detection from blood cultures by MALDI-TOF mass spectrometry.

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De Carolis, Elena; Paoletti, Silvia; Nagel, Domenico; Vella, Antonietta; Mello, Enrica; Palucci, Ivana; De Angelis, Giulia; D'Inzeo, Tiziana; Sanguinetti, Maurizio; Posteraro, Brunella; Spanu, Teresa

2017-01-01

Nowadays, the global spread of resistance to oxyimino-cephalosporins in Enterobacteriaceae implies the need for novel diagnostics that can rapidly target resistant organisms from these bacterial species. In this study, we developed and evaluated a Direct Mass Spectrometry assay for Beta-Lactamase (D-MSBL) that allows direct identification of (oxyimino)cephalosporin-resistant Escherichia coli or Klebsiella pneumoniae from positive blood cultures (BCs), by using the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) technology. The D-MSBL assay was performed on 93 E. coli or K. pneumoniae growing BC samples that were shortly co-incubated with cefotaxime (CTX) as the indicator cephalosporin. Susceptibility and resistance defining peaks from the samples' mass spectra were analyzed by a novel algorithm for bacterial organism classification. The D-MSBL assay allowed discrimination between E. coli and K. pneumoniae that were resistant or susceptible to CTX with a sensitivity of 86.8% and a specificity of 98.2%. The proposed algorithm-based D-MSBL assay, if integrated in the routine laboratory diagnostic workflow, may be useful to enhance the establishment of appropriate antibiotic therapy and to control the threat of oxyimino-cephalosporin resistance in hospital.

Genomic Characterization of Nonclonal mcr-1-Positive Multidrug-Resistant Klebsiella pneumoniae from Clinical Samples in Thailand.

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Srijan, Apichai; Margulieux, Katie R; Ruekit, Sirigade; Snesrud, Erik; Maybank, Rosslyn; Serichantalergs, Oralak; Kormanee, Rosarin; Sukhchat, Prawet; Sriyabhaya, Jossin; Hinkle, Mary; Crawford, John M; McGann, Patrick; Swierczewski, Brett E

2018-05-01

Multidrug-resistant Klebsiella pneumoniae strains are one of the most prevalent causes of nosocomial infections and pose an increasingly dangerous public health threat. The lack of remaining treatment options has resulted in the utilization of older drug classes, including colistin. As a drug of last resort, the discovery of plasmid-mediated colistin resistance by mcr-1 denotes the potential development of pandrug-resistant bacterial pathogens. To address the emergence of the mcr-1 gene, 118 gram-negative Enterobacteriaceae isolated from clinical samples collected at Queen Sirikit Naval Hospital in Chonburi, Thailand were screened for colistin resistance using automated antimicrobial susceptibility testing and conventional PCR screening. Two K. pneumoniae strains, QS17-0029 and QS17-0161, were positive for mcr-1, and both isolates were sequenced to closure using short- and long-read whole-genome sequencing. QS17-0029 carried 16 antibiotic resistance genes in addition to mcr-1, including 2 carbapenemases, bla NDM-1 and bla OXA-232 . QS17-0161 carried 13 antibiotic resistance genes in addition to mcr-1, including the extended-spectrum β-lactamase bla CTX-M-55 . Both isolates carried multiple plasmids, but mcr-1 was located alone on highly similar 33.9 Kb IncX4 plasmids in both isolates. The IncX4 plasmid shared considerable homology to other mcr-1-containing IncX4 plasmids. This is the first report of a clinical K. pneumoniae strain from Thailand carrying mcr-1 as well as the first strain to simultaneously carry mcr-1 and multiple carbapenemase genes (QS17-0029). The identification and characterization of these isolates serves to highlight the urgent need for continued surveillance and intervention in Southeast Asia, where extensively drug-resistant pathogens are being increasingly identified in hospital-associated infections.

Infecção ou colonização por micro-organismos resistentes: identificação de preditores Infection or colonization with resistant microorganisms: identification of predictors

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Graciana Maria de Moraes

2013-01-01

Full Text Available OBJETIVO: Identificar os fatores preditores de infecção ou colonização por micro-organismos resistentes. MÉTODOS: Foi realizado estudo quantitativo de coorte prospectivo. Foram realizadas a análise descritiva, para conhecimento da população do estudo, e a análise discriminante, para identificação dos fatores preditores. RESULTADOS: Foram incluídos 85 pacientes com infecções por micro-organismos resistentes: Pseudomonas aeruginosas resistente aos carbapenêmicos (24,7%, Acinetobacter resistente aos carbapenêmicos (21,2%, Staphylococcus aureus resistente à meticilina (25,9%, Enterococcus spp. resistente à vancomicina (17,6% e Klebsiella pneumoniae resistente aos carbapenêmicos (10,6%. A análise discriminante identificou transferências de outros hospitais e internação na Unidade de Terapia Intensiva como fatores preditores para ocorrência de infecção pelos grupos S. aureus resistente à meticilina, Acinetobacter resistente aos carbapenêmicos e K. pneumoniae resistente aos carbapenêmicos. Nenhuma das variáveis estudadas foi discriminante para Enterococcus spp. resistente à vancomicina e P. aeruginosas resistente aos carbapenêmico. CONCLUSÃO: Os fatores preditores encontrados foram: internação na UTI e a transferências de outros hospitais.OBJECTIVE: Identifying predictors of infection or colonization with resistant microorganisms. METHODS: A quantitative study of prospective cohort was carried out. A descriptive analysis was performed in order to know the population of the study and a discriminant analysis was performed to identify the predictors. RESULTS: In this study were included 85 patients with infections caused by resistant microorganisms: carbapenem-resistant Pseudomonas aeruginosas (24.7%; carbapenem-resistant Acinetobacter (21.2%; methicillin-resistant Staphylococcus aureus (25.9%, vancomycin-resistant Enterococcus spp (17.6% and carbapenem-resistant Klebsiella pneumonia (10.6%. The discriminant analysis

Multicenter evaluation of resistance patterns of Klebsiella pneumoniae, Escherichia coli, Salmonella spp and Shigella spp isolated from clinical specimens in Brazil: RESISTNET surveillance program

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Carmen Paz Oplustil

Full Text Available Surveillance programs are essential to detect the increase of antimicrobial resistance, and several different programs are being conducted in many countries. The RESISTNET is a surveillance program for bacterial resistance against several antimicrobial agents initiated in 1998 among Latin American countries. In Brazil, several centers were invited to join this surveillance and a total of 11 centers (6 from São Paulo and 5 from other states participated in the study. All results were analyzed using the WHONET program. A total of 894 Escherichia coli, 386 Klebsiella pneumoniae, 70 Shigella spp and 57 Salmonella spp strains were analyzed in this study from April, 1998, to April, 1999. Susceptibility testing was performed by the disk diffusion method using NCCLS 1998 guidelines for several different drugs. For all strains, imipenem was the most effective drug (100% of the strains were susceptible. Klebsiella pneumoniae presented a high resistance rate to ampicillin (96.4%. The rate of probable ESBL producers among K. pneumoniae strains was 36.3%, most of them being isolated from catheters (58.8%. Among all Escherichia coli strains analyzed, the highest resistance rate was found for trimethoprim/sulfamethoxazole (46.9% and the majority of the resistant strains were isolated from urine samples (47.8%. Among Salmonella spp, the resistance rates were low for all antibiotics tested. For Shigella spp strains there was a high resistance to trimethoprim/sulfamethoxazole (80.0%. No resistance to ceftriaxone was observed in these strains. Surveillance of antimicrobial resistance is critical for the successful management of infectious diseases. The results of this survey show significant resistance rates among these bacteria which are responsible for several types of human infections.

Genome Sequence of Klebsiella pneumoniae KpQ3, a DHA-1 β-Lactamase-Producing Nosocomial Isolate

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Tobes, Raquel; Codoñer, Francisco M.; López-Camacho, Elena; Salanueva, Iñigo J.; Manrique, Marina; Brozynska, Marta; Gómez-Gil, Rosa; Martínez-Blanch, Juan F.; Álvarez-Tejado, Miguel; Pareja, Eduardo

2013-01-01

Klebsiella pneumoniae KpQ3 is a multidrug-resistant isolate obtained from a blood culture of a patient in a burn unit in the Hospital Universitario La Paz (Madrid, Spain) in 2008. The genome contains multiple antibiotic resistance genes, including a plasmid-mediated DHA-1 cephalosporinase gene. PMID:23469341

Rapid label-free identification of Klebsiella pneumoniae antibiotic resistant strains by the drop-coating deposition surface-enhanced Raman scattering method

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Cheong, Youjin; Kim, Young Jin; Kang, Heeyoon; Choi, Samjin; Lee, Hee Joo

2017-08-01

Although many methodologies have been developed to identify unknown bacteria, bacterial identification in clinical microbiology remains a complex and time-consuming procedure. To address this problem, we developed a label-free method for rapidly identifying clinically relevant multilocus sequencing typing-verified quinolone-resistant Klebsiella pneumoniae strains. We also applied the method to identify three strains from colony samples, ATCC70063 (control), ST11 and ST15; these are the prevalent quinolone-resistant K. pneumoniae strains in East Asia. The colonies were identified using a drop-coating deposition surface-enhanced Raman scattering (DCD-SERS) procedure coupled with a multivariate statistical method. Our workflow exhibited an enhancement factor of 11.3 × 106 to Raman intensities, high reproducibility (relative standard deviation of 7.4%), and a sensitive limit of detection (100 pM rhodamine 6G), with a correlation coefficient of 0.98. All quinolone-resistant K. pneumoniae strains showed similar spectral Raman shifts (high correlations) regardless of bacterial type, as well as different Raman vibrational modes compared to Escherichia coli strains. Our proposed DCD-SERS procedure coupled with the multivariate statistics-based identification method achieved excellent performance in discriminating similar microbes from one another and also in subtyping of K. pneumoniae strains. Therefore, our label-free DCD-SERS procedure coupled with the computational decision supporting method is a potentially useful method for the rapid identification of clinically relevant K. pneumoniae strains.

A multiple antibiotic and serum resistant oligotrophic strain, Klebsiella pneumoniae MB45 having novel dfrA30, is sensitive to ZnO QDs

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Chakrabarti Pinak

2011-05-01

Full Text Available Abstract Background The aim of this study was to describe a novel trimethoprim resistance gene cassette, designated dfrA30, within a class 1 integron in a facultatively oligotrophic, multiple antibiotic and human serum resistant test strain, MB45, in a population of oligotrophic bacteria isolated from the river Mahananda; and to test the efficiency of surface bound acetate on zinc oxide quantum dots (ZnO QDs as bactericidal agent on MB45. Methods Diluted Luria broth/Agar (10-3 media was used to cultivate the oligotrophic bacteria from water sample. Multiple antibiotic resistant bacteria were selected by employing replica plate method. A rapid assay was performed to determine the sensitivity/resistance of the test strain to human serum. Variable region of class 1 integron was cloned, sequenced and the expression of gene coding for antibiotic resistance was done in Escherichia coli JM 109. Identity of culture was determined by biochemical phenotyping and 16S rRNA gene sequence analyses. A phylogenetic tree was constructed based on representative trimethoprim resistance-mediating DfrA proteins retrieved from GenBank. Growth kinetic studies for the strain MB45 were performed in presence of varied concentrations of ZnO QDs. Results and conclusions The facultatively oligotrophic strain, MB45, resistant to human serum and ten antibiotics trimethoprim, cotrimoxazole, ampicillin, gentamycin, netilmicin, tobramycin, chloramphenicol, cefotaxime, kanamycin and streptomycin, has been identified as a new strain of Klebsiella pneumoniae. A novel dfr gene, designated as dfrA30, found integrated in class 1 integron was responsible for resistance to trimethoprim in Klebsiella pneumoniae strain MB45. The growth of wild strain MB45 was 100% arrested at 500 mg/L concentration of ZnO QDs. To our knowledge this is the first report on application of ZnO quantum dots to kill multiple antibiotics and serum resistant K. pneumoniae strain.

Antimicrobial activity evaluation and comparison of methods of susceptibility for Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter spp. isolates.

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Rechenchoski, Daniele Zendrini; Dambrozio, Angélica Marim Lopes; Vivan, Ana Carolina Polano; Schuroff, Paulo Alfonso; Burgos, Tatiane das Neves; Pelisson, Marsileni; Perugini, Marcia Regina Eches; Vespero, Eliana Carolina

The production of KPC (Klebsiella pneumoniae carbapenemase) is the major mechanism of resistance to carbapenem agents in enterobacterias. In this context, forty KPC-producing Enterobacter spp. clinical isolates were studied. It was evaluated the activity of antimicrobial agents: polymyxin B, tigecycline, ertapenem, imipenem and meropenem, and was performed a comparison of the methodologies used to determine the susceptibility: broth microdilution, Etest ® (bioMérieux), Vitek 2 ® automated system (bioMérieux) and disc diffusion. It was calculated the minimum inhibitory concentration (MIC) for each antimicrobial and polymyxin B showed the lowest concentrations for broth microdilution. Errors also were calculated among the techniques, tigecycline and ertapenem were the antibiotics with the largest and the lower number of discrepancies, respectively. Moreover, Vitek 2 ® automated system was the method most similar compared to the broth microdilution. Therefore, is important to evaluate the performance of new methods in comparison to the reference method, broth microdilution. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

(ESBL) producing Escherichia coli and Klebsiella pneumoniae

African Journals Online (AJOL)

use

2011-11-21

Nov 21, 2011 ... the most common serious bacterial infections in infants ... UTI is a common cause of morbidity .... of ESBL and non-ESBL producing Escherichia coli and Klebsiella pneumonia. ... in hospital and community acquired infections.

Ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae carrying multiple metallo-beta-lactamase genes

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Dwivedi Mayank

2009-07-01

Full Text Available Context: Ventilator-associated pneumonia (VAP is a leading nosocomial infection in the intensive care unit (ICU. Members of Enterobacteriaceae are the most common causative agents and carbapenems are the most commonly used antibiotics. Metallo-beta-lactamase (MBL production leading to treatment failure may go unnoticed by routine disc diffusion susceptibility testing. Moreover, there is not much information on association of MBL-producing Enterobacteriaceae with ICU-acquired VAP. Therefore, a study was undertaken to find out the association of MBL-producing Enterobacteriaceae with VAP. Settings: This study was conducted in a large tertiary care hospital of North India with an eight-bed critical care unit. Materials and Methods: The respiratory samples (bronchoalveolar lavage, protected brush catheter specimens and endotracheal or transtracheal aspirates obtained from VAP patients (during January 2005-December 2006 were processed, isolated bacteria identified and their antibiotic susceptibilities tested as per standard protocols. The isolates of Enterobacteriaceae resistant to carbapenem were subjected to phenotypic and genotypic tests for the detection of MBLs. Results: Twelve of 64 isolates of Enterobacteriaceae were detected as MBL producers, bla IMP being the most prevalent gene. Additionally, in three strains, simultaneous coexistence of multiple MBL genes was detected. Conclusion: The coexistence of multiple MBL genes in Enterobacteriaceae is an alarming situation. As MBL genes are associated with integrons that can be embedded in transposons, which in turn can be accommodated on plasmids thereby resulting in a highly mobile genetic apparatus, the further spread of these genes in different pathogens is likely to occur.

Clonal emergence of Klebsiella pneumoniae ST14 co-producing OXA-48-type and NDM carbapenemases with high rate of colistin resistance in Dubai, United Arab Emirates.

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Moubareck, Carole Ayoub; Mouftah, Shaimaa F; Pál, Tibor; Ghazawi, Akela; Halat, Dalal H; Nabi, Anju; AlSharhan, Mouza A; AlDeesi, Zulfa O; Peters, Christabel C; Celiloglu, Handan; Sannegowda, Manjunath; Sarkis, Dolla K; Sonnevend, Ágnes

2018-03-09

Few studies have addressed the molecular epidemiology of carbapenem resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 - June 2016 were determined. Thirty three percent of the collection of 70 K. pneumoniae, 13 E. coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4.5% (four K. pneumoniae isolates) were resistant to all antibiotics tested. The colistin resistance rate in K. pneumoniae was 31.4%. None of the isolates carried mobile colistin resistance genes. Seventy-seven isolates produced carbapenemase: 53.3% OXA-48-like, 24.7% NDM, and 22.1% both OXA-48-like and NDM, respectively. PFGE clustered 50% of K. pneumoniae into a 35-membered group, which showed significant association with double carbapenemase production, with extreme drug resistance, and with being isolated from Emirati patients. Members of the cluster belonged to sequence type ST14. The rate of colistin resistance in K. pneumoniae ST14 was 37.1% vs. 27.1% of K. pneumoniae isolates outside of the cluster. Two of the panresistant K. pneumoniae isolates also belonged to ST14, whereas the other two were ST15 and ST231, respectively. In conclusion, beyond the overall high colistin resistance rate in CRE, the emergence of a highly resistant clone of K. pneumoniae ST14 in all Dubai hospitals investigated is a serious problem requiring immediate attention. Copyright © 2018. Published by Elsevier B.V.

Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in Unrelated Health Care Centers

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Bosch, Thijs; Lutgens, Suzanne P M; Hermans, Mirjam H A; Wever, Peter C; Schneeberger, Peter M.; Renders, Nicole H M; Leenders, Alexander C. A. P.; Kluytmans, Jan A. J. W.; Schoffelen, Annelot F; Notermans, Daan; Witteveen, Sandra; Bathoorn, Erik; Schouls, Leo M.

In the Netherlands, the number of cases of infection with New Delhi metallo-beta-lactamase (NDM)-positive Enterobacteriaceae is low. Here, we report an outbreak of NDM-1-producing Klebsiella pneumoniae infection in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected

Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in Unrelated Health Care Centers.

NARCIS (Netherlands)

Bosch, Thijs; Lutgens, Suzanne P M; Hermans, Mirjam H A; Wever, Peter C; Schneeberger, Peter M; Renders, Nicole H M; Leenders, Alexander C A P; Kluytmans, Jan A J W; Schoffelen, Annelot; Notermans, Daan; Witteveen, Sandra; Bathoorn, Erik; Schouls, Leo M

In the Netherlands, the number of cases of infection with New Delhi metallo-beta-lactamase (NDM)-positive Enterobacteriaceae is low. Here, we report an outbreak of NDM-1-producing Klebsiella pneumoniae infection in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected

Potency of carbapenems for the prevention of carbapenem-resistant mutants of Pseudomonas aeruginosa: the high potency of a new carbapenem doripenem.

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Sakyo, Shihomi; Tomita, Haruyoshi; Tanimoto, Koichi; Fujimoto, Shuhei; Ike, Yasuyoshi

2006-04-01

The potencies of the carbapenems; doripenem (DRPM), meropenem (MEPM) and imipenem (IPM) in preventing the emergence of carbapenem-resistant mutants were examined in Pseudomonas aeruginosa strains. The carbapenems predominantly selected carbapenem-resistant mutants or carbapenem mutants with reduced susceptibilities that were specifically resistant to carbapenems and had arisen as a result of the reduced level of expression of the outer membrane protein with a molecular weight of about 48,000 (OprD). The potency of carbapenems in preventing the growth of the mutants differed for DRPM, MEPM and IPM. The isolation frequency of the mutant was examined on agar plates containing each of the carbapenems at a concentration of 1/2 or 1/4 MIC of each carbapenem for that mutant. Mutants were not selected on agar containing DRPM at a frequency of greater than 10(-9) per cell per generation, whereas mutants of each strain were selected on agar containing MEPM or IPM at frequencies of 10(-7) to 10(-9) per cell per generation. The drug concentrations and the drug concentration range for the selective increase of carbapenem resistant mutants in the broth culture containing each carbapenem differed for each carbapenem. DRPM exhibited both the lowest drug concentration and the narrowest range of drug concentration for selection of the carbapenem-resistant mutants. The results shown in this report indicated that DRPM exhibited the greatest ability to prevent the emergence of the mutant.

"Klebsiella Pneumonia" Liver Abscess Syndrome: Case Presentation to a College Student Health Clinic

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Woll, Christopher; Spotts, P. Hunter

2016-01-01

The authors describe a case of "Klebsiella pneumoniae" liver abscess (KPLA) in a student presenting to a university student health center. The authors also provide a review of KPLA and invasive "Klebsiella pneumoniae" liver abscess syndrome (IKPLAS), including epidemiology, common clinical manifestations, standard diagnostic…

High-dose Sulbactam Treatment for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant

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In Beom Jeong

2016-11-01

Full Text Available Background Several antibiotics can be used to treat ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii (CRAB-VAP including high-dose sulbactam. However, the effectiveness of high-dose sulbactam therapy is not well known. We report our experience with high-dose sulbactam for treatment of CRAB-VAP. Methods Medical records of patients with CRAB-VAP who were given high-dose sulbactam between May 2013 and June 2015 were reviewed. Results Fifty-eight patients with CRAB-VAP were treated with high-dose sulbactam. The mean age was 72.0 ± 15.2 years, and the acute physiology and chronic health evaluation II (APACHE II score was 15.1 ± 5.10 at the time of CRAB-VAP diagnosis. Early clinical improvement was observed in 65.5% of patients, and 30-day mortality was 29.3%. Early clinical failure (odds ratio [OR]: 8.720, confidence interval [CI]: 1.346-56.484; p = 0.023 and APACHE II score ≥ 14 at CRAB-VAP diagnosis (OR: 10.934, CI: 1.047-114.148; p = 0.046 were associated with 30-day mortality. Conclusions High-dose sulbactam therapy may be effective for the treatment of CRAB-VAP. However, early clinical failure was observed in 35% of patients and was associated with poor outcome.

Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome.

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Huang, Weihua; Wang, Guiqing; Sebra, Robert; Zhuge, Jian; Yin, Changhong; Aguero-Rosenfeld, Maria E; Schuetz, Audrey N; Dimitrova, Nevenka; Fallon, John T

2017-07-01

The extended-spectrum-β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae , we identified three clinical isolates, CN1, CR14, and NY9, carrying both bla CTX-M and bla KPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, bla CTX-M and bla KPC were carried on two different plasmids. In contrast, CN1 had one copy of bla KPC-2 and three copies of bla CTX-M-15 integrated in the chromosome, for which the bla CTX-M-15 genes were linked to an insertion sequence, IS Ecp1 , whereas the bla KPC-2 gene was in the context of a Tn 4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn 4401a-bla KPC-2 -prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)- cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR- cas in K. pneumoniae strains and suggested that the evolving CRISPR- cas , with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of bla CTX-M and bla KPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae Additionally, the implications from this study also raise concerns for the application of a CRISPR- cas strategy against antimicrobial resistance. Copyright © 2017 American Society for Microbiology.

Options for treating carbapenem-resistant Enterobacteriaceae.

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Rafailidis, Petros I; Falagas, Matthew E

2014-12-01

To address the therapeutic management of carbapenem-resistant Enterobacteriaceae on the basis of literature of the last 12 months. Retrospective and prospective (nonrandomized noncontrolled) studies provide data regarding the management of infections due to carbapenem-resistant Enterobacteriaceae. The combination of a carbapenem with colistin or high-dose tigecycline or aminoglycoside or even triple carbapenem-containing combinations if the minimum inhibitory concentration (MIC) range of carbapenem (meropenem and imipenem) resistance is 8 mg/l or less seems to have an advantage over monotherapy with either colistin or tigecycline or fosfomycin. For Enterobacteriaceae with MIC for carbapenems over 8 mg/l, combination regimens involve colistin, tigecycline usually administered in a double dose than that suggested by its manufacturer, fosfomycin and aminoglycosides in various combinations. Suggestions based on the limited literature cannot be made safely. Combination regimens involving carbapenems for Enterobacteriaceae with MICs 8 mg/l or less for carbapenems (in dual combination with colistin or high-dose tigecycline or aminoglycoside or even triple combinations) seem to confer some therapeutic advantage over monotherapy. For Enterobacteriaceae with higher than the above-mentioned MICs, a combination of two or even three antibiotics among colistin, high-dose tigecycline, aminoglycoside and fosfomycin seems to confer decreased mortality.

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

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Lanini, Simone; Costa, Alessandro Nanni; Puro, Vincenzo; Procaccio, Francesco; Grossi, Paolo Antonio; Vespasiano, Francesca; Ricci, Andrea; Vesconi, Sergio; Ison, Michael G; Carmeli, Yehuda; Ippolito, Giuseppe

2015-01-01

Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

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Simone Lanini

Full Text Available Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients.Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively. Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days. Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%. Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not.The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant

The outcome of treating ESBL infections with carbapenems vs. non carbapenem antimicrobials.

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Trivedi, Mayuri; Trivedi, Mayur; Patel, Vipul; Soman, Rajeev; Rodriguez, Camilla; Singhal, Tanu

2012-08-01

In India where the prevalence of extended spectrum beta lactamase (ESBL) producing organisms among gram negative organisms is 60-70% and Ertapenem was unavailable at the beginning of this study, exclusive use of Group 2 Carbapenems (Imipenem and Meropenem) for treatment raises issues of cost and development of resistance. Therefore the role of non-Carbapenem alternatives, chiefly Betalactam + Betalactamase inhibitors (BL-BLI) was explored in this prospective observational study at a private tertiary care teaching hospital. 522 consecutive in door patients from the period between June 2006 to March 2007and June 2008 to December 2008, who had true infections with ESBL producing organisms were enrolled in the study. Antimicrobials were prescribed or changed by the treating physicians on the basis of the nature and severity of infection, the susceptibility of the organism and the affordability of the patient. Patients who received a Carbapenem at any time during treatment were considered in the Carbapenem group. Those who never received a Carbapenem at any time during treatment were considered in the non-Carbapenem group. Of the 522 infections, 287 were urinary tract infections, 60 were skin structure infections, 60 were bacteremias, 55 were hospital acquired pneumonias, 31 were intra-abdominal infections and 29 were other infections. There were 351 E. coli, 119 K. pneumoniae, 23 K. oxytoca, 16 Enterobacter aerogenes, 5 Kozoanae, 4 Enterobacter agglomerans, 3 Citrobacter freundi, 1 E. cloacae, 1 Enterobacterspp. and 1 Morgenella morganii isolates. Clinical outcomes were available for 486 patients. 339 patients who were in the non-Carbapenem group and who might have had less serious infections had a clinical success rate of 79.6%. 147 patients who were in the Carbapenem group and who might have had more serious infections had a clinical success rate of 85.71%. It is possible to successfully treat at least the less serious infections due to ESBL producing gram negative

Carbapenem-resistant-only Pseudomonas aeruginosa infection in patients formerly infected by carbapenem-susceptible strains.

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Tsai, Ming-Han; Wu, Tsu-Lan; Su, Lin-Hui; Lo, Wei-Lin; Chen, Chyi-Liang; Liang, Yi-Hua; Chiu, Cheng-Hsun

2014-12-01

Pseudomonas aeruginosa isolates that were initially carbapenem-susceptible and later became selective carbapenem-resistant following antimicrobial therapy were identified from individual cases during the same hospitalisation. Cross-resistance to other β-lactams was not found and their susceptibilities remained identical in consecutive isolates. Real-time quantitative reverse transcription PCR was performed to investigate the role of OprD, an outer membrane protein regulating the entry of carbapenems, in the appearance of carbapenem-resistant-only P. aeruginosa (CROPA). Fifteen paired isolates of carbapenem-susceptible P. aeruginosa (CS-PA) and CROPA were identified. All of the cases had carbapenem exposure history within 1 month before the appearance of CROPA (mean 10 days). Reduced OprD expression was found in 93% (14/15) of the isolates, suggesting that oprD inactivation was the major contributor to selective carbapenem resistance. Of the 14 cases with CROPA due to oprD mutation, 71% (10/14) were persistent infection, as genotype analysis revealed that their paired strains were isogenic; 29% (4/14) represented re-infections as they were heterogenic, suggesting that oprD-deficient CROPA existed in the hospital and that carbapenem selective pressure promoted its spread to patients. We conclude that CROPA may occur soon after the use of carbapenems to treat CS-PA infections and that oprD mutation is the major mechanism of resistance in CROPA. Restriction of empirical use of carbapenems by antibiotic stewardship is important to halt the occurrence of CROPA. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Discrepancy between effects of carbapenems and flomoxef in treating nosocomial hemodialysis access-related bacteremia secondary to extended spectrum beta-lactamase producing Klebsiella pneumoniae in patients on maintenance hemodialysis.

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Yang, Chih-Chao; Li, Shau-Hsuan; Chuang, Feng-Rong; Chen, Chih-Hung; Lee, Chih-Hsiung; Chen, Jin-Bor; Wu, Chien-Hsing; Lee, Chien-Te

2012-09-05

Hemodialysis (HD) patients are susceptible to extended spectrum beta-lactamase (ESBL)-producing bacterial infections. Because the optimal treatment and clinical significance of ESBL-producing Klebsiella pneumoniae (ESBL-Kp) HD access-related bacteremia remain unclear, we conducted this retrospective study to determine the clinical outcomes of patients treated with either flomoxef or a carbapenem. The eligibility criterion was fistula or graft- or catheter- related ESBL-Kp bacteremia in patients on maintenance HD. The clinical characteristics and antibiotic management were analyzed. Outcome was determined by mortality resulting from bacteremia during the 14-day period after the first positive blood culture for flomoxef-susceptible ESBL-Kp. The 57 patients studied were predominantly elderly, malnourished, with a history of severe illnesses and broad-spectrum antibiotic use before the onset of bacteremia, and with severe septicemia as determined by the Pitt bacteremia score (PBS). The study population comprised 7 fistula, 8 graft, and 42 HD catheter-related bacteremia (CRB) cases, and the mortality rate was high (36/57, 63.2%) in these 57 patients. Of 42 patients with CRB, those in the deceased group (27/42, 64.3%) had significantly lower levels of serum albumin, longer prior hospital stay and duration of catheter-dependent HD, and higher PBS than patients in the survived group. Failure to receive effective antibiotics (flomoxef or a carbapenem) within 5 days after onset of bacteremia and treatment with flomoxef both significantly contributed to higher mortality. Multivariate analyses revealed that flomoxef use, PBS, and catheter-dependent HD >30 days were independently associated with increased mortality (OR, 3.52; 95% CI, 1.19-58.17, OR, 2.92; 95% CI, 1.36-6.26 and OR, 5.73; 95% CI, 1.21-63.2, respectively). Considering the high mortality rate, ESBL-Kp should be recognized as a possible pathogen in patients on maintenance HD at high risk of acquiring HD access

Discrepancy between effects of carbapenems and flomoxef in treating nosocomial hemodialysis access-related bacteremia secondary to extended spectrum beta-lactamase producing klebsiella pneumoniae in patients on maintenance hemodialysis

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Yang Chih-Chao

2012-09-01

Full Text Available Abstract Background Hemodialysis (HD patients are susceptible to extended spectrum beta-lactamase (ESBL-producing bacterial infections. Because the optimal treatment and clinical significance of ESBL-producing Klebsiella pneumoniae (ESBL-Kp HD access-related bacteremia remain unclear, we conducted this retrospective study to determine the clinical outcomes of patients treated with either flomoxef or a carbapenem. Methods The eligibility criterion was fistula or graft- or catheter- related ESBL-Kp bacteremia in patients on maintenance HD. The clinical characteristics and antibiotic management were analyzed. Outcome was determined by mortality resulting from bacteremia during the 14‐day period after the first positive blood culture for flomoxef-susceptible ESBL-Kp. Results The 57 patients studied were predominantly elderly, malnourished, with a history of severe illnesses and broad-spectrum antibiotic use before the onset of bacteremia, and with severe septicemia as determined by the Pitt bacteremia score (PBS. The study population comprised 7 fistula, 8 graft, and 42 HD catheter-related bacteremia (CRB cases, and the mortality rate was high (36/57, 63.2% in these 57 patients. Of 42 patients with CRB, those in the deceased group (27/42, 64.3% had significantly lower levels of serum albumin, longer prior hospital stay and duration of catheter-dependent HD, and higher PBS than patients in the survived group. Failure to receive effective antibiotics (flomoxef or a carbapenem within 5 days after onset of bacteremia and treatment with flomoxef both significantly contributed to higher mortality. Multivariate analyses revealed that flomoxef use, PBS, and catheter-dependent HD >30 days were independently associated with increased mortality (OR, 3.52; 95% CI, 1.19–58.17, OR, 2.92; 95% CI, 1.36–6.26 and OR, 5.73; 95% CI, 1.21–63.2, respectively. Conclusions Considering the high mortality rate, ESBL-Kp should be recognized as a possible pathogen in

Frequency of Carbapenem, Colistin and Tigecycline Resistant Enterobacteriacae in Medical ICU of a Tertiary Care Hospital in Karachi

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Shobha Luxmi

2018-01-01

Full Text Available BACKGROUND: Resistance to antibiotics among Enterobacteriacae represents a serious therapeutic and infection control challenge. The objective of this study was to determine the frequency of carbapenem, colistin and tigecycline resistant Enterobacteriaceae isolates obtained from patients admitted in medical intensive care unit (ICU of a tertiary care hospital in Karachi, Pakistan. METHODS: This was a descriptive cross sectional study that was conducted at Liaquat National Postgraduate Medical Centre, Karachi, Pakistan during December 2015 to May 2016. Patients admitted in the medical ICU with systemic inflammatory response syndrome were included. The culture positive samples were analyzed for further identification and antimicrobial sensitivity was performed according to clinical laboratory standard institute (CLSI 2014 guidelines. RESULTS: Of the 748 samples, 177 were positive for Enterobactericae. Most samples were taken from blood 75(42.2% or tracheal secretions 67(37.9%. Most common organism isolated were Klebsiella pneumoniae 77(43.5% and Escherichia coli 71(40.1%. Out of these 10.7% organisms were resistant to meropenem, while 2.8% and 20.3% were resistant to colistin and tigecycline respectively. CONCLUSION: Increasing spread of drug resistance among Enterobacteriacae reflects an important problem that can be controlled with effective policies of infection control, surveillance and antimicrobial stewardship.

Profiles of phenotype resistance to antibiotic other than β-lactams in Klebsiella pneumoniae ESBLs-producers, carrying blaSHV genes

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Pawel Sacha

2010-04-01

Full Text Available Extended spectrum β-lactamases production is one of the most common mechanism of resistance to extendedspectrum β-lactam antibiotics is increasing worldwide. Twenty five strains of Klebsiella pneumoniae isolated from clinicalspecimens were tested. Based on the phenotypic confirmatory test all these strains were defined as ESBL producers namedESBL(+. The plasmid DNA from each strains was used to investigate the presence of blaSHV genes responsible for extendedspectrum β-lactamases production. Moreover, susceptibility of these strains to antibiotic other than β-lactams in was tested.

SURVEILLANCE of CARBAPENEM NON-SUSCEPTIBLE GRAM NEGATIVE STRAINS and CHARACTERIZATION of CARBAPENEMASES of CLASSES A, B and D in a LEBANESE HOSPITAL.

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Hammoudi, Dalal; Moubareck, Carole Ayoub; Kanso, Abeer; Nordmann, Patrice; Sarkis, Dolla Karam

2015-01-01

The production of carbapenem-hydrolyzing enzymes has been recognized as one of the most currently relevant resistance mechanisms in gram negative bacterial isolates, and is being detected in various countries. In Lebanon, carbapenem resistance was studied among gram negative pathogens collected from a university hospital from January to June of years 2011 and 2012. All isolates were subjected to phenotypic tests including antibiotic susceptibility, cloxacillin effect, modified Hodge test, and Etest for metallo-β-lactamase detection. They were also subjected to genotyping by PCR sequencing to characterize β-lactamases. Between January and June 2011, 48 carbapenem non-susceptible strains were collected. Of these, one Klebsiella pneumoniae harbored OXA-48 and insertion sequence IS 1999; four Acinetobacter baumanni harbored simultaneously OXA-23 and GES-11, and three Pseudomonas harbored VIM-2 carbapenemase. Between January and June 2012, 100 carbapenem non-susceptible strains were collected. Of these, one K. pneumoniae harbored simultaneously OXA-48, IS 1999, and an acquired AmpC of the ACC group; four Serratia marcescens harbored OXA-48, while among eight A. baumannii, one strain co-harbored OXA-23 and GES-11, six harbored OXA-23 and one OXA-24. Fifteen P, aeruginosa and two Pseudomonas species harbored VIM-2; two P. aeruginosa strains produced IMP-1 and two others IMP-2. This epidemiological survey demonstrates the presence of carbapenemases of Ambler classes A, B, and D in a Lebanese hospital and indicates increase in the number and variety of such enzymes.

Identification of carbapenemase-mediated resistance among Enterobacteriaceae bloodstream isolates: A molecular study from India

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Srujana Mohanty

2017-01-01

Full Text Available Acquired resistance in carbapenem-resistant Enterobacteriaceae (CRE conferred by carbapenemases is a major concern worldwide. Consecutive, non-duplicate isolates of Escherichia coli (EC and Klebsiella pneumoniae from clinically diagnosed bloodstream infections were screened for the presence of carbapenem resistance by standard disk-diffusion method and minimum inhibitory concentration breakpoints using the Clinical and Laboratory Standards Institute guidelines. Carbapenemase-encoding genes were amplified by polymerase chain reaction. Of 387 isolates (214 K. pneumoniae, 173 EC tested, 93 (24.03% were found to be CRE. Of these, 71 (76.3% were positive for at least one tested carbapenemase gene. The frequency of carbapenemase genes was New Delhi metallo-β-lactamse-1 (65.6%, oxacillinase (OXA-48 (24.7%, OXA-181 (23.6%, Verona integron-encoded metallo-β-lactamase (6.4% and K. pneumoniae carbapenemase (2.1%. Our study identified presence of carbapenemases in a large proportion of CRE isolates. Delineation of resistance mechanisms is important in view of future therapeutics concerned with the treatment of CRE and for aiding control efforts by surveillance and infection control interventions.

The diversity of Klebsiella pneumoniae surface polysaccharides.

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Follador, Rainer; Heinz, Eva; Wyres, Kelly L; Ellington, Matthew J; Kowarik, Michael; Holt, Kathryn E; Thomson, Nicholas R

2016-08-01

Klebsiella pneumoniae is considered an urgent health concern due to the emergence of multi-drug-resistant strains for which vaccination offers a potential remedy. Vaccines based on surface polysaccharides are highly promising but need to address the high diversity of surface-exposed polysaccharides, synthesized as O-antigens (lipopolysaccharide, LPS) and K-antigens (capsule polysaccharide, CPS), present in K. pneumoniae . We present a comprehensive and clinically relevant study of the diversity of O- and K-antigen biosynthesis gene clusters across a global collection of over 500 K. pneumoniae whole-genome sequences and the seroepidemiology of human isolates from different infection types. Our study defines the genetic diversity of O- and K-antigen biosynthesis cluster sequences across this collection, identifying sequences for known serotypes as well as identifying novel LPS and CPS gene clusters found in circulating contemporary isolates. Serotypes O1, O2 and O3 were most prevalent in our sample set, accounting for approximately 80 % of all infections. In contrast, K serotypes showed an order of magnitude higher diversity and differ among infection types. In addition we investigated a potential association of O or K serotypes with phylogenetic lineage, infection type and the presence of known virulence genes. K1 and K2 serotypes, which are associated with hypervirulent K. pneumoniae , were associated with a higher abundance of virulence genes and more diverse O serotypes compared to other common K serotypes.

Suppurative peritonitis by Klebsiella pneumoniae in captive gold-handed tamarin (Saguinus midas midas).

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Guerra, Maria F L; Teixeira, Rodrigo H F; Ribeiro, Vanessa L; Cunha, Marcos P V; Oliveira, Maria G X; Davies, Yamê M; Silva, Ketrin C; Silva, Ana P S; Lincopan, Nilton; Moreno, Andrea M; Knöbl, Terezinha

2016-02-01

This report describes an outbreak of suppurative peritonitis caused by Klebsiella pneumoniae in an adult female of captive golden-handed tamarin (Saguinus midas midas). Two virulent and multidrug-resistant strains were isolated and classified through MLST as ST60 and ST1263. The microbiological diagnosis works as a support tool for preventive measures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluating Different Virulence Traits of Klebsiella pneumoniae Using Dictyostelium discoideum and Zebrafish Larvae as Host Models

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Andrés E. Marcoleta

2018-02-01

Full Text Available Multiresistant and invasive hypervirulent Klebsiella pneumoniae strains have become one of the most urgent bacterial pathogen threats. Recent analyses revealed a high genomic plasticity of this species, harboring a variety of mobile genetic elements associated with virulent strains, encoding proteins of unknown function whose possible role in pathogenesis have not been addressed. K. pneumoniae virulence has been studied mainly in animal models such as mice and pigs, however, practical, financial, ethical and methodological issues limit the use of mammal hosts. Consequently, the development of simple and cost-effective experimental approaches with alternative host models is needed. In this work we described the use of both, the social amoeba and professional phagocyte Dictyostelium discoideum and the fish Danio rerio (zebrafish as surrogate host models to study K. pneumoniae virulence. We compared three K. pneumoniae clinical isolates evaluating their resistance to phagocytosis, intracellular survival, lethality, intestinal colonization, and innate immune cells recruitment. Optical transparency of both host models permitted studying the infective process in vivo, following the Klebsiella-host interactions through live-cell imaging. We demonstrated that K. pneumoniae RYC492, but not the multiresistant strains 700603 and BAA-1705, is virulent to both host models and elicits a strong immune response. Moreover, this strain showed a high resistance to phagocytosis by D. discoideum, an increased ability to form biofilms and a more prominent and irregular capsule. Besides, the strain 700603 showed the unique ability to replicate inside amoeba cells. Genomic comparison of the K. pneumoniae strains showed that the RYC492 strain has a higher overall content of virulence factors although no specific genes could be linked to its phagocytosis resistance, nor to the intracellular survival observed for the 700603 strain. Our results indicate that both zebrafish

Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study.

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Karampatakis, Theodoros; Geladari, Anastasia; Politi, Lida; Antachopoulos, Charalampos; Iosifidis, Elias; Tsiatsiou, Olga; Karyoti, Aggeliki; Papanikolaou, Vasileios; Tsakris, Athanassios; Roilides, Emmanuel

2017-07-31

Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004). The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii

Frequency of colistin and fosfomycin resistance in carbapenem-resistant Enterobacteriaceae from a tertiary care hospital in Karachi

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Qamar S

2017-07-01

Full Text Available Salima Qamar, Najma Shaheen, Sadia Shakoor, Joveria Farooqi, Kauser Jabeen, Rumina Hasan Clinical Microbiology, Department of Pathology And Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan Introduction: Management of infections with carbapenem-resistant Enterobacteriaceae (CRE is challenging. In recent times, agents such as colistin and fosfomycin have been used in combination with other antibiotics to treat such infections. In this study, we aim to seek frequency of colistin and fosfomycin resistance in CRE from Pakistan.Methods: This study was conducted at clinical laboratories, Aga Khan University Hospital. In total, 251 CRE were included in the study. Colistin minimum inhibitory concentrations (MICs were performed using broth microdilution (BMD method and VITEK® 2 system, whereas fosfomycin susceptibility was performed using Kirby–Bauer method. MIC50 and MIC90 were calculated for colistin and agreement between VITEK and BMD was also calculated.Results: Out of 251 strains colistin MIC of ≥4 µg/mL was seen in 40 (15.9%. Of these strains 20 (50% were Klebsiella pneumoniae. Colistin MIC50 and MIC90 were found to be 0.5 and 16 µg/mL, respectively. BMD and VITEK 2 showed 100% categorical agreement. Essential agreement was 88.5% with kappa score 0.733 indicating strong agreement between VITEK and BMD. 31 out of 251 (12.3% CREs were resistant to fosfomycin.Conclusion: Study shows frequency of colistin and fosfomycin resistance to be 15.9% and 12.3%, respectively. In countries where rate of CREs is high, emerging resistance against these last resort antibiotics is alarming as it leaves clinicians with almost no options to manage such multidrug resistant and extensively drug resistant infections. Keywords: emerging drug resistance, colistin resistance, fosfomycin resistance, carbapenam resistant enterobacteriaceae, salvage antibiotics 

Lactobacillus casei triggers a TLR mediated RACK-1 dependent p38 MAPK pathway in Caenorhabditis elegans to resist Klebsiella pneumoniae infection.

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Kamaladevi, Arumugam; Balamurugan, Krishnaswamy

2016-07-13

In the present study, the effect of Lactic Acid Bacteria (LAB) was investigated at the molecular level using the model organism Caenorhabditis elegans against Klebsiella pneumoniae. Out of the 13 LAB screened, Lactobacillus casei displayed excellent protective efficacy by prolonging the survival of K. pneumoniae-infected nematodes. Pretreatment with L. casei significantly decreased bacterial colonization and rescued K. pneumoniae-infected C. elegans from various physiological impairments. The concomitant upregulation of key immune genes that regulate the TLR, RACK-1 as well as the p38 MAPK pathway rather than the IIS and ERK pathway suggested that the plausible immunomodulatory mechanism of L. casei could be by triggering the TLR, RACK-1 and p38 MAPK pathway. Furthermore, the hyper-susceptibility of L. casei treated loss-of-function mutants of the tol-1, RACK-1 and p38 MAPK pathway (sek-1 and pmk-1) to K. pneumoniae infection and gene expression analysis suggested that L. casei triggered a TLR mediated RACK-1 dependent p38 MAPK pathway to increase host resistance and protect nematodes against K. pneumoniae infection.

Regions on plasmid pCU1 required for the killing of Klebsiella pneumoniae.

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Thatte, V; Gill, S; Iyer, V N

1985-01-01

Plasmid pCU1 was Kik+ (promotes killing of Klebsiella pneumoniae). All Tn5 insertions within the tra region of pCU1 were Kik-. Two other regions, kikA and kikB, were needed. They may be separated on different plasmids, but both must be mobilized into Klebsiella pneumoniae. Establishment of one kik region in K. pneumoniae followed by receipt of the second did not lead to killing. Kik was therefore intracellular and required concerted and transient action of both regions.

Empiric Piperacillin-Tazobactam versus Carbapenems in the Treatment of Bacteraemia Due to Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae.

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Ng, Tat Ming; Khong, Wendy X; Harris, Patrick N A; De, Partha P; Chow, Angela; Tambyah, Paul A; Lye, David C

2016-01-01

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a common cause of bacteraemia in endemic countries and may be associated with high mortality; carbapenems are considered the drug of choice. Limited data suggest piperacillin-tazobactam could be equally effective. We aimed to compare 30-day mortality of patients treated empirically with piperacillin-tazobactam versus a carbapenem in a multi-centre retrospective cohort study in Singapore. Only patients with active empiric monotherapy with piperacillin-tazobactam or a carbapenem were included. A propensity score for empiric carbapenem therapy was derived and an adjusted multivariate analysis of mortality was conducted. A total of 394 patients had ESBL-Escherichia.coli and ESBL-Klebsiella pneumoniae bacteraemia of which 23.1% were community acquired cases. One hundred and fifty-one received initial active monotherapy comprising piperacillin-tazobactam (n = 94) or a carbapenem (n = 57). Patients who received carbapenems were less likely to have health-care associated risk factors and have an unknown source of bacteraemia, but were more likely to have a urinary source. Thirty-day mortality was comparable between those who received empiric piperacillin-tazobactam and a carbapenem (29 [30.9%] vs. 17 [29.8%]), P = 0.89). Those who received empiric piperacillin-tazobactam had a lower 30-day acquisition of multi-drug resistant and fungal infections (7 [7.4%] vs. 14 [24.6%]), Pcarbapenem.

Collateral damage of flomoxef therapy: in vivo development of porin deficiency and acquisition of blaDHA-1 leading to ertapenem resistance in a clinical isolate of Klebsiella pneumoniae producing CTX-M-3 and SHV-5 beta-lactamases.

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Lee, Chen-Hsiang; Chu, Chishih; Liu, Jien-Wei; Chen, Yi-Shung; Chiu, Chiung-Jung; Su, Lin-Hui

2007-08-01

The study aimed to characterize the genetic basis of flomoxef and collateral ertapenem resistance in a clinical isolate of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) after flomoxef exposure. Four ESBL-KP isolates (Lkp11-14) were recovered sequentially from four episodes of bacteraemia in an elderly patient. Laboratory investigations included genotyping by PFGE, resistance gene analysis by PCR and sequencing, and outer membrane protein analysis by SDS-PAGE. Plasmid analysis by DNA-DNA hybridization, electroporation and conjugation was also performed. Lkp14 was recovered after 21 days of flomoxef therapy. It demonstrated an indistinguishable PFGE pattern when compared with those produced by Lkp11-13. However, resistance to both flomoxef and ertapenem emerged in Lkp14. Molecular characterization revealed that, in addition to the pre-existing ESBL production (CTX-M-3 and SHV-5) and OmpK35 deficiency found in Lkp11-13, Lkp14 had acquired an extra plasmid-mediated AmpC beta-lactamase gene (blaDHA-1) and failed to express OmpK36, because of insertional inactivation by an insertion sequence IS5. Other resistance mechanisms, such as production of carbapenem-hydrolysing enzymes or expression of chromosomal efflux, were apparently not involved. Conjugational transfer of the plasmid-mediated blaDHA-1 gene into Lkp11 resulted in a significant increase in the MICs of cephamycins and beta-lactamase inhibitors, but not in those of carbapenems. Lkp14 was apparently derived from the previously flomoxef-susceptible isolates, Lkp11-13. After flomoxef exposure, the in vivo acquisition of the plasmid-mediated blaDHA-1 gene has led to flomoxef resistance in Lkp14, and the concomitant depletion of OmpK36 expression has resulted in a collateral effect of ertapenem resistance and diminished susceptibilities to imipenem and meropenem.

Over expression of AdeABC and AcrAB-TolC efflux systems confers tigecycline resistance in clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae

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Yin Yuhan

2016-04-01

Full Text Available Abstract: INTRODUCTION: Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR bacteria, clinical resistance to tigecycline has increased in recent years. Here, we investigated the relationship between tigecycline resistance and the expression of efflux pumps. METHODS: Clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae were consecutively collected from hospitalized patients in three hospitals. The minimum inhibitory concentration (MIC of tigecycline was determined using the broth microdilution method. Expression levels of efflux pump genes and regulators were examined by quantitative real-time reverse transcription polymerase chain reaction. The correlations between tigecycline MICs and gene expression levels were analyzed. RESULTS: Overall, 1,026 A. baumannii and 725 K. pneumoniae strains were collected. Most strains were isolated from sputum. The tigecycline resistance rate was 13.4% in A. baumannii isolates and 6.5% in K. pneumoniae isolates. Overexpression of AdeABC and AcrAB-TolC efflux systems was observed found in clinical tigecycline-resistant isolates. The tigecycline MIC had a linear relationship with the adeB expression level in A. baumannii isolates, but not with the acrB expression level in K. pneumoniae isolates. There were significant linear trends in the overexpression of ramA as the tigecycline MIC increased in K. pneumoniae isolates. CONCLUSIONS: Tigecycline resistance in A. baumannii and K. pneumoniae was strongly associated with the overexpression of efflux systems. More studies are needed to elucidate whether there are other regulators that affect the expression of adeB in A. baumannii and how ramA affects the expression of acrB in K. pneumoniae.

Case report 558: Multicentric Klebsiella pneumoniae (Friedlaenders bacillus) osteomyelitis in sickle cell anemia

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Malpani, A.R.; Sundaram, M.; Ramani, S.K.

1989-01-01

This patient represents a unique combination of multicentric osteomyelitis due to Klebsiella pneumoniae, lesions in the skull, pathological fracture of a long bone and no evidence of pulmonary disease. That Klebsiella pneumoniae osteomyelitis can occur in sickle cell anemia should be considered when such bone changes are seen. The remarkable resolution on conservative management also needs to be noted. (orig./GDG)

Assessment of genetic relationship between Klebsiella pneumoniae and Klebsiella oxytoca samples isolated from a dental office

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MV Pimenta-Rodrigues

2008-01-01

Full Text Available The present study aimed to analyze the genetic similarity between genomic profiles of thirteen Klebsiella oxytoca and seven Klebsiella pneumoniae samples isolated from two different collections carried out in different places of dental offices. Random amplified polymorphic DNA (RAPD technique and similarity coefficients (calculated by Sorensen-Dice and simple matching were applied to determine their genetic profile of randomic DNA sequences. The majority of the isolates of K. pneumoniae and K. oxytoca presented similar coefficient values (e" 0.80. Thus, it was possible to identify that strain dissemination occurred mainly via the hands of the surgeon-dentists and, finally, to determine the genetic similarity of the strains from dental office environments.

Antibiotic consumption and resistance: results of the SPIN-UTI project of the GISIO-SItI.

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Agodi, Antonella; Auxilia, Francesco; Barchitta, Martina; Brusaferro, Silvio; D'Errico, Marcello Mario; Montagna, Maria Teresa; Pasquarella, Cesira; Tardivo, Stefano; Mura, Ida

2015-01-01

To evaluate trends and association between antibiotic consumption and resistance during an eight-year period, from 2006 to 2013. Prospective multicenter study. Intensive Care Units (ICUs) participating in the four editions of the Italian nosocomial infections surveillance in the ICU Network (Sorveglianza Prospettica delle Infezioni Nosocomiali nelle Unità di Terapia Intensiva, SPIN-UTI project). The isolation density of selected species of microorganisms, antibiotic resistance rates (RRs), incidence density of resistant isolates and antimicrobial usage density were calculated. RRs of carbapenem-resistant Acinetobacter baumannii, of carbapenem-resistant Klebsiella pneumoniae, of third-generation cephalosporin (3GC)-resistant K. pneumoniae and of 3GC-resistant Escherichia coli showed significant increasing trends (p ≤0.001). The consumption of each antibiotic class varied with years, although not significantly. Significant strongly positive correlations were detected between RRs and antibiotic consumption. The present study describes high RRs and increasing trends of resistant microorganisms and highlights the need for continuous comprehensive strategies targeting not only the prudent use of antibiotics, but also infection control measures to limit the epidemic spread of resistant isolates.

Acute Placental Infection Due to Klebsiella pneumoniae: Report of a Unique Case

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Janice M. Lage

2005-01-01

Full Text Available A 40-year-old woman, gravida 9, with seven healthy children and a history of one abortion (p 7 + 1 , presented at 18 weeks of gestation with fever and malodorous vaginal discharge. Ultrasound revealed a macerated fetus. The placenta showed acute chorioamnionitis and acute villitis with microabscess formation. Blood and vaginal cultures both grew Klebsiella pneumoniae. This is the first reported case in English literature of Klebsiella pneumoniae causing suppurative placentitis leading to fetal demise.

Association of ertapenem and antipseudomonal carbapenem usage and carbapenem resistance in Pseudomonas aeruginosa among 12 hospitals in Queensland, Australia.

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McDougall, David A J; Morton, Anthony P; Playford, E Geoffrey

2013-02-01

The objective of this study was to determine the association between ertapenem and antipseudomonal carbapenem use and carbapenem resistance in Pseudomonas aeruginosa in 12 hospitals in Queensland, Australia. Data on usage of ertapenem and other antipseudomonal carbapenems, measured in defined daily doses per 1000 occupied bed-days, were collated using statewide pharmacy dispensing and distribution software from January 2007 until June 2011. The prevalence of unique carbapenem-resistant P. aeruginosa isolates derived from statewide laboratory information systems was collected for the same time period. Mixed-effects models were used to determine any relationship between ertapenem and antipseudomonal carbapenem usage and carbapenem resistance among P. aeruginosa isolates in the 12 hospitals analysed. No relationship between ertapenem usage and P. aeruginosa carbapenem resistance was observed. The introduction of ertapenem did not replace antipseudomonal carbapenem prescribing to any significant extent. However, an association between greater usage of antipseudomonal carbapenems and greater P. aeruginosa carbapenem resistance was demonstrated. It is likely that the only mechanism by which ertapenem can improve P. aeruginosa resistance patterns is by being used as a substitute for, rather than in addition to, antipseudomonal carbapenems.

Phenotypic and genotypic characterization of Klebsiella pneumonia recovered from nonhuman primates

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Klebsiella pneumoniae is a zoonotic, Gram-negative member of the family Enterobacteriaceae and is the causative agent of nosocomial septicemic, pneumonic, and urinary tract infections. Recently, pathogenic strains of K. pneumoniae sharing a hypermucoviscosity (HMV) phenotype have been attributed to ...

Phenotypic and genotypic detection of ESBL mediated cephalosporin resistance in Klebsiella pneumoniae: emergence of high resistance against cefepime, the fourth generation cephalosporin.

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Grover, S S; Sharma, Meenakshi; Chattopadhya, D; Kapoor, Hema; Pasha, S T; Singh, Gajendra

2006-10-01

Cephalosporins belonging to second and third generation are commonly used in India for the treatment of Klebsiella pneumoniae. Report on resistance among K. pneumoniae strains to second and third generation cephalosporins are on rise in this country, which has been attributed to emergence of strains expressing extended-spectrum beta-lactamases (ESBLs). The aim of this study was to evaluate the in vitro susceptibility of K. pneumoniae to broad-spectrum cephalosporins particularly to cefepime, a recently introduced fourth generation cephalosporin in relation to ESBL production. This study has been carried out in two phases among K. pneumoniae strains isolated between October 2001 and September 2002 (phase I, before marketing of cefepime in India) and between August 2003 and July 2004 (phase II, after marketing of cefepime in India). Minimum Inhibitory Concentration (MIC) was determined by a commercial strip containing gradient of antimicrobials (Strip E-test). Detection for ESBL production was carried out by DDST, E-test ESBL and PCR. Antimicrobial resistance profile of K. pneumoniae strains to five cephalosporins as analyzed by WHONET 5 identified 15 different resistance profiles among the 108 phase I isolates, ranging from resistance to none (19.44%) to all the five cephalosporin (8.33%) and eight different resistance profiles among the 99 phase II isolates, ranging from resistance to none (9.1%) to all the five cephalosporins (36.4%). Among the 108 phase I isolates a total of 71 (65.72%) and out of 99 phase II isolates, a total of 87 (88.0%) could be identified as ESBL producers. Among the isolates, regardless of the phase of the isolation, those characterized by production of ESBL showed overall higher frequency of resistance to cephalosporins (range 19.7-85.9% and 51.7-100% in phase I and phase II, respectively) compared to those for ESBL non-producers (range 0-13.5% and 0-25% in phase I and phase II, respectively). Ten randomly selected isolates from the most

Effect of carbapenem consumption patterns on the molecular epidemiology and carbapenem resistance of Acinetobacter baumannii.

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Mózes, Julianna; Ebrahimi, Fatemeh; Gorácz, Orsolya; Miszti, Cecília; Kardos, Gábor

2014-12-01

This study investigated the molecular epidemiology of Acinetobacter baumannii in the University of Debrecen in relation to antibiotic consumption. Overall and ward-specific antibiotic consumption was measured by the number of defined daily doses (DDD) per 100 bed-days between 2002 and 2012. Consumption was analysed against the number of A. baumannii positive patients per 100 bed-days, number of isolates per positive sample, and proportion of carbapenem resistant A. baumannii, using time-series analysis. Altogether 160 A. baumannii isolates from different wards were collected and analysed. Carbapenemase genes bla(OXA-23-like), bla(OXA-24-like), bla(OXA-48-like), bla(OXA-51-like), bla(OXA-58-like) and integrons were sought by PCR. Relatedness of isolates was assessed by PFGE. Prevalence and carbapenem resistance of A. baumannii were statistically associated with carbapenem consumption. Prevalence data followed carbapenem usage with three quarterly lags (r = 0.51-0.53, Pcarbapenem consumption was associated with the carbapenem-susceptible cluster, as well as with the carbapenem-susceptible isolates in the cluster with variable susceptibility. Wards with high carbapenem usage almost exclusively harboured isolates from carbapenem-resistant clusters. All clusters were dominated by isolates of one or two wards, but most wards were represented in multiple clusters. Increases in prevalence and carbapenem resistance of A. baumannii were associated with usage of meropenem and ertapenem but not of imipenem, which led to the spread of multiple clones in the University. © 2014 The Authors.

Acute renal failure caused by Klebsiella pneumoniae pyelonephritis

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Creyghton, W. M.; Lobatto, S.; Weening, J. J.

2001-01-01

We report a 34-year-old male patient without prior medical history who presented with acute renal failure due to acute bacterial pyelonephritis. Both blood and urine cultures grew Klebsiella pneumoniae. Although a kidney biopsy revealed extensive necrosis and no viable glomeruli, renal function

First emergence of acrAB and oqxAB mediated tigecycline resistance in clinical isolates of Klebsiella pneumoniae pre-dating the use of tigecycline in a Chinese hospital.

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Xue Zhong

Full Text Available Tigecycline is one of the few therapeutic options for treating infections caused by some multi-drug resistant pathogens, such as Klebsiella pneumoniae. However, tigecycline-resistant K. pneumoniae has been discovered recently in China. From 2009 to 2013, nine tigecycline-resistant K. pneumoniae isolates were identified in our hospital. Six of nine strains were identified before using tigecycline. To investigate the efflux-mediated resistance mechanisms of K. pneumoniae, the expression of efflux pump genes (acrA, acrB, tolC, oqxA and oqxB and pump regulators (acrR, marA, soxS, rarA, rob and ramA were examined by real-time RT-PCR. Molecular typing of the tigecycline resistant strains was performed. ST11 was the predominant clone of K. pneumoniae strains, while ST1414 and ST1415 were novel STs. Efflux pump inhibitor (EPI-carbonyl cyanide chlorophenylhydrazone (CCCP was able to reverse the resistance patterns of 5 resistant K. pneumoniae strains. In comparison with strain A111, a tigecycline-susceptible strain (negative control, we found that the expression levels of efflux pump genes and pump regulators were higher in a majority of resistant strains. Higher expression levels of regulators rarA (2.41-fold, 9.55-fold, 28.44-fold and 18.31-fold, respectively and pump gene oqxB (3.87-fold, 31.96-fold, 50.61-fold and 29.45-fold, respectively were observed in four tigecycline resistant strains (A363, A361, A368, A373, respectively. Increased expression of acrB was associated with ramA and marA expression. To our knowledge, studies on tigecycline resistance mechanism in K. pneumoniae are limited especially in China. In our study, we found that both efflux pump AcrAB-TolC and OqxAB contributed to tigecycline resistance in K. pneumoniae isolates.

Cefmetazole for bacteremia caused by ESBL-producing enterobacteriaceae comparing with carbapenems.

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Fukuchi, Takahiko; Iwata, Kentaro; Kobayashi, Saori; Nakamura, Tatsuya; Ohji, Goh

2016-08-18

ESBL (Extended spectrum beta-lactamase) producing enterobacteriaceae are challenging organisms with little treatment options. Carbapenems are frequently used, but the emergence of carbapenem resistant enterobacteriaceae is a concerning issue, which may hinder the use of carbapenems. Although cephamycins such as cefoxitin, cefmetazole or cefotetan are effective against ESBL-producers in vitro, there are few clinical data demonstrating effects against bacteremia caused by these organisms. We performed a retrospective observational study on cases of bacteremia caused by ESBL-producers to investigate the efficacy of cefmetazole compared with carbapenems. We also evaluated whether the trend of antibiotic choice changed over years. Sixty-nine patients (male 34, age 69.2 ± 14.4), including two relapse cases, were reviewed for this analysis. The most common causative organisms were Escherichia coli (64, 93 %), followed by Klebsiella pneumoniae and K. oxytoca (2 each, 4 %). The group that received carbapenem therapy (43, 62 %) had increased severity in the Pittsburgh Bacteremic score than the group that received cefmetazole therapy, (1.5 ± 1.5 vs 2.5 ± 2.1, p = 0.048), while analysis of other factors didn't reveal any statistical differences. Five patients in the carbapenem group and one patient in the cefmetazole group died during the observation period (p = 0.24). CTX-M-9 were predominant in this series (59 %). Infectious disease physicians initially recommended carbapenems at the beginning of the current research period, which gradually changed over time favoring the use of cefmetazole instead (p = 0.002). Cefmetazole may be safely given to patients with bacteremia caused by ESBL-producers as a definitive therapy, if one can select out relatively stable patients.

Adult Klebsiella pneumoniae meningitis in Qatar:clinical pattern of ten cases

Institute of Scientific and Technical Information of China (English)

Fahmi Yousef Khan; Mohammed Abukhattab; Mohammed AbuKamar; Deshmukh Anand

2014-01-01

Objective: To describe the clinical presentation, underlying diseases, antimicrobial susceptibility, treatment and outcome of Klebsiella pneumoniae meningitis patients. Methods:This retrospective study involved all patients with 15 years of age or older who admitted to Hamad General Hospital with culture proven Klebsiella pneumoniae meningitis from January 1, 2007 to December 31, 2012. Results: A total of ten cases were identified (nine males and one female). Their mean age was (43.3±12.8) years. Eight patients (80%) had nosocomial meningitis with neurosurgery being the most frequent associated condition. Fever and altered consciousness were the most frequent symptom. Cerebrospinal fluid showed elevated protein and glucose levels. Gram stain showed Gram-negative rods in 50%of cases, while positive cerebrospinal fluid culture results were found in all patients. Multidrug resistance was observed in two cases, and all patients had received appropriate empirical and definitive antibiotic treatments. The mean duration of intravenous antimicrobial treatment was (19.3±7.0) d and all patients with external ventricular drains underwent removal of the device, while in-hospital mortality was 50%. Conclusions: The number of cases was too small to come up with therapeutic and prognostic conclusions. Further large-scale prospective study is needed.

Adult Klebsiella pneumoniae meningitis in Qatar:clinical pattern of ten cases

Institute of Scientific and Technical Information of China (English)

Fahmi; Yousef; Khan; Mohammed; Abukhattab; Mohanuned; Abukamar; Deshmukh; Anand

2014-01-01

Objective:To describe the clinical presentation,underlying diseases,antimicrobial susceptibility,treatment and outcome of Klebsiella pneumoniae meningitis patients.Methods:This retrospective study involved all patients with 15 years of age or older who admit ted to Hamad General Hospital with culture proven Klebsiella pneumoniae meningitis from January 1,2007 to December 31,2012.Results:A total of ten cases were identified mine males and one female).Their mean age was i43.3±12.8) years.Eight patients(80%) had nosocomial meningitis with neurosurgery being the most frequent associated condition.Fever and altered consciousness were the most frequent symptom.Cerebrospinal fluid showed elevated protein and glucose levels.Oram slain showed Gram—negative rods in 50%of cases,while positive cerebrospinal fluid culture results were found in all patients.Multidrug resistance was observed in two cases,and all patients had received appropriate empirical and definitive antibiotic treatments.The mean duration of intravenous antimicrobial treatment was(19.3±7.0) d and all patients with external ventricular drains underwent removal of the device,while in—hospital mortality was 50%.Conclusions:The number of cases was too small to come up with therapeutic and prognostic conclusions.Further large-scale prospective study is needed.

Investigation of next-generation sequencing data of Klebsiella pneumoniae using web-based tools.

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Brhelova, Eva; Antonova, Mariya; Pardy, Filip; Kocmanova, Iva; Mayer, Jiri; Racil, Zdenek; Lengerova, Martina

2017-11-01

Rapid identification and characterization of multidrug-resistant Klebsiella pneumoniae strains is necessary due to the increasing frequency of severe infections in patients. The decreasing cost of next-generation sequencing enables us to obtain a comprehensive overview of genetic information in one step. The aim of this study is to demonstrate and evaluate the utility and scope of the application of web-based databases to next-generation sequenced (NGS) data. The whole genomes of 11 clinical Klebsiella pneumoniae isolates were sequenced using Illumina MiSeq. Selected web-based tools were used to identify a variety of genetic characteristics, such as acquired antimicrobial resistance genes, multilocus sequence types, plasmid replicons, and identify virulence factors, such as virulence genes, cps clusters, urease-nickel clusters and efflux systems. Using web-based tools hosted by the Center for Genomic Epidemiology, we detected resistance to 8 main antimicrobial groups with at least 11 acquired resistance genes. The isolates were divided into eight sequence types (ST11, 23, 37, 323, 433, 495 and 562, and a new one, ST1646). All of the isolates carried replicons of large plasmids. Capsular types, virulence factors and genes coding AcrAB and OqxAB efflux pumps were detected using BIGSdb-Kp, whereas the selected virulence genes, identified in almost all of the isolates, were detected using CLC Genomic Workbench software. Applying appropriate web-based online tools to NGS data enables the rapid extraction of comprehensive information that can be used for more efficient diagnosis and treatment of patients, while data processing is free of charge, easy and time-efficient.

Antimicrobial susceptibility of urinary Klebsiella pneumoniae and the emergence of carbapenem-resistant strains: A retrospective study from a university hospital in Morocco, North Africa

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M.C. El Bouamri

2015-03-01

Conclusions: Antimicrobial susceptibility testing of urinary K. pneumoniae isolates showed a significantly high resistance to commonly used antimicrobial agents. These data highlight the need for regular surveillance of microbial resistance to improve infection control and guide the use of antimicrobial agents.

Antimicrobial resistance in Enterobacteriaceae in Brazil: focus on β-lactams and polymyxins.

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Sampaio, Jorge Luiz Mello; Gales, Ana Cristina

2016-12-01

During the last 30 years there has been a dissemination of plasmid-mediated β-lactamases in Enterobacteriaceae in Brazil. Extended spectrum β-lactamases (ESBL) are widely disseminated in the hospital setting and are detected in a lower frequency in the community setting. Cefotaximases are the most frequently detected ESBL type and Klebsiella pneumoniae is the predominant species among ESBL producers. Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae became widely disseminated in Brazil during the last decade and KPC production is currently the most frequent resistance mechanism (96.2%) in carbapenem resistant K. pneumoniae. To date KPC-2 is the only variant reported in Brazil. Polymyxin B resistance in KPC-2-producing K. pneumoniae has come to an alarming rate of 27.1% in 2015 in São Paulo, the largest city in Brazil. New Delhi metallo-β-lactamase was detected in Brazil in 2013, has been reported in different Brazilian states but are not widely disseminated. Antimicrobial resistance in Enterobacteriaceae in Brazil is a very serious problem that needs urgent actions which includes both more strict adherence to infection control measures and more judicious use of antimicrobials. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Effect of radiation processing in elimination of Klebsiella pneumoniae from food

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Gautam, Raj Kamal; Nagar, Vandan; Shashidhar, Ravindranath

2015-01-01

Klebsiella pneumoniae has been considered as an important foodborne pathogen which causes severe infections that include meningitis, bronchitis, bacteremia, pneumonia, and urinary tract infections in humans and animals. It is well known to most clinicians as a cause of community-acquired bacterial pneumonia. Klebsiella is an opportunistic pathogen, that primarily attacks neonates, infants, elderly and immuno-compromised patients and therefore impose a serious, emerging public health hazard globally. Contaminated sprouts, vegetables, seafood and other animal meat products are considered as main sources of Klebsiella infection. In the current study, radiation sensitivity of K. pneumoniae MTCC 109 was determined in different food samples. The decimal reduction dose (D 10 ) values of K. pneumoniae MTCC 109 in saline and nutrient broth at 0–4 °C were 0.116±0.009, 0.136±0.005 kGy, respectively. The mixed sprouts, fish and poultry samples were inoculated with K. pneumoniae MTCC 109 and exposed to gamma radiation to evaluate the effectiveness of radiation treatment in the elimination of K. pneumoniae. D 10 values of K. pneumoniae in mixed sprouts, poultry and fish samples were found to be 0.142±0.009, 0.125±0.0004 and 0.277±0.012 kGy, respectively. Radiation treatment with a 1.5 kGy dose resulted in the complete elimination of 3.1±1.8×10 5 CFU/g of K. pneumoniae from these food samples. No recovery of K. pneumoniae was observed in the 1.5 kGy treated samples stored at 4 °C up to 12 days, even after enrichment and selective plating. This study shows that a 1.5 kGy dose of irradiation treatment could lead to the complete elimination of 3.1±1.8×10 5 CFU/g of K. pneumoniae from mixed sprouts, poultry and fish samples. - Highlights: • K. pneumoniae MTCC 109 is sensitive to gamma radiation. • D 10 values is in the range of 0.116–0.277 kGy. • Dose of 1.5 kGy reduced K. pneumonia from 3.1±1.8×10 5 CFU/g to undetectable. • No recovery of K. pneumoniae

CLINICAL ISOLATES OF MECA, METHICILLIN, VANCOMYCIN RESISTANCE S. AUREUS; ESBLs PRODUCING K.PNEUMONIA, E.COLI, P. AUREGENOSA FROM VARIOUS CLINICAL SOURCE AND ITS ANTIMICROBIAL RESISTANCE PATTERNS

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Ismail Mahmud Ali, Amirthalingam R

2015-01-01

Full Text Available Background and Objective: Antimicrobial resistance has turned into a key medical and public health crisis globally since the injudicious use of magic bullets (drugs. Aim of this study is focused on the clinical isolate and their percentages of resistant to antibiotics in gram positive bacteria such as MRSA, VRSA, and MSSA are common causes of nosocomical, skin structure infections, bacteremia and infection of other systems; ESBLs producing Enterobacteriaceae (E. coli, Klebsiella spp. is common agent of urinary tract, bloodstream, pulmonary and intra-abdominal infections and carbapenem resistant P. aeruginosa with its complete antimicrobial patterns which are currently practiced in this population. Methods: There are one hundred and fourteen (114 various clinical isolates, isolated from various clinical samples like throat swab, urine, pus, sputum, and blood culture, identified as specific isolate with resistance patterns were analyzed by BD phoenix-100 the auto analyzer. Results: Off 114 clinical isolate, 6 mecA-mediated resistance (cefoxitin>8mgc/ml, 11 methicillin resistance, 18 β lactam/βlactamase inhibitor, 12 methicillin sensitive and 3 vancomycin (>16µg/ml resistance S. aureus have been isolated from overall 50 isolate of S.aureus. In addition, there are 27 P.aeruginosa, 15 ESBLs from overall of 25 K. pneumoniae and 7 ESBLs out of 12 Escherichia coli species have been isolated. The resistance and susceptibility pattern percentages have been graphically represented for each isolates. Conclusion: Current study revealed that the drug classes of β lactam/βlactamase inhibitor having high resistance rate with S.aureus, P.aureginosa, K. pneumoniae and E. coli isolate. Also, some of other drug classes such as cepham and tetracycline having higher resistance rate with P.aureginosa and K.pneumoniae. In addition, the vancomycin resistances S. aureus have been isolated and reported as first time in this population.

The impact of the increased use of piperacillin/tazobactam on the selection of antibiotic resistance among invasive Escherichia coli and Klebsiella pneumoniae isolates.

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Lee, Jina; Oh, Chi Eun; Choi, Eun Hwa; Lee, Hoan Jong

2013-08-01

Increasing antimicrobial resistance is related to the selective pressure exerted by antibiotic usage. This study evaluated the impact of the increased use of piperacillin/tazobactam (TZP) on the selection of antibiotic resistance. From 1999 to 2010, Escherichia coli and Klebsiella pneumoniae invasive isolates obtained from hospitalized Korean children were analyzed in antibiotic susceptibility tests and subjected to characterization of the β-lactamase types. Antibiotic consumption data were also analyzed. Between January 1999 and December 2010, 409 invasive isolates of E. coli (n=170) and K. pneumoniae (n=239) were obtained. A rebound of extended-spectrum β-lactamase (ESBL) prevalence with an increase in total antibiotics was noted. Non-susceptibility to TZP was determined in 7.6% of E. coli isolates and 20.9% of K. pneumoniae isolates. Despite the increase in TZP usage, the overall prevalence of TZP resistance did not significantly increase over time, especially in E. coli. The mechanisms for TZP resistance included the presence of AmpC producers, possible TEM-1 hyperproducers, and multiple β-lactamases in individual organisms of a given isolate. Replacement of only the antibiotic class appears to be insufficient to control antibiotic resistance, and continued efforts to decrease overall antibiotic pressure are needed, especially in highly endemic situations. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Klebsiella pneumoniae triggers a cytotoxic effect on airway epithelial cells

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Llobet-Brossa Enrique

2009-08-01

Full Text Available Abstract Background Klebsiella pneumoniae is a capsulated Gram negative bacterial pathogen and a frequent cause of nosocomial infections. Despite its clinical relevance, little is known about the features of the interaction between K. pneumoniae and lung epithelial cells on a cellular level, neither about the role of capsule polysaccharide, one of its best characterised virulence factors, in this interaction. Results The interaction between Klebsiella pneumoniae and cultured airway epithelial cells was analysed. K. pneumoniae infection triggered cytotoxicity, evident by cell rounding and detachment from the substrate. This effect required the presence of live bacteria and of capsule polysaccharide, since it was observed with isolates expressing different amounts of capsule and/or different serotypes but not with non-capsulated bacteria. Cytotoxicity was analysed by lactate dehydrogenase and formazan measurements, ethidium bromide uptake and analysis of DNA integrity, obtaining consistent and complementary results. Moreover, cytotoxicity of non-capsulated strains was restored by addition of purified capsule during infection. While a non-capsulated strain was avirulent in a mouse infection model, capsulated K. pneumoniae isolates displayed different degrees of virulence. Conclusion Our observations allocate a novel role to K. pneumoniae capsule in promotion of cytotoxicity. Although this effect is likely to be associated with virulence, strains expressing different capsule levels were not equally virulent. This fact suggests the existence of other bacterial requirements for virulence, together with capsule polysaccharide.

JST Thesaurus Headwords and Synonyms: Klebsiella pneumoniae [MeCab user dictionary for science technology term[Archive

Lifescience Database Archive (English)

Full Text Available MeCab user dictionary for science technology term Klebsiella pneumoniae 名詞 一般 * * *... * 肺炎桿菌 ハイエンカンキン ハイエンカンキン Thesaurus2015 200906081834698320 C LS07 UNKNOWN_2 Klebsiella pneumoniae

Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae.

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Derrick R Samuelson

2017-06-01

Full Text Available Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis. To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein

Alterations in Outer Membrane Permeability Favor Drug-Resistant Phenotype of Klebsiella pneumoniae

Czech Academy of Sciences Publication Activity Database

Pulzová, L.; Navrátilová, Lucie; Comor, L.

2017-01-01

Roč. 23, č. 4 (2017), s. 413-420 ISSN 1076-6294 Institutional support: RVO:61389030 Keywords : drug resistance * efflux pumps * influx * Klebsiella * porin Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.306, year: 2016

Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering.

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Barnes, Melissa D; Winkler, Marisa L; Taracila, Magdalena A; Page, Malcolm G; Desarbre, Eric; Kreiswirth, Barry N; Shields, Ryan K; Nguyen, Minh-Hong; Clancy, Cornelius; Spellberg, Brad; Papp-Wallace, Krisztina M; Bonomo, Robert A

2017-10-31

The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging. We engineered 19 KPC-2 variants bearing targeted mutations at amino acid residue Ambler position 179 in Escherichia coli and identified a unique antibiotic resistance phenotype. We focus particularly on the CAZ-AVI resistance of the clinically relevant Asp179Asn variant. Although this variant demonstrated less hydrolytic activity, we demonstrated that there was a prolonged period during which an acyl-enzyme intermediate was present. Using mass spectrometry and transient kinetic analysis, we demonstrated that Asp179Asn "traps" β-lactams, preferentially binding β-lactams longer than AVI owing to a decreased rate of deacylation. Molecular dynamics simulations predict that (i) the Asp179Asn variant confers more flexibility to the Ω-loop and expands the active site significantly; (ii) the catalytic nucleophile, S70, is shifted more than 1.5 Å and rotated more than 90°, altering the hydrogen bond networks; and (iii) E166 is displaced by 2 Å when complexed with ceftazidime. These analyses explain the increased hydrolytic profile of KPC-2 and suggest that the Asp179Asn substitution results in an alternative complex mechanism leading to CAZ-AVI resistance. The future design of novel β-lactams and β-lactamase inhibitors must consider the mechanistic basis of resistance of this and other threatening carbapenemases. IMPORTANCE Antibiotic resistance is emerging at unprecedented rates and threatens to reach crisis levels. One key

Bulgecin A as a β-lactam enhancer for carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates containing various resistance mechanisms.

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Skalweit, Marion J; Li, Mei

2016-01-01

Genetic screening of Pseudomonas aeruginosa (PSDA) and Acinetobacter baumannii (ACB) reveals genes that confer increased susceptibility to β-lactams when disrupted, suggesting novel drug targets. One such target is lytic transglycosylase. Bulgecin A (BlgA) is a natural product of Pseudomonas mesoacidophila and a lytic transglycosolase inhibitor that works synergistically with β-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly inhibits di-Zn 2+ metallo-β-lactamases like L1 of Stenotrophomonas maltophilia . We hypothesized that because of its unique mechanism of action, BlgA could restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA) and carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA-containing extract was prepared using a previously published protocol. CR-PSDA clinical isolates demonstrating a variety of carbapenem resistance mechanisms (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression) were characterized with agar dilution minimum inhibitory concentration (MIC) testing and polymerase chain reaction. Growth curves using these strains were prepared using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated Blg A extract combined with low concentrations of meropenem, was able to inhibit the growth of clinical strains of CR-PSDA for strains that had meropenem MICs ≥8 mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility. Similar experiments were conducted on a TEM-1 producing ACB strain resistant to sulbactam. BlgA with ampicillin/sulbactam inhibited the growth of this organism. As in Enterobacteriaceae, BlgA appears to restore the efficacy of meropenem in suppressing the growth of CR-PSDA and carbapenem-resistant ACB strains with a variety of common carbapenem resistance mechanisms. BlgA extract also inhibits VIM-2 β-lactamase in vitro. BlgA may prove to be

Development of a new trend conjugate vaccine for the prevention of Klebsiella pneumoniae

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Tarek A. Ahmad

2012-07-01

Full Text Available Klebsiella pneumoniae is a major cause of nosocomial pneumonia, septicemia and urinary tract infections, especially in newborns, blood cancer patients, and other immunocompromised candidates. The control of K. pneumoniae is a complicated issue due to its tight pathogenesis. Immuno-prophylactic preparations, especially those directed toward the bacterium O-antigen, showed to be the most successful way to prevent the infection incidence. However, all previously proposed preparations were either of limited spectrum or non-maternal, and hence not targeting the main Klebsiella patients. Moreover, all preparations were directed only to prevent the respiratory diseases due to that pathogen. This article addresses the development of a method originally used to purify the non-capsular bacterial- endotoxins, as a new and easy method for vaccine production against K. pneumoniae. The application of this method was preceded by a biotechnological control of capsular polysaccharide production in K. pneumoniae. The new produced natural conjugate between the bacterial O-antigen and its outer membrane proteins was evaluated by physicochemical and immunological methods to investigate its purity, integrity, safety and immunogenicity. It showed to be pure, stable, safe for use, and able to elicit a protective immunoglobulin titer against different Klebsiella infections. This immune-response proved to be transferable to the offspring of the vaccinated experimental rabbits via placenta.

Investigating of four main carbapenem-resistance mechanisms in high-level carbapenem resistant Pseudomonas aeruginosa isolated from burn patients

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Soodabeh Rostami

2018-02-01

Conclusion: Emerging antimicrobial resistance in burn wound bacterial pathogens is a serious therapeutic challenge for clinicians. In the present study, most of the isolates were MDR. This finding indicated an alarming spread of resistant isolates and suggested that infection control strategies should be considered. Resistance to carbapenems is influenced by several factors, not all of which were evaluated in our study; however, the results showed that production of MBLs and overexpression of the mexB gene were the most frequent mechanisms in carbapenem-resistant isolates.

Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems.

Science.gov (United States)

Zusman, Oren; Avni, Tomer; Leibovici, Leonard; Adler, Amos; Friberg, Lena; Stergiopoulou, Theodouli; Carmeli, Yehuda; Paul, Mical

2013-10-01

Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies.

Systematic Review and Meta-Analysis of In Vitro Synergy of Polymyxins and Carbapenems

Science.gov (United States)

Avni, Tomer; Leibovici, Leonard; Adler, Amos; Friberg, Lena; Stergiopoulou, Theodouli; Carmeli, Yehuda; Paul, Mical

2013-01-01

Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies. PMID:23917322

Presence of quinolone resistance to qnrB1 genes and blaOXA-48 carbapenemase in clinical isolates of Klebsiella pneumoniae in Spain.

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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.

Community-acquired Klebsiella pneumoniae liver abscess: an emerging infection in Ireland and Europe.

LENUS (Irish Health Repository)

Moore, R

2013-02-05

INTRODUCTION: Klebsiella pneumoniae has emerged as a predominant cause of community-acquired mono-microbial pyogenic liver abscess. This was first described in Taiwan and has been widely reported in Asia. This infectious entity has been described in Europe, with single case reports predominating. METHODS: We present three cases in one year from our institution in Ireland and review the European literature to date. RESULTS\\/CONCLUSION: Klebsiella pneumoniae invasive liver abscess syndrome is now emerging in Europe and notably is not restricted to individuals of Asian descent.

Multidrug-resistant Gram-negative bacteria: a product of globalization.

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Hawkey, P M

2015-04-01

Global trade and mobility of people has increased rapidly over the last 20 years. This has had profound consequences for the evolution and the movement of antibiotic resistance genes. There is increasing exposure of populations all around the world to resistant bacteria arising in the emerging economies. Arguably the most important development of the last two decades in the field of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group. A consequence of the very high rates of ESBL production among Enterobacteriaceae in Asian countries is that there is a substantial use of carbapenem antibiotics, resulting in the emergence of plasmid-mediated resistance to carbapenems. This article reviews the emergence and spread of multidrug-resistant Gram-negative bacteria, focuses on three particular carbapenemases--imipenem carbapenemases, Klebsiella pneumoniae carbapenemase, and New Delhi metallo-β-lactamase--and highlights the importance of control of antibiotic use. Copyright © 2015. Published by Elsevier Ltd.

Monomicrobial necrotizing fasciitis in a white male caused by hypermucoviscous Klebsiella pneumoniae

DEFF Research Database (Denmark)

Gunnarsson, Gudjon L; Brandt, Pernille B; Gad, Dorte

2009-01-01

We report a case of monomicrobial necrotizing fasciitis caused by hypermucoviscous Klebsiella pneumoniae in an immunocompromised white male after travel to China. The K. pneumoniae isolate belonged to the K2 serotype, and carried the virulence factors RmpA and aerobactin. To the best of our...... knowledge this is the first report of necrotizing fasciitis caused by hypermucoviscous K. pneumoniae resembling the highly virulent K. pneumoniae isolates associated with liver abscess syndrome in Asia....

Carbapenemase producing Klebsiella pneumoniae in Peru: a case report and antimicrobial resistance discussion

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Jhosef Franck Quispe Pari

2018-04-01

Full Text Available Resumen Las carbapenemasas son uno de los mecanismos enzimáticos de resistencia antimicrobiana, que compromete la mayor parte de los antibióticos betalactámicos. Por lo general, su producción se debe al uso indiscriminado de antimicrobianos. A nivel mundial, la expansión de este mecanismo de resistencia es inminente y las medidas de control son limitadas. Con el objeto de discutir los problemas relacionados a este mecanismo emergente de resistencia, reportamos un caso de Klebsiella pneumoniae productora de carbapenemasas en Huancayo, la Región de la Sierra Central de Perú.

Occurrence of false positive results for the detection of carbapenemases in carbapenemase-negative Escherichia coli and Klebsiella pneumoniae isolates.

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Peng Wang

Full Text Available Adequate detection of the production of carbapenemase in Enterobacteriaceae isolates is crucial for infection control measures and the appropriate choice of antimicrobial therapy. In this study, we investigated the frequency of false positive results for the detection of carbapenemases in carbapenemase-negative Escherichia coli and Klebsiella pneumoniae clinical isolates by the modified Hodge test (MHT. Three hundred and one E. coli and K. pneumoniae clinical isolates were investigated. All produced extended spectrum β-lactamases (ESBLs but were susceptible to carbapenems. Antimicrobial susceptibility testing was performed by the disk diffusion and agar dilution methods. The MHT was performed using the standard inoculum of test organisms recommended by the CLSI. Genes that encoded ESBLs and carbapenemases were identified by PCR and DNA sequencing. Among the 301 clinical isolates, none of the isolates conformed to the criteria for carbapenemase screening recommended by the CLSI. The susceptibility rates for imipenem, meropenem, and ertapenem all were 100.0%, 100.0%, and 100.0%, respectively. Of the 301 E. coli and K. pneumoniae isolates, none produced carbapenemase. The MHT gave a positive result for 3.3% (10/301 of the isolates. False positive results can occur when the MHT is used to detect carbapenemase in ESBL-producing isolates and clinical laboratories must be aware of this fact.

The rapid spread of carbapenem-resistant Enterobacteriaceae

Science.gov (United States)

Potter, Robert F.; D’Souza, Alaric W.; Dantas, Gautam

2016-01-01

Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. PMID:27912842

Klebsiella Pneumoniae Liver Abscess: A Case Series of Six Asian Patients.

Science.gov (United States)

Oikonomou, Katerina G; Aye, Myint

2017-09-26

BACKGROUND Liver abscesses represent a serious infection of hepatic parenchyma and are associated with significant morbidity and mortality. The emergence of a new hypervirulent variant of Klebsiella pneumoniae, which can cause serious infections in the Asian population, is under investigation. We report a case series of six Asian patients hospitalized at our institution from January 2013 to November 2015 for liver abscess due to Klebsiella pneumoniae. CASE REPORT Charts of six Asian patients were retrospectively reviewed. Four patients were male and two were female. The mean age was 53 years (range: 35-64 years). All patients had no known past medical history of immunodeficiency. Three patients had multiple liver abscesses at the time of initial presentation. In five patients, the source of entry of the pathogenic microorganism was unknown and in one patient the suspected source of entry was the gastrointestinal tract. In three patients there was also concomitant Klebsiella pneumoniae bacteremia. The mean duration of antibiotic treatment was seven weeks and the mean duration of hospital stay was 13.5 days. CONCLUSIONS Liver abscess should always be included in the differential diagnosis in cases of sepsis without obvious source and/or in the clinical scenarios of fever, abdominal pain, and liver lesions.

Chromogenic culture media or rapid immunochromatographic test: Which is better for detecting Klebsiella pneumoniae that produce OXA-48 and can they be used in blood and urine specimens.

Science.gov (United States)

Genc, Ozlem; Aksu, Evrim

2018-05-01

Our goal was to compare a rapid test (OXA-48K-SeT) and four different chromogenic media (CHROMagar KPC, CHROMagar mSuperCARBA, ChromID Carba and ChromID OXA-48) for the detection of OXA-48 producing Klebsiella pneumoniae isolates and spiked urine/blood samples with these bacteria. In total 100 K.pneumoniae isolates, including 60 OXA-48 positive, 15 other carbapenemase producing, 15 Extended spectrum betalactamases (ESBL) positive and 10 carbapenem sensitive K.pneumoniae were included in the study. After all samples were inoculated into all chromogenic media, temocillin discs were placed onto the media. OXA-48K-SeT was studied according to the manufacturer's instructions and the lower detection limit was determined. Sensitivities and specificities of all chromogenic media and rapid test were detected as 100%. All of the OXA-48 producers were found resistant to temocillin on all chromogenic media. The lower detection limit of the rapid assay was determined as 10 6 in both direct bacterial samples and in spiked urine/blood samples. As a result, four chromogenic culture media and OXA-48 K-SeT can be used safely for detection of OXA-48 positive K.pneumoniae isolates. Although direct clinical specimens were not used, our study suggests that this media and OXA-48 K-SeT may be used in patient samples like blood and urine. Further studies are needed to assess this suggestion. Copyright © 2018 Elsevier B.V. All rights reserved.

Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease

OpenAIRE

Vani Gopal; T Mangaiyarkarasi; R Gopal

2014-01-01

Klebsiella is a Gram-negative bacterium that causes different types of health care-associated infections including pneumonia, bloodstream infections, surgical site infections and meningitis. We report here a case of Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease. A middle-aged man with a known case of diabetes mellitus and Hansen′s disease presented with the complaints of blurred vision in the left eye and the patient was found to have cataract. Pati...

A Novel Approach for Combating Klebsiella pneumoniae Biofilm Using Histidine Functionalized Silver Nanoparticles

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Sanjay Chhibber

2017-06-01

Full Text Available Treating pathogens is becoming challenging because of multidrug resistance and availability of limited alternative therapies which has further confounded this problem. The situation becomes more alarming when multidrug resistant pathogens form a 3D structure known as biofilm. Biofilms are formed in most of the infections especially in chronic infections where it is difficult to eradicate them by conventional antibiotic therapy. Chemically synthesized nanoparticles are known to have antibiofilm activity but in the present study, an attempt was made to use amino acid functionalized silver nanoparticles alone and in combination with gentamicin to eradicate Klebsiella pneumoniae biofilm. Amino acid functionalized silver nanoparticles were not only able to disrupt biofilm in vitro but also led to the lowering of gentamicin dose when used in combination. To the best of our knowledge, this is the first study demonstrating the application of amino acid functionalized silver nanoparticles in the eradication of young and old K. pneumoniae biofilm.

Evaluating the Frequency of aac(6')-IIa, ant(2″)-I, intl1, and intl2 Genes in Aminoglycosides Resistant Klebsiella pneumoniae Isolates Obtained from Hospitalized Patients in Yazd, Iran.

Science.gov (United States)

Mokhtari, Hesam; Eslami, Gilda; Zandi, Hengameh; Dehghan-Banadkouki, Amin; Vakili, Mahmood

2018-01-01

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen that could be resistant to many antimicrobial agents. Resistance genes can be carried among gram-negative bacteria by integrons. Enzymatic inactivation is the most important mechanism of resistance to aminoglycosides. In this study, the frequencies of two important resistance gene aac(6')-II a and ant(2″)-I, and genes coding integrase I and II, in K. pneumoniae isolates resistant to aminoglycosides were evaluated. In this cross-sectional study, an attempt was made to assess the antibiotic susceptibility of 130 K. pneumoniae isolates obtained from different samples of patients hospitalized in training hospitals of Yazd evaluated by disk diffusion method. The frequencies of aac(6')-II a, ant(2″)-I, intl1 , and intl2 genes were determined by PCR method. Data were analyzed by chi-square method using SPSS software (Ver. 16). our results showed that resistance to gentamicin, tobramycin, kanamycin, and amikacin were 34.6, 33.8, 43.8, and 14.6%, respectively. The frequencies of aac (6')-II a, ant(2″)-I, intl1 , and intl2 genes were 44.6, 27.7, 90, and 0%, respectively. This study showed there are high frequencies of genes coding aminoglycosides resistance in K. pneumoniae isolates. Hence, it is very important to monitor and inhibit the spread of antibiotic resistance genes.

In vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin against carbapenem-resistant Acinetobacter baumannii clinical isolates.

Science.gov (United States)

Singkham-In, Uthaibhorn; Chatsuwan, Tanittha

2018-01-31

Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin. Major carbapenem resistance mechanism was OXA-23 production. The vast majority of these isolates were OXA-23-producing A. baumannii ST195 and ST542, followed by novel STs, ST1417, and ST1423. The interuption of carO by a novel insertion sequence, ISAba40, was found in two isolates. The combinations of imipenem and fosfomycin, meropenem and amikacin, imipenem and amikacin, and imipenem and colistin were synergistic against carbapenem-resistant A. baumannii by 65.2%, 46.2%, 30.8%, and 17.4%, respectively. Surprisingly, the combination of imipenem and fosfomycin was the most effective in this study against A. baumannii, which is intrinsically resistant to fosfomycin. Imipenem and fosfomycin inhibit cell wall synthesis; therefore, fosfomycin may be an adjuvant and enhance the inhibition of cell wall synthesis of carbapenem-resistant A. baumannii when combined with imipenem. Copyright © 2018. Published by Elsevier Inc.

Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens.

Science.gov (United States)

Poulakou, Garyphallia; Giamarellou, Helen

2008-05-01

Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. This drug evaluation focuses on the position of doripenem, a novel forthcoming carbapenem. Mechanisms of resistance and new drugs with anti-Gram-negative activity are also briefly reviewed. Literature search was performed for new carbapenems, new antibiotics, doripenem, metallo-beta-lactamase inhibitors, multidrug-resistant pathogens, antipseudomonal antibiotics and multidrug-resistant epidemiology. Doripenem possesses a broad spectrum of activity against Gram-negative bacteria, similar to that of meropenem, while retaining the spectrum of imipenem against Gram-positive pathogens. Against P. aeruginosa, doripenem exhibits rapid bactericidal activity with 2 - 4-fold lower MIC values, compared to meropenem. Exploitation of pharmacokinetic/pharmacodynamic applications could offer a treatment opportunity against strains exhibiting borderline resistance to doripenem. Stability against numerous beta-lactamases, low adverse event potential and more potent in vitro antibacterial activity against P. aeruginosa and A. baumanni compared to the existing carbapenems, are its principal features.

Whole genome sequence analysis of the first Australian OXA-48-producing outbreak-associated Klebsiella pneumoniae isolates: the resistome and in vivo evolution.

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Björn A Espedido

Full Text Available Whole genome sequencing was used to characterize the resistome of intensive care unit (ICU outbreak-associated carbapenem-resistant K. pneumoniae isolates. Importantly, and of particular concern, the carbapenem-hydrolyzing β-lactamase gene bla(OXA-48 and the extended-spectrum β-lactamase gene bla(CTX-M-14, were identified on a single broad host-range conjugative plasmid. This represents the first report of bla(OXA-48 in Australia and highlights the importance of resistance gene surveillance, as such plasmids can silently spread amongst enterobacterial populations and have the potential to drastically limit treatment options. Furthermore, the in vivo evolution of these isolates was also examined after 18 months of intra-abdominal carriage in a patient that transited through the ICU during the outbreak period. Reflecting the clonality of K. pneumoniae, only 11 single nucleotide polymorphisms (SNPs were accumulated during this time-period and many of these were associated with genes involved in tolerance/resistance to antibiotics, metals or organic solvents, and transcriptional regulation. Collectively, these SNPs are likely to be associated with changes in virulence (at least to some extent that have refined the in vivo colonization capacity of the original outbreak isolate.

Whole Genome Sequence Analysis of the First Australian OXA-48-Producing Outbreak-Associated Klebsiella pneumoniae Isolates: The Resistome and In Vivo Evolution

Science.gov (United States)

Espedido, Björn A.; Steen, Jason A.; Ziochos, Helen; Grimmond, Sean M.; Cooper, Matthew A.; Gosbell, Iain B.; van Hal, Sebastiaan J.; Jensen, Slade O.

2013-01-01

Whole genome sequencing was used to characterize the resistome of intensive care unit (ICU) outbreak-associated carbapenem-resistant K. pneumoniae isolates. Importantly, and of particular concern, the carbapenem-hydrolyzing β-lactamase gene bla OXA-48 and the extended-spectrum β-lactamase gene bla CTX-M-14, were identified on a single broad host-range conjugative plasmid. This represents the first report of bla OXA-48 in Australia and highlights the importance of resistance gene surveillance, as such plasmids can silently spread amongst enterobacterial populations and have the potential to drastically limit treatment options. Furthermore, the in vivo evolution of these isolates was also examined after 18 months of intra-abdominal carriage in a patient that transited through the ICU during the outbreak period. Reflecting the clonality of K. pneumoniae, only 11 single nucleotide polymorphisms (SNPs) were accumulated during this time-period and many of these were associated with genes involved in tolerance/resistance to antibiotics, metals or organic solvents, and transcriptional regulation. Collectively, these SNPs are likely to be associated with changes in virulence (at least to some extent) that have refined the in vivo colonization capacity of the original outbreak isolate. PMID:23555831

The rapid spread of carbapenem-resistant Enterobacteriaceae.

Science.gov (United States)

Potter, Robert F; D'Souza, Alaric W; Dantas, Gautam

2016-11-01

Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rapid increase in resistance to third generation cephalosporins, imipenem and co-resistance in Klebsiella pneumoniae from isolated from 7,140 blood-cultures (2010-2014) using EARS-Net data in Spain.

Science.gov (United States)

Aracil-García, Belén; Oteo-Iglesias, Jesús; Cuevas-Lobato, Óscar; Lara-Fuella, Noelia; Pérez-Grajera, Isabel; Fernández-Romero, Sara; Pérez-Vázquez, María; Campos, José

2017-10-01

An analysis was made about the evolution of resistance to 3rd generation cephalosporins, imipenem, and other antibiotics in invasive isolates of Klebsiella pneumoniae (K. pneumoniae) according to the Spanish EARS-Net database (2010-2014). Forty-two hospitals from 16 Autonomous Communities with an approximate population coverage of 33% participated. A total 7,140 pneumoniae corresponding to the same number of patients were studied. Overall resistance percentages (I+R) were: cefotaxime 15.8%, ceftazidime 13.7%, imipenem 1.7%, ciprofloxacin 20.1%, tobramycin 14.1%, gentamicin 10.4%, and amikacin 1.9%. Resistance to 3rd generation cephalosporins increased from 9.8% (2010) to 19% (2014); to ciprofloxacin from 15.4% (2010) to 19.6% (2014); to gentamicin from 6.2% (2010) to 10.3% (2014) and to tobramycin from 7.1% (2010) to 14.2% (2014) (presistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides increased from 3.3% (2010) to 9.7% (2014) (pResistance to imipenem also increased from 0.27% (2010) to 3.46% (2014) (presistant to imipenem, of which 104 (86%) produced carbapenemases: 74 OXA-48, 14 VIM, 9 KPC (6 KPC-2 and 3 KPC-3), 6 IMP, and 1 GES. Over the 5 year period (2010-2014), resistance to 3rd generation cephalosporins in invasive K. pneumoniae in Spain has doubled. The combined resistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides has tripled, and imipenem resistance has increased almost 13 times, mostly due to the spread of carbapenemase-producing isolates. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Treatment Options for Carbapenem-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections

Science.gov (United States)

Viehman, J. Alexander; Nguyen, Minh-Hong; Doi, Yohei

2014-01-01

Acinetobacter baumannii is a leading cause of healthcare-associated infections worldwide. Due to various intrinsic and acquired mechanisms of resistance, most β-lactam agents are not effective against many strains, and carbapenems have played an important role in therapy. Recent trends show many infections are caused by carbapenem-resistant, or even extensively drug-resistant (XDR) strains, for which effective therapy is not well established. Evidence to date suggests that colistin constitutes the backbone of therapy, but the unique pharmacokinetic properties of colistin have led many to suggest the use of combination antimicrobial therapy. However, the combination of agents and dosing regimens that delivers the best clinical efficacy while minimizing toxicity is yet to be defined. Carbapenems, sulbactam, rifampin and tigecycline have been the most studied in the context of combination therapy. Most data regarding therapy for invasive, resistant A. baumannii infections come from uncontrolled case series and retrospective analyses, though some clinical trials have been completed and others are underway. Early institution of appropriate antimicrobial therapy is shown to consistently improve survival of patients with carbapenem-resistant and XDR A. baumannii infection, but the choice of empiric therapy in these infections remains an open question. This review summarizes the most current knowledge regarding the epidemiology, mechanisms of resistance, and treatment considerations of carbapenem-resistant and XDR A. baumannii. PMID:25091170

Prostatic Abscess after Stapled Hemorrhoidopexy Caused by ESBL Extended Spectrum Beta Lactamase Producing Klebsiella pneumoniae: An Additional Challenge to Postoperative Sepsis

Directory of Open Access Journals (Sweden)

Asem Saleh

2017-01-01

Full Text Available Postoperative septic complications of hemorrhoids surgical interventions are rare, but very serious with high mortality rate. Early diagnosis and prompt therapy are essential to save patient’s life. There are a good number of articles and case reports about these septic complications. We are presenting a case report of a prostatic abscess caused by extended spectrum beta lactamase (ESBL producing Klebsiella pneumoniae after hemorrhoidopexy. Our patient was a healthy middle aged Saudi male who has no significant medical history apart from morbid obesity and recurrent urinary tract infections. ESBL producing K. pneumoniae could be detected only after aspiration of the prostatic abscess, but proper antibiotic was introduced intravenously on admission before culture of aspirate of the abscess was available. Antibiotic was continued for 30 days and abscess resolved completely. In our electronic search, we could not find any case report of prostatic abscess after stapled hemorrhoidopexy caused by ESBL producing organism. This is an additional challenge for treating physicians as these organisms are sensitive only to one group of antibiotics (carbapenem group.

Fatal Klebsiella pneumoniae meningitis and concomitant disseminated intravascular coagulation in a patient with diabetes mellitus

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Ho Min-Po

2009-01-01

Full Text Available Bacterial meningitis remains a major cause of death and long-term neurologic sequelae worldwide. We present a case of fatal Klebsiella pneumoniae meningitis and concomitant disseminated intravascular coagulation (DIC in a 72-year-old woman with diabetes mellitus (DM. Both blood and cerebrospinal fluid cultures grew Klebsiella pneumoniae . Due to advanced age, newly recognized DM, K. pneumoniae bacteremia, and DIC, the prognosis of our patient was poor. Eight hours after arrival to the emergency department, cardiopulmonary resuscitation was necessary in this patient, but she died despite an early diagnosis and appropriate antibiotic therapy.

CURRENT STATE OF RESISTANCE TO ANTIBIOTICS OF LAST-RESORT IN SOUTH AFRICA: A REVIEW FROM A PUBLIC HEALTH PERSPECTIVE

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JOHN OSEI SEKYERE

2016-09-01

Full Text Available A review of the literature was undertaken to delineate the current level and mechanisms of resistance to carbapenems, colistin and tigecycline in South Africa. Thirty-two English publications and 32 National Institute of Communicable Diseases (NICD communiqués identified between early January 2000 and 20th May, 2016 showed substantial reports of NDM (n=860, OXA-48 (n=584, VIM (n=131 and IMP (n=45 carbapenemases within this period, mainly in Klebsiella pneumoniae (n=1138, Acinetobacter baumannii (n=332, Enterobacter cloacae (n=201 and Serratia marcescens (n=108. Colistin and tigecycline resistance was prevalent among K. pneumoniae, A. baumannii, S. marcescens and E. cloacae. The first mcr-1 colistin resistance gene to be detected in South Africa was reported in E. coli from livestock as well as from hospitalized and out patients. There are increasing reports of NDM and OXA-48 carbapenemases among Enterobacteriaceae and A. baumannii in South Africa. Mcr-1 is now present in South African patients and livestock. Resistance to carbapenems, colistin and tigecycline restricts infection management options for clinicians.

Outbreak of carbapenem-resistant Providencia rettgeri in a tertiary hospital

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V S Tshisevhe

2017-01-01

Full Text Available The emergence of resistance to multiple antimicrobial agents in pathogenic bacteria is a significant public health threat, as there are limited effective antimicrobial agents for infections caused by multidrug-resistant (MDR bacteria. Several MDR bacteria are now frequently detected. Carbapenem resistance in Enterobacteriaceae is often plasmid mediated, necessitating stringent infection control practices. We describe an outbreak of carbapenem-resistant Providencia rettgeri involving 4 patients admitted to intensive care and high-care units at a tertiary hospital. Clinical and demographic characteristics of 4 patients with carbapenem-resistant P. rettgeri were documented. All P. rettgeri isolated in these cases had a carbapenem-resistant antibiogram, with resistance to imipenem, ertapenem and meropenem. These cases could be epidemiologically linked. A multiprong approach, simultaneously targeting antibiotic stewardship, universal precautions and appropriate transmission-based precaution practices, is integral to prevention and control of nosocomial infections.

Heat-resistant, extended-spectrum β-lactamase-producing Klebsiella pneumoniae in endoscope-mediated outbreak

DEFF Research Database (Denmark)

Jørgensen, S.B.; Bojer, Martin Saxtorph; Boll, E.J.

2016-01-01

disinfection in a decontaminator designated for such use. The genetic marker clpK, which increases microbial heat resistance, has previously been described in K. pneumoniae outbreak strains. Aim To investigate the role of clpK in biofilm formation and heat-shock stability in the outbreak strain. Methods...... construction and heat-shock assays. Findings Five patients and one intubation endoscope contained K. pneumoniae with the same amplified fragment length polymorphism pattern. The outbreak strain contained the clpK genetic marker, which rendered the strain its increased heat resistance. The survival rate....... Heat resistance of certain K. pneumoniae strains may facilitate survival in biofilms on medical equipment and hence increase the potential of those strains to persist and disperse in the hospital environment....

Antibacterial activity of exogenous glutathione and its synergism on antibiotics sensitize carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

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Alharbe, Roaa; Almansour, Ayidh; Kwon, Dong H

2017-10-01

A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear. Seventy clinical isolates of A. baumannii including 63 carbapenem-associated multidrug resistant isolates and a type strain A. baumannii ATCC 19606 were used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional inhibitory concentration (FIC) and time-killing activity with meropenem and/or glutathione were also determined in the carbapenem-associated multidrug resistant isolates. In addition, the roles of exogenous glutathione in multidrug efflux pumps and β-lactamase production were examined. Levels of MIC and MBC were ranged from 10 to 15mM of exogenous glutathione. All tested carbapenem-associated multidrug resistant isolates were sensitized by all tested antibiotics in combination with subinhibitory concentrations of glutathione. FIC levels of glutathione with carbapenem (meropenem) were allcarbapenem-associated multidrug resistant isolates were killed by subinhibitory concentrations of both glutathione and meropenem at>2log10 within 12h, suggesting glutathione synergistically interacts with meropenem. The roles of multidrug efflux pumps and β-lactamase production were excluded for the glutathione-mediated antibiotic susceptibility. Overall results demonstrate that the antibacterial activity of glutathione is clinically relevant and its synergism on antibiotics sensitizes clinical isolates of A. baumannii regardless

Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections.

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Tal-Jasper, Ruthy; Katz, David E; Amrami, Nadav; Ravid, Dor; Avivi, Dori; Zaidenstein, Ronit; Lazarovitch, Tsilia; Dadon, Mor; Kaye, Keith S; Marchaim, Dror

2016-05-01

Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Efecto del uso de alcohol en gel sobre las infecciones nosocomiales por Klebsiella pneumoniae multirresistente

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J. Bermejo

2003-12-01

Full Text Available El lavado de manos es la medida de control más efectiva para interrumpir la transmisión de microorganismos patógenos nosocomiales. Sin embargo, la adherencia por parte del personal de salud es baja. Una nueva modalidad para la higiene de las manos, el frotado con alcohol-gel (AG, permite reducir el tiempo requerido y ofrece mayor comodidad. Con la finalidad de evaluar el efecto de la introducción del AG sobre las tasas de infecciones debidas a los tres agentes nosocomiales multirresistentes (Staphylococcus aureus, Klebsiella pneumoniae y Pseudomonas aeruginosa más frecuentes en nuestro hospital, se realizó un estudio observacional, comparando la incidencia de infecciones en los 12 meses previos y posteriores a la intervención. Luego de la introducción del AG se redujo de manera significativa la incidencia de infecciones debidas a Klebsiella pneumoniae BLEE (RR: 0.38, especialmente las bacteriemias (RR:0.10. El uso de AG ofrece condiciones que probablemente mejoren la adherencia del personal a la higiene de manos. Sin embargo, sobre la base de este estudio, no podemos concluir que el resultado observado se deba al AG en sí mismo o a una mayor adherencia a la práctica higiénica.Handwashing is considered the most important and effective infection control measure to prevent transmission of nosocomial pathogens. However, compliance with handwashing by health care workers is low. A new modality for hand hygiene is alcohol gel rub, which reduces time required, does not damage the skin and increases health care workers compliance. An observational study was conducted to assess the effect of alcohol-gel hand antiseptic on infection rates due to the 3 more frequent multi-resistant bacteria (Staphylococcus aureus, Klebsiella pneumoniae y Pseudomonas aeruginosa in our hospital. Two periods were compared, 12 months before and 12 months after starting alcohol gel use. The second period (AG use showed a significant reduction on incidence rates of

Wastewater as a Source of Carbapenem Resistant Escherichia coli

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Clinical studies have reported that the occurrence of carbapenem resistant E. coli is on the rise. This is of concern because carbapenem antibiotics are typically reserved for treating infections caused by bacteria resistant to other classes of antibiotics. Current literature st...

Clonal spread of highly successful ST15-CTX-M-15 Klebsiella pneumoniae in companion animals and horses

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Ewers, Christa; Stamm, Ivonne; Pfeifer, Yvonne

2014-01-01

OBJECTIVES: To investigate the clinical relevance and molecular epidemiology of extended-spectrum β-lactamase (ESBL)-producing Klebsiella species in animals. METHODS: Antimicrobial susceptibilities and presence of ESBLs were examined among Klebsiella spp. (n = 1519) from clinical samples (>1200...... senders from Germany and other European countries) mainly from companion animals and horses from October 2008 to March 2010. Multilocus sequence typing (MLST) and PFGE were performed including human isolates for comparative purposes. RESULTS: The overall ESBL rate was 8% for Klebsiella pneumoniae subsp....... pneumoniae. Most K. pneumoniae subsp. pneumoniae ESBL producers were isolated from soft tissue infections (29.3%) and urinary tract infections (14.9%). The major ESBL type was CTX-M-15 (85.4%), located on different plasmid scaffolds (HI2, I1, FIA, FIB, FII, A/C, R and N). Other ESBL genes, such as bla...

Outbreak of carbapenem-resistant Providencia rettgeri in a tertiary ...

African Journals Online (AJOL)

Carbapenem resistance in Enterobacteriaceae is often plasmid mediated, necessitating stringent infection control practices. We describe an outbreak of carbapenem-resistant Providencia rettgeri involving 4 patients admitted to intensive care and high-care units at a tertiary hospital. Clinical and demographic characteristics ...

Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility

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Rodrigo de Carvalho Santana

2016-04-01

Full Text Available Abstract: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260. From 2007-2013, this percentage was 18.1% (965/5331. Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

High Gastrointestinal Colonization Rate with Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Hospitalized Patients: Emergence of Carbapenemase-Producing K. pneumoniae in Ethiopia

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Desta, Kassu; Woldeamanuel, Yimtubezinash; Azazh, Aklilu; Mohammod, Halima; Desalegn, Dawit; Shimelis, Damte; Gulilat, Dereje; Lamisso, Biruk; Makonnen, Eyasu; Worku, Alemayehu; Mannerqvist, Kerstin; Struwe, Johan; Aspevall, Olov; Aklillu, Eleni

2016-01-01

We investigated the gastrointestinal colonization rate and antibiotic resistance patterns of Extended-Spectrum Beta-Lactamase (ESBL)- producing Escherichia coli and Klebsiella pneumoniae in hospitalized patients admitted at Ethiopia’s largest tertiary hospital. Fecal samples/swabs from 267 patients were cultured on chrome agar. ESBL. Bacterial species identification, verification of ESBL production and antibiotic susceptibility testing were done using Vitek 2 system (bioMérieux, France). Phenotype characterization of ESBL-E.coli and ESBL- K.pneumoniae was done using Neo-Sensitabs™. ESBL positivity rate was much higher in K. pneumoniae (76%) than E. coli (45%). The overall gastrointestinal colonization rate of ESBL producing Enterobacteriaceae (ESBL-E) in hospitalized patients was 52% (95%CI; 46%–58%) of which, ESBL-E. coli and K.pneumoniae accounted for 68% and 32% respectively. Fecal ESBL-E carriage rate in neonates, children and adults was 74%, 59% and 46% respectively. Gastrointestinal colonization rate of ESBL-E.coli in neonates, children and adults was 11%, 42% and 42% respectively. Of all E. coli strains isolated from adults, children and neonates, 44%, 49% and 22% were ESBL positive (p = 0.28). The prevalence of ESBL-K.pneumoniae carriage in neonates, children and adults was 68%, 22% and 7% respectively. All K. pneumoniae isolated from neonates (100%) and 88% of K. pneumoniae isolated from children were ESBL positive, but only 50% of K.pneumoniae isolated from adults were ESBL positive (p = 0.001). Thirteen patients (5%) were carriers of both ESBL-E.coli and ESBL-KP. The overall carrier rate of ESBL producing isolates resistant to carbapenem was 2% (5/267), all detected in children; three with E.coli HL cephalosporinase (AmpC), resistant to ertapenem and two with K. pneumoniae Carbapenemase (KPC) resistant to meropenem, ertapenem and impenem. We report a high gastrointestinal colonization rate with ESBL-E and the emergence of carbapenems-resistant K

Molecular Characteristics and Antibiotic Resistance Profiles of Klebsiella Isolates in Mthatha, Eastern Cape Province, South Africa

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Sandeep Vasaikar

2017-01-01

Full Text Available The increase in the incidence of extended-spectrum β-lactamase- (ESBL- producing Klebsiella species has become a serious problem worldwide, because of their incrimination in antibiotic resistance. The objective of this study is to investigate the resistance genes responsible for ESBL-producing Klebsiella species and carbapenemase-producing Klebsiella (CRE isolated in Mthatha and to study their epidemiology. A prospective, descriptive study of 202 nonrepetitive samples from patients was obtained from Nelson Mandela Academic Hospital. The cultured Klebsiella isolates were subjected to antimicrobial susceptibility tests and the polymerase chain reaction of blaCTX-M, blaTEM, blaSHV, blaKPC, and blaNDM genes. Overall K. pneumoniae were the majority with 169 (83.7% species isolates, followed by K. oxytoca with 29 (14.4%, while K. ozaenae and Raoultella ornithinolytica were 2 (0.9% each. The prevalence of ESBL production in all Klebsiella species was 117 (57.9%. ESBL-genotypic resistance is driven in Mthatha by blaSHV 121 (77.1% followed by blaTEM 105 (66.9% and blaCTX-M at 89 (56.7%. The most common ESBL genotype combination among the Klebsiella was blaTEM+blaSHV + blaCTX-M at 79 (50.3%. There is a steady increase in the rate of ESBL genes in the last five years.

Molecular Characteristics and Antibiotic Resistance Profiles of Klebsiella Isolates in Mthatha, Eastern Cape Province, South Africa.

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Vasaikar, Sandeep; Obi, Larry; Morobe, Isaac; Bisi-Johnson, Mary

2017-01-01

The increase in the incidence of extended-spectrum β -lactamase- (ESBL-) producing Klebsiella species has become a serious problem worldwide, because of their incrimination in antibiotic resistance. The objective of this study is to investigate the resistance genes responsible for ESBL-producing Klebsiella species and carbapenemase-producing Klebsiella (CRE) isolated in Mthatha and to study their epidemiology. A prospective, descriptive study of 202 nonrepetitive samples from patients was obtained from Nelson Mandela Academic Hospital. The cultured Klebsiella isolates were subjected to antimicrobial susceptibility tests and the polymerase chain reaction of bla CTX-M , bla TEM , bla SHV , bla KPC , and bla NDM genes. Overall K. pneumoniae were the majority with 169 (83.7%) species isolates, followed by K. oxytoca with 29 (14.4%), while K. ozaenae and Raoultella ornithinolytica were 2 (0.9%) each. The prevalence of ESBL production in all Klebsiella species was 117 (57.9%). ESBL-genotypic resistance is driven in Mthatha by bla SHV 121 (77.1%) followed by bla TEM 105 (66.9%) and bla CTX-M at 89 (56.7%). The most common ESBL genotype combination among the Klebsiella was bla TEM + bla SHV + bla CTX-M at 79 (50.3%). There is a steady increase in the rate of ESBL genes in the last five years.

Clinical laboratory detection of carbapenem-resistant and carbapenemase-producing Enterobacteriaceae.

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Miller, Shelley; Humphries, Romney M

2016-08-01

Carbapenemases, enzymes that hydrolyze carbapenem-class antimicrobials, pose serious clinical and diagnostic challenges, including their recent rapid spread among members of the Enterobacteriaceae, a family with no inherent carbapenem resistance. Currently there is no one-size-fits-all method for detecting carbapenem-resistant Enterobacteriaceae (CRE) in the laboratory, nor how to differentiate carbapenemase-producers (CP) from isolates that are carbapenem-resistant via other or combined mechanisms. This article reviews definitions for CRE and CP-CRE, and discusses current phenotypic and molecular methods available to the clinical laboratory for the detection of both CP and non-CP CRE. Expert commentary: Routine evaluation of carbapenem resistance mechanism by the routine clinical laboratory are not necessary for patient care, as clinical breakpoints best predict response. However, evaluation for carbapenemase is integral to infection control efforts, and laboratories should have the capacity to do such testing, either in house or by submitting isolates to a reference laboratory.

Low Prevalence of Carbapenem-Resistant Bacteria in River Water: Resistance Is Mostly Related to Intrinsic Mechanisms.

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Tacão, Marta; Correia, António; Henriques, Isabel S

2015-10-01

Carbapenems are last-resort antibiotics to handle serious infections caused by multiresistant bacteria. The incidence of resistance to these antibiotics has been increasing and new resistance mechanisms have emerged. The dissemination of carbapenem resistance in the environment has been overlooked. The main goal of this research was to assess the prevalence and diversity of carbapenem-resistant bacteria in riverine ecosystems. The presence of frequently reported carbapenemase-encoding genes was inspected. The proportion of imipenem-resistant bacteria was on average 2.24 CFU/ml. Imipenem-resistant strains (n=110) were identified as Pseudomonas spp., Stenotrophomonas maltophilia, Aeromonas spp., Chromobacterium haemolyticum, Shewanella xiamenensis, and members of Enterobacteriaceae. Carbapenem-resistant bacteria were highly resistant to other beta-lactams such as quinolones, aminoglycosides, chloramphenicol, tetracyclines, and sulfamethoxazole/trimethoprim. Carbapenem resistance was mostly associated with intrinsically resistant bacteria. As intrinsic resistance mechanisms, we have identified the blaCphA gene in 77.3% of Aeromonas spp., blaL1 in all S. maltophilia, and blaOXA-48-like in all S. xiamenensis. As acquired resistance mechanisms, we have detected the blaVIM-2 gene in six Pseudomonas spp. (5.45%). Integrons with gene cassettes encoding resistance to aminoglycosides (aacA and aacC genes), trimethoprim (dfrB1b), and carbapenems (blaVIM-2) were found in Pseudomonas spp. Results suggest that carbapenem resistance dissemination in riverine ecosystems is still at an early stage. Nevertheless, monitoring these aquatic compartments for the presence of resistance genes and its host organisms is essential to outline strategies to minimize resistance dissemination.

Potential virulence of Klebsiella sp. isolates from enteral diets

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S.C.L. Pereira

2015-01-01

Full Text Available We aimed to evaluate the potential virulence of Klebsiella isolates from enteral diets in hospitals, to support nosocomial infection control measures, especially among critical-care patients. Phenotypic determination of virulence factors, such as capsular expression on the external membrane, production of aerobactin siderophore, synthesis of capsular polysaccharide, hemolytic and phospholipase activity, and resistance to antibiotics, which are used therapeutically, were investigated in strains of Klebsiella pneumoniae and K. oxytoca. Modular industrialized enteral diets (30 samples as used in two public hospitals were analyzed, and Klebsiella isolates were obtained from six (20% of them. The hypermucoviscous phenotype was observed in one of the K. pneumoniae isolates (6.7%. Capsular serotypes K1 to K6 were present, namely K5 and K4. Under the conditions of this study, no aerobactin production, hemolytic activity or lecithinase activity was observed in the isolates. All isolates were resistant to amoxicillin and ampicillin and sensitive to cefetamet, imipenem, chloramphenicol, gentamicin and sulfamethoxazole-trimethoprim. Most K. pneumoniae isolates (6/7, 85.7% from hospital B presented with a higher frequency of resistance to the antibiotics tested in this study, and multiple resistance to at least four antibiotics (3/8; 37.5% compared with isolates from Hospital A. The variations observed in the antibiotic resistance profiles allowed us to classify the Klebsiella isolates as eight antibiotypes. No production of broad-spectrum β-lactamases was observed among the isolates. Our data favor the hypothesis that Klebsiella isolates from enteral diets are potential pathogens for nosocomial infections.

A ten years (2000–2009 surveillance of resistant Enterobacteriaceae in Zhejiang Province, China

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Rong Zhang

2012-03-01

Full Text Available Objective: In Zhejiang Province, there are several highly developed cities near the coast and several relatively under-developed mountain areas. Analysis of the composition of bacteria isolated from patients as well as their antibiotic resistance profile from various areas of this province, and tracing of such data year-by-year, will help to delineate the bacterial resistance profile of these areas and to understand how the stage of socio-economical development impacts on the composition of clinical micro-flora and their resistance profile. Methods: In order to investigate variation in resistance rates and isolation rates of Enterobacteriaceae, from 2000 to 2009 in Zhejiang Province, China, Enterobacteriaceae isolated from 15 hospitals located in different regions of the province were surveyed. Results: The total numbers of the Enterobacteriaceae isolated increased more than 20-fold from 2000 to 2009. Among the Enterobacteriaceae, Escherichia coli and Klebsiella pneumoniae were the dominant isolates. The percentage of E. coli and K. pneumoniae that produced detectable extended-spectrum ?-lactamases (ESBLs increased from 2000 to 2007, and then declined slightly in 2008 and 2009. The percentages of K. pneumoniae and E. coli that were resistant to ceftazidime increased sharply from 2000 to 2009. There were remarkable increases in the carbapenem resistant rates during the decade, but they were much higher for the isolates from the developed cities than from the rural areas. In 2002, carbapenem-resistant E. coli was first found in Hangzhou, one of the highly developed cities in Zhejiang Province. By 2009, carbapenem-resistant bacteria were found for all species of Enterobacteriaceae surveyed in almost all areas of the province, although they were more frequently identified in developed areas than in rural areas. Conclusion: Much restrictive actions have to be taken in terms of rational use of antibiotics and nosocomial control to prevent the further

High Prevalence of Antimicrobial-resistant Gram-negative Colonization in Hospitalized Cambodian Infants.

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Turner, Paul; Pol, Sreymom; Soeng, Sona; Sar, Poda; Neou, Leakhena; Chea, Phal; Day, Nicholas Pj; Cooper, Ben S; Turner, Claudia

2016-08-01

Antimicrobial-resistant Gram-negative infections are a significant cause of mortality in young infants. We aimed to determine characteristics of, and risk factors for, colonization and invasive infection caused by 3rd generation cephalosporin (3GC) or carbapenem-resistant organisms in outborn infants admitted to a neonatal unit (NU) in Cambodia. During the first year of operation, patients admitted to the Angkor Hospital for Children NU, Siem Reap, Cambodia, underwent rectal swabbing on admission and twice weekly until discharge. Swabs were taken also from 7 environmental sites. Swabs were cultured to identify 3GC or carbapenem-resistant Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The study included 333 infants with a median age at NU admission of 10 days (range, 0-43). Colonization by ≥1 3GC-resistant organism was detected in 85.9% (286/333). Admission swabs were collected in 289 infants: 61.9% were colonized by a 3GC-resistant organism at the time of admission, and a further 23.2% were colonized during hospitalization, at a median of 4 days [95% confidence interval: 3-5]. Probiotic treatment (hazard ratio: 0.58; 95% confidence interval: 0.35-0.98) was associated with delayed colonization. Colonization by a carbapenem-resistant organism occurred in 25 (7.5%) infants. Six infants had NU-associated K. pneumoniae bacteremia; phenotypically identical colonizing strains were found in 3 infants. Environmental colonization occurred early. Colonization by antimicrobial-resistant Gram-negative organisms occurred early in hospitalized Cambodian infants and was associated with subsequent invasive infection. Trials of potential interventions such as probiotics are needed.

Clonality and Resistome analysis of KPC-producing Klebsiella pneumoniae strain isolated in Korea using whole genome sequencing.

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Lee, Yangsoon; Kim, Bong-Soo; Chun, Jongsik; Yong, Ji Hyun; Lee, Yeong Seon; Yoo, Jung Sik; Yong, Dongeun; Hong, Seong Geun; D'Souza, Roshan; Thomson, Kenneth S; Lee, Kyungwon; Chong, Yunsop

2014-01-01

We analyzed the whole genome sequence and resistome of the outbreak Klebsiella pneumoniae strain MP14 and compared it with those of K. pneumoniae carbapenemase- (KPC-) producing isolates that showed high similarity in the NCBI genome database. A KPC-2-producing multidrug-resistant (MDR) K. pneumoniae clinical isolate was obtained from a patient admitted to a Korean hospital in 2011. The strain MP14 was resistant to all tested β-lactams including monobactam, amikacin, levofloxacin, and cotrimoxazole, but susceptible to tigecycline and colistin. Resistome analysis showed the presence of β-lactamase genes including bla KPC-2, bla SHV-11, bla TEM-169, and bla OXA-9. MP14 also possessed aac(6'-)Ib, aadA2, and aph(3'-)Ia as aminoglycoside resistance-encoding genes, mph(A) for macrolides, oqxA and oqxB for quinolone, catA1 for phenicol, sul1 for sulfonamide, and dfrA12 for trimethoprim. Both SNP tree and cgMLST analysis showed the close relatedness with the KPC producers (KPNIH strains) isolated from an outbreak in the USA and colistin-resistant strains isolated in Italy. The plasmid-scaffold genes in plasmids pKpQil, pKpQil-IT, pKPN3, or pKPN-IT were identified in MP14, KPNIH, and Italian strains. The KPC-2-producing MDR K. pneumoniae ST258 stain isolated in Korea was highly clonally related with MDR K. pneumoniae strains from the USA and Italy. Global spread of KPC-producing K. pneumoniae is a worrying phenomenon.

Clonality and Resistome Analysis of KPC-Producing Klebsiella pneumoniae Strain Isolated in Korea Using Whole Genome Sequencing

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Yangsoon Lee

2014-01-01

Full Text Available We analyzed the whole genome sequence and resistome of the outbreak Klebsiella pneumoniae strain MP14 and compared it with those of K. pneumoniae carbapenemase- (KPC- producing isolates that showed high similarity in the NCBI genome database. A KPC-2-producing multidrug-resistant (MDR K. pneumoniae clinical isolate was obtained from a patient admitted to a Korean hospital in 2011. The strain MP14 was resistant to all tested β-lactams including monobactam, amikacin, levofloxacin, and cotrimoxazole, but susceptible to tigecycline and colistin. Resistome analysis showed the presence of β-lactamase genes including blaKPC-2, blaSHV-11, blaTEM-169, and blaOXA-9. MP14 also possessed aac(6′-Ib, aadA2, and aph(3′-Ia as aminoglycoside resistance-encoding genes, mph(A for macrolides, oqxA and oqxB for quinolone, catA1 for phenicol, sul1 for sulfonamide, and dfrA12 for trimethoprim. Both SNP tree and cgMLST analysis showed the close relatedness with the KPC producers (KPNIH strains isolated from an outbreak in the USA and colistin-resistant strains isolated in Italy. The plasmid-scaffold genes in plasmids pKpQil, pKpQil-IT, pKPN3, or pKPN-IT were identified in MP14, KPNIH, and Italian strains. The KPC-2-producing MDR K. pneumoniae ST258 stain isolated in Korea was highly clonally related with MDR K. pneumoniae strains from the USA and Italy. Global spread of KPC-producing K. pneumoniae is a worrying phenomenon.

Application of zwitterionic detergent to the solubilization of Klebsiella pneumoniae outer membrane proteins for two-dimensional gel electrophoresis.

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Bednarz-Misa, I; Serek, P; Dudek, B; Pawlak, A; Bugla-Płoskońska, G; Gamian, A

2014-12-01

Klebsiella pneumoniae is a frequent cause of nosocomial respiratory, urinary and gastrointestinal tract infections and septicemia with the multidrug-resistant K. pneumoniae being a major public health concern. Outer membrane proteins (OMPs) are important virulence factors responsible for the appropriate adaptation to the host environment. They constitute of the antigens being the first in contact with infected organism. However, K. pneumoniae strains are heavily capsulated and it is important to establish the OMPs isolation procedure prior to proteomics extensive studies. In this study we used Zwittergent Z 3-14® as a detergent to isolate the OMPs from K. pneumoniae cells and resolve them using two-dimensional electrophoresis (2-DE). As a result we identified 134 protein spots. The OMPs identified in this study are possible candidates for the development of a protein-based vaccine against K. pneumoniae infections. Copyright © 2014 Elsevier B.V. All rights reserved.

High burden of Carbapenem-resistant Enterobacteriaceae (CRE) fecal carriage at a teaching hospital: cost-effectiveness of screening in low-resource setting.

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Zaidah, Abdul Rahman; Mohammad, Nurul Izzah; Suraiya, Siti; Harun, Azian

2017-01-01

Infections by multidrug-resistant gram-negative bacteria (MDR-GNB) have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE) was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia. A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds. This hospital treats patients with various medical and surgical conditions. Suspected CRE from any clinical specimens received by the laboratory was identified and confirmed using standard protocols. Polymerase chain reaction (PCR) assay was performed to determine the genotype. Altogether, 8306 Enterobacteriaceae was isolated from various clinical specimens during the study period and 477/8306 (5.74%) were CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%)], of which Klebsiella pneumoniae was the predominant species, 388/408 (95%). CRE were mainly isolated from rectal swab (screening), 235/477 (49.3%); urine, 76/477 (15.9%); blood, 46/477 (9.6%) and about 7.1% from tracheal aspirate. One hundred and thirty-six isolates were subjected to genotype determination and., 112/136 (82.4%) showed positive detection of New Delhi metallo-β-lactamase 1 (NDM-1) gene ( bla NDM1 ). The study noted a high numbers of CRE isolated especially from rectal swabs. Active screening results in significant cost pressures and therefore should be revisited and revised, especially in low resource settings.

Wastewater as a Source of Carbapenem-Resistant E. coli (Webinar)

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Clinical studies have reported that the occurrence of carbapenem-resistant E. coli is on the rise. This is of concern because carbapenem antibiotics are typically reserved for treating infections caused by bacteria resistant to other classes of antibiotics. Current literature st...

Characterization of ESBL-producing Escherichia coli and Klebsiella pneumoniae strains isolated from urine of nonhospitalized patients in the Zagreb region

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Branka Bedenić,

2010-02-01

Full Text Available Aim To determine the prevalence of ESBL-producing Escherichia coli and Klebsiella pneumoniae strains isolated from urine of nonhospitalized patients during a three-year period, to determine their antibiotic susceptibility, investigate the transfer of ESBL genes with cotransfer of resistance and to characterize isolated beta-lactamases. Methods Antimicrobial susceptibility was determined by disk diffusion and broth microdilution methods. The double-disk test was used for ESBL detection. Transfer of resistance was performed by broth mating method and characterization of isolated beta-lactamases by polymerase chain reaction. Results The prevalence of ESBL-producing E. coli was 1.5% and of K. pneumoniae 4.1% with its different distribution according to patients`age and gender. ESBL-producing K. pneumoniae showed high resistance rates to aminoglycosides, cotrimoxazole, nitrofurantoin and quinolones while ESBL-producing E. coli isolates, with exception of high aminoglycoside resistance, showed low resistance rates to other antibiotics. Successful conjugation of ESBL genes was obtained with 25% E. coli and 76.2% K. pneumoniae strains. Comparing to E. coli, K. pneumoniae strains showed higher rates of aminoglycosideand cotrimoxazole resistance cotransfer. Beta-lactamases of investigated strains belonged to TEM, SHV and CTX-M families.Conclusion The existence of multiple-resistant ESBL-producing E. coli and K. pneumoniae strains was confirmed in observed outpatient population. ESBL-producing K. pneumoniae isolates, in contrast toESBL-producing E. coli, showed higher resistance rates to non-beta-lactam antibiotics, probably caused by cotransfer of resistance genes located on the same plasmid as ESBL genes. It is important to monitor the prevalence of such strains and their possible spreading in the outpatient population of the Zagreb region

The clinical consequences of antimicrobial resistance.

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Rice, Louis B

2009-10-01

The continued evolution of antimicrobial resistance in the hospital and more recently in the community threatens to seriously compromise our ability to treat serious infections. The major success of the seven-valent Streptococcus pneumoniae vaccine at reducing both infection and resistance has been followed by the emergence of previously minor serotypes that express multiresistance. The almost universal activity of cephalosporins and fluoroquinolones against community Escherichia coli strains has been compromised by the spread of CTX-M beta-lactamase-producing, fluoroquinolone-resistant strains, and the emergence of community-onset methicillin-resistant Staphylococcus aureus, particularly in the United States, has forced us to re-think our empirical treatment guidelines for skin and soft-tissue infections. Finally, our most potent and reliable class of antibiotics, the carbapenems, is compromised by the growth, primarily in intensive care units, of multiresistant Klebsiella pneumoniae, Acinetobacter baumanni, and Pseudomonas aeruginosa. The lack of a robust pipeline of new agents, particularly against resistant Gram-negative bacteria, emphasizes the importance of optimizing our use of current antimicrobials and promoting strict adherence to established infection control practices.

Characterization and genome analysis of novel bacteriophages infecting the opportunistic human pathogens Klebsiella oxytoca and K. pneumoniae.

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Park, Eun-Ah; Kim, You-Tae; Cho, Jae-Hyun; Ryu, Sangryeol; Lee, Ju-Hoon

2017-04-01

Klebsiella is a genus of well-known opportunistic human pathogens that are associated with diabetes mellitus and chronic pulmonary obstruction; however, this pathogen is often resistant to multiple drugs. To control this pathogen, two Klebsiella-infecting phages, K. oxytoca phage PKO111 and K. pneumoniae phage PKP126, were isolated from a sewage sample. Analysis of their host range revealed that they infect K. pneumoniae and K. oxytoca, suggesting host specificity for members of the genus Klebsiella. Stability tests confirmed that the phages are stable under various temperature (4 to 60 °C) and pH (3 to 11) conditions. A challenge assay showed that PKO111 and PKP126 inhibit growth of their host strains by 2 log and 4 log, respectively. Complete genome sequencing of the phages revealed that their genome sizes are quite different (168,758 bp for PKO111 and 50,934 bp for PKP126). Their genome annotation results showed that they have no human virulence-related genes, an important safety consideration. In addition, no lysogen-formation gene cluster was detected in either phage genome, suggesting that they are both virulent phages in their bacterial hosts. Based on these results, PKO111 and PKP126 may be good candidates for development of biocontrol agents against members of the genus Klebsiella for therapeutic purposes. A comparative analysis of tail-associated gene clusters of PKO111 and PKP126 revealed relatively low homology, suggesting that they might differ in the way they recognize and infect their specific hosts.

Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen's disease.

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Gopal, Vani; Mangaiyarkarasi, T; Gopal, R

2014-01-01

Klebsiella is a Gram-negative bacterium that causes different types of health care-associated infections including pneumonia, bloodstream infections, surgical site infections and meningitis. We report here a case of Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen's disease. A middle-aged man with a known case of diabetes mellitus and Hansen's disease presented with the complaints of blurred vision in the left eye and the patient was found to have cataract. Patient was operated for cataract and Intraocular lens implanted. Patient developed headache and vomiting on the 4th post-operative day. Lumbar puncture was carried out and gram stain of cerebrospinal fluid showed Gram-negative bacilli in the direct smear and culture yielded a heavy growth of K. pneumoniae. The patient was treated with antimicrobials according to the susceptibility pattern. He initially showed improvement but later on developed altered sensorium and hypotension. Patient succumbed to infection in spite of all medical attention.

Outbreak of OXA-48-Producing Klebsiella pneumoniae Involving a Sequence Type 101 Clone in Batna University Hospital, Algeria.

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Loucif, Lotfi; Kassah-Laouar, Ahmed; Saidi, Mahdia; Messala, Amina; Chelaghma, Widad; Rolain, Jean-Marc

2016-12-01

Seven nonredundant ertapenem-resistant Klebsiella pneumoniae isolates were collected between May 2014 and 19 January 2015 in the nephrology and hematology units of Batna University Hospital in Algeria. All strains coproduced the bla OXA-48 , bla CTX-M-15 , bla SHV-1 , and bla TEM-1D genes. Six of these isolates belonged to the pandemic clone sequence type 101 (ST101). The bla OXA-48 gene was located on a conjugative IncL/M-type plasmid. This is the first known outbreak of OXA-48-producing K. pneumoniae isolates involving an ST101 clone in Batna University Hospital. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Hospital Water Environment as a Reservoir for Carbapenem-Resistant Organisms Causing Hospital-Acquired Infections-A Systematic Review of the Literature.

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Kizny Gordon, Alice E; Mathers, Amy J; Cheong, Elaine Y L; Gottlieb, Thomas; Kotay, Shireen; Walker, A Sarah; Peto, Timothy E A; Crook, Derrick W; Stoesser, Nicole

2017-05-15

Over the last 20 years there have been 32 reports of carbapenem-resistant organisms in the hospital water environment, with half of these occurring since 2010. The majority of these reports have described associated clinical outbreaks in the intensive care setting, affecting the critically ill and the immunocompromised. Drains, sinks, and faucets were most frequently colonized, and Pseudomonas aeruginosa the predominant organism. Imipenemase (IMP), Klebsiella pneumoniae carbapenemase (KPC), and Verona integron-encoded metallo-β-lactamase (VIM) were the most common carbapenemases found. Molecular typing was performed in almost all studies, with pulse field gel electrophoresis being most commonly used. Seventy-two percent of studies reported controlling outbreaks, of which just more than one-third eliminated the organism from the water environment. A combination of interventions seems to be most successful, including reinforcement of general infection control measures, alongside chemical disinfection. The most appropriate disinfection method remains unclear, however, and it is likely that replacement of colonized water reservoirs may be required for long-term clearance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Intrinsic Klebsiella pneumoniae contamination of liquid germicidal hand soap containing chlorhexidine.

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Brooks, Steven E; Walczak, Mary A; Malcolm, Sharon; Hameed, Rizwanullah

2004-10-01

We describe intrinsic contamination with Klebsiella pneumoniae occurring during the manufacture of germicidal hand soap, labeled as containing 2% chlorhexidine, used throughout a 350-bed community medical center. A 3-year retrospective study failed to find evidence of increased incidence of clinical isolates of this strain.

Isolation of a bacteriophage specific for a new capsular type of Klebsiella pneumoniae and characterization of its polysaccharide depolymerase.

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Chun-Ru Hsu

Full Text Available BACKGROUND: Klebsiella pneumoniae is one of the major pathogens causing hospital-acquired multidrug-resistant infections. The capsular polysaccharide (CPS is an important virulence factor of K. pneumoniae. With 78 capsular types discovered thus far, an association between capsular type and the pathogenicity of K. pneumoniae has been observed. METHODOLOGY/PRINCIPAL FINDINGS: To investigate an initially non-typeable K. pneumoniae UTI isolate NTUH-K1790N, the cps gene region was sequenced. By NTUH-K1790N cps-PCR genotyping, serotyping and determination using a newly isolated capsular type-specific bacteriophage, we found that NTUH-K1790N and three other isolates Ca0507, Ca0421 and C1975 possessed a new capsular type, which we named KN2. Analysis of a KN2 CPS(- mutant confirmed the role of capsule as the target recognized by the antiserum and the phage. A newly described lytic phage specific for KN2 K. pneumoniae, named 0507-KN2-1, was isolated and characterized using transmission electron microscopy. Whole-genome sequencing of 0507-KN2-1 revealed a 159 991 bp double-stranded DNA genome with a G+C content of 46.7% and at least 154 open reading frames. Based on its morphological and genomic characteristics, 0507-KN2-1 was classified as a member of the Myoviridae phage family. Further analysis of this phage revealed a 3738-bp gene encoding a putative polysaccharide depolymerase. A recombinant form of this protein was produced and assayed to confirm its enzymatic activity and specificity to KN2 capsular polysaccharides. KN2 K. pneumoniae strains exhibited greater sensitivity to this depolymerase than these did to the cognate phage, as determined by spot analysis. CONCLUSIONS/SIGNIFICANCE: Here we report that a group of clinical strains possess a novel Klebsiella capsular type. We identified a KN2-specific phage and its polysaccharide depolymerase, which could be used for efficient capsular typing. The lytic phage and depolymerase also have potential as

Molecular mechanisms associated with nosocomial carbapenem-resistant Acinetobacter baumannii in Mexico.

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Alcántar-Curiel, María Dolores; García-Torres, Luis Francisco; González-Chávez, María Inés; Morfín-Otero, Rayo; Gayosso-Vázquez, Catalina; Jarillo-Quijada, Ma Dolores; Fernández-Vázquez, José Luis; Giono-Cerezo, Silvia; Rodríguez-Noriega, Eduardo; Santos-Preciado, José Ignacio

2014-10-01

Acinetobacter baumannii is an emerging pathogen worldwide that is most commonly associated with nosocomial infections and multi-drug resistance. In the present study we determined the mechanisms of carbapenem resistance and clonal diversity of A. baumannii nosocomial isolates in Hospital Civil de Guadalajara, Mexico. A total of 303 clinical isolates of A. baumannii identified during a period expanding from 2004-2011 were analyzed for carbapenem resistance using several microbiological and molecular methods. Clonal relatedness of these isolates was determined using pulsed-field gel electrophoresis. Of the 303 isolates, 84% were resistant to meropenem, 71.3% to imipenem and 78.3% the resistant isolates were positive for metallo-β-lactamases as determined by the phenotypic assay. In addition, 49.6% of carbapenem-intermediate or -resistant isolates carried the blaOXA-72 gene and 1.2% carried the blaVIM-1 gene. Efflux pump phenotype was responsible for reduced susceptibility to meropenem in 14.5% and to imipenem in 31.6% of the resistant isolates, respectively in the presence of the efflux pump inhibitor, carbonyl cyanide 3-chlorophenylhydrazone. Strains representing different carbapenem-resistant patterns exhibited reduced expression of 22, 29, 33, and 43 kDa OMPs. Among the bacterial collection studied, 48 different clones were identified, two of which were predominant and persistently transmitted. Carbapenemase production in combination with efflux pump expression, reduction in OMPs expression and the cross-transmission of clones appear to be major contributors to the high frequency of carbapenem-resistance observed in A. baumannii. To our knowledge, this is the first study to define the molecular mechanisms associated with carbapenem-resistance in A. baumannii in Mexico. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

RESISTENCIA A LOS ANTIBIÓTICOS EN CEPAS DE KLEBSIELLA PNEUMONIAE, SERRATIA SPP. Y ACINETOBACTER SPP.AISLADAS DE PACIENTES CON INFECCIÓN DEL TRACTO URINARIO - LIMA, PERU

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Luján Roca DA

2013-01-01

Full Text Available INFECTION - LIMA, PERU Introduction: Urinary tract infection (UTI is one of the most common infections in clinical practice. Gram negative bacteria as Klebsiella pneumoniae, Serratia spp. and Acinetobacter spp. can cause UTI. Objective: To study antibiotic resistance in K. pneumoniae, Serratia spp. and Acinetobacter spp. strains isolated from UTI Material and methods: Urine cultures were collected from January 2003 to December 2003. Identification of isolated bacteria included biochemical characteristics. Bauer-Kirby disc diffusion test was performed. Results: A total of 106 strains were evaluated (41 of K. pneumoniae, 28 of Serratia spp. and 37 of Acinetobacter spp.. Among K. pneumoniae isolates resistance to ampicillin (83% was remarkable. The Serratia spp. isolates displayed a high level of resistance to nalidixic acid (79% and gentamicin (75%. In Acinetobacter spp. isolates high resistance rates were observed against amikacin (81%, gentamicin (67% and trimethoprim/sulfamethoxazole(71%. Conclusions: In general, antibiotic resistance patterns were high. Acinetobacter spp. showed elevated resistance rates (>50% against antibiotics included.

Ventilator-Associated Pneumonia and Causative Microorganisms in Intensive Care Unit: A Two Year Retrospective Analysis

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Onur Palabıyık

2016-12-01

Full Text Available Objective: Ventilator-associated pneumonia (VAP is the most common nosocomial infection in the intensive care units (ICUs. It causes prolonged hospital stay and increases mortality. In this study, we aimed to investigate the rate of VAP, causative microorganisms, and their antibiotic susceptibilities in anaesthesiology and reanimation ICU (ARICU. Material and Method: This retrospective study included patients who were admitted to 12-bed ARICU between January 2013 and December 2014. The detection of VAP was done according to Centers for Disease Control and Prevention criteria. The rate of VAP, VAP ratio, and ventilator utilization ratio (VUR were calculated according to guidelines of Turkish National Infection Surveillance Control Group. Endotracheal aspiration samples were collected and cultivated. The identification of the isolates was performed by using VITEK-2 automated system. Antibiotic susceptibilities were determined by the disc diffusion method according to the Clinical and Laboratory Standards Institute criteria. Results: VAP was determined in 16 of 359 patients who required invasive mechanic ventilation for longer than 48 hours and hospitalized in ARICU. VUR was 65%, VAP ratio was 4.5% and the rate of VAP was 3.3 per 1000 ventilator days. Seventeen microorganisms were isolated from endotracheal aspiration samples, including Acinetobacter baumannii (n=6, Pseudomonas aeruginosa (n=4, methicillin-resistant Staphylococcus aureus (n=4, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens. The most sensitive antibiotics for microorganisms are listed as follows; Acinetobacter baumannii: colistin, Pseudomonas aeruginosa: amikacin, carbapenems; Methicillin-resistant Staphylococcus aureus: linezolid, teicoplanin, vancomycin, trimethoprim sulfamethoxazole; Klebsiella and Enterobacteriaceae species: carbapenems, trimethoprim sulfamethoxazole, gentamicin. Conclusion: Intermittent analyses and antibiotic susceptibilities of VAP

Characterization of the etiological structure and genotypically determined phenotypic resistance to carbapenems of infectious complications leading pathogens in critically ill patients

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O. A. Nazarchuk

2018-06-01

Full Text Available The aim is to investigate the genotypically determined phenotypic resistance to carbapenems of gram-negative microorganisms isolated from patients with critical states. Material and methods. Microbiological etiology of infectious complications in critically ill patients (n = 726 was investigated. In total, during the years 2011–2016, 933 clinical strains of infectious complications pathogens from patients with severe burns (n = 435 and from patients treated in intensive care units (n = 291 were isolated and identified. The sensitivity of microorganisms clinical isolates to antibiotics was investigated by means of the standard microbiological methods. In gram-negative bacteria resistant to carbapenems, a molecular genetic study of mechanisms of resistance, determined by the presence of VIM genes, was carried out using the method of real-time polymerase chain reaction. Results. Studies have shown that gram-negative microorganisms (Acinetobacter spp. – 36.3 %, P. aeruginosa – 31.7 %, Enterobacter spp. – 13.5 %, Proteus spp. – 7.9 %, E. coli – 3.8 %; K. pneumoniae – 3.6 %, etc. account for a significant part of infectious complications pathogens structure in critically ill patients. A. baumannii strains (67 % have expressed phenotypic resistance to most antibiotics, in particular to carbapenems (up to 63.2 %. Poly-antibiotic resistance was also found in P. aeruginosa (72 %, and above one the 3rd part of strains of this pathogen was found to have phenotypic resistance to carbapenems. In-depth study of molecular genetic determinants of the resistance mechanism to β-lactam antibiotics among clinical strains of gram-negative bacteria there was proved VIM-induced resistance to carbapenems in A. baumannii, P. aeruginosa, P. mirabilis. Conclusions. Enterobacteriaceae and non-fermenting gram-negative microorganisms (P. aeruginosa, P. mirabilis, A. baumannii, which are the leading causative agents of infectious complications in patients with

Detection of an IncA/C plasmid encoding VIM-4 and CMY-4 β-lactamases in Klebsiella oxytoca and Citrobacter koseri from an inpatient in a cardiac rehabilitation unit.

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Caltagirone, Mariasofia; Bitar, Ibrahim; Piazza, Aurora; Spalla, Melissa; Nucleo, Elisabetta; Navarra, Antonella; Migliavacca, Roberta

2015-07-01

A 62-year-old patient was transferred to the cardiac rehabilitation unit of the I.R.C.C.S. Fondazione S. Maugeri after undergoing a heart transplantation at the Acute Care Hospital I.R.C.C.S. S. Matteo of Pavia. On 1 August 2013 and during hospitalization in the rehabilitation unit, Klebsiella oxytoca and Citrobacter koseri clinical isolates were simultaneously recovered from the patient's preputial swab. Both the K. oxytoca and C. koseri strains were carbapenem- resistant by MicroScan System (Beckman Coulter). Carbapenem-resistant K. pneumoniae had previously been reported in the same rehabilitation facility. The aim of the study was to identify the carbapenem resistance mechanisms among the enterobacterial species recovered. Phenotypic screening tests useful to detect the β-lactamases/carbapenemases were performed. Carbapenem MICs were obtained by Etest. AmpC and MBL encoding genes were identified by PCR and sequencing. Conjugation assays and plasmid characterization were performed. Both of the K. oxytoca and C. koseri isolates were multi drug resistant, showing resistance to amoxicillin-clavulanic acid, three generation cephalosporins, ertapenem (K. oxytoca MIC, >32 mg/L; C. koseri MIC, 4 mg/L), imipenem (K. oxytoca MIC, 4 mg/L; C. koseri MIC, 12 mg/L), thrimethoprim sulphamethoxazole and gentamicin. Susceptibility was retained to fluoroquinolones, colistin and tigecycline. Molecular characterization confirmed the co-presence of blaCMY-4 and blaVIM-4 determinants in a 150 Kb transferable plasmid of IncA/C group. This case is the first detection in Italy of the K. oxytoca and C. koseri clinical isolates co-producing the CMY-4 and VIM-4 enzymes.

Phenotypic characterization and colistin susceptibilities of carbapenem-resistant of Pseudomonas aeruginosa and Acinetobacter spp.

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Mohanty, Srujana; Maurya, Vijeta; Gaind, Rajni; Deb, Monorama

2013-11-15

Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin. Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non-repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-β-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest. Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin. Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered.

Absceso hepático por Klebsiella pneumoniae, asociado con bacteriemia y meningitis: Reporte de un caso

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Yucumá-Gutiérrez, Samuel; Duran-Gutiérrez, Luis F; Osorio-Pinzón, Johanna V; Álzate-Carvajal, Verónica; Mondragón-Cardona, Álvaro

2016-01-01

El absceso hepático, continúa siendo un importante problema de salud pública. El causado por Klebsiella pneumoniae, se ha descrito en un 29% de los casos en algunas series. Con una mortalidad hasta del 11,3%, se presenta con mayor frecuencia en pacientes con diabetes mellitus, relacionándose con complicaciones a distancia, como meningitis, absceso cerebral y afección pulmonar. Se presenta el caso de un hombre sin factores de riesgo, con síndrome de absceso hepático por Klebsiella pneumoniae c...

Necrotizing Fasciitis Caused by Hypermucoviscous Klebsiella pneumoniae in a Filipino Female in North America

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Ng, Daniel

2014-12-01

Full Text Available Necrotizing fasciitis caused by Klebsiella pneumoniae has been described in Southeast Asia, but has only recently begun to emerge in North America. The hypermucoviscous strain of K. pneumoniae is a particularly virulent strain known to cause devastatingly invasive infections, including necrotizing fasciitis. Here we present the first known case of necrotizing fasciitis caused by hypermucoviscous K. pneumoniae in North America. [West J Emerg Med. 2015;16(1:165–168.

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients.

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Karaaslan, Ayşe; Çağan, Eren; Kadayifci, Eda Kepenekli; Atıcı, Serkan; Akkoç, Gülşen; Yakut, Nurhayat; Demir, Sevliya Öcal; Soysal, Ahmet; Bakır, Mustafa

2016-11-01

The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB) has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. This study has a retrospective study design. Sixty-one critically ill children were identified through the department's patient files archive during the period from January 2011 to November 2014. Twenty-nine females and thirty-two males with a mean±standard deviation (SD) age of 61±9 months (range 0-216, median 12 months) received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7%) was the leading diagnosis, followed by pneumonia (n=19, 31%), clinical sepsis (n=7, 11.4%), wound infection (n=6, 9.8%), urinary tract infection (n=5, 8.1%) and meningitis (n=1, 1.6%). All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%), Pseudomonas aeruginosa (n=17, 27.8%), Klebsiella pneumoniae (n=6, 9.8%), K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%), K. pneumoniae and A. baumanni (n=1, 1.6%), K. oxytoca (n=1, 1.6%) and Enterobacter cloacae (n=1, 1.6%). In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45). Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82), ampicillin-sulbactam (n=5, 8%), quinolones (n=5, 8%), rifampicin (n=1, 1.6%). Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin (colisthimethate) at a dosage of 5 mg/kg daily by dividing it

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

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Ayşe Karaaslan

2016-12-01

Full Text Available Background: The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. Aims: In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. Study Design: This study has a retrospective study design. Methods: Sixty-one critically ill children were identified through the department’s patient files archive during the period from January 2011 to November 2014. Results: Twenty-nine females and thirty-two males with a mean±standard deviation (SD age of 61±9 months (range 0-216, median 12 months received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7% was the leading diagnosis, followed by pneumonia (n=19, 31%, clinical sepsis (n=7, 11.4%, wound infection (n=6, 9.8%, urinary tract infection (n=5, 8.1% and meningitis (n=1, 1.6%. All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%, Pseudomonas aeruginosa (n=17, 27.8%, Klebsiella pneumoniae (n=6, 9.8%, K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%, K. pneumoniae and A. baumanni (n=1, 1.6%, K. oxytoca (n=1, 1.6% and Enterobacter cloacae (n=1, 1.6%. In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45. Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82, ampicillin-sulbactam (n=5, 8%, quinolones (n=5, 8%, rifampicin (n=1, 1.6%. Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin

Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon

NARCIS (Netherlands)

Hagen, ten T.L.; Vianen, van W.; Savelkoul, H.F.J.; Heremans, H.; Buurman, W.A.; Bakker-Woudenberg, I.A.

1998-01-01

We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae.

Two cases of monomicrobial intraabdominal abscesses due to KPC - 3 Klebsiella pneumoniae ST258 clone

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Madonia Simona

2011-09-01

Full Text Available Abstract Background Knowledge of the etiology of pyogenic liver and pancreatic abscesses is an important factor in determining the success of combined surgical and antibiotic treatment. Literature shows geographical variations in the prevalence and distribution of causative organisms, and the spread of Klebsiella pneumoniae carbapenemase-producing bacteria is an emerging cause of abdominal infections. Case presentation We herein describe two cases of intra-abdominal abscesses due to monomicrobial infection by Klebsiella pneumoniae Sequence Type 258 producing K. pneumoniae carbapenemase 3 (KPC-Kp. In case 1, a 50-year-old HIV-negative Italian woman with chronic pancreatitis showed infection of a pancreatic pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV- negative Italian woman with pancreatic neoplasm and liver metastases developed a liver abscess due to KPC after surgery. Both women were admitted to our hospital but to different surgical units. The clonal relationship between the two isolates was investigated by pulsed-field gel electrophoresis (PFGE. In case 2, the patient was already colonized at admission and inter-hospital transmission of the pathogen was presumed. A long-term combination regimen of colistin with tigecycline and percutaneous drainage resulted in full recovery and clearance of the multidrug-resistant (MDR pathogen. Conclusions Timely microbiological diagnosis, the combined use of new and old antibiotics and radiological intervention appeared to be valuable in managing these serious conditions. The emergence and dissemination of MDR organisms is posing an increasing challenge for physicians to develop new therapeutic strategies and control and prevention frameworks.

High burden of Carbapenem-resistant Enterobacteriaceae (CRE fecal carriage at a teaching hospital: cost-effectiveness of screening in low-resource setting

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Abdul Rahman Zaidah

2017-05-01

Full Text Available Abstract Background Infections by multidrug-resistant gram-negative bacteria (MDR-GNB have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia. Methods A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds. This hospital treats patients with various medical and surgical conditions. Suspected CRE from any clinical specimens received by the laboratory was identified and confirmed using standard protocols. Polymerase chain reaction (PCR assay was performed to determine the genotype. Results Altogether, 8306 Enterobacteriaceae was isolated from various clinical specimens during the study period and 477/8306 (5.74% were CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%], of which Klebsiella pneumoniae was the predominant species, 388/408 (95%. CRE were mainly isolated from rectal swab (screening, 235/477 (49.3%; urine, 76/477 (15.9%; blood, 46/477 (9.6% and about 7.1% from tracheal aspirate. One hundred and thirty-six isolates were subjected to genotype determination and., 112/136 (82.4% showed positive detection of New Delhi metallo-β-lactamase 1 (NDM-1 gene (bla NDM1. Conclusion The study noted a high numbers of CRE isolated especially from rectal swabs. Active screening results in significant cost pressures and therefore should be revisited and revised, especially in low resource settings.

Diversity of carbapenemases in clinical isolates of Enterobacteriaceae in Croatia--the results of a multicentre study.

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Zujić Atalić, V; Bedenić, B; Kocsis, E; Mazzariol, A; Sardelić, S; Barišić, M; Plečko, V; Bošnjak, Z; Mijač, M; Jajić, I; Vranić-Ladavac, M; Cornaglia, G

2014-11-01

Since the first carbapenem-resistant Klebsiella pneumoniae strain was isolated in 2008, Enterobacteriaceae with reduced susceptibility to one or more carbapenems have emerged sporadically in different geographical regions in Croatia. These observations gave rise to a multicenter study on carbapenem resistance in Enterobacteriaceae from Croatia. Fifty-seven carbapenem-non-susceptible strains of Enterobacteriaceae were collected during 2011-2012 from four large hospital centres in Croatia. Overall, 36 strains produced VIM-1 β-lactamase, three produced NDM-1, and one produced KPC-2. A high degree of clonal relatedness was observed in Enterobacter cloacae and Citrobacter freundii strains, in contrast to K. pneumoniae strains. BlaVIM genes were located within class1 integron which contained genes encoding resistance to aminoglycosides (aacA4 ). The study found strong association between blaVIM and qnrB6 and between blaNDM and qnrA6 genes. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307.

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Long, S Wesley; Olsen, Randall J; Eagar, Todd N; Beres, Stephen B; Zhao, Picheng; Davis, James J; Brettin, Thomas; Xia, Fangfang; Musser, James M

2017-05-16

Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae , it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research. IMPORTANCE Klebsiella pneumoniae causes human infections that are increasingly difficult to

Dichotomy between Lactobacillus rhamnosus and Klebsiella pneumoniae on dendritic cell phenotype and function

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Braat, Henri; de Jong, Esther C.; van den Brande, Jan M. H.; Kapsenberg, Martien L.; Peppelenbosch, Maikel P.; van Tol, Eric A. F.; van Deventer, Sander J. H.

2004-01-01

The reaction of the intestinal immune system to intestinal bacteria shows striking differences between various bacterial strains. Whereas Klebsiella pneumoniae induces a fierce proinflammatory reaction, the probiotic strain Lactobacillus rhamnosus has clear anti-inflammatory effect in

Role of the two component signal transduction system CpxAR in conferring cefepime and chloramphenicol resistance in Klebsiella pneumoniae NTUH-K2044.

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Vijaya Bharathi Srinivasan

Full Text Available BACKGROUND: Klebsiella pneumoniae is a gram-negative, non-motile, facultative anaerobe belonging to the Enterobacteriaceae family of the γ-Proteobacteria class in the phylum Proteobacteria. Multidrug resistant K. pneumoniae have caused major therapeutic problems worldwide due to emergence of extended-spectrum β-lactamase producing strains. Two-component systems serve as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions including antibiotic stress. PRINCIPAL FINDINGS: In the present study, we investigated the role of an uncharacterized cpxAR operon in bacterial physiology and antimicrobial resistance by generating isogenic mutant (ΔcpxAR deficient in the CpxA/CpxR component derived from the hyper mucoidal K1 strain K. pneumoniae NTUH-K2044. The behaviour of ΔcpxAR was determined under hostile conditions, reproducing stresses encountered in the gastrointestinal environment and deletion resulted in higher sensitivity to bile, osmotic and acid stresses. The ΔcpxAR was more susceptible to β-lactams and chloramphenicol than the wild-type strain, and complementation restored the altered phenotypes. The relative change in expression of acrB, acrD, eefB efflux genes were decreased in cpxAR mutant as evidenced by qRT-PCR. Comparison of outer membrane protein profiles indicated a conspicuous difference in the knock out background. Gel shift assays demonstrated direct binding of CpxR(KP to promoter region of ompC(KP in a concentration dependent manner. CONCLUSIONS AND SIGNIFICANCE: The Cpx envelope stress response system is known to be activated by alterations in pH, membrane composition and misfolded proteins, and this systematic investigation reveals its direct involvement in conferring antimicrobial resistance against clinically significant antibiotics for the very first time. Overall results displayed in this report reflect the pleiotropic role of the Cpx

Kadar Protein Klebsiella pneumoniae Hasil Pemanasan 65 Derajat Celcius

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Irawan Sugoro

2016-03-01

Full Text Available Klebsiella pneumoniae is one of a coliform bacteria that causing mastitis. This disease were founded in dairy cows and can be prevented by vaccination. The research has been conducted to determine the inactive times, the protein concentration and profile of K. pneumoniae which inactivated by heating of 65oC as material of mastitis vaccine. The cells culture inactivated by the different times, i.e. 0, 10, 20, 30, 40, 50 and 60 minutes. The inactive times was determined by the drop test method, whereas the protein concentration of cells were determined by Lowry method. The results showed that the inactive times occured after 30 minute, and has a significant different on the protein concentration of bacteria cells that inactivated by the different times.

Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease

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Vani Gopal

2014-01-01

Full Text Available Klebsiella is a Gram-negative bacterium that causes different types of health care-associated infections including pneumonia, bloodstream infections, surgical site infections and meningitis. We report here a case of Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease. A middle-aged man with a known case of diabetes mellitus and Hansen′s disease presented with the complaints of blurred vision in the left eye and the patient was found to have cataract. Patient was operated for cataract and Intraocular lens implanted. Patient developed headache and vomiting on the 4 th post-operative day. Lumbar puncture was carried out and gram stain of cerebrospinal fluid showed Gram-negative bacilli in the direct smear and culture yielded a heavy growth of K. pneumoniae. The patient was treated with antimicrobials according to the susceptibility pattern. He initially showed improvement but later on developed altered sensorium and hypotension. Patient succumbed to infection in spite of all medical attention.

Molecular detection of genes encoding AcrAB , Qep A efflux pumps in Klebsiella pneumoniae strains isolated from hospitalized patients in selected hospitals in Tehran

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Mohsen Heidary

2017-03-01

Full Text Available Abstract Background and Objectives: Increasing emergence of fluoroquinolone resistance among clinical isolates of Klebsiella pneumoniae  (K. pneumoniae, has limited the treatment options for treatment of infections caused by these bacteria. The aim of this study was to investigate the dissemination of genes encoding AcrAB and QepA efflux pumps among K. pneumoniae strains. Methods: This study was carried out on 117 K. pneumoniae strains isolated from patients hospitalized in selected hospitals in Tehran city, 2015-2016, Iran. Antimicrobial susceptibility tests were performed using disk diffusion method (based on CLSI guidelines and identification of acr A, acr B and qep A genes using PCR assay. Results: In this study, colistin and tigecycline had the best effect against clinical isolates of K. pneumoniae. According to PCR results, 110 (94% isolates had acrA gene and 102 (87% isolates had acrB gene, respectively. The qepA gene was not found in any of the K. pneumoniae strains. Conclusion: According to the results of the present study, dissemination of the genes encoding AcrAB efflux pumps among K. pneumoniae strains, which cause resistance to fluoroquinolones, is a matter of concern. Therefore, infection control and prevention of the spread of drug-resistant bacteria requires careful management in drug prescription and identification of resistant isolates.

AÇÃO DA TERAPIA FOTODINÂMICA EM Klebsiella pneumoniae (ATCC 4352 UTILIZANDO MODELO DE INFECÇÃO Galleria mellonella

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Raquel Teles de Menezes

2017-05-01

Full Text Available Klebsiella pneumoniae é um dos patógenos que possui grande resistência a vários antimicrobianos. A Terapia Fotodinâmica Antimicrobiana (PDT vem sendo estudada como novo recurso no combate à resistência bacteriana. Objetivo: Avaliar a ação antimicrobiana da PDT em K. pneumoniae utilizando como modelo de infecção in vivo Galleria mellonella. Métodos: Foram inoculados 10µL da suspensão padronizada de K. pneumoniae ATCC 4352 na última proleg esquerda de cada larva selecionada de G. mellonella. Decorridos 30 minutos, as larvas foram submetidas a PDT, com o uso do fotossensibilizador Azul de metileno e Laser de Arseneto de Gálio Alumínio. Passadas 24h, por sete dias o número de lagartas mortas foi anotado para a realização da curva de sobrevivência. Resultados: A PDT contribuiu para melhora da sobrevida das larvas, porém sem apresentar diferença estatística significante. Conclusão: A PDT apresentou atividade antimicrobiana contra a cepa de K. pneumoniae ATCC 4352.

Capacidad de los laboratorios nacionales de referencia en Latinoamérica para detectar mecanismos de resistencia emergentes Capability of national reference laboratories in Latin America to detect emerging resistance mechanisms

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Alejandra Corso

2011-12-01

Control Program in Bacteriology and Antibiotic Resistance (LA-EQAS to detect emerging resistance mechanisms- namely: resistance of enterobacteria to carbapenems due to the presence of Klebsiella pneumoniae carbapenemase (KPC and metallo-beta-lactamase (MBL type IMP, and intermediate resistance of Staphylococcus aureus isolates to vancomycin (vancomycin-intermediate resistant S. aureus-VISA. METHODS: The following three isolates were sent to the 17 participating LA-EQAS laboratories: KPC -producing Klebsiella pneumoniae PAHO-161, IMP-producing Enterobacter cloacae PAHO-166, and S. aureus PAHO-165 with intermediate resistance to vancomycin. Performance of each of the following operations was evaluated: interpretation of sensitivity tests, detection of the resistance mechanism, and assessment of either inhibition halo size (disk diffusion method or minimum inhibitory concentration (MIC. RESULTS: Concordance in the detection of resistance mechanisms was 76.4%, 73.3%, and 66.7% for the K. pneumoniae PAHO-161, E. cloacae PAHO-166, and S. aureus PAHO-165 strains, respectively. Concordance between the inhibition areas observed by the participating laboratories and the ranges established by the coordinating laboratory was acceptable for all three isolates, at 90.8%, 92.8%, and 88.9%, respectively. CONCLUSIONS: Overall concordance in on the detection of KPC, MBL, and VISA resistance mechanisms was 72.1%. We consider the national reference laboratories in Latin America capable of recognizing these emerging resistance mechanisms and expect that maximum levels of concordance will be reached in the future.

Outbreak of Ampicillin/Piperacillin-Resistant Klebsiella Pneumoniae in a Neonatal Intensive Care Unit (NICU): Investigation and Control Measures

OpenAIRE

Fabbri, Giuliana; Panico, Manuela; Dallolio, Laura; Suzzi, Roberta; Ciccia, Matilde; Sandri, Fabrizio; Farruggia, Patrizia

2013-01-01

Klebsiella pneumoniae is a frequent cause of infectious outbreaks in Neonatal Intensive Care Units (NICUs). The aim of this paper is to describe an outbreak occurred in a 13-bed NICU and the control measures adopted in order to interrupt the chain of transmission. We described the microbiological investigations, the NICU staff compliance to the infection control measures by means of a specifically designed check-list and the control measures adopted. Six cases of primary bloodstream infection...

Detection of Amp C genes encoding for beta-lactamases in Escherichia coli and Klebsiella pneumoniae

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M Shanthi

2012-01-01

Full Text Available Purpose : Amp C beta-lactamase are Ambler class C enzymes that confer resistance to extended spectrum cephalosporins and are not inhibited by beta-lactamase inhibitors. Their detection is crucial, since the phenotypic tests are not standardised leading to ambiguity in interpretation of results. This study was done to detect the types of Amp C prevalent in Escherichia coli and Klebsiella pneumoniae by multiplex polymerase chain reaction (PCR. Materials and Methods : Seventy-seven consecutive cefoxitin resistant clinical isolates of E. coli (n = 25 and K. pneumoniae (n = 52 were included in the study. Antibiotic susceptibility testing to various classes of antibiotics was performed by disc diffusion using Clinical Laboratory Standards Institute (CLSI guidelines. Minimum inhibitory concentration (MIC to cefoxitin, imipenem and meropenem were determined by broth microdilution method. Isolates were screened for production of Extended Spectrum Beta-Lactamase (ESBL. Multiplex PCR was performed for the detection of Amp C genes after phenotypic testing (Hodge test and inhibitor based test. Results : Cefoxitin Hodge test was positive in 40 isolates which included 20 E. coli and 20 K. pneumoniae. There was zone enhancement with boronic acid in 55 isolates, of which 36 were K. pneumoniae and 19 were E. coli. Multiplex PCR detected Amp C in 11/25 E. coli and 12/52 K. pneumoniae isolates. The Amp C genes detected were CIT (Amp C origin - Citrobacter freundii, DHA (Dhahran Hospital, Saudi Arabia, ACC (Ambler class C, EBC (Amp C origin - Enterobacter cloacae groups. ESBL was co-produced in 54 isolates. Conclusions : Amp C was detected in 29.87% of the study isolates. Majority of them co-produced ESBL. The most common Amp C was the CIT family. Screen tests for cefoxitin resistance may be falsely positive due to production of carbapenamases.

Susceptibility of chemostat-grown Yersinia enterocolitica and Klebsiella pneumoniae to chlorine dioxide.

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Harakeh, M S; Berg, J D; Hoff, J C; Matin, A

1985-01-01

The resistance of bacteria to antimicrobial agents could be influenced by growth environment. The susceptibility of two enteric bacteria, Yersinia enterocolitica and Klebsiella pneumoniae, to chlorine dioxide was investigated. These organisms were grown in a defined medium in a chemostat and the influence of growth rate, temperature, and cell density on the susceptibility was studied. All inactivation experiments were conducted with a dose of 0.25 mg of chlorine dioxide per liter in phosphate-buffered saline at pH 7.0 and 23 degrees C. The results indicated that populations grown under conditions that more closely approximate natural aquatic environments, e.g., low temperatures and growth at submaximal rates caused by nutrient limitation, were most resistant. The conclusion from this study is that antecedent growth conditions have a profound effect on the susceptibility of bacteria to disinfectants, and it is more appropriate to use the chemostat-grown bacteria as test organisms to evaluate the efficacy of a certain disinfectant.

Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam.

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Horii, T; Arakawa, Y; Ohta, M; Ichiyama, S; Wacharotayankun, R; Kato, N

1993-01-01

Klebsiella pneumoniae NU2936 was isolated from a patient and was found to produce a plasmid-encoded beta-lactamase (MOX-1) which conferred resistance to broad spectrum beta-lactams, including moxalactam, flomoxef, ceftizoxime, cefotaxime, and ceftazidime. Resistance could be transferred from K. pneumoniae NU2936 to Escherichia coli CSH2 by conjugation with a transfer frequency of 5 x 10(-7). The structural gene of MOX-1 (blaMOX-1) was cloned and expressed in E. coli HB101. The MIC of moxalactam for E. coli HB101 producing MOX-1 was > 512 micrograms/ml. The apparent molecular mass and pI of this enzyme were calculated to be 38 kDa and 8.9, respectively. Hg2+ and Cu2+ failed to block enzyme activity, and the presence of EDTA in the reaction buffer did not reduce the enzyme activity. However, clavulanate and cloxacillin, serine beta-lactamase inhibitors, inhibited the enzyme activity competitively (Kis = 5.60 and 0.35 microM, respectively). The kinetic study of MOX-1 suggested that it effectively hydrolyzed broad-spectrum beta-lactams. A hybridization study confirmed that blaMOX-1 is encoded on a large resident plasmid (pRMOX1; 180 kb) of strain NU2936. By deletion analysis, the functional region was localized within a 1.2-kb region of the plasmid. By amino acid sequencing, 18 of 33 amino acid residues at the N terminus of MOX-1 were found to be identical to those of Pseudomonas aeruginosa AmpC. These findings suggest that MOX-1 is a plasmid-mediated AmpC-type beta-lactamase that provides enteric bacteria resistance to broad-spectrum beta-lactams, including moxalactam. Images PMID:8517725

Generation and Validation of the iKp1289 Metabolic Model for Klebsiella pneumoniae KPPR1

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Henry, Christopher S.; Rotman, Ella; Lathem, Wyndham W.; Tyo, Keith E. J.; Hauser, Alan R.; Mandel, Mark J.

2017-02-15

Klebsiella pneumoniae has a reputation for causing a wide range of infectious conditions, with numerous highly virulent and antibiotic-resistant strains. Metabolic models have the potential to provide insights into the growth behavior, nutrient requirements, essential genes, and candidate drug targets in these strains. Here we develop a metabolic model for KPPR1, a highly virulent strain of K. pneumoniae. We apply a combination of Biolog phenotype data and fitness data to validate and refine our KPPR1 model. The final model displays a predictive accuracy of 75% in identifying potential carbon and nitrogen sources for K. pneumoniae and of 99% in predicting nonessential genes in rich media. We demonstrate how this model is useful in studying the differences in the metabolic capabilities of the low-virulence MGH 78578 strain and the highly virulent KPPR1 strain. For example, we demonstrate that these strains differ in carbohydrate metabolism, including the ability to metabolize dulcitol as a primary carbon source. Our model makes numerous other predictions for follow-up verification and analysis.

Hospital Outcomes of Adult Respiratory Tract Infections with Extended-Spectrum B-Lactamase (ESBL) Producing Klebsiella Pneumoniae

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Loh, Li-Cher; Nor Izran Hanim bt Abdul Samad,; Rosdara Masayuni bt Mohd Sani,; Raman, Sree; Thayaparan, Tarmizi; Kumar, Shalini

2007-01-01

Klebsiella pneumoniae ranks high as a cause of adult pneumonia requiring hospitalization in Malaysia. To study whether extended-spectrum b-lactamase (ESBL) producing K. pneumoniae was linked to hospital outcomes, we retrospectively studied 441 cases of adult respiratory tract infections with microbial proven K. pneumoniae from an urban-based university teaching hospital between 2003 and 2004. 47 (10.6%) cases had ESBL. Requirement for ventilation and median length of hospital stay, were great...

Isolation of Enterobacter aerogenes carrying blaTEM-1 and blaKPC-3 genes recovered from a hospital Intensive Care Unit.

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Pulcrano, Giovanna; Pignanelli, Salvatore; Vollaro, Adriana; Esposito, Matilde; Iula, Vita Dora; Roscetto, Emanuela; Soriano, Amata Amy; Catania, Maria Rosaria

2016-06-01

Enterobacter aerogenes has recently emerged as an important hospital pathogen. In this study, we showed the emergence of E. aerogenes isolates carrying the blaKPC gene in patients colonized by carbapenem-resistant Klebsiella pneumoniae strains. Two multiresistant E. aerogenes isolates were recovered from bronchial aspirates of two patients hospitalized in the Intensive Care Unit at the "Santa Maria della Scaletta" Hospital, Imola. The antimicrobial susceptibility test showed the high resistance to carbapenems and double-disk synergy test confirmed the phenotype of KPC and AmpC production. Other investigation revealed that ESBL and blaKPC genes were carried on the conjugative pKpQIL plasmid. This is a relevant report in Italy that describes a nosocomial infection due to the production of KPC beta-lactamases by an E. aerogenes isolate in patients previously colonized by K. pneumoniae carbapenem-resistant. In conclusion, it's necessary a continuous monitoring of multidrug-resistant strains for the detection of any KPC-producing bacteria that could expand the circulation of carbapenem-resistant pathogens. © 2016 APMIS. Published by John Wiley & Sons Ltd.

[Risk factors for Pseudomonas aeruginosa infections, resistant to carbapenem].

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Ghibu, Laura; Miftode, Egidia; Teodor, Andra; Bejan, Codrina; Dorobăţ, Carmen Mihaela

2010-01-01

Since their introduction in clinical practice,carbapenems have been among the most powerful antibiotics for treating serious infections cased by Gram-negative nosocomial pathogens, including Pseudomonas aeruginosa. The emergence of betalactamases with carbapenem-hydrolyzing activity is of major clinical concern. Pseudomonas aeruginosa is a leading cause of nosocomial infection. Risk factors for colonization with carbapenems-resistant Pseudomonas in hospital are: history of P. aeruginosa infection or colonization within the previous year, (length of hospital stay, being bedridden or in the ICU, mechanical ventilation, malignant disease, and history of chronic obstructive pulmonary disease have all been identified as independent risk factors for MDR P. aeruginosa infection. Long-term-care facilities are also reservoirs of resistant bacteria. Risk factors for colonization of LTCF residents with resistant bacteria included age > 86 years, antibiotic treatment in the previous 3 months, indwelling devices, chronic obstructive pulmonary disease, physical disability, and the particular LTCF unit.

[Systematic review of antimicrobial resistance in Enterobacteriaceae isolates from Colombian hospitals].

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González, Leidy; Cortés, Jorge Alberto

2014-01-01

Bacterial resistance is a public health problem worldwide that seriously compromises the possibility to treat infections. To identify levels of resistance to antibiotic markers in Enterobacteriaceae isolates from Colombian hospitals. A systematic literature survey was done including articles indexed in Medline, Embase and LILACS. A manual search was made of Colombian scientific journals and other publications on infectious disease that were not available electronically. In total, 43 observational studies and epidemiological reports were identified with information about resistance among Enterobacteriaceae isolates in Colombian hospitals, mainly from Bogotá, Cali and Medellín. The resistance rate of Escherichia coli ranges from 3 to 11%, 5 to 20% and from 0.2 to 0.8% for piperacillin-tazobactam, third generation cephalosporins and carbapenems, respectively. For Klebsiella pneumoniae resistance rates ranges from 21.8 to 48.1% to piperacillin-tazobactam, 20 to 35% to broad-spectrum cephalosporins and 3 to 8% to carbapenems, with significant variations by cities, levels of care and clinical settings. The spread of bacterial resistance in Enterobacteriaceae isolated in Colombian hospitals is a growing problem that calls for priority action to cut the chains of transmission.

Pharmacodynamics of colistin and fosfomycin: a 'treasure trove' combination combats KPC-producing Klebsiella pneumoniae.

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Zhao, Miao; Bulman, Zackery P; Lenhard, Justin R; Satlin, Michael J; Kreiswirth, Barry N; Walsh, Thomas J; Marrocco, Amanda; Bergen, Phillip J; Nation, Roger L; Li, Jian; Zhang, Jing; Tsuji, Brian T

2017-07-01

KPC-producing Klebsiella pneumoniae are an emerging public health problem around the globe. We defined the combinatorial pharmacodynamics and ability to suppress resistance of two 'old' antibiotics, fosfomycin and colistin, in time-kill experiments and hollow-fibre infection models (HFIM). Two KPC-2-producing K. pneumoniae isolates were used: one susceptible to both colistin and fosfomycin (KPC 9A: MIC colistin 0.25 mg/L and MIC fosfomycin ≤8 mg/L) and the other resistant to colistin and susceptible to fosfomycin (KPC 5A: MIC colistin 64 mg/L and MIC fosfomycin 32 mg/L). Time-kill experiments assessed an array of colistin and fosfomycin concentrations against both isolates. Colistin and fosfomycin pharmacokinetics from critically ill patients were simulated in the HFIM to define the pharmacodynamic activity of humanized regimens over 5 days against KPC 9A. In time-kill experiments, synergy was demonstrated for all colistin/fosfomycin combinations containing >8 mg/L fosfomycin against the double-susceptible KPC strain, 9A. Synergy versus KPC strain 5A was only achieved at the highest concentrations of colistin (4 mg/L) and fosfomycin (512 mg/L) at 48 h. In the HFIM, colistin or fosfomycin monotherapies resulted in rapid proliferation of resistant subpopulations; KPC 9A regrew by 24 h. In contrast to the monotherapies, the colistin/fosfomycin combination resulted in a rapid 6.15 log 10  cfu/mL reduction of KPC 9A by 6 h and complete suppression of resistant subpopulations until 120 h. Colistin and fosfomycin may represent an important treatment option for KPC-producing K. pneumoniae otherwise resistant to traditional antibiotics. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Toward repurposing ciclopirox as an antibiotic against drug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae.

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Carlson-Banning, Kimberly M; Chou, Andrew; Liu, Zhen; Hamill, Richard J; Song, Yongcheng; Zechiedrich, Lynn

2013-01-01

Antibiotic-resistant infections caused by gram-negative bacteria are a major healthcare concern. Repurposing drugs circumvents the time and money limitations associated with developing new antimicrobial agents needed to combat these antibiotic-resistant infections. Here we identified the off-patent antifungal agent, ciclopirox, as a candidate to repurpose for antibiotic use. To test the efficacy of ciclopirox against antibiotic-resistant pathogens, we used a curated collection of Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates that are representative of known antibiotic resistance phenotypes. We found that ciclopirox, at 5-15 µg/ml concentrations, inhibited bacterial growth regardless of the antibiotic resistance status. At these same concentrations, ciclopirox reduced growth of Pseudomonas aeruginosa clinical isolates, but some of these pathogens required higher ciclopirox concentrations to completely block growth. To determine how ciclopirox inhibits bacterial growth, we performed an overexpression screen in E. coli. This screen revealed that galE, which encodes UDP-glucose 4-epimerase, rescued bacterial growth at otherwise restrictive ciclopirox concentrations. We found that ciclopirox does not inhibit epimerization of UDP-galactose by purified E. coli GalE; however, ΔgalU, ΔgalE, ΔrfaI, or ΔrfaB mutant strains all have lower ciclopirox minimum inhibitory concentrations than the parent strain. The galU, galE, rfaI, and rfaB genes all encode enzymes that use UDP-galactose or UDP-glucose for galactose metabolism and lipopolysaccharide (LPS) biosynthesis. Indeed, we found that ciclopirox altered LPS composition of an E. coli clinical isolate. Taken together, our data demonstrate that ciclopirox affects galactose metabolism and LPS biosynthesis, two pathways important for bacterial growth and virulence. The lack of any reported fungal resistance to ciclopirox in over twenty years of use in the clinic, its excellent safety

Changes in antimicrobial susceptibility patterns of Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus over the past decade

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Barfod, Toke Seierøe; Wibroe, Elisabeth Arnberg; Braüner, Julie Vestergaard

2015-01-01

in resistance patterns were noted up to 2014. CONCLUSIONS: A comprehensive and manageable inventory of the resistance patterns of the major bacteria covering the 2004-2008 period is presented. Clinicians are encouraged to use the pocket-size table as guidance when choosing antibiotic treatment. FUNDING: none......INTRODUCTION: Development of antimicrobial resistance is an ongoing and increasing problem. To provide the best possible treatment for patients it is crucial that clinicians are aware of the local antimicrobial susceptibility patterns. The aim of this study was to present an overview...... susceptibility at Hvidovre Hospital, Denmark, from 2004 to 2008. Due to a suspected rise in resistance in Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae after this period, updated data for these bacteria are shown for selected antibiotics until 2014. The department receives samples from...

Antibacterial effects of Apis mellifera and stingless bees honeys on susceptible and resistant strains of Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae in Gondar, Northwest Ethiopia.

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Ewnetu, Yalemwork; Lemma, Wossenseged; Birhane, Nega

2013-10-19

Honey is a natural substance produced by honeybees and has nutritional and therapeutic uses. In Ethiopia, honeys are used traditionally to treat wounds, respiratory infections and diarrhoea. Recent increase of drug resistant bacteria against the existing antibiotics forced investigators to search for alternative natural remedies and evaluate their potential use on scientific bases. Thus, the aim of this study was to evaluate the antibacterial effects of different types of honeys in Ethiopia which are used traditionally to treat different types of respiratory and gastrointestinal infections. Mueller Hinton agar (70191) diffusion and nutrient broth culture medium assays were performed to determine susceptibility of Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and resistant clinical isolates (Methicillin resistant Staphylococcus aureus(MRSA), Escherichia coli(R) and Klebsiella pneumoniae (R), using honeys of Apis mellifera and stingless bees in northern and north western Ethiopia. Honey of the stingless bees produced the highest mean inhibition (22.27 ± 3.79 mm) compared to white honey (21.0 ± 2.7 mm) and yellow honey (18.0 ± 2.3 mm) at 50% (v/v) concentration on all the standard and resistant strains. Stingless bees honey was found to have Minimum Inhibitory Concentration (MIC) of 6.25% (6.25 mg/ml) for 80% of the test organisms compared to 40% for white and yellow Apis mellifera honeys. All the honeys were found to have minimum bactericidal concentration (MBC) of 12.5% (12.5 mg/ml) against all the test organisms. Staphylococcus aureus (ATCC 25923) was susceptible to amoxicillin, methicillin, kanamycine, tetracycline, and vancomycine standard antibiotic discs used for susceptibility tests. Similarly, Escherichia coli (ATCC 25922) was found susceptible for kanamycine, tetracycline and vancomycine. Escherichia coli (ATCC 25922) has not been tested for amoxicillin ampicillin and methicillin. The susceptibility tests performed against

Oxygen sensitivity of the nifLA promoter of Klebsiella pneumoniae.

OpenAIRE

Kong, Q T; Wu, Q L; Ma, Z F; Shen, S C

1986-01-01

Oxygen sensitivity of the nifLA promoter of Klebsiella pneumoniae has been demonstrated. Studies on the oxygen regulation of nifB-lacZ and nifH-lacZ fusions in the presence of the nifLA operon, which contains either an intact or a deleted nifL gene, indicate that possibly both the nifL promoter and the nifL product are responsible for nif repression by oxygen.

CARBAPENEM-RESISTANT ACINETOBACTER BAUMANII POSTOPERATIVE MENINGITIS

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Laura Ghibu; Egidia Miftode; Olivia Dorneanu; Carmen Dorobat

2011-01-01

Acinetobacter baumannii is an opportunistic pathogen of increasing relevance in hospital infections during the last 15 years.This organism causes a wide range of infection .Extensive use of antibiotics within hospitals has contribute to the emergence of multidrug-resistent A.baumannii strains that exhibit resistance to a wide range of antibiotics ,including carbapenems.We report the case of an 37 years old man diagnosed with Acinetobacter multidrug-resistant post-neurosurgical meningitis with...

Investigation of class 1 integrons in Klebsiella pneumoniae clinical and microbiota isolates belonging to different phylogenetic groups in Recife, State of Pernambuco

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Alexsandra Maria Silva Lima

2014-04-01

Full Text Available Introduction The high prevalence of Klebsiella pneumoniae infections is related to the ability of K. pneumoniae to acquire and disseminate exogenous genes associated with mobile elements, such as R plasmids, transposons and integrons. This study investigated the presence of class 1 integrons in clinical and microbiota isolates of K. pneumoniae belonging to different phylogenetic groups and correlated these results with the antimicrobial resistance profiles of the studied isolates. Methods Of the 51 isolates of K. pneumoniae selected for this study, 29 were from multidrug-resistant clinical isolates, and 22 were from children's microbiota. The susceptibility profile was determined using the disk diffusion method, and class 1 integrons were detected through polymerase chain reaction (PCR. Results The results showed that none of the 22 microbiota isolates carried class 1 integrons. Among the 29 clinical isolates, 19 (65.5% contained class 1 integrons, and resistance to sulfamethoxazole/trimethoprim was identified in 18 of these isolates (94.7%. Among the K. pneumoniae isolates with class 1 integrons, 47% belonged to the KpI phylogenetic group, and one isolate (14.3% carrying these genetic elements belonged to the KpIII group. Conclusions The wide variety of detected class 1 integrons supports the presence of high rates of antimicrobial resistance, genetic variability, and rapid dissemination of beta-lactamase genes among K. pneumoniae clinical isolates in recent years in hospitals in Recife-PE, Brazil. The findings of this study indicate that the surveillance of K. pneumoniae integrons in clinical isolates could be useful for monitoring the spread of antibiotic resistance genes in the hospital environment.

125 ORIGINAL ARTICLE

African Journals Online (AJOL)

boaz

resistance pattern depends on using the antimicrobial regimen of best choice. Therefore the ... different genera of Enterobacteriaceae and Pseudomonas aeruginosa.(3) However, they are more common in. Klebsiella pneumoniae and. Escherichia coli.(4). Carbapenems are the drugs of first choice in most infections due to ...

Anti-biofilm activity: a function of Klebsiella pneumoniae capsular polysaccharide.

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Marina Dos Santos Goncalves

Full Text Available Competition and cooperation phenomena occur within highly interactive biofilm communities and several non-biocides molecules produced by microorganisms have been described as impairing biofilm formation. In this study, we investigated the anti-biofilm capacities of an ubiquitous and biofilm producing bacterium, Klebsiella pneumoniae. Cell-free supernatant from K. pneumoniae planktonic cultures showed anti-biofilm effects on most Gram positive bacteria tested but also encompassed some Gram negative bacilli. The anti-biofilm non-bactericidal activity was further investigated on Staphylococcus epidermidis, by determining the biofilm biomass, microscopic observations and agglutination measurement through a magnetic bead-mediated agglutination test. Cell-free extracts from K. pneumoniae biofilm (supernatant and acellular matrix also showed an influence, although to a lesser extend. Chemical analyses indicated that the active molecule was a high molecular weight polysaccharide composed of five monosaccharides: galactose, glucose, rhamnose, glucuronic acid and glucosamine and the main following sugar linkage residues [→ 2-α-L-Rhap-(1 →]; [→ 4-α-L-Rhap-(1 →]; [α-D-Galp-(1 →]; [→ 2,3-α-D-Galp-(1 →]; [→ 3-β-D-Galp-(1 →] and, [→ 4-β-D-GlcAp-(1 →]. Characterization of this molecule indicated that this component was more likely capsular polysaccharide (CPS and precoating of abiotic surfaces with CPS extracts from different serotypes impaired the bacteria-surface interactions. Thus the CPS of Klebsiella would exhibit a pleiotropic activity during biofilm formation, both stimulating the initial adhesion and maturation steps as previously described, but also repelling potential competitors.

Klebsiella pneumonia, a Microorganism that Approves the Non-linear Responses to Antibiotics and Window Theory after Exposure to Wi-Fi 2.4 GHz Electromagnetic Radiofrequency Radiation

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Taheri M.

2015-09-01

Full Text Available Background: Drug resistance is widely believed to be an increasingly serious threat to global public health. We have previously reported that short term exposure of microorganisms to diagnostic ultrasound waves could significantly alter their sensitivity to antibiotics. In our previous studies, Klebsiella pneumoniae showed major differences in the sensitivity to antibiotics in exposed and non-exposed samples. This study was aimed at investigating the alteration of antibiotic resistance of Klebsiella pneumonia, after exposure to Wi-Fi 2.4 GHz electromagnetic radiofrequency radiation. Materials and Methods: In this in vitro study, three replicate agar plates were used for each test. The antibiotic susceptibility test was carried out using disc diffusion method on Mueller Hinton agar plates and the inhibition zones in both control and exposed groups were measured. A common Wi-Fi router was used in this study as the radiofrequency exposure source. Irradiated samples were exposed to Wi-Fi radiofrequency radiation for 3, 4.5 and 8 hours. Results: Statistically significant variations of sensitivity to antibiotics were found for all studied antibiotics after 4.5 hours of RF exposure, compared to non-exposed bacteria. Interestingly, the mean diameters of the inhibition zones after 3 hours of exposure were less than those exposed for 4.5 hours. Following this rise in the sensitivity to antibiotics, a fall was observed in the bacteria exposed for 8 hours for all studied antibiotics. Conclusion: The findings of this study show a statistically significant rise in the sensitivity of Klebsiella pneumoniae to different antibiotics after 4.5 hours of exposure to 2.4 GHz Wi-Fi radiation, followed by a fall after 8 hours of exposure. These observations can be interpreted by the concept of non-linearity in the responses of Klebsiella pneumoniae to different antibiotics after exposure to electromagnetic radiofrequency radiation. As in this study a minimum level of

Biological Treatment of Cyanide by Using Klebsiella pneumoniae Species

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Isil Seyis Bilkay

2016-01-01

Full Text Available In this study, optimization conditions for cyanide biodegradation by Klebsiella pneumoniae strain were determined to be 25 °C, pH=7 and 150 rpm at the concentration of 0.5 mM potassium cyanide in the medium. Additionally, it was found that K. pneumoniae strain is not only able to degrade potassium cyanide, but also to degrade potassium hexacyanoferrate(II trihydrate and sodium ferrocyanide decahydrate with the efficiencies of 85 and 87.5 %, respectively. Furthermore, this strain degraded potassium cyanide in the presence of different ions such as magnesium, nickel, cobalt, iron, chromium, arsenic and zinc, in variable concentrations (0.1, 0.25 and 0.5 mM and as a result the amount of the bacteria in the biodegradation media decreased with the increase of ion concentration. Lastly, it was also observed that sterile crude extract of K. pneumoniae strain degraded potassium cyanide on the fifth day of incubation. Based on these results, it is concluded that both culture and sterile crude extract of K. pnemoniae will be used in cyanide removal from different wastes.

Bilateral scrotal abscesses caused by Klebsiella pneumoniae in a newborn.

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Di Renzo, Dacia; Pappalepore, Nicola; Colangelo, Maurizia; Chiesa, Pierluigi Lelli

2010-03-01

The management of acute scrotal swelling can be challenging in neonatal age, with scrotal infections being great mimickers of testicular torsion. Only a few unilateral cases of scrotal abscess have been previously reported, mostly caused by Staphylococcus and Salmonella. We describe the case of a newborn who developed bilateral scrotal abscesses caused by Klebsiella pneumoniae and discuss the rarity of the case, regarding both the bilaterality and the pathogen, never reported before.

An outbreak of ESBL-producing Klebsiella pneumoniae in an Iranian referral hospital: epidemiology and molecular typing.

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Mahmoudi, Shima; Pourakbari, Babak; Rahbarimanesh, Aliakbar; Abdolsalehi, Mohammad Reza; Ghadiri, Keyghobad; Mamishi, Setareh

2018-05-07

Klebsiella pneumoniae is a common cause of nosocomial infections; however, there is limited information in Iran regarding nosocomial outbreaks due to extended-spectrum β-lactamase (ESBL) producing K pneumoniae strains, particularly using molecular methods. The present study focused on the molecular mechanism of ESBL resistance and genetic relatedness in K. pneumoniae isolates causing nosocomial infections in an Iranian referral hospital. This study was evaluated the antimicrobial resistance and molecular epidemiology of K. pneumoniae causing nosocomial infections between October 2013 and March 2014. The ESBL detection was carried out for all the isolates by the CLSI method and PCR was carried out for the detection of the blaSHV, blaTEM, and blaCTX-M genes among ESBL-producing K. pneumonia. Molecular typing of the K. pneumoniae was performed using random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). A total of 30 isolates of K. pneumoniae were used for epidemiological analysis. High rates of resistance to cefotaxime (n=29, 97%), cefazolin (n=29, 97%), cefepime (n=25, 83%) and gentamicin (n=23, 77%) were observed. A total of 29 strains (97%) produced ESBLs. The frequency of blaSHV, blaCTX-M and blaTEM genes among these isolates were 83% (n=25), 70% (n=21) and 57% (n=17), respectively. Surprisingly 11 isolated (37%) carried blaSHV, blaCTX-M and blaTEM genes simultaneously. Moreover, the concurrent presence of "blaSHV and blaCTX-M" and "blaSHV and blaTEM" was seen in 8 (27%) and 4 (13%) isolates, respectively. RAPD-PCR analyses revealed that K. pneumoniae isolates belonged to 2 RAPD-PCR types among which one cluster counted for 28 isolates. To our knowledge this is the first published report of nosocomial outbreak of ESBL-producing K. pneumoniae in children in Iran. Although the epidemiology of nosocomial infections with ESBL-producing organisms has not yet been explored in depth in Iran, our findings suggest that ESBL-producing organisms are

Plasmid borne Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) and AdeABC efflux pump conferring carbapenem-tigecycline resistance among Acinetobacter baumannii isolates harboring TnAbaRs.

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Savari, Mohammad; Ekrami, Alireza; Shoja, Saeed; Bahador, Abbas

2017-03-01

Here we studied the prevalence and mechanisms of simultaneous resistance to carbapenem and tigecycline and accumulation of resistance determinants reservoirs in genome of Acinetobacter baumannii (A. baumannii) clinical isolates. Susceptibility of the isolates were measured to 18 antimicrobial agents. Genetic diversity of the microbial population was determined using the International Clonal lineage typing (IC typing), multiple locus VNTR analysis (MLVA) and plasmid profiling methods. To detect the AbaRs, Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) genes, AdeABC efflux pump genes and resistance determinants, PCR was used. Filter mating experiments were used to prove that if carbapenem resistance genes are located on conjugative plasmids or not. Among the A. baumannii clinical isolates, 40.8% were carbapenem-tigecycline resistant and in this population, 46.9% were belonging to IC I, IC II or IC III and 53.1% were IC variants. These isolates had fallen in 40 MLVA types and were harboring plasmids in multiple numbers and sizes. In this study, bla OXA-23-like was the most prevalent CHDL and conjugation analysis proved that the carbapenem resistance genes are located on conjugative plasmids. All efflux pump genes, except for adeC, were detected in all carbapenem-tigecycline resistant A. baumannii (CTRAb) isolates. Resistance determinants were distributed in both TnAbaRs and R plasmids with a shift toward the R plasmids. Emerging of carbapenem resistant A. baumannii (CRAB) with simultaneous resistance to the last line therapy including tigecycline represent emerging of extensively drug resistance (XDR) and pandrug resistance (PDR) phenotypes that would be a great threat to our public health system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carbapenem susceptibilities and non-susceptibility concordance to different carbapenems amongst clinically important Gram-negative bacteria isolated from intensive care units in Taiwan: results from the Surveillance of Multicentre Antimicrobial Resistance in Taiwan (SMART) in 2009.

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Jean, Shio-Shin; Hsueh, Po-Ren; Lee, Wen-Sen; Yu, Kwok-Woon; Liao, Chun-Hsing; Chang, Feng-Yi; Ko, Wen-Chien; Wu, Jiunn-Jong; Chen, Yen-Hsu; Chen, Yao-Shen; Liu, Jien-Wei; Lu, Min-Chi; Liu, Cheng-Yi; Lam, Carlos; Chen, Ray-Jade

2013-05-01

To investigate the in vitro susceptibilities to various carbapenems amongst clinical Gram-negative bacteria isolated from patients in intensive care units of ten major teaching hospitals in Taiwan in 2009, a survey was conducted to determine the minimum inhibitory concentrations (MICs) of ertapenem, imipenem, meropenem and doripenem against isolates of Enterobacteriaceae (n = 594), Pseudomonas aeruginosa (n = 185), Acinetobacter baumannii (n = 192) and Burkholderia cepacia (n = 23) using the agar dilution method. Susceptibilities were determined according to 2009, 2011 and 2012 MIC breakpoints recommended by the CLSI as well as 2012 MIC breakpoints recommended by EUCAST. Based on CLSI 2012 criteria, the ertapenem susceptible rate was 93%, 81%, 68% and 92% for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens, respectively. All Proteus mirabilis and Morganella morganii isolates were susceptible to ertapenem; however, 64% of P. mirabilis and all M. morganii isolates were non-susceptible to imipenem. Meropenem and doripenem had better activities than imipenem against ertapenem-non-susceptible Enterobacteriaceae isolates. E. coli, K. pneumoniae and E. cloacae with ertapenem MICs≥4 mg/L were synchronously not susceptible to imipenem, meropenem and doripenem. Imipenem susceptibility was 65% and 29% for P. aeruginosa and A. baumannii, respectively. Additionally, P. aeruginosa and A. baumannii isolates with imipenem MICs≥8 mg/L were also not susceptible to meropenem and doripenem. These data provide a better understanding of choosing appropriate carbapenem agents to treat infections caused by ertapenem-non-susceptible Enterobacteriaceae as well as P. aeruginosa and A. baumannii isolates with imipenem MICs≥4 mg/L. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.

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Zhang, Hui; Yang, Qiwen; Liao, Kang; Ni, Yuxing; Yu, Yunsong; Hu, Bijie; Sun, Ziyong; Huang, Wenxiang; Wang, Yong; Wu, Anhua; Feng, Xianju; Luo, Yanping; Chu, Yunzhuo; Chen, Shulan; Cao, Bin; Su, Jianrong; Duan, Qiong; Zhang, Shufang; Shao, Haifeng; Kong, Haishen; Gui, Bingdong; Hu, Zhidong; Badal, Robert; Xu, Yingchun

2017-12-18

To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study

Caracterización de Klebsiella pneumoniae productora de la beta-lactamasa SHV-5, en una unidad de cuidados intensivos Characterization of SHV-5 beta-lactamase-producing Klebsiella pneumoniae in an intensive care unit

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Verónica Andrade

2004-12-01

Full Text Available OBJETIVO: Caracterizar molecularmente los aislamientos de Klebsiella pneumoniae obtenidos de pacientes pediátricos y del personal de salud en la unidad de cuidados intensivos de un hospital de tercer nivel de atención en la Ciudad de México, Distrito Federal. MATERIAL Y MÉTODOS: Se analizaron 15 aislamientos de Klebsiella pneumoniae colectadas de un brote durante el mes de junio de 1996, ocho de pacientes y siete de personal del Hospital Infantil de México. Los aislamientos fueron caracterizados por electroforesis en gel de campos pulsados (EGCP, amplificación azarosa del polimorfismo de ADN por reacción en cadena de la polimerasa (AAPD-PCR, y serotipificación, isoelectroenfoque de beta-lactamasas y secuenciación nucleotídica de productos de la reacción en cadena de la polimerasa. RESULTADOS: El serotipo predominante fue el 61 y correlacionó con los perfiles de AAPD-PCR y EGCP en 11 de los 15 aislamientos. Se identificó una clona predominante productora de SHV-5 con una alta letalidad. CONCLUSIONES: Las técnicas de biología molecular fueron herramientas muy útiles en la caracterización de la clona de K. pneumoniae identificada en pacientes y el personal hospitalario, que sugirieron una posible transmisión cruzada. Estos resultados ilustran que se debe apoyar el fortalecimiento de los programas de control para evitar la diseminación de infecciones nosocomiales en esa unidad en estudio.OBJECTIVE: To perform the molecular characterization of Klebsiella pneumoniae isolates from pediatric patients and health care workers at the intensive care unit of a tertiary care hospital in Mexico City. MATERIAL AND METHODS: Fifteen Klebsiella pneumoniae isolates collected during an outbreak in June 1996 were analyzed; eight were from patients and seven from health care workers of Mexico's Children's Hospital. Characterization of isolates was carried out by pulsed field gel electrophoresis (PFGE, random amplified polymorphic DNA polymerase

Role of nutrient limitation and stationary-phase existence in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin.

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Anderl, Jeff N; Zahller, Jeff; Roe, Frank; Stewart, Philip S

2003-04-01

Biofilms formed by Klebsiella pneumoniae resisted killing during prolonged exposure to ampicillin or ciprofloxacin even though these agents have been shown to penetrate bacterial aggregates. Bacteria dispersed from biofilms into medium quickly regained most of their susceptibility. Experiments with free-floating bacteria showed that stationary-phase bacteria were protected from killing by either antibiotic, especially when the test was performed in medium lacking carbon and nitrogen sources. These results suggested that the antibiotic tolerance of biofilm bacteria could be explained by nutrient limitation in the biofilm leading to stationary-phase existence of at least some of the cells in the biofilm. This mechanism was supported by experimental characterization of nutrient availability and growth status in biofilms. The average specific growth rate of bacteria in biofilms was only 0.032 h(-1) compared to the specific growth rate of planktonic bacteria of 0.59 h(-1) measured in the same medium. Glucose did not penetrate all the way through the biofilm, and oxygen was shown to penetrate only into the upper 100 micro m. The specific catalase activity was elevated in biofilm bacteria to a level similar to that of stationary-phase planktonic cells. Transmission electron microscopy revealed that bacteria were affected by ampicillin near the periphery of the biofilm but were not affected in the interior. Taken together, these results indicate that K. pneumoniae in this system experience nutrient limitation locally within the biofilm, leading to zones in which the bacteria enter stationary phase and are growing slowly or not at all. In these inactive regions, bacteria are less susceptible to killing by antibiotics.

Klebsiella pneumoniae yfiRNB operon affects biofilm formation, polysaccharide production and drug susceptibility.

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Huertas, Mónica G; Zárate, Lina; Acosta, Iván C; Posada, Leonardo; Cruz, Diana P; Lozano, Marcela; Zambrano, María M

2014-12-01

Klebsiella pneumoniae is an opportunistic pathogen important in hospital-acquired infections, which are complicated by the rise of drug-resistant strains and the capacity of cells to adhere to surfaces and form biofilms. In this work, we carried out an analysis of the genes in the K. pneumoniae yfiRNB operon, previously implicated in biofilm formation. The results indicated that in addition to the previously reported effect on type 3 fimbriae expression, this operon also affected biofilm formation due to changes in cellulose as part of the extracellular matrix. Deletion of yfiR resulted in enhanced biofilm formation and an altered colony phenotype indicative of cellulose overproduction when grown on solid indicator media. Extraction of polysaccharides and treatment with cellulase were consistent with the presence of cellulose in biofilms. The enhanced cellulose production did not, however, correlate with virulence as assessed using a Caenorhabditis elegans assay. In addition, cells bearing mutations in genes of the yfiRNB operon varied with respect to the WT control in terms of susceptibility to the antibiotics amikacin, ciprofloxacin, imipenem and meropenem. These results indicated that the yfiRNB operon is implicated in the production of exopolysaccharides that alter cell surface characteristics and the capacity to form biofilms--a phenotype that does not necessarily correlate with properties related with survival, such as resistance to antibiotics. © 2014 The Authors.

Spread of ISCR1 elements containing blaDHA-₁ and multiple antimicrobial resistance genes leading to increase of flomoxef resistance in extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae.

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Lee, Chen-Hsiang; Liu, Jien-Wei; Li, Chia-Chin; Chien, Chun-Chih; Tang, Ya-Fen; Su, Lin-Hui

2011-09-01

Increasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae exacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producing Klebsiella pneumoniae (ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producing K. pneumoniae isolates, ISCR1 was detected in 13 (72%) isolates, qnr genes (1 qnrA and 17 qnrB genes) were detected in 18 (100%), aac(6')-Ib-cr was detected in 11 (61%), and 16S rRNA methylase (all armA genes) was detected in 14 (78%). Four transconjugants were available for further analysis, and qnrB4, aac(6')-Ib-cr, armA, and bla(DHA-1) were all identified on these self-transferable bla(CTX-M)-carrying plasmids. The genetic environments of ISCR1 associated with armA, bla(DHA-1), and qnrB4 genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1 element-carrying plasmids has a clinical impact and warrants close monitoring and further study.

Case of Meningitis in a Neonate Caused by an Extended-Spectrum-Beta-Lactamase-Producing Strain of Hypervirulent Klebsiella pneumoniae

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Khalit S. Khaertynov

2017-08-01

Full Text Available Klebsiella pneumoniae is one of the most important infectious agents among neonates. This pathogen has a potential to develop an increased antimicrobial resistance and virulence. The classic non-virulent strain of K. pneumoniae, producing an extended-spectrum beta-lactamases (ESBL, is associated with nosocomial infection mainly in preterm neonates. Hypervirulent K. pneumoniae strains are associated with invasive infection among previously healthy ambulatory patients, and most of them exhibit antimicrobial susceptibility. During the last few years, several cases of diseases caused by hypervirulent K. pneumoniae producing ESBL have been registered in different geographical regions of the world. However, reports of such cases in neonates are rare. Here, we reported that this pathogen can cause pyogenic meningitis in full-term neonate with poor prognosis. A previously healthy, full-term, 12-day-old neonate was admitted to the infectious diseases hospital with suspected meningitis. The clinical symptoms included loss of appetite, irritability, fever, seizures, and a bulging anterior fontanelle. The analysis of the cerebrospinal fluid confirmed the diagnosis of meningitis. Blood and cerebrospinal fluid cultures were positive for K. pneumoniae, producing ESBL. K. pneumoniae isolates were resistant to aminopenicillins, 3rd generation cephalosporins but were sensitive to imipenem and meropenem. The “string test” was positive. The study of the virulence factors of K. pneumoniae by PCR revealed the presence of the rmpA gene. A combination of K. pneumoniae virulence and drug resistance complicated by cerebral oedema led to the death of the neonate. We concluded that both the risk of developing severe forms of infection and the outcome of the disease due to K. pneumonia are associated with the phenotypic features of the pathogen such as its antibiotic susceptibility and virulence factors. Emergence of the ESBL-producing strain of hypervirulent K

Nasopharyngeal bacterial carriage and antimicrobial resistance in underfive children with community acquired pneumonia

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Cissy B. Kartasasmita

2002-09-01

Full Text Available Pathogens in nasopharynx is a significant risk factor of pneumonia. According to WHO, isolates to be tested for antimicrobial resistance in the community should be obtained from nasopharyngeal (NP swabs. The aim of this study is to know the bacterial patterns of the nasopharynx and cotrimoxazole resistance in under five-year old children with community acquired pneumonia. The study was carried out in 4 primary health clinic (Puskesmas in Majalaya sub-district, Bandung, West Java, Indonesia. All underfive children with cough and/or difficult breathing and classified as having non-severe pneumonia (WHO guidelines were placed in Amies transport medium and stored in a sterile jar, before taken to the laboratory for further examination, in the same day. During this nine month study, 698 children with clinical signs of non-severe pneumonia were enrolled. About 25.4% (177/698 of the nasopharyngeal specimens yielded bacterial isolates; i.e. 120 (67.8% were positive for S pneumoniae, 21 for S epidermidis and alpha streptococcus, 6 for Hafnia alvei, 5 for S aureus, 2 for B catarrhalis, and 1(0.6% for H influenza and Klebsiella, respectively. The antimicrobial resistance test to cotrimoxazole showed that 48.2% of S pneumoniae strain had full resistance and 32.7% showed intermediate resistance to cotrimoxazole. This result is almost similar to the other studies from Asian countries. It seems that H influenza is not a problem in the study area, however, a further study is needed. (Med J Indones 2002; 11: 164-8 Keywords: nasopharyngeal swab, S pneumoniae, cotrimoxazole

Complete nucleotide sequence of the multidrug resistance IncA/C plasmid pR55 from Klebsiella pneumoniae isolated in 1969.

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Doublet, Benoît; Boyd, David; Douard, Gregory; Praud, Karine; Cloeckaert, Axel; Mulvey, Michael R

2012-10-01

To determine the complete nucleotide sequence of the multidrug resistance IncA/C plasmid pR55 from a clinical Klebsiella pneumoniae strain that was isolated from a urinary tract infection in 1969 in a French hospital and compare it with those of contemporary emerging IncA/C plasmids. The plasmid was purified and sequenced using a 454 sequencing approach. After draft assembly, additional PCRs and walking reads were performed for gap closure. Sequence comparisons and multiple alignments with other IncA/C plasmids were done using the BLAST algorithm and CLUSTAL W, respectively. Plasmid pR55 (170 810 bp) revealed a shared plasmid backbone (>99% nucleotide identity) with current members of the IncA/C(2) multidrug resistance plasmid family that are widely disseminating antibiotic resistance genes. Nevertheless, two specific multidrug resistance gene arrays probably acquired from other genetic elements were identified inserted at conserved hotspot insertion sites in the IncA/C backbone. A novel transposon named Tn6187 showed an atypical mixed transposon configuration composed of two mercury resistance operons and two transposition modules that are related to Tn21 and Tn1696, respectively, and an In0-type integron. IncA/C(2) multidrug resistance plasmids have a broad host range and have been implicated in the dissemination of antibiotic resistance among Enterobacteriaceae from humans and animals. This typical IncA/C(2) genetic scaffold appears to carry various multidrug resistance gene arrays and is now also a successful vehicle for spreading AmpC-like cephalosporinase and metallo-β-lactamase genes, such as bla(CMY) and bla(NDM), respectively.

NNDSS - Table II. Carbapenemase-producing carbapenem-resistant Enterobacteriaceae

Data.gov (United States)

U.S. Department of Health & Human Services — NNDSS - Table II. Carbapenemase-producing carbapenem-resistant Enterobacteriaceae - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000...

Deaths Attributable to Carbapenem-Resistant Enterobacteriaceae Infections

Centers for Disease Control (CDC) Podcasts

2014-08-06

Dr. Mike Miller reads an abridged version of the article, Deaths Attributable to Carbapenem-Resistant Enterobacteriaceae Infections.  Created: 8/6/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/13/2014.

Enterobacter and Klebsiella species isolated from fresh vegetables marketed in Valencia (Spain) and their clinically relevant resistances to chemotherapeutic agents.

Science.gov (United States)

Falomir, María Pilar; Rico, Hortensia; Gozalbo, Daniel

2013-12-01

Occurrence of antibiotic-resistant pathogenic or commensal enterobacteria in marketed agricultural foodstuffs may contribute to their incorporation into the food chain and constitutes an additional food safety concern. In this work, we have determined the clinically relevant resistances to 11 common chemotherapeutic agents in Enterobacter and Klebsiella isolates from fresh vegetables from various sources (supermarkets and greengrocers' shops in Valencia, Spain). A total of 96 isolates were obtained from 160 vegetables analyzed (50% positive samples): 68 Enterobacter isolates (59 E. cloacae, two E. aerogenes, two E. cancerogenus, one E. gergoviae, and four E. sakazakii, currently Cronobacter spp.), and 28 Klebsiella isolates (19 K. oxytoca and 9 K. pneumoniae). Only seven isolates were susceptible to all agents tested, and no resistances to ceftazidime, ciprofloxacin, gentamicin, and chloramphenicol were detected. Most isolates were resistant to amoxicillin/clavulanic acid (74 [58 Enterobacter and 16 Klebsiella]) or to ampicillin (80 [55/25]). Other resistances were less frequent: nitrofurantoin (13 isolates [12/1]), tetracycline (6 [5/1]), co-trimoxazole (3 [3/0]), cefotaxime (1 [1/0]), and streptomycin (2 [1/1]). Multiresistant isolates to two (56 [41/15]), three (10 E. cloacae isolates), four (one E. cloacae and one K. pneumoniae isolate), and five (two E. cloacae isolates) chemotherapeutic agents were also detected. The presence of potential pathogens points to marketed fresh produce, which often is eaten raw, as a risk factor for consumer health. In addition, these results support the usefulness of these bacterial species as indicators of the spreading of antibiotic resistances into the environment, particularly in the food chain, and suggest their role as carriers of resistance determinants from farms to consumers, which may constitute an additional "silent" food safety concern. Therefore, there is a need to improve the hygienic quality of marketed fresh

Emergence and mechanism of carbapenem-resistant Escherichia coli in Henan, China, 2014

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Wen-juan Liang

2018-05-01

Full Text Available The emergence and dissemination of carbapenem-resistant Escherichia coli (E. coli strains is a main risk for global public health, but little is known of carbapenemase producing E. coli in Henan, China. The study was undertaken to investigate the prevalence and mechanism of carbapenem-resistant E. coli strains in a hospital in Xinxiang, Henan, China, 2014. A total of 5 carbapenemase-producing E. coli strains were screened from 1014 isolates. We found that they were all resistant to meropenem and imipenem. Amikacin showed the best sensitivity, with gentamicin coming up next. The positive rate of blaNDM was 80% (4/5. The sequencing results showed that two isolates belonged to blaNDM-1 whereas other 2 isolates carried the blaNDM-5. Other carbapenemase genes including blaIMP, blaVIM, blaKPC and blaOXA-48 were not detected. The blaCTX-M-15, blaTEM-1, sul2, aad, and aac(6”–Ib–cr were also detected. MLST analysis showed that NDM-producing E. coli were sporadic. Conjugation test indicated blaNDM could be transferred. In conclusion, the blaNDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital, Henan, China. Keywords: blaNDM, Carbapenem-resistant, Escherichia coli

Changes in antimicrobial susceptibility patterns of Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus over the past decade

DEFF Research Database (Denmark)

Barfod, Toke Seierøe; Wibroe, Elisabeth Arnberg; Braüner, Julie Vestergaard

2015-01-01

of the percentage of bacterial isolates that are covered by the most commonly used antibiotics in the area of Copenhagen and to provide clinicians with a practical tool to help chose the right antimicrobial treatment for their patients. METHODS: We conducted a study of all bacteria isolates tested for antimicrobial...... susceptibility at Hvidovre Hospital, Denmark, from 2004 to 2008. Due to a suspected rise in resistance in Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae after this period, updated data for these bacteria are shown for selected antibiotics until 2014. The department receives samples from...... in resistance patterns were noted up to 2014. CONCLUSIONS: A comprehensive and manageable inventory of the resistance patterns of the major bacteria covering the 2004-2008 period is presented. Clinicians are encouraged to use the pocket-size table as guidance when choosing antibiotic treatment. FUNDING: none...

Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF-κB/MAPK signaling.

Science.gov (United States)

Mei, Xue; Wang, Hao-Xun; Li, Jian-Sheng; Liu, Xiao-Hui; Lu, Xiao-Fan; Li, Ya; Zhang, Wei-Yu; Tian, Yan-Ge

2017-04-17

Dusuqing granules (DSQ) have been used in the treatment of bacterial pneumonia clinically, with remarkable benefits. This study was initiated to explore the effects of DSQ on pulmonary inflammation by regulating nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signaling in bacterial pneumonia rats. Rat model was duplicated with Klebsiella pneumonia by a one-time intratracheal injection. Rats were randomized into control, model, DSQ and levofloxacin (LVX) groups. After administrated with appropriate medicines for 7 days, lung tissues were harvested and prepared for pathological analysis, and interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP)-1and macrophage inflammatory protein (MIP)-2 detections. NF-κB mRNA was measured by real-time qPCR, and the phosphorylation and total proteins of P38MAPK, JNK46/54, ERK42/44 were determined by Western blotting. Marked pathological impairments were observed in model rats, whereas were improved in DSQ group. The cytokines levels, NF-κB mRNA expression and the phosphorylation of P38MAPK, JNK46/54 and ERK42/44 proteins were significantly higher in model group, and were significantly depressed in DSQ group. The protective effects of DSQ on Klebsiella pneumonia might be attributed to its inactivative effects of NF-κB/ MAPK pathway.

Carbapenemase-producing Enterobacteriaceae: a 2-year surveillance in a hospital in Iaşi, Romania.

Science.gov (United States)

Braun, Sascha D; Dorneanu, Olivia S; Vremeră, Teodora; Reißig, Annett; Monecke, Stefan; Ehricht, Ralf

2016-01-01

Limited information is currently available about the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in Romania. Routine tests of 1,993 clinical isolates at a hospital in Iaşi yielded 46 isolates that were resistant to carbapenems. All 46 isolates were phenotypically and genotypically analyzed using VITEK-2 and DNA microarray-based assays. Isolates were assigned to Klebsiella pneumoniae and Enterobacter cloacae. For 39 isolates, carbapenem resistance was confirmed and 37 harbored at least one carbapenem resistance gene. Two isolates were probably resistant due to AmpC β-lactamases in combination with a porin loss. The overall concordance between detected phenotype and genotype was 95%. Our data show that carbapenemase-producing isolates with different underlying resistance mechanisms are still rare in Iaşi, but the global rise of CPE warrants intensified surveillance.

Browse Title Index

African Journals Online (AJOL)

Items 1 - 50 of 721 ... Vol 21, No 1 (2015), Antimicrobial susceptibility of urinary Klebsiella pneumoniae and the emergence of carbapenem-resistant strains: A retrospective study from a university hospital in Morocco, North Africa, Abstract PDF. MC El Bouamri, L Arsalane, Y El Kamouni, S Zouhair. Vol 23, No 2 (2017) ...

Occurrence of qnr-positive clinical isolates in Klebsiella pneumoniae producing ESBL or AmpC-type beta-lactamase from five pediatric hospitals in China.

Science.gov (United States)

Wang, Aihua; Yang, Yonghong; Lu, Quan; Wang, Yi; Chen, Yuan; Deng, Li; Ding, Hui; Deng, Qiulian; Wang, Li; Shen, Xuzhuang

2008-06-01

The plasmid-mediated quinolone resistance qnr genes in clinical isolates in adults have been described in different countries; however, the frequency of their occurrence has not been detected in pediatric patients. A total of 410 clinical isolates of Klebsiella pneumoniae, identified as producers of an extended-spectrum beta-lactamase (ESBL), or AmpC beta-lactamase, were collected from five children's hospitals in China during 2005-2006. The isolates were screened for the presence of the qnrA, qnrB, and qnrS genes, and then the harboring qnr gene isolates were detected for a bla gene coding for the TEM, SHV, CTX-M, and plasmid-mediated ampC gene by a PCR experiment. Ninety-two isolates (22.7%) were positive for the qnr gene, including 10 of qnrA (2.4%), 25 of qnrB (6.1%), and 62 of qnrS (15.1%). Eighty-one of the 92 (88.0%) qnr-positive isolates carried at least one bla gene for TEM, SHV, CTX-M, or DHA-1. The ciprofloxacin resistance increased 16-256-fold and oflaxacin resistance increased 2-32-fold in transconjugants, respectively. These results indicated that the plasmid-mediated qnr quinolone resistance gene was qnrS, followed by qnrB and qnrA. Most of the isolates also carried a bla gene coding ESBL or ampC gene coding DHA-1 among Klebsiella pneumoniae isolated from Chinese pediatric patients.

A case of acute postoperative keratitis after deep anterior lamellar keratoplasty by multidrug resistant Klebsiella

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Leena Bajracharya

2015-01-01

Full Text Available A healthy lady of 42 years underwent deep anterior lamellar keratoplasty for granular dystrophy. The very next day, it was complicated by development of infectious keratitis. The organism was identified as multidrug resistant Klebsiella pneumoniae. Donor corneal button may be implicated in the transmission of infection in an otherwise uneventful surgery and follow-up. Nosocomial infections are usually severe, rapidly progressive and difficult to treat. Finally, the lady had to undergo therapeutic penetrating keratoplasty for complete resolution of infection.

Molecular detection of β-lactamase and integron genes in clinical strains of Klebsiella pneumoniae by multiplex polymerase chain reaction

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Mansour Sedighi

Full Text Available Abstract INTRODUCTION: Infections caused by β-lactamase-producing gram-negative bacteria, such as Klebsiella pneumoniae, are increasing globally with high morbidity and mortality. The aim of the current study was to determine antimicrobial susceptibility patterns and the prevalence of antibiotic resistance genes (β-lactamase and integron genes using multiplex PCR. METHODS One-hundred K. pneumoniae isolates were collected from different clinical samples. Antibiotic susceptibility testing was performed with thirteen different antibiotics. Multiplex-PCR was used to detect β-lactamase (bla TEM, bla CTX-M, bla SHV , bla VEB, bla PER, bla GES, bla VIM, bla IMP, bla OXA, and bla KPC and integron genes (int I, int II, and int III. RESULTS: The highest and lowest rate of resistance was exhibited against amikacin (93% and imipenem (8%, respectively. The frequency of β-lactamase-positive K. pneumoniae was 37%, and the prevalence of the bla TEM, bla CTX-M, bla SHV , bla VEB, bla PER, bla GES, bla VIM, bla IMP, bla OXA, and bla KPC genes was 38%, 24%, 19%, 12%, 6%, 11%, 33%, 0%, 28%, and 23%, respectively. Of the 100 isolates, eight (8% were positive for class I integrons; however, class II and III integrons were not detected in any of the strains. CONCLUSIONS: These results indicate co-carriage of a number of β-lactamase genes and antibiotic resistance integrons on the same plasmids harboring multi-drug resistance genes. It seems that these properties help to decrease treatment complications due to resistant bacterial infections by rapid detection, infection-control programs and prevention of transmission of drug resistance.

Sustained pediatric antimicrobial stewardship program with consultation to infectious diseases reduced carbapenem resistance and infection-related mortality.

Science.gov (United States)

Horikoshi, Yuho; Suwa, Junichi; Higuchi, Hiroshi; Kaneko, Tetsuji; Furuichi, Mihoko; Aizawa, Yuta; Fukuoka, Kahoru; Okazaki, Kaoru; Ito, Kenta; Shoji, Takayo

2017-11-01

The impact of pediatric antimicrobial stewardship programs (ASP) on antimicrobial resistance (AMR) remains largely unknown. This study aimed to evaluate the AMR for carbapenem of Gram-negative bacilli (GNB) and carbapenem use with infectious diseases consultation after the implementation of an ASP. This quasi-experimental study was conducted at Tokyo Metropolitan Children's Medical Center in Japan. The pre- and post-intervention periods were April 2010 to September 2011 and October 2011 to March 2017, respectively. The pre-intervention phase consisted of consultations with the infectious diseases service alone. The ASP was implemented during the post-intervention phase. The carbapenem resistance rates of GNB were calculated. The correlation between carbapenem resistance rates and carbapenem day of therapy (DOT) was examined. The outcome metrics were compared by average length of hospitalization, all-cause mortality, and infection-related mortality. A positive correlation was observed between the carbapenem resistance rate in Pseudomonas aeruginosa and DOT (0.76, p=0.04). The carbapenem resistance rate in P. aeruginosa (pcarbapenem use and resistance in P. aeruginosa, leading to favorable outcomes in terms of length of hospitalization and infection-related mortality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Biofilm Production in Carbapenem Resistant Isolates from Chronic Wound Infections

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Swarna SR

2017-02-01

Full Text Available Biofilms are communities of microorganisms covered with extracellular polymeric substances. Such biofilm phenotype makes the microorganism resistant to antibiotics and plays a role in wound chronicity. This results in prolonged hospital stays in ICU, greater cost, and increased mortality. Methods: Pus swabs (59 were collected from a tertiary care hospital near Chennai were processed and identified using standard procedure followed by antibiotic susceptibility testing and identification of carbapenem resistance by Modified Hodge test as per CLSI guidelines. The biofilm formation was tested using plastic microtiter plate method. Results: Out of 59 pus swabs, 51 yielded growth with 69 isolates and 8 yielded no growth. Among the 69 isolates, 51 were GNB and 18 were GPC. Biofilm detection was noted in 84.31% (43/51 GNB isolates with 0.1% crystal violet whereas 100% (51/51 showed biofilm positive with 0.1% safranin. About 74.50% (38/51 isolates of GNB were carbapenem resistant by screening with disk diffusion method. Only 24% (6/25 of GNB isolates among Enterobacteriaceae were positive by Modified Hodge test method. Conclusion: The result shows the association of biofilm production among carbapenem resistant isolates obtained from chronic wound infections.

Factors associated with carriage of carbapenem-non-susceptible Enterobacteriaceaein North-Eastern France and outcomes of infected patients.

Science.gov (United States)

Muggeo, Anaëlle; Guillard, Thomas; Barbe, Coralie; Thierry, Aurore; Bajolet, Odile; Vernet-Garnier, Véronique; Limelette, Anne; Brasme, Lucien; De Champs, Christophe

2017-05-01

Carbapenems are frequently used as a last resort to treat infections caused by multidrug-resistant Gram-negative organisms, thus carbapenem-non-susceptible Enterobacteriaceae (CNSE) is an emerging health threat. To assess risk factors and outcomes of CNSE carriage. We conducted a matched case-control study in six hospitals in North-Eastern France. The controls were patients harbouring carbapenem-susceptible Enterobacteriaceae. Fifty-five cases and 110 controls were included. Most of the CNSE isolates were Enterobacter cloacae and Klebsiella pneumoniae . Carbapenemase production was observed in 40% of isolates and they produced OXA-48 only. CNSE carriage was significantly associated with recent antibiotic use ( P =  0.014), particularly carbapenems ( P =  0.03) and fluoroquinolones ( P =  0.016). A multivariate analysis using conditional logistic regression showed that the presence of concomitant infection(s) (OR: 9.83; 95% CI 3.04-21.39, P =  0.0031), nosocomial infections (OR: 7.84; 95% CI 2.00-12.54, P  =   0.0063) and a high age (OR: 1.07; 95% CI 1.01-1.06, P =  0.038) were independently associated with CNSE carriage. Moreover, patients infected with CNSE had worse outcomes: fewer resolved infections at 1 month ( P =  0.02), and they had a higher mortality rate ( P =  0.0004) and longer hospital stays ( P =  0.02). We identified three independent risk factors for CNSE carriage as well as worse outcomes in infected patients in North-Eastern France. This highlights the importance of early detection of CNSE and the need for antimicrobial therapy re-evaluation after bacteriological analysis has been performed. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore.

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Marimuthu, Kalisvar; Venkatachalam, Indumathi; Khong, Wei Xin; Koh, Tse Hsien; Cherng, Benjamin Pei Zhi; Van La, My; De, Partha Pratim; Krishnan, Prabha Unny; Tan, Thean Yen; Choon, Raymond Fong Kok; Pada, Surinder Kaur; Lam, Choong Weng; Ooi, Say Tat; Deepak, Rama Narayana; Smitasin, Nares; Tan, Eng Lee; Lee, Jia Jun; Kurup, Asok; Young, Barnaby; Sim, Nancy Tee Wen; Thoon, Koh Cheng; Fisher, Dale; Ling, Moi Lin; Peng, Brenda Ang Sze; Teo, Yik-Ying; Hsu, Li Yang; Lin, Raymond Tzer Pin; Ong, Rick Twee-Hee; Teo, Jeanette; Ng, Oon Tek

2017-05-15

Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five

CRYSTAL STRUCTURE ANALYSIS OF A PUTATIVE OXIDOREDUCTASE FROM KLEBSIELLA PNEUMONIAE

Energy Technology Data Exchange (ETDEWEB)

Baig, M.; Brown, A.; Eswaramoorthy, S.; Swaminathan, S.

2009-01-01

Klebsiella pneumoniae, a gram-negative enteric bacterium, is found in nosocomial infections which are acquired during hospital stays for about 10% of hospital patients in the United States. The crystal structure of a putative oxidoreductase from K. pneumoniae has been determined. The structural information of this K. pneumoniae protein was used to understand its function. Crystals of the putative oxidoreductase enzyme were obtained by the sitting drop vapor diffusion method using Polyethylene glycol (PEG) 3350, Bis-Tris buffer, pH 5.5 as precipitant. These crystals were used to collect X-ray data at beam line X12C of the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL). The crystal structure was determined using the SHELX program and refi ned with CNS 1.1. This protein, which is involved in the catalysis of an oxidation-reduction (redox) reaction, has an alpha/beta structure. It utilizes nicotinamide adenine dinucleotide phosphate (NADP) or nicotine adenine dinucleotide (NAD) to perform its function. This structure could be used to determine the active and co-factor binding sites of the protein, information that could help pharmaceutical companies in drug design and in determining the protein’s relationship to disease treatment such as that for pneumonia and other related pathologies.

The potential of methylethylpiridinol in treatment of bacterial infections caused by Klebsiella pneumoniae (experimental study

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V. M. Brykhanov

2016-01-01

Full Text Available Aim. Investigated the activity of methylethylpiridinol (6-methyl-2-ethyl-pyridin-3-ol hydrochloride in the comprehensive treatment of the experimental bacterial infection caused by Klebsiella pneumoniae.Materials and methods. The study was conducted on clinical isolates of Klebsiella pneumoniae. At the first stage of the study (in vitro studied the effect of methylethylpiridinol in concentrations 0,25–4 mM on the growth of the strain and the activity of the sublethal concentrations of antibiotics – gentamicin, ciprofloxacin, tetracycline, ceftazidime. In the second stage of the study (in vivo in rats Wistar simulated bacterial peritonitis by intraperitoneal injection of a suspension of Klebsiella pneumoniae and investigated the effect of methylethylpiridinol (80 mg/kg on the effectiveness of antibiotic therapy with gentamicin (30 mg/kg, ciprofloxacin (50 mg/kg, ceftazidime (120 mg/kg or tetracycline (80 mg/kg. The animal blood plasma was determined ceruloplasmin concentration (marker of the intensity of infectious-inflammatory process and thiobarbiturate-jet products, erythrocytes – the concentration of reduced glutathione, catalase and glutathione peroxidase.Results. It is found that a methylethylpiridinol inhibits the development of periodic bacterial cultures, but exhibits a pronounced antagonism with respect to gentamicin. Antioxidant slightly increases the activity of ciprofloxacin and tetracycline. The bacteriostatic effect of antioxidant reduces the action of ceftazidime in vitro. In conditions of chemotherapy by using of gentamicin and ciprofloxacin additional injection of methylethylpiridinol leads to the preservation of ceruloplasmin level to the level of non-treated animals without showing the antioxidant effect. Ceftazidime exhibits antioxidant effect, reduces the introduction of methylethylpiridinol. The antioxidant properties of methylethylpiridinol did not appear in the application of

Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

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Fangcong Dong

Full Text Available Bacteremia, the presence of viable bacteria in the blood stream, is often associated with several clinical conditions. Bacteremia can lead to multiple organ failure if managed incorrectly, which makes providing suitable nutritional support vital for reducing bacteremia-associated mortality. In order to provide such information, we investigated the metabolic consequences of a Klebsiella pneumoniae (K. pneumoniae infection in vivo by employing a combination of (1H nuclear magnetic resonance spectroscopy and multivariate data analysis. K. pneumoniae was intravenously infused in rats; urine and plasma samples were collected at different time intervals. We found that K. pneumoniae-induced bacteremia stimulated glycolysis and the tricarboxylic acid cycle and also promoted oxidation of fatty acids and creatine phosphate to facilitate the energy-demanding host response. In addition, K. pneumoniae bacteremia also induced anti-endotoxin, anti-inflammatory and anti-oxidization responses in the host. Furthermore, bacteremia could cause a disturbance in the gut microbiotal functions as suggested by alterations in a range of amines and bacteria-host co-metabolites. Our results suggest that supplementation with glucose and a high-fat and choline-rich diet could ameliorate the burdens associated with bacteremia. Our research provides underlying pathological processes of bacteremia and a better understanding of the clinical and biochemical manifestations of bacteremia.

Prevalence of CTX-M and TEM β-lactamases in Klebsiella pneumoniae Isolates from Patients with Urinary Tract Infection, Al-Zahra Hospital, Isfahan, Iran

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Nafiseh Maleki

2018-01-01

Full Text Available Background: Extended-spectrum β-lactamase (ESBL-producing is a significant resistant mechanism to β-lactams in Enterobacteriaceae, especially in Klebsiella pneumoniae. The main objectives of this study were to genetically characterize urinary clinical isolates of K. pneumoniae through the investigating of blaTEM, blaCTX-M and using molecular typing by Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR method. We also determined the frequency of antibiotic resistance of K. pneumoniae strains to characterize the β-lactamases included. Materials and Methods: A cross-sectional study was carried out to evaluate 98 strains of K. pneumoniae isolated from urine culture of outpatients referred to Al-Zahra Hospital, Isfahan, Iran. Antibiotic susceptibility testing was performed using Kirby–Bauer's method. Screening of ESBLs was carried out using double-disk screening test. PCR technique was performed to detect TEM and CTX-M genes. The total DNA of each strain was tested by ERIC-PCR. Results: In 98 K. pneumoniae studied clinical isolates, 25.5% were ESBL producing and 44.9% multidrug-resistant (MDR. From 25 ESBL isolates, 23 (92% cases showed MDR phenotype. In ESBL producing isolates, 23 (92% were blaCTX-M and 19 (76% blaTEM positive. The antimicrobial drug susceptibilities of ESBL isolates indicated high resistant rates for cefotaxime and ceftazidime. All 25 ESBL producing isolates were resistant to cefotaxime. Complex patterns of fingerprints isolates showed that 36% of the isolates were belonged to the cluster no 5. Conclusion: This study revealed high antimicrobial resistance rates among ESBL isolates which can lead to various health difficulties. Epidemiological data collection from patients is recommended to develop the strategies to manage antibiotic resistance.

Invasive carbapenem-resistant Enterobacteriaceae infection at a ...

African Journals Online (AJOL)

Background. There are no paediatric reports of invasive infection caused by carbapenem-resistant Enterobacteriaceae (CRE) from Africa. Objectives. To document a series of cases of CRE infections at a tertiary children's hospital in Cape Town, South Africa, describing the clinical and microbiological findings in these ...

Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae strains isolated from liver abscess patients and stool samples from noninfectious subjects in Hong Kong, Singapore, and Taiwan.

Science.gov (United States)

Siu, L Kristopher; Fung, Chang-Phone; Chang, Feng-Yee; Lee, Nelson; Yeh, Kuo-Ming; Koh, Tse Hsien; Ip, Margaret

2011-11-01

Serotype K1 Klebsiella pneumoniae with multilocus sequence type 23 (ST23) has been strongly associated with liver abscess in Taiwan. Few data regarding the strain types and virulence of this serotype from other Asian countries are available. Serotype K1 K. pneumoniae strains isolated from liver abscess and stool samples from subjects hospitalized in Hong Kong, Singapore, and Taiwan hospitals were examined. Forty-seven serotype K1 isolates were identified: 26 from liver abscess samples and 21 from stool samples. MLST revealed 7 sequence types: 85.1% (40 of 47 isolates) belonged to ST23, 1 isolate belonged to ST163 (a single-locus variant of ST23), and 2 isolates were ST249 (a 3-locus variant of ST23). New STs, namely, ST367, ST425, and ST426, were allocated to 3 of 4 isolates from stool samples. The virulence of these strains was determined by neutrophil phagocytosis and mouse infection models. Except for two ST23 isolates, all Klebsiella pneumoniae isolates were resistant to phagocytosis. Resistance to serum killing varied in isolates of ST23, while all non-ST23 strains were susceptible to serum killing except one with ST249 from a liver abscess. All hypervirulent isolates with a 50% lethal dose of serum killing, and also carried both virulence-associated genes, rmpA and aerobactin. Multilocus sequence typing genotype 23 was the most prevalent sequence type among serotype K1 K. pneumoniae isolates from both liver abscess and stool samples in the Asia Pacific region. Serotype K1 K. pneumoniae isolates with capsule expression leading to phagocytic resistance and with the aerobactin gene were associated with hypervirulence.

Photoexcited quantum dots for killing multidrug-resistant bacteria

Science.gov (United States)

Courtney, Colleen M.; Goodman, Samuel M.; McDaniel, Jessica A.; Madinger, Nancy E.; Chatterjee, Anushree; Nagpal, Prashant

2016-05-01

Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

MCR-1 and OXA-48 In Vivo Acquisition in KPC-Producing Escherichia coli after Colistin Treatment.

Science.gov (United States)

Beyrouthy, Racha; Robin, Frederic; Lessene, Aude; Lacombat, Igor; Dortet, Laurent; Naas, Thierry; Ponties, Valérie; Bonnet, Richard

2017-08-01