Prevalence, mechanisms, and risk factors of carbapenem resistance in bloodstream isolates of Pseudomonas aeruginosa

Tam, Vincent H.; Chang, Kai-Tai; LaRocco, Mark; Schilling, Amy N.; McCauley, Shana K.; Poole, Keith; Garey, Kevin W.

doi:10.1016/j.diagmicrobio.2007.05.006

Cited by 42 publications

(31 citation statements)

References 23 publications

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“…To our knowledge, there has been no report that demonstrated the correlation between gender and the overexpression of efflux pump genes. However, Tam et al reported that there was a significant correlation between female gender and carbapenem-resistant Pseudomonas aeruginosa (30). We suggest that the expression level of the AcrAB efflux pump that was overproduced by the MarA transcriptional activator may differ by gender.…”

Section: Discussionmentioning

confidence: 93%

Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

et al. 2011

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Escherichia coli is one of the most common pathogens in urinary tract infections (UTIs), and antibiotic resistance in E. coli is becoming a serious problem in treating UTI. Efflux system overexpression is reported to contribute to E. coli resistance to several antibiotics. This study investigated the correlation of antibiotic susceptibilities with the overexpression of the efflux pump genes such as marA, yhiU, yhiV, and mdfA and with risk factors for antibiotic resistance in E. coli isolated from UTI patients. We examined the expression level of efflux pump genes using quantitative real-time reverse transcription-PCR (qRT-PCR). We also tested the in vitro susceptibilities to 12 kinds of antibiotics in 64 clinical strains of E. coli isolated from UTI patients. By multivariate analyses we revealed significant relationships between the overexpression of (i) marA and MICs of cefepime (FEP) and nalidixic acid (NAL), (ii) yhiV and MICs of minocycline (MIN), and (iii) mdfA and MICs of sitafloxacin (STX). In our investigation of the efflux pump genes, risk factors such as gender and the previous use of fluoroquinolones correlated with the overexpression of marA, and indwelling catheter use correlated with the overexpression of mdfA. In conclusion, we demonstrated that the increased expression of efflux pump genes such as marA and mdfA can lead to fluoroquinolone resistance in E. coli. These results contribute to our knowledge of the efflux system and raise the possibility of developing new agents, such as efflux pump inhibitors (EPIs), to antibiotic-resistant E. coli.There are many examples of multidrug resistance (MDR) in clinical isolates of Enterobacteriaceae, such as extended-spectrum ␤-lactamase (ESBL)-producing strains (6). The overexpression of efflux pumps was reported to contribute to MDR in E. coli (3,12). Almost all Gram-negative bacteria have genes for efflux pumps belonging to the resistance nodulation division (RND) family (3), and seven homologous RND-type pumps are known in E. coli. Five of these (AcrB, AcrF, MdtB, MdtC, and YhiV) are known to expel many kinds of drugs. Most of these efflux genes are not expressed or are expressed at low levels in clinical isolates (3). The tripartite efflux pump, AcrAB-TolC complex, contains AcrA, a fusion protein; AcrB, a cytoplasmic membrane transporter protein; and TolC, an outer membrane channel (12). The overexpression of this pump often is associated with the MDR phenotype in E. coli (3,15,27,32). YhiUV is regulated by the EvgAS, the twocomponent system (20), and helps expel doxorubicin and erythromycin by cooperating with TolC (3,7,10,14,20,21). A previous report showed that a point mutation in yhiV, coding for YhiV, was associated with differences in the MDR phenotype (3). The overexpression of efflux pump genes such as marA, yhiU, yhiV, and mdfA is related to antibiotic resistance, especially fluoroquinolones (3,12). This study investigated the relationship between the overexpression of these efflux pump genes and antibiotic resistance and risk factors for urin...

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Section: Discussionmentioning

confidence: 93%

Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

et al. 2011

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“…The clonal relatedness of the multidrug-resistant isolates was assessed using repetitive-element-based PCR (rep-PCR) (22,24,25). Genomic DNA was extracted using the UltraClean microbial DNA isolation kit…”

Section: Methodsmentioning

confidence: 99%

“…However, all the multidrug-resistant isolates examined were nonsusceptible (defined by a MIC of Ͼ2 mg/ liter) to doripenem (MIC 50 , 12 mg/liter; MIC 90 , Ͼ32 mg/liter). Based on our previous investigations, the most common mechanism of imipenem/meropenem resistance in our hospital was reduced OprD expression (25). We suspected this would also be the mechanism of doripenem resistance.…”

Section: ϫ5mentioning

confidence: 99%

Prevalence, Resistance Mechanisms, and Susceptibility of Multidrug-Resistant Bloodstream Isolates of Pseudomonas aeruginosa

Tam

Chang

Abdelraouf

et al. 2010

Antimicrob Agents Chemother

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135

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Pseudomonas aeruginosa is an important pathogen commonly implicated in nosocomial infections. The occurrence of multidrug-resistant (MDR) P. aeruginosa strains is increasing worldwide and limiting our therapeutic options. The MDR phenotype can be mediated by a variety of resistance mechanisms, and the corresponding relative biofitness is not well established. We examined the prevalence, resistance mechanisms, and susceptibility of MDR P. aeruginosa isolates (resistant to >3 classes of antipseudomonal agents [penicillins/cephalosporins, carbapenems, quinolones, and aminoglycosides]) obtained from a large, university-affiliated hospital. Among 235 nonrepeat bloodstream isolates screened between 2005 and 2007, 33 isolates (from 20 unique patients) were found to be MDR (crude prevalence rate, 14%). All isolates were resistant to carbapenems and quinolones, 91% were resistant to penicillins/cephalosporins, and 21% were resistant to the aminoglycosides. By using the first available isolate for each bacteremia episode (n ‫؍‬ 18), 13 distinct clones were revealed by repetitive-element-based PCR. Western blotting revealed eight isolates (44%) to have MexB overexpression. Production of a carbapenemase (VIM-2) was found in one isolate, and mutations in gyrA (T83I) and parC (S87L) were commonly found. Growth rates of most MDR isolates were similar to that of the wild type, and two isolates (11%) were found to be hypermutable. All available isolates were susceptible to polymyxin B, and only one isolate was nonsusceptible to colistin (MIC, 3 mg/liter), but all isolates were nonsusceptible to doripenem (MIC, >2 mg/liter). Understanding and continuous monitoring of the prevalence and resistance mechanisms of MDR P. aeruginosa would enable us to formulate rational treatment strategies to combat nosocomial infections.Pseudomonas aeruginosa is an important pathogen commonly implicated in serious nosocomial infections such as pneumonia and sepsis. The occurrence of multidrug-resistant P. aeruginosa strains is increasing worldwide and limiting our therapeutic options. Resistance in P. aeruginosa may be mediated via several distinct mechanisms (3, 13). In multidrug-resistant isolates, the relative contributions of different molecular mechanisms toward phenotypic multidrug resistance are not well established. While there are multiple surveillance studies tracking the resistance of P. aeruginosa to various antimicrobial agents over the years (6, 7), studies reporting trends in concomitant resistance to multiple agents over time are scarce.A hypermutable state is often observed in multidrug-resistant pathogens causing chronic infections in cystic fibrosis patients. It is often related to defects in genes involved in the mismatch repair system (e.g., mutS and mutL). It is also commonly believed that in multidrug-resistant P. aeruginosa isolates, reduced virulence may result due to decreased biofitness. However, recent data suggest otherwise, and multidrug-resistant P. aeruginosa may remain fully pathogenic (8).Many first-line agents are ...

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“…Carbapenems are commonly used as last-resort drugs for the treatment of infections caused by multidrug-resistant P. aeruginosa isolates. However, intensive use of carbapenems in the treatment of nosocomial P. aeruginosa infections has facilitated the emergence of mechanisms that confer resistance to carbapenems, such as diminished permeability, overexpression of the intrinsic efflux systems, and production of carbapenemases (21). Acquisition of class B metallo-␤-lactamases (MBLs) constitutes a growing family of carbapenem-hydrolyzing ␤-lactamases among P. aeruginosa strains (26).…”

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confidence: 99%

Large Dissemination of VIM-2-Metallo-β-Lactamase-Producing Pseudomonas aeruginosa Strains Causing Health Care-Associated Community-Onset Infections

et al. 2009

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a series of 45 outpatients presented with community-onset urinary tract infections due to carbapenem-resistant Pseudomonas aeruginosa isolates. Forty of them had a history of previous hospitalization or exposure to healthcare facilities, while the remaining five had not been previously admitted to our healthcare facilities or elsewhere within the preceding 12 months. In 18 outpatients, the carbapenem-resistant organisms caused recurrent community-onset urinary tract infections, while in three outpatients the organisms were also implicated in bacteremic episodes. All 45 single-patient P. aeruginosa isolates harbored the bla VIM-2 metallo-␤-lactamase (MBL) gene in a common class 1 integron structure. They belonged to one predominant pulsed-field gel electrophoresis type and three sporadically detected types; two of the sporadic clonal types were identified among outpatients without previous exposure to healthcare facilities, while the predominant clonal type was also identified to cause infections in hospitalized patients. This is the first study documenting that MBL-producing P. aeruginosa isolates cause community-onset infections that are related or not with exposure to healthcare facilities. Community-onset infections in our patients most likely resulted from the nosocomial acquisition of MBL producers, followed by a prolonged digestive carriage. The high rate of recurrent infections in the community underlies the difficulty of constraining infections caused by such microorganisms in the extrahospital setting.

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Prevalence, mechanisms, and risk factors of carbapenem resistance in bloodstream isolates of Pseudomonas aeruginosa

Cited by 42 publications

References 23 publications

Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

Correlation of Overexpression of Efflux Pump Genes with Antibiotic Resistance inEscherichia coliStrains Clinically Isolated from Urinary Tract Infection Patients

Prevalence, Resistance Mechanisms, and Susceptibility of Multidrug-Resistant Bloodstream Isolates of Pseudomonas aeruginosa

Large Dissemination of VIM-2-Metallo-β-Lactamase-Producing Pseudomonas aeruginosa Strains Causing Health Care-Associated Community-Onset Infections

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