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

Abstract

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 ...

Detection of GES-2, a Class A β-Lactamase Produced by Pseudomonas aeruginosa in a Teaching Hospital in Iran

“…Same results were obtained by Hirakawa et al (12). Resistance in P. aeruginosa may be mediated via several distinct mechanisms including the production of β-lactamases, efflux pumps, and target-site or outer membrane modifications (13). Efflux pump systems have been revealed as the extremely important causes of multi-drug resistance in P. aeruginosa.…”

Multidrug binding properties of the AcrB efflux pump characterized by molecular dynamics simulations

“…Of particular concern is the appearance of multidrug-resistant (MDR) Gramnegative bacteria (1,2), where the efflux pumps of the resistance nodulation division (RND) family make a major contribution to the MDR phenotype (3,4). Substrates of these pumps include antibiotics and biocides with very different structural features, although they all seem to have a significant lipophilic portion (5).…”

“…bacterial drug efflux pump | drug-binding pocket | efflux inhibitors T he past decades have seen the return of bacterial resistance as a major problem in public health (1,2). Of particular concern is the appearance of multidrug-resistant (MDR) Gramnegative bacteria (1,2), where the efflux pumps of the resistance nodulation division (RND) family make a major contribution to the MDR phenotype (3,4).…”

Treatment of extensively drug-resistant Gram-negative infections in critically ill patients: Outcome of a consensus meeting at the 13th Asia-Pacific Congress of Clinical Microbiology and Infection, October 2012

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