Respiratory infections caused by Klebsiella pneumoniae are characterized by high rates of mortality and morbidity. Management of these infections is often difficult, due to the high frequency of strains that are resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. In the present study, we investigated the role of the K. pneumoniae AcrRAB operon in antimicrobial resistance and virulence by using isogenic knockouts deficient in the AcrB component and the AcrR repressor, both derived from the virulent strain 52145R. We demonstrated that the AcrB knockout was more susceptible, not only to quinolones, but also to other antimicrobial agents, including β-lactams, than the wild-type strain and the AcrR knockout. We further showed that the AcrB knockout was more susceptible to antimicrobial agents present in human bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild-type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced capacity to cause pneumonia in a murine model, in contrast to the wild-type strain. The results of this study suggest that, in addition to contributing to the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel virulence factor required for K. pneumoniae to resist innate immune defense mechanisms of the lung, thus facilitating the onset of pneumonia.

Infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) in nonhospitalized patients seem to be emerging in different countries. Their incidence, epidemiology, and clinical impact in the community have not been studied. We describe the epidemiology and clinical features of infections caused by ESBLEC in nonhospitalized patients in Spain and the results of a case-control study performed to investigate the risk factors associated with the acquisition of these organisms. The clonal relatedness of the organisms was assessed by repetitive extragenic palindromic sequence PCR. The ESBLs and the genes encoding the ESBLs were initially characterized by isoelectric focusing and PCR, respectively. Forty-nine patients (76% with urinary tract infections, 22% with asymptomatic bacteriuria, and 2% with acute cholangitis) were included. Six patients were bacteremic. Diabetes mellitus (odds ratio, 5.5; 95% confidence interval, 1.6 to 18.7), previous fluoroquinolone use (odds ratio, 7.6; 95% confidence interval, 1.9 to 30.1), recurrent urinary tract infections (odds ratio, 4.5; 95% confidence interval, 1.3 to 15.1), a previous hospital admission (odds ratio, 18.2; 95% confidence interval, 5.3 to 61.1), and older age in male patients (odds ratio per year, 1.03; 95% confidence interval, 1.03 to 1.05) were identified as risk factors by multivariate analysis. The ESBLEC isolates were not clonally related. The ESBLs were characterized as members of the CTX-M-9 group, the SHV group, and the TEM group in 64, 18, and 18% of the isolates, respectively. ESBLEC is an emergent cause of urinary tract infections in nonhospitalized patients. There was no evidence of horizontal transmission of ESBLEC strains. Avoidance of fluoroquinolone use in high-risk patients should be considered whenever possible in order to avoid the selection of these organisms.

Acquired carbapenemases are emerging resistance determinants in Gram-negative pathogens, including Enterobacteriaceae, Pseudomonas aeruginosa and other Gram-negative non-fermenters. A consistent number of acquired carbapenemases have been identified during the past few years, belonging to either molecular class B (metallo-β-lactamases) or molecular classes A and D (serine carbapenemases), and genes encoding these enzymes are associated with mobile genetic elements that allow their rapid dissemination in the clinical setting. Therefore, detection and surveillance of carbapenemase-producing organisms have become matters of major importance for the selection of appropriate therapeutic schemes and the implementation of infection control measures. As carbapenemase production cannot be simply inferred from the resistance profile, criteria must be established for which isolates should be suspected and screened for carbapenemase production, and for which tests (phenotypic and/or genotypic) should be adopted for confirmation of the resistance mechanism. Moreover, strategies should be devised for surveillance of carbapenemase producers in order to enable the implementation of effective surveillance programmes. The above issues are addressed in this article, as a follow-up to an expert meeting on acquired carbapenemases that was recently organized by the ESCMID Study Group for Antibiotic Resistance Surveillance.