Isolation of Imipenem-Resistant Enterobacter Species: Emergence of KPC-2 Carbapenemase, Molecular Characterization, Epidemiology, and Outcomes

Abstract

The prevalence of isolation of imipenem-resistant Enterobacter (IRE) strains is rising, with potential serious consequences in terms of patients' outcomes and general care. The study objective was to define the various epidemiological aspects of the isolation of these strains in comparison to cases of isolation of imipenemsusceptible Enterobacter (ISE) strains. Molecular analysis of IRE strains included genotyping and defining the presence of carbapenemases. We conducted a matched retrospective case-control study of patients hospitalized from April 2003 to December 2006. Each IRE case was matched with an ISE case by age and source of isolation. A multivariate analysis using conditional logistic regression was performed to compare the two patient groups. There were 33 cases of IRE isolations during the study period. Twenty isolates were analyzed and found to belong to three distinct pulsotypes. Cell extracts of all of these isolates hydrolyzed imipenem. PCR and sequencing revealed that these isolates harbored a KPC-2 gene. In multivariate analysis, a high invasive-device score (P ‫؍‬ 0.02) remained a predictor of IRE isolation. The mortality in the IRE group was 33%, compared to 9% among controls. Being an IRE case was significantly associated with increased mortality after controlling for confounders in a multivariate model (odds ratio, 8.3 ؎ 8.6; 95% confidence interval, 1.07 to 64; P ‫؍‬ 0.043). Resistance to imipenem due to bla KPC-2 among Enterobacter isolates has occurred in several clones in Tel Aviv, affecting particularly patients with multiple invasive devices compared to ISE controls. IRE infections are associated with increased mortality. Enhanced measures to control the hospital spread of IRE are warranted.Enterobacter species are among the most common causes of gram-negative health care-associated infections (12,20,24,28,30,35), causing 8% of nosocomial bacteremia cases, and are the second most common gram-negative pathogens causing pneumonia in patients admitted to intensive care units (ICUs) (19,24,28,30). In addition, in recent years, they are an increasing cause of community-acquired infections as well (30).Resistance to a variety of broad-spectrum antimicrobials among Enterobacter strains, including ␤-lactams, is frequently encountered (20,26,35). Moreover, the emergence of resistance to extended-spectrum cephalosporins occurs often during therapy (8). Enterobacter isolates contain a chromosomal group 1 ␤-lactamase (AmpC), which, when expressed in large quantities by either the induction or the selection of derepressed mutants, can hydrolyze expanded-spectrum cephalosporins, penicillins, and monobactams (29,30). Resistance to ␤-lactams is usually mediated through ␤-lactamase production or an alteration of porins, although other mechanisms such as target site modifications (e.g., in penicillin binding proteins) and drug efflux pumps have also been reported (35). Risk factors for Enterobacter infections and for extended-spectrum cephalosporin-resistant Enterobacter infections have been extensivel...

Resistance to carbapenems in sequence type 11 Klebsiella pneumoniae is related to DHA-1 and loss of OmpK35 and/or OmpK36

“…A recent study by Marchaim et al (2008) showed that the mortality rate was significantly higher for patients infected with KPC-producing Enterobacter species (33 %, 11/33) than for those infected with imipenem-susceptible strains (6 %, 2/33) (2008). Another case-control study reported by Patel et al (2008) showed that patients associated with carbapenem-resistant K. pneumoniae (mostly KPC-producing) infection were more likely to die during hospitalization than those associated with carbapenem-susceptible K. pneumoniae infection (48 vs 20 %; Patel et al, 2008).…”

Caracterização molecular dos mecanismos de resistência aos carbapenêmicos de isolados clínicos de Enterobacter aerogenes e Enterobacter cloacae

“…As espécies de Enterobacter estão entre os Gram-negativos mais comuns em IRAS, sendo consideradas patógenos hospitalares emergentes, que comprometem principalmente pacientes internados em Unidades de Terapia Intensiva (UTI) e imunodeprimidos (6)(7)(8)(9). Estudos demonstram que estão associados com até 8 % de casos de bacteremias hospitalares e são o segundo patógeno Gram-negativo mais comum em pneumonias em pacientes de UTI em algumas casuísticas (6)(7)(8)(9) .…”

“…Estudos demonstram que estão associados com até 8 % de casos de bacteremias hospitalares e são o segundo patógeno Gram-negativo mais comum em pneumonias em pacientes de UTI em algumas casuísticas (6)(7)(8)(9) .…”

“…É considerado o terceiro patógeno mais comumente recuperado do trato respiratório em algumas casuísticas e frequentemente é isolado na urina e no trato gastrointestinal de pacientes hospitalizados. Também é responsável por 8% dos casos de bacteremias nosocomias, com mortalidade de 29%, apresentando alta resistência a antibióticos de largo espectro (6,27,28) . (7,29,30) .…”

“…O primeiro relato desta enzima ocorreu em 2001 nos EUA (6,55) . A enzima KPC confere resistência a todos os β-lactâmicos, incluindo: Penicilinas, Cefalosporinas, Monobactâmicos e Carbapenêmicos.…”