Carbapenem Therapy for Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli or Klebsiella pneumoniae: Implications of Ertapenem Susceptibility

Abstract

A retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs < 0.25 g/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P ‫؍‬ 0.1) or sepsis-related mortality rate (P ‫؍‬ 0.2) for patients with bacteremia caused by ESBL-producing K. pneumoniae (140 isolates, 55.8%) and E. coli (111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34; P < 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24; P ‫؍‬ 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88; P ‫؍‬ 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P ‫؍‬ 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs < 0.25 g/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 g/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of <0.5 g/ml was similar to the mortality for those whose isolates had MICs of >0.5 g/ml (P ‫؍‬ 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems for Enterobacteriaceae.

Recurrent urinary tract infection due to co‐infection with extended spectrum β‐lactamase‐producer uropathogenic Escherichia coli and enteroaggregative E. coli

“…The infrequency of earlier reports on community-acquired ESBL-mediated infection in the United States does not suggest a high prevalence of these pathogens in the community. The wider distribution of ESBL-producer bacteraemia in patients visiting emergency departments has been reported by other investigators (Lee et al, 2012). Although regularly culturing urine samples for microbiological analysis is difficult, without continuous surveillance to detect and control ESBL-producer pathogens, the frequency of these pathogens can only be expected to increase.…”

Pediatric extended spectrum β‐lactamase infection: Community‐acquired infection and treatment options

“…This limits the options of previously effective antibiotics, resulting in poorer outcome . Given that the production of ESBL confers resistance to most cephalosporins, the choice of antibiotics used in infection caused by these organisms relies mostly upon carbapenems . Frequent or inappropriate use of these drugs, however, poses the risk of resistance development.…”

Carbapenem susceptibility among Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates obtained from patients in intensive care units in Taiwan in 2005, 2007, and 2009

“…However, Lee et al (2012b) noted that bloodstream infections caused by the ESBLproducing E. coli and K. pneumoniae with ertapenem MICs N0.25 mg/L were significantly less responsive to ertapenem than to other carbapenems, a finding that contradicts the data reported in another Taiwanese study that supports the in vitro efficacy of ertapenem against the ESBL-producing GNB pathogens when the MIC breakpoints of CLSI 2009 were employed (Lee et al, 2013). It is noteworthy that an in vitro frequent (approximately 56%) and rapid (≤48 h) development of ESBL-producing E. coli strains that showed intermediate nonsusceptibility to ertapenem (MIC range, 0.75-1.5 mg/L) after administration of the first conventional dose of ertapenem was recently verified for an originally ertapenem-susceptible E. coli isolate (MIC value, 0.023 mg/L) with ESBL production (Tängdén et al, 2013).…”