Cefepime vs Other Antibacterial Agents for the Treatment of Enterobacter Species Bacteremia

Clinical Infectious Diseases, Jun 2014

Background. Carbapenems are recommended for treatment of Enterobacter infections with AmpC phenotypes. Although isolates are typically susceptible to cefepime in vitro, there are few data supporting its clinical efficacy. Methods. We reviewed all cases of Enterobacter species bacteremia at 2 academic hospitals from 2005 to 2011. Outcomes of interest were (1) persistent bacteremia ≥1 calendar day and (2) in-hospital mortality. We fit logistic regression models, adjusting for clinical risk factors and Pitt bacteremia score and performed propensity score analyses to compare the efficacy of cefepime and carbapenems. Results. Three hundred sixty-eight patients experienced Enterobacter species bacteremia and received at least 1 antimicrobial agent, of whom 52 (14%) died during hospitalization. Median age was 59 years; 19% were neutropenic, and 22% were in an intensive care unit on the day of bacteremia. Twenty-nine (11%) patients had persistent bacteremia for ≥1 day after antibacterial initiation. None of the 36 patients who received single-agent cefepime (0%) had persistent bacteremia, as opposed to 4 of 16 (25%) of those who received single-agent carbapenem (P < .01). In multivariable models, there was no association between carbapenem use and persistent bacteremia (adjusted odds ratio [aOR], 1.52; 95% CI, .58–3.98; P = .39), and a nonsignificant lower odds ratio with cefepime use (aOR, 0.52; 95% CI, .19–1.40; P = .19). In-hospital mortality was similar for use of cefepime and carbapenems in adjusted regression models and propensity-score matched analyses. Conclusions. Cefepime has a similar efficacy as carbapenems for the treatment of Enterobacter species bacteremia. Its use should be further explored as a carbapenem-sparing agent in this clinical scenario.

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Cefepime vs Other Antibacterial Agents for the Treatment of Enterobacter Species Bacteremia

CID Cefepime vs Other Antibacterial Agents for the Treatment of Enterobacter Species Bacteremia Mark J. Siedner 0 Alicia Galar 0 Belisa B. Guzmán-Suarez 0 David W. Kubiak 0 2 Nour Baghdady 2 Mary Jane Ferraro 1 0 David C. Hooper 0 Thomas F. O'Brien 0 Francisco M. Marty 0 0 Division of Infectious Diseases 1 Department of Pathology, Massachusetts General Hospital , Boston , USA 2 Department of Pharmacy, Brigham and Women's Hospital , Boston, Massachusetts , USA Background. Carbapenems are recommended for treatment of Enterobacter infections with AmpC phenotypes. Although isolates are typically susceptible to cefepime in vitro, there are few data supporting its clinical efficacy. Methods. We reviewed all cases of Enterobacter species bacteremia at 2 academic hospitals from 2005 to 2011. Outcomes of interest were (1) persistent bacteremia ≥1 calendar day and (2) in-hospital mortality. We fit logistic regression models, adjusting for clinical risk factors and Pitt bacteremia score and performed propensity score analyses to compare the efficacy of cefepime and carbapenems. Results. Three hundred sixty-eight patients experienced Enterobacter species bacteremia and received at least 1 antimicrobial agent, of whom 52 (14%) died during hospitalization. Median age was 59 years; 19% were neutropenic, and 22% were in an intensive care unit on the day of bacteremia. Twenty-nine (11%) patients had persistent bacteremia for ≥1 day after antibacterial initiation. None of the 36 patients who received single-agent cefepime (0%) had persistent bacteremia, as opposed to 4 of 16 (25%) of those who received single-agent carbapenem (P < .01). In multivariable models, there was no association between carbapenem use and persistent bacteremia (adjusted odds ratio [aOR], 1.52; 95% CI, .58-3.98; P = .39), and a nonsignificant lower odds ratio with cefepime use (aOR, 0.52; 95% CI, .19-1.40; P = .19). In-hospital mortality was similar for use of cefepime and carbapenems in adjusted regression models and propensity-score matched analyses. Conclusions. Cefepime has a similar efficacy as carbapenems for the treatment of Enterobacter species bacteremia. Its use should be further explored as a carbapenem-sparing agent in this clinical scenario. - can develop resistance during therapy through enzyme induction and stable derepression [ 5–8 ]. Not unexpectedly, the resultant delays in initiation of active antimicrobial therapy in these infections are associated with substantially increased mortality [9]. Because of these concerns, many experts have recommended carbapenems as the preferred treatment for resistant GNR bloodstream infections [ 4, 10, 11 ]. On the other hand, there has been an increased awareness that these bacteria may also exhibit resistance to carbapenems, either directly from carbapenemase production or through combinations of other β-lactamases with outer membrane porin changes [ 12–15 ], making empirical and isolate-specific choices difficult in daily practice. Cefepime is a poor inducer of and relatively more stable to the AmpC β-lactamase [ 6 ]. Moreover, because of its zwitteronic structure, cefepime rapidly passes through bacterial cell membranes, thereby enhancing access to its enzymatic target [ 16 ].In vitro data suggest that cefepime, unlike other cephalosporins, maintains activity against AmpC-producing isolates [ 17 ]. A recent study using phenotypic testing to identify AmpC β-lactamases found 96% of AmpC-producing isolates were susceptible to cefepime in vitro [ 18 ]. Moreover, surveillance data suggest that 80%–90% of Enterobacter spp. bloodstream infections are susceptible to cefepime (based on European Committee on Antimicrobial Susceptibility Testing threshold of a cefepime minimum inhibitory concentration [MIC] of ≤1 µg/mL for susceptible isolates), a rate similar to or higher than that of many Enterobacteriaceae [ 19 ], and that cefepime maintains activity for ceftazidime-resistant Enterobacter spp. isolates [ 20 ]. Yet, human studies of the comparative efficacy of cefepime vs carbapenems for resistant GNR bacteremia have shown contrasting results [ 21–24 ]. Notably, a recent study of patients with extended-spectrum β-lactamase (ESBL)–producing bacteria found higher failure and mortality for patients receiving cefepime vs carbapenems, especially among those who had isolates with MICs at the higher end of the susceptible range (eg, 4 or 8 µg/mL), although the number of patients who received cefepime was small (n = 17) [22]. In contrast, a recent study found no differences in mortality or length of hospital stay among patients receiving cefepime or carbapenems specifically for AmpC-producing βlactamase enteric GNR blood stream infections [ 18 ]. There is a relative paucity of data on the efficacy of cefepime specifically for Enterobacter spp. infections, which usually harbor AmpC and variably harbor plasmid-encoded ESBL-type β-lactamases. If effective, cefepime might serve an importa (...truncated)


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Mark J. Siedner, Alicia Galar, Belisa B. Guzmán-Suarez, David W. Kubiak, Nour Baghdady, Mary Jane Ferraro, David C. Hooper, Thomas F. O'Brien, Francisco M. Marty. Cefepime vs Other Antibacterial Agents for the Treatment of Enterobacter Species Bacteremia, Clinical Infectious Diseases, 2014, pp. 1554-1563, 58/11, DOI: 10.1093/cid/ciu182