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.
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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)