Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates

Abstract

A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P ‫؍‬ 0.7) among those treated with cefepime (n ‫؍‬ 72) or a carbapenem (n ‫؍‬ 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 g/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P ‫؍‬ 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.

Impact of Revised Broad-Spectrum Cephalosporin Clinical and Laboratory Standards Institute Breakpoints on Susceptibility inEnterobacteriaceaeproducing AmpC β-Lactamase

“…This finding is in line with the recent results by Lee et al [13]. They reported that 63.6% of 217 E. cloacae blood isolates were cefepime-susceptible and 19.8% were cefepime-SDD [13]. Hence, laboratories that choose to implement the new CLSI criteria for Enterobacteriaceae should clearly inform treating physicians regarding the SDD category, so that they can be alert to the possible need for higher doses of cefepime in treating infections caused by these organisms.…”

“…In contrast, we found that applying the new cefepime CLSI criteria led to a substantial change in the susceptibility rates of cefepime against Enterobacteriaceae producing AmpC β-lactamase. This finding is in line with the recent results by Lee et al [13]. They reported that 63.6% of 217 E. cloacae blood isolates were cefepime-susceptible and 19.8% were cefepime-SDD [13].…”

“…In patients with ESBL-producing Enterobacteriaceae infection who received cefepime, the crude mortality rate was higher for isolates with a MIC of 2–8 μg/mL than for those with a MIC of ≤1 μg/mL (68.8% versus 30.0%; P = 0.045] [14]. Of patients with E. cloacae bacteremia who were treated with definite cefepime therapy, 30-day mortality rate of those infected by cefepime-susceptible isolates was significantly lower than that of patients infected by cefepime-SDD isolates (16.1% [9/56] versus 62.5% [10/16]; P <0.001)[13]. …”

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

“…Clinical data on outcomes for patients with infections caused by ESBL-E who were treated with active cephalosporins versus other options are limited and sometimes contradictory (68,(74)(75)(76)(77)(78)(79). Goethaert et al found similar mortality rates for 21 and 23 patients with BSI due to TEM-23-producing Enterobacter aerogenes who were treated empirically with cefepime (2 g every 8 h) and carbapenems, respectively (74).…”

The growing threat of multidrug-resistant Gram-negative infections in patients with hematologic malignancies

“…Cefepime, a 4 th -generation cephalosporin, may have a role in the treatment of AmpC-E infections, as it has relative stability against AmpC β-lactamases compared to other cephalosporins. Two observational studies of AmpC-E infections showed no differences in outcomes between patients treated with either carbapenems or cefepime [28,29]. The role of PTZ in the treatment of serious AmpC-E infections is not well established.…”