Impact of Cefepime Therapy on Mortality among Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae and Escherichia coli

Abstract

Extended-spectrum-␤-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producing Klebsiella pneumoniae or Escherichia coli. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, including K. pneumoniae (83%) and E. coli (16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality (P < 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio When added to the model, receipt of empirical cefepime alone (n ‫؍‬ 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.[

The Use of Noncarbapenem β-Lactams for the Treatment of Extended-Spectrum β-Lactamase Infections

“…Results of observational studies comparing the activity of cefepime and carbapenems for invasive ESBL infections have been conflicting with some studies showing no difference [39,40] and others suggesting cefepime therapy is inferior [38,41,42] (Table 4). Lee and colleagues conducted an observational study including 17 patients with ESBL bacteremia receiving cefepime therapy and 161 patients receiving carbapenem therapy [42].…”

Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology

“…9,10 These breakpoints are supported mainly by PK/PD data 111 ; however, available clinical data evaluating the efficacy of "active" cephalosporins in invasive infections caused by ESBL-producers are still limited and sometimes contradictory. [112][113][114][115][116][117] As regards cefepime, higher mortality than carbapenem was observed considering CLSI breakpoints, but mortality was lower for isolates with MIC ≤1 mg/L than for isolates with higher MIC. 117 As regards cephamycins, which are typically active against ESBL producers if no other mechanism of resistance is present, there are scarce data.…”

Evaluation of clinical outcomes in patients with Gram-negative bloodstream infections according to cefepime MIC

“…Although immune compromise and neutropenia in our population was higher than Bhat et al (2007), neutropenia status was evaluated and did not influence our findings. Chopra et al (2012) evaluated the extent to which empiric or directed use of cefepime or a carbapenem for ESBL-producing GNBSI impacted clinical outcomes. When empiric cefepime use was evaluated in the multivariate model, there was no association with increased mortality.…”

“…However, most patients received the dose equivalent of 1-2 g every 12 hours, which is less than the PK/ PD optimized dosing (Bhat et al, 2007;Kuti et al, 2004;Lee et al, 2007;Nicasio et al, 2009). Others have observed worse outcomes with increased cefepime MICs (8-16 mg/L) in the setting of extendedspectrum beta-lactamase (ESBL)-positive GNBSI, but these investigations did not evaluate the impact of cefepime dosing or the effect of incremental increases in cefepime MIC on clinical outcomes (Chopra et al, 2012;Lee et al, 2013;Tumbarello et al, 2007). Given the clinical data, findings from PK/PD modeling and simulation, and the common use of lower cefepime doses, the 2014 update to the CLSI guidelines have included a reduced susceptibility breakpoint for cefepime at ≤2 mg/L with dose-dependent susceptibility defined between 4 and 8 mg/L and resistant defined at ≥16 mg/L for Enterobacteriaceae (CLSI, 2014).…”