Effects of an alternative cefepime dosing strategy in pulmonary and bloodstream infections caused by Enterobacter spp, Citrobacter freundii, and Pseudomonas aeruginosa: a single-center, open-label, prospective, observational study.
BACKGROUND
Various dosing strategies for cefepime have been developed in an effort to maximize pharmacodynamic exposure of this agent against gram-negative infections. An assessment of cefepime dosing strategies is warranted given recent reports of poorer treatment outcomes associated with cefepime compared with other antibiotics, particularly in patients infected with gram-negative organisms with elevated MICs.


OBJECTIVE
The aims of this study were to compare the efficacy of cefepime IV at a dose of 1 g q8h (adjusted based on renal function) with those of other appropriate antimicrobials in the treatment of gramnegative pulmonary and bloodstream infections and to identify risk factors for treatment failure.


METHODS
This single-center, open-label, prospective, observational study was conducted at a tertiary care center (Barnes-Jewish Hospital, St. Louis, Missouri). Isolates from infections in adult patients with bacteremia or pulmonary infection caused by Pseudomonas aeruginosa, Enterobacter aerogenes, Enterobacter cloacae, or Citrobacter freundii were assessed in a noninterventional manner. Infections were identified using an electronic notification system. Patients receiving appropriate monotherapy against the studied isolate within 24 hours of culture attainment were stratified into 1 of 3 cohorts according to treatment outcome, as follows: treatment success (resolution of initial fever or elevated white blood cell count to normal values plus the presence of repeat negative cultures from the initial site or below the quantitative definition for infection), improvement (treatment success without repeat negative cultures), or treatment failure (persistent or repeat positive cultures for the original organism at the infected site despite appropriate and adequate antimicrobial therapy, lack of resolution in fever or leukocytosis, switch to an alternative antibiotic, or the addition of another antibiotic with gram-negative coverage after > or =3 days of the initial regimen, relapse of infection within 14 days, or mortality attributable to the index infection). Multivariate regression analysis was used to examine risk factors associated with treatment failure.


RESULTS
Data from 120 patients (56.7% male; mean age, 62.2 years) were analyzed. Treatment failure occurred in 48.6% (36/74) of patients who received cefepime versus 32.6% (15/46) of those who received other antibiotics; this difference was not statistically significant. The proportion of patients with markers of increased severity of illness (intensive care unit [P = 0.005] and mechanical ventilation [P = 0.002]) was significantly greater in the cefepime group compared with the group that received other antibiotics. Multivariate logistic regression identified infection with Pseudomonas aeruginosa (adjusted odds ratio [AOR], 1.40 [95% CI, 1.01-2.00]) and mechanical ventilation (AOR, 7.08 [95% CI, 1.80-31.3]) as being associated with treatment failure in patients who received cefepime. Mechanical ventilation (AOR, 3.97 [95% CI, 1.47-11.1]) and neutropenia (AOR, 5.26 [95% CI, 1.28-20.0]) were independent predictors of treatment failure among all patients studied.


CONCLUSIONS
Based on these results in this small cohort, the efficacy of this cefepime dosing strategy (1 g q8h) appeared to be similar to that of other antimicrobials.
Deal
Eli N
EN
Department of Pharmacy, Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA. end0164@bjc.org
Micek
Scott T
ST
Reichley
Richard M
RM
Ritchie
David J
DJ
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000627:therapeutic use*; D016971:Citrobacter freundii / Q000187:drug effects / Q000302:isolation & purification; D004754:Enterobacter / Q000187:drug effects / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime