Effect of cefepime dose on mortality of patients with Gram-negative bacterial bloodstream infections: a prospective cohort study.
OBJECTIVE
There are controversies regarding the association of cefepime therapy with increased mortality among patients with infections caused by Gram-negative bacteria (GNB). We evaluated the effect of cefepime on the mortality of patients with GNB bloodstream infections (BSIs).


METHODS
A prospective cohort study was conducted in adult patients with creatinine ≤1.5 mg/dL who received empirical therapy with cefepime for at least 48 h for BSIs caused by GNB. The outcome was hospital mortality. Potential clinical predictors, including a high-dose regimen (2 g every 8 h), were assessed.


RESULTS
One hundred and thirteen patients were included. Most (78.8%) isolates had low cefepime MICs (≤0.25 mg/L). The overall hospital mortality was 35.4% [25.6% (10/39) and 40.5% (30/74) in patients receiving high-dose and usual-dose cefepime, respectively (P = 0.17)]. In a Cox regression model adjusted for cefepime MIC and propensity score, a high-dose regimen was independently associated with lower mortality rates [adjusted hazard ratio (aHR) 0.41; 95% CI 0.18-0.91; P = 0.029] while presentation with severe sepsis or septic shock was independently associated with higher mortality rates (aHR 4.10; 95% CI 1.78-9.40; P = 0.001). A trend to lower mortality rates was also found in the subgroup analysis of patients who had not switched antibiotic during therapy after adjustment for the latter variables.


CONCLUSIONS
High-dose cefepime therapy was associated with lower mortality rates in patients with GNB BSIs, even for GNB with low cefepime MICs.
Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos St, Porto Alegre 90.035-903, Brazil.
Marcelle D
MD
Alves
Laboratório de Resistência Bacteriana (LABRESIS), Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Vanessa B
VB
Ribeiro
School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Jardel P
JP
Tessari
School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Francine
F
Mattiello
School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Giordanna
G
De Bacco
Laboratório de Resistência Bacteriana (LABRESIS), Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Daniela I
DI
Luz
School of Biomedicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Fabiane J
FJ
Vieira
Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos St, Porto Alegre 90.035-903, Brazil.
Tainá F
TF
Behle
School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
Alessandro C
AC
Pasqualotto
Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos St, Porto Alegre 90.035-903, Brazil Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil azavascki@hcpa.ufrgs.br.
Alexandre P
AP
Zavascki
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage*; D024881:Drug Resistance, Bacterial; D057915:Drug Substitution; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime
Enterobacteriaceae; antimicrobial therapy; bacteraemia; pharmacokinetic/pharmacodynamic