Randomized comparison of cefepime and ceftazidime for treatment of skin, surgical wound, and complicated urinary tract infections in hospitalized subjects

Abstract

We undertook a prospective, randomized open comparison of the broad-spectrum cephalosporins cefepime and ceftazidime in treatment of hospitalized subjects with skin or wound infections and complicated nosocomial urinary tract infections. Cefepime treatment (dosage, 2.0 g intravenously twice daily for 4 to 28 days) was successful in 36 (90%) of 40 infections of the skin and skin structure or wounds and in 16 (84%) of 19 nosocomial urinary tract infections. Ceftazidime treatment, 2.0 g every 8 h, was successful in 34 (96%) of 36 infections of the skin and skin structure and in 15 (88%) of 17 urinary tract infections. Microbiological eradication rates of each agent overall and for Pseudomonas aeruginosa were greater than 90%. In the cefepime group, one death occurred, contributed to by an enterococcal superinfection acquired during study drug therapy, and there were two mild and transient adverse experiences observed. Cefepime was comparable to ceftazidime in treatment of infections of the skin and skin structure requiring hospitalization and of complicated nosocomial urinary tract infections.Cefepime, a novel alpha-methoxyimino aminothiazolyl cephalosporin, is active in vitro against many gram-positive and gram-negative bacteria which are responsible for serious infections (1, 2). Of particular interest are compelling in vitro data establishing that cefepime is active against Pseudomonas aeruginosa (4, 8) and more active than established broad-spectrum cephalosporins against multiply resistant strains of the family Enterobacteriaceae. (3, 5-7); these pathogens tend to be overwhelming producers of P-lactamases, for which cefepime has a low affinity and is resistant to hydrolysis. We undertook an open, randomized comparison of cefepime and ceftazidime in treatment of bacterial infections of the skin and skin structures and urinary tract in hospitalized subjects. MATERIALS AND METHPDSEligible patients for study enrollment included adults hospitalized in St. Luke's Episcopa} Hospital, Houston, Tex., or Hospital Mexico, Sgn Jose, Costa Rica, with culture-proven infections due to bacteria susceptible to both cefepime and ceftazidime. Included were infections of the skin or skin structures which reqijired hospitalization for therapy and complicated nosocomial infections of the urinary' tract which required antibiotic therapy because of fever, positive cultures, and the ahsence of another identified source of infection. fpr the -purposes of this study,

A multicenter comparative study of cefepime versus broad-spectrum antibacterial therapy in moderate and severe bacterial infections

“…Cefepime eradicated 97% of all pathogens, similar to comparator therapy (94%). Accordingly, this study extends the findings of previously published clinical studies, which found cefepime to be effective for the treatment of moderate to serious infections of the lower respiratory tract [19][20][21][22][23] and the urinary tract [24], as well as intraabdominal infections [25] and bacteremia [26].…”

Cefepime: a reappraisal in an era of increasing antimicrobial resistance

“…Results comparable to those obtained with ceftazidime are observed with the use of cefepime in complicated UTI [92,104]. A total of 300 episodes of pyelonephritis were observed in pediatric patients enrolled in a randomized, open label, multicenter trial where cefepime was compared with ceftazidime (both administered parenterally at 50 mg/kg every 8 h).…”

Continuous beta-lactam infusion in critically ill patients: the clinical evidence

“…However, several reviews have suggested that prolonged antibiotic exposures will achieve better PD profile [7,49,50]. Apparent benefits with regards to maximum bacterial killing also were reported in several studies when antibiotic concentrations were maintained above the MIC for extended periods, ideally four to five times the MIC especially when less susceptible microorganisms were involved [33,44,51-55]. In combination with other PK/PD data, it is suggested that therapeutic targets for CI therapy should be a steady-state concentration (C ss ) that is at least 4 x MIC [33].…”