Many antibiotics and antibiotic combinations are used for the treatment of peritonitis because of advanced (gangrenous or perforated) appendicitis. An aminoglycoside combined with an antianaerobe antibiotic is one standard treatment, but there is concern about the potential nephrotoxicity of the aminoglycoside and the necessity for monitoring aminoglycoside blood levels. Cefepime, a new broad-spectrum cephalosporin with a prolonged serum half-life, has excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to the aminoglycosides, but it has less potential for inducing renal injury. A double-blind, randomized study compared cefepime, 2 grams every 12 hours IVPB plus metronidazole 0.5 grams every eight hours IVPB (C/M) with gentamicin 1.5 milligrams per kilograms of IVPB plus clindamycin 0.9 grams q eight hours IVPB (G/C), administered up to 14 days, in 96 surgically treated patients with gangrenous or perforated appendicitis. Fifty patients had advanced appendicitis (nine gangrenous and 41 perforated) in the C/M group and 46 patients (six gangrenous and 40 perforated) in the G/C group. The mean number of days of postoperative fever (C/M, 4.4 +/- 2.7 versus G/C, 5.0 +/- 2.2), postoperative hospitalization (C/M, 2.0 +/- 1.9 versus G/C, 2.0 +/- 2.1) and antibiotic therapy (C/M, 6.3 +/- 1.9 versus G/C, 6.9 +/- 1.9) was similar in the two treatment groups. There were 11 treatment failures (C/M, three; G/C, eight; p = 0.13), six of which were probably a result of enterococci. No deaths occurred. Our study results show that the efficacy of cefepime plus metronidazole is equivalent to that of clindamycin plus gentamicin.