A RANDOMIZED STUDY OF CEFEPIME VERSUS THE COMBINATION OF GENTAMICIN AND MEZLOCILLIN AS AN ADJUNCT TO SURGICAL-TREATMENT IN PATIENTS WITH ACUTE CHOLECYSTITIS

In patients with acute cholecystitis, antibiotics are used as an adjun ct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of pen icillins, or cephalosporins or aminoglycosides, or both, are often use d. Cefepime is a fourth-generation cephalosporin with excellent activi ty against gram-positive and gram-negative bacteria, including Pseudom onas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determin e whether or not cefepime was as effective as the combination of genta micin and mezlocillin in patients with acute cholecystitis. One hundre d and forty-nine patients were randomized, two to one, to receive cefe pime or gentamicin and mezlocillin. Cefepime was given intravenously a t 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilogr ams every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obt ained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 5 6 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocill in-treated patients. Bactibilia was present in 17 of 56 cefepime-treat ed patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-tr eated patients (29.4 percent). Enterococci were recovered in six cefep ime-treated patients. Clinical and bacteriologic responses were simila r for the cefepime-treated and gentamicin and mezlocillin-treated grou ps, with one failure in each group, a wound infection in a patient rec eiving cefepime and a subhepatic abscess in a patients receiving genta micin and mezlocillin. Other measures of outcome, such as the number o f days of fever, days nothing by mouth, days of hospitalization and da ys of antibiotic therapy were similar in both groups. Cefepime, with e very 12 hour dosing, achieved extremely high concentrations in all tis sues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatmen t groups. Cefepime is as effective as gentamicin and mezlocillin in pr eventing septic complications after cholecystectomy for acute cholecys titis. Cefepime requires fewer doses, does not require drug monitoring , is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination therapy that uses an amino glycoside.