In patients with
acute cholecystitis,
antibiotics are used as an adjunct to
cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of
penicillins, or
cephalosporins or
aminoglycosides, or both, are often used.
Cefepime is a fourth-generation
cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not
cefepime was as effective as the combination of
gentamicin and
mezlocillin in patients with
acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive
cefepime or
gentamicin and
mezlocillin.
Cefepime was given intravenously at 2 grams every 12 hours;
gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and
mezlocillin, 3 to 4 grams every four to six hours. All patients underwent
cholecystectomy. Bile cultures were obtained, and concentrations of
cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable
cefepime-treated and 34 evaluable
gentamicin and
mezlocillin-treated patients. Bactibilia was present in 17 of 56
cefepime-treated patients (30.4 percent) and ten of 34
gentamicin and
mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six
cefepime-treated patients. Clinical and bacteriologic responses were similar for the
cefepime-treated and
gentamicin and
mezlocillin-treated groups, with one failure in each group, a
wound infection in a patient receiving
cefepime and a subhepatic
abscess in a patients receiving
gentamicin and
mezlocillin. Other measures of outcome, such as the number of days of
fever, days nothing by mouth, days of hospitalization and days of
antibiotic therapy were similar in both groups.
Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups.
Cefepime is as effective as
gentamicin and
mezlocillin in preventing septic complications after
cholecystectomy for
acute cholecystitis.
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
aminoglycoside.