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 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.

Interactions of zinc and selenium on the binding of cadmium to rat tissue proteins.

The administration of cadmium to rats by either oral or injection routes causes zinc to accumulate in the low molecular weight (MW) protein metallothionein (MT) of liver and kidney, but not in a low MW protein in the testis. Preliminary evidence indicates that the low MW cadmium-binding protein in testes is not MT. Feeding high levels of zinc to rats results in its accumulation with tissue MT, and the zinc is very labile. In contrast, the zinc that accumulates in MT as the result of cadmium exposure is not very labile. In the reverse situation, zinc does not cause cadmium to accumulate in MT. The turnover of MT is shorter when saturated with zinc than when cadmium is the predominant metal bound to it. Even though selenium will counteract testicular damage due to cadmium, it causes cadmium to accumulate in this organ at higher levels than in animals exposed to cadmium without selenium. Injection of selenate, and selenide--but not selenomethionine or selenocystine--diverts the binding of injected cadmium from low MW proteins to high MW ones in the testes. Selenium injections had only minor influences on the binding of zinc to testicular proteins. In contrast, very little diversion occurred in the binding of either cadmium or zinc in tissues of rats fed high levels of selenium. The data suggest that it is the selenide form of selenium that causes the diversion of cadmium binding in tissues, thus providing protection of testes against cadmium exposure.