Adjunctive antimicrobial therapy for complicated appendicitis: bacterial overkill by combination therapy

Although single antimicrobials with broad-spectrum aerobic and anaerobic coverage are effective in patients with appendicitis, many general surgeons continue to use multiple agents. A prospective, double-blind, randomized trial was designed to detect any clinical correlate of in vitro susceptibility advantage of multiple antimicrobials as adjunctive therapy for 114 patients undergoing operation for complicated appendicitis. There was clinical resolution of intraabdominal infections with no occurrence of postoperative infectious complications in 90% (36 of 40) of the cefotetan group and 86% (31 of 36) of the clindamycin/amikacin group (p = 0.11). The number of patients who had changes in antibiotic therapy due to postoperative complications was higher in the clindamycin/amikacin group: five (12.5%), compared to one (2.8%) in the cefotetan group (p = 0.07). Although Bacteroides fragilis group organisms resistant to cefotetan were identified, none was responsible for the postoperative infections. Adverse drug events in 28% of the cefotetan group and 26% of the clindamycin/amikacin group consisted primarily of transient elevations of liver function tests. Monotherapy with a second-generation, broad-spectrum cephalosporin, such as cefotetan, given twice a day is an economical and effective adjunctive regimen in patients with complicated appendicitis for which operation is the definitive treatment. Aminoglycosides and other, more potent antimicrobials should be reserved for resistant organisms or nosocomial infections.