Matched Case-Control Study of Adjusted versus Nonadjusted Gentamicin Dosing in Perforated and Gangrenous Appendicitis

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Abstract
A matched case-control study of the efficacy of gentamicin dosage adjustment through the use of pharmacokinetic analysis of serum drug concentrations in patients treated by appendectomy for perforated or gangrenous appendicitis was performed. Two groups of patients were compared. In one group gentamicin was initiated preoperatively at 1.5 mg/kg Intravenous Piggy Back (IVPB) every 8 h. Postoperatively, serum levels were obtained to maintain peak concentrations within a range of 6–8 μg/ml. The comparison group was given gentamicin without measurement of drug levels. Both groups received clindamycin 600 mg IVPB every six h. Matched cases and control subjects were compared, controlling for pathologic state of the appendicitis, age, and sex. The patients were predominantly young men with normal renal function. More patients in the nonadjusted group had infectious complications than in the dose-adjusted group. There were seven failures (11.3%) in the nonadjusted group compared with only one failure (1.6%) in the dose-adjusted group, a significant difference (p = 0.03). Among the nonadjusted group, the complications were four abdominal abscesses, two wound infections, and one persistent high fever. There was no evidence of nephrotoxicity in either group. Our recommendations are that patients who are to undergo appendectomy for perforated/gangrenous appendicitis should be treated with clindamycin and gentamicin at a dose of 1.5 mg/kg. With normal renal function, an interval of 8 h is appropriate. Serum gentamicin levels should be obtained and the dose adjusted to maintain peak concentrations of 6–8 μg/ml.