Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic review.

BACKGROUND Single-dose antimicrobial prophylaxis for major surgery is a widely accepted principle; recommendations have been based on laboratory studies and numerous clinical trials published in the last 25 years. In practice, single-dose prophylaxis has not been universally accepted and multiple-dose regimens are still used in some centres. Moreover, the principle has recently been challenged by the results of an Australian study of vascular surgery. The aim of this current systematic review is to determine the overall efficacy of single versus multiple-dose antimicrobial prophylaxis for major surgery and across surgical disciplines. METHODS Relevant studies were identified in the medical literature using the MEDLINE database and other search strategies. Trials included in the review were prospective and randomized, had the same antimicrobial in each treatment arm and were published in English. Rates of postoperative surgical site infections (SSI) were extracted, 2 x 2 tables prepared and odds ratios (OR) [with 95% confidence intervals (95% CI)] calculated. Data were then combined using fixed and random effects models to provide an overall figure. In this context, a high value for the combined OR, with 95% CI > 1.0, indicates superiority of multiple-dose regimens and a low OR, with 95% CI < 1.0, suggests the opposite. A combined OR close to 1.0, with narrow 95% CI straddling 1.0, indicates no clear advantage of one regimen over another. Further subgroup analyses were also performed. RESULTS Combined OR by both fixed (1.06, 95% CI, 0.89-1.25) and random effects (1.04, 95% CI, 0.86-1.25) models indicated no clear advantage of either single or multiple-dose regimens in preventing SSI. Likewise, subgroup analysis showed no statistically significant differences associated with type of antimicrobial used (beta-lactam vs other), blinded wound assessment, length of the multiple-dose arm (> 24 h vs 24 h or less) or type of surgery (obstetric and gynaecological vs other). CONCLUSIONS Continued use of single-dose antimicrobial prophylaxis for major surgery is recommended. Further studies are required, especially in previously neglected surgical disciplines.