SINGLE-DOSE 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 labor atory studies and numerous clinical trials published in the last 25 ye ars. in practice, single-dose prophylaxis has not been universally acc epted and multiple-dose regimens are still used in some centres. Moreo ver, the principle has recently been challenged by the results of an A ustralian study of vascular surgery. The aim of this current systemati c review is to determine the overall efficacy of single versus multipl e-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. Tr ials included in the review were prospective and randomized, had the s ame 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 inter vals (95% CI)] calculated. Data were then combined using fixed and ran dom effects models to provide an overall figure. in this context, a hi gh 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 th e 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 f ixed (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 n o statistically significant differences associated with type of antimi crobial used (beta-lactam iis 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 recommende d. Further studies are required, especially in previously neglected su rgical disciplines.