Randomized clinical trial of intra-operative antimicrobial prophylaxis of infection after neurosurgical procedures.

A randomized, placebo-controlled, double-blind and sequentially analysed clinical trial to determine the efficacy of intra-operative parenteral gentamicin and vancomycin (with streptomycin in the irrigating solution) in preventing infection at the operative site following neurosurgical procedures is described. Patients receiving prophylaxis had a significantly (P = 0.046) lower operative site infection rate (2/71 = 2.8%) than those receiving placebo (9/77 = 11.7%). This difference was most apparent during an epidemic, the source of which was not evident. Moreover, a total of 13 infections (two operative site, five pneumonia and six urinary tract) occurred among 12 patients receiving prophylaxis, whereas there was a total of 31 infections (nine operative site, nine pneumonia, 10 urinary tract and three septicaemia) among 24 patients receiving placebo. A smaller quantity of antimicrobial drugs was administered postoperatively to patients receiving prophylaxis (3.96 'antibiotic-days' per patient) than to those receiving placebo (6.87 'antibiotic-days' per patient).

A sequential test for comparing two infection rates in a randomized clinical trial, and incorporation of data accumulated after stopping.

A randomized sequential test is considered for deciding whether prophylactic antibiotic is successful in reducing infection rates following neurosurgical operations. The test is of the curtailed "gambler's ruin" type. Its operating characteristics are obtained and tabulated, and the actual medical experiment is described in some detail. The problem of how additional accumulated data, observed after stopping, due to delayed response, should be incorporated in evaluation of sequential P-values and confidence intervals is also considered.