Systemic Timentin® is superior to oral tinidazole for antibiotic prophylaxis in elective colorectal surgery

A prospective, randomized, single-blind, controlled clinical trial was undertaken to compare two different prophylactic antibiotic regimens in patients undergoing elective colorectal surgery. Systemic Timentin^®, a combination of ticarcillin and the beta-lactamase inhibitor clavulanic acid, was assigned to 101 patients. Oral tinidazole, an agent active only against anaerobic bacteria, was assigned to 102 patients. The wound infection rate was 2.4 percent in the patients receiving Timentin and 14 percent in those receiving tinidazole (P=0.01). Multivariate analysis of factors affecting the wound infection rate showed that the only factor that independently reached statistical significance was the prophylactic antibiotic used. The mortality of patients receiving Timentin prophylaxis was 3.4 percent compared with 8.9 percent of those receiving tinidazole (P=0.15). The clinical anastomotic leakage rate was 1.3 percent in patients receiving Timentin and 13 percent in those receiving tinidazole (P=0.01). These results, together with those of two previously published clinical trials by this group, indicate that antibiotic prophylaxis in elective colorectal surgery should consist of a short course of an agent effective against both aerobic and anaerobic bowel flora.     

Positive direct antiglobulin tests and haemolytic anaemia following therapy with beta-lactamase inhibitor containing drugs may be associated with nonimmunologic adsorption of protein onto red blood cells

A high incidence (39%) of positive direct antiglobulin tests (DATs) has been reported in patients taking Unasyn [ampicillin sodium plus sulbactam sodium (a beta-lactamase inhibitor)]. Three of four patients, with positive DATs, receiving Unasyn or Timentin [ticarcillin disodium plus clavulanate potassium (also a beta-lactamase inhibitor)] developed a haemolytic anaemia (HA) associated with a positive DAT, which resolved when drug therapy was stopped. The patients' sera did not react with red blood cells (RBCs) in the presence of Unasyn or Timentin, but when drug-treated RBCs were tested, patients' sera and normal sera reacted equally by indirect antiglobulin test. Following incubation in normal sera, RBCs treated with Unasyn, Timentin, Augmentin (amoxicillin + clavulanate), sulbactam and clavulanate reacted with anti-human globulin and anti-human albumin (an index of non-specific adsorption); RBCs treated with ampicillin and amoxicillin were nonreactive.
The beta-lactamase inhibitors sulbactam and clavulanate seem to cause nonimmunologic adsorption of protein onto RBCs in vitro . This may explain the high incidence of positive DATs detected in patients taking Unasyn, which contains sulbactam. It was not possible to prove that there was a direct association between the nonspecific uptake of protein onto drug-treated RBCs in vitro with the positive DATs or the HA.