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We have reviewed experience with aminoglycosides in cardiac surgical prophylaxis from 1984 to 1989. In the first two years, prospectively randomized trials (517 patients) allowed comparison of tobramycin (three-day course) with a non-toxic antibiotic, teicoplanin. A significant excess rise in serum creatinine was present at the end of the first postoperative week in patients given tobramycin (165 vs 149 patients, 95% CI 3-17 microM. P less than 0.01, which was most marked in ten oliguric patients with trough serum levels over 2 mg/l (95% CI 7-52 microM). However, no patient needed haemodialysis and only one case of possible ototoxicity was identified. During the next three years, of 912 patients given two to three days gentamicin, 29 patients were shown to have potentially toxic serum levels and oliguria. Three individual cases are described, including one of ototoxicity and one of nephrotoxicity neeeding haemodialysis. The hazards of aminoglycoside toxicity are probably small compared with the failure of other antibiotics to cover staphylococci that may later cause wound infection or endocarditis. However, surgeons should probably be advised to check the aminoglycoside level in all patients on the first post-operative day.

A controlled trial of antibiotic prophylaxis in cardiac surgery compared a two-dose regimen of teicoplanin with a longer conventional course of flucloxacillin and tobramycin. In 12 patients the susceptibility of the bacterial skin flora of four different sites to each of the three antibiotics was determined and the results are reported here. Less than 1% of the Gram-positive colonies showed reduced sensitivity to teicoplanin (MIC greater than or equal to 4 mg l-1). Before operation, 99% inhibition of Gram-positive growth was achieved at 26 (54%) of 48 sites by 1 mg l-1 of flucloxacillin and 13 (27%) sites by 2 mg l-1 tobramycin. By the 7th day after operation there was a significant reduction in the number of sites showing similar sensitivity to flucloxacillin [16 (33%) sites, P less than 0.05]. The use of teicoplanin was not associated with the emergence of Gram-negative skin flora but tobramycin promoted acquisition of aminoglycoside-resistant strains.

To compare antibiotic regimens for their effectiveness in preventing or treating wound sepsis, well-defined criteria for outcome are needed. A method of assessing wound healing has been devised that defines carefully the characteristics to be considered and how they are to be awarded points. Objective criteria are also included in the assessment. Points are given for the need for Additional treatment, the presence of Serous discharge, Erythema, Purulent exudate, and Separation of the deep tissues, the Isolation of bacteria, and the duration of inpatient Stay (ASEPSIS).

A prospective randomized clinical trial is in progress to compare the efficacy of teicoplanin with flucloxacillin and tobramycin in the prevention of endocarditis and wound infection following cardiac surgery. To date, 198 patients have completed the trial, of whom 95 have received teicoplanin and 103 flucloxacillin and tobramycin. One patient developed prosthetic valve endocarditis 3 months after surgery covered by flucloxacillin and tobramycin. There was no significant difference in the incidence of sternal wound infection (P = 0.15). Severe sternal sepsis occurred in four patients in the teicoplanin group and two in the flucloxacillin/tobramycin group. There were more postoperative urinary tract infections among those given teicoplanin (15 of 95 patients compared to six of 103 patients P less than 0.05). The trial continues.

In this study, the pharmacokinetics of teicoplanin have been studied in serum, fat and bone during and after cardiac surgery with two dose (400 and 200 mg) and three dose (400 mg each) regimens in a total of 49 patients. For comparison, 20 other patients, who had received a regimen of flucloxacillin (500 mg qds for five days) and tobramycin (1.5 mg/kg initially then 80 mg tds for three days), were similarly investigated. The lowest mean serum level of teicoplanin during operation was 6.9 mg/l in the two dose regimen and 9.7 mg/l with the three dose regimen. Mean serum levels of flucloxacillin and tobramycin fell to 7 and 1.4 mg/l respectively by the end of operation. At the end of bypass, fat washings contained a mean of 1.2 mg/l of teicoplanin and bone washings a mean of 6.3 mg/l. Mean tobramycin levels were 0.4 and 0.9 mg/l respectively and flucloxacillin less than 1 mg/l in washings from both tissues. The low levels of teicoplanin in fat may explain an excess of Gram-positive sternal infections in the accompanying clinical trial.

Teicoplanin, a new glycopeptide antibiotic, has a serum half-life of 47 h and excellent activity against Gram-positive bacteria, including methicillin resistant staphylococci, making it a potentially useful drug for cardiac surgical prophylaxis. In two prospective randomized studies, we have compared it with a broad spectrum regimen of an aminoglycoside and flucloxacillin. In the first trial, teicoplanin (400 mg on induction of anaesthesia and 200 mg 24 h later), was compared with tobramycin (80 mg tds for three days) and flucloxacillin (500 mg qds for 5 days) in 314 patients. Teicoplanin prophylaxis resulted in a significantly greater number of sternal wound infections (P less than 0.01), due to Gram-positive bacteria. Furthermore, Gram-negative bacteria were responsible for more respiratory and urinary infections after teicoplanin prophylaxis. In the second trial, comprising 203 patients, the teicoplanin dose regimen was changed to three doses of 400 mg but this did not improve the rates of infection.

Despite antibiotic prophylaxis in cardiac surgery, gram-positive bacteria can be isolated in up to 10% of intraoperative blood cultures. During a prospective randomized trial, blood was collected from the oxygenator at the end of bypass in 58 patients given teicoplanin and in 60 others given flucloxacillin and tobramycin. Coagulase-negative staphylococci were cultured from 16 patients given teicoplanin but in only four cases after flucloxacillin and tobramycin (Fisher's exact test, P = 0.005). In contrast, Propionibacterium spp. or coryneforms were isolated from 22 patients given flucloxacillin and tobramycin and from only one patient in the teicoplanin group. There were no cases of prosthetic valve endocarditis. After 3 h exposure to 4 x MIC of teicoplanin there was only a 10-60 fold reduction in cfus of Staphylococcus epidermidis, which may partly explain the excess of these organisms.

A survey was conducted of the current practice of antibiotic prophylaxis in cardiac surgery throughout the United Kingdom. Most surgeons (84%) use a regimen covering a broad spectrum of bacterial species that is continued for two to three days after the operation. The most used regimens are a combination of beta lactamase resistant penicillin with an aminoglycoside (44%) or a single broad spectrum cephalosporin (30%). Just 16% of surgeons preferred a narrow spectrum regimen effective against only the Gram positive organisms commonly responsible for postoperative infection in these patients. Antibiotic prophylaxis has been adopted by all cardiac surgeons in the United Kingdom but is sometimes continued longer than is indicated by the clinical or experimental evidence.