TEICOPLANIN VERSUS VANCOMYCIN IN THE EMPIRICAL-TREATMENT OF FEBRILE NEUTROPENIC PATIENTS

Gram-positive infections have become prevalent among neutropenic patie nts with cancer. A prospective, randomized, double-blind trial of teic oplanin, 6 mg/kg every 12 h for three doses then every 24 h, versus va ncomycin hydrochloride, 15 mg/kg every 12 h, in the empirical treatmen t of febrile neutropenic patients was undertaken among 50 consecutive patients with haematological malignancy. The patients also received pi peracillin sodium, 3 g every 4 h, and tobramycin sulphate, 1.5-2 mg/kg every 8 h. Both groups (25 teicoplanin and 25 vancomycin) were compar able in age, sex, renal function, underlying disease and concurrent th erapy. Among 22 patients (44%) with culture-proven infection, Gram-pos itive organisms were isolated in 15 (9 with bacteraemia) and Gram-nega tive in 11 (4 with bacteraemia). Mixed or polymicrobial infection occu rred in 8 patients. Serum 1-h peak and trough levels at steady state w ere 41+/-15 and 12+/-3 mg/l for teicoplanin (at 14+/-4 days), and 40+/ -10 and 8+/-5 mg/l for vancomycin (at 0.9+/-0.6 days). Mean eliminatio n half-life and apparent volume of distribution at steady state were 8 0.5+/-21.5 h and 1.4+/-0.8 l/kg for teicoplanin, and 5.6+/-1.8 h and 0 .6+/-0.2 l/kg for vancomycin. Empirical antimicrobial therapy was succ essful in 23 teicoplanin and 21 vancomycin patients, respectively (p=0 .67; two-tailed Fisher's exact test). Nephrotoxicity (serum creatinine > 110 mmol/l), however, was more common among vancomycin patients (10 versus 2; p=0.02), while termination of treatment due to adverse effe cts was also more common among vancomycin patients (10 versus 2; p=0.0 2). Concurrent treatment with cyclosporin A and vancomycin, but not wi th cyclosporin A and teicoplanin, resulted in significant renal dysfun ction (p=0.02). At the dose employed, teicoplanin was tolerated better than vancomycin in the empirical treatment of fever and neutropenia.