TEICOPLANIN - A WELL-TOLERATED AND EASILY ADMINISTRATED ALTERNATIVE TO VANCOMYCIN FOR GRAM-POSITIVE INFECTIONS IN INTENSIVE-CARE PATIENTS

A prospective, randomized multicentre study was conducted in order to evaluate the potentially superior tolerability profile of teicoplanin plus netilmicin compared with vancomycin plus netilmicin in patients in ICUs. We considered that these glycopeptides have been shown to have comparable efficacy and that comparative tolerability is of paramount importance, particularly in severely ill patients. A total of 56 patients were enrolled into the study (36 males and 20 females). Twenty-four patients were included in the teicoplanin plus netilmicin group (15 males, 9 females: mean age 56.8 years). The mean simplified acute physiological score (SAPS) was 9.4 (range 4-20). Thirty-two patients were randomized to receive vancomycin plus netilmicin (21 males, 11 females; mean age 56.4 years). The mean SAPS was 9.3 (range 2-16). Septicaemia was the most common infection (14 cases in each group). Most infections were caused by Staphylococcus aureus or coagulase-negative staphylococci. The mean daily doses were: for teicoplanin, 457 mg (6.7 mg/kg); for vancomycin, 1678 mg (24.4 mg/kg); and for netilmicin 263.3 mg (3.9 mg/kg) in the teicoplanin group and 248 mg (3.8 mg/kg) in the vancomycin group. The trough levels of teicoplanin in the serum remained mostly between 7 and 10 mg/l, while more fluctuation was seen in patients receiving vancomycin. The mean trough levels of netilmicin in the serum were 1.2 (SD 0.9) mg/l in the teicoplanin group, compared with 1.7 (SD 1.4) mg/l in the vancomycin group (NS: p > 0.05). The trough levels of netilmicin in the serum were often higher in the vancomycin group, resulting in decreases in the dose of netilmicin eight times in this group (25% of patients) and once in the teicoplanin group (4.2% of patients). Adjustments to the dose of vancomycin were made in six patients, due to nephrotoxicity or undesirable levels in the serum, but no adjustments to the dose were made in the teicoplanin group (p = 0.032). Overall, adjustments to the dose were made to one or both study drugs in 10 patients in the vancomycin group and one in the teicoplanin group (p<0.02). Clinical and bacteriological efficacy was similar: clinical success was achieved in 80% of the patients in the teicoplanin group compared with 83% in the vancomycin group. The bacteriological response rates were 81 and 84%, respectively. Adverse events were reported in 24 patients: 7 (29%) in the teicoplanin group and 17 (53%) in the vancomycin group (p>0.05). Nephrotoxicity was reported as an adverse event in 21 patients: 6 (25%) in the teicoplanin group and 15 (47%) in the vancomycin group (p = 0.09). The mean increase in the levels of creatinine in the serum at the end of therapy or up to 1 week after therapy, compared with the baseline, was significantly higher for vancomycin (56.6%), but not teicoplanin (15.3%, p<0.02). Creatinine clearance in the vancomycin group was significantly lower than baseline throughout the study period, while for teicoplanin there was no difference until the third week of treatment, and this improved again during the fourth week. It is concluded that teicoplanin is an efficacious, well-tolerated and convenient antibiotic for the treatment of Gram-positive infection in ICU patients.