Treatment of bone, joint, and vascular-access-associated gram-positive bacterial infections with teicoplanin

Teicoplanin, a glycopeptide antibiotic, was evaluated for safety and efficacy in the treatment of vascular-access-associated bacteremias and of bone and joint infections due to susceptible gram-positive organisms. Of 35 patients enrolled, 26 had osteomyelitis, 8 had vascular-access-associated bacteremias, and 1 had a joint infection. A total of 38 gram-positive isolates were identified: 23 Staphylococcus aureus and 6 coagulase-negative staphylococcus and 9 streptococcus isolates. After at least 6 months of follow-up, 17 patients were evaluable for efficacy: 10 of 14 (71%) with osteomyelitis and 3 of 3 with vascular-access-associated bacteremias had full resolution of their infections. Inadequate debridement, the presence of metal, and inadequate dosing were likely causes of two failures and two relapses in patients with osteomyelitis. For all but two organisms, teicoplanin MICs were less than or equal to 2 micrograms/ml. Patients who responded had median peak and trough serum bactericidal levels at serum dilutions of 1:64 and 1:16; trough levels of teicoplanin in serum were greater than 30 micrograms/ml. Patients did not respond as expected to daily doses of 4 mg/kg of body weight, which consequently were increased to greater than or equal to 15 mg/kg. Audiology testing of 20 patients found 2 with a mild loss of high-frequency hearing; 1 patient complained of tinnitus. Patients tolerated peak levels in serum as high as 127 micrograms/ml and trough levels of 49 micrograms/ml. However, 5 of 18 patients (28%) whose daily dose was greater than or equal to 12 mg/kg developed drug fever and rash and had teicoplanin discontinued. Further study of the antibiotic at such higher doses is needed.