Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious gram-positive infections

Abstract

Nineteen patients hospitalized for serious gram-positive infections were treated with teicoplanin, a new glycopeptide antibiotic. A variety of infections were treated, including endocarditis, septic thrombophlebitis, osteomyelitis, pyogenic arthritis, and soft tissue infection. Of 13 infections that could be evaluated in 12 patients, there were 8 clinical cures, 2 improvements, 1 recurrence, and 2 failures. Of the eight patients with Staphylococcus aureus bacteremia, seven were clinically cured or improved with teicoplanin therapy. Of the nine patients in whom the bacteriological response to treatment could be fully evaluated, six were cured; there was recurrence of infection in one, and treatment failed in two patients. In vitro testing showed the 13 bacterial isolates (9 S. aureus, 3 S. epidermidis, and 1 group B streptococcus) to be uniformly susceptible to teicoplanin, with MICs ranging from 0.12 to 0.5 microgram/ml. Every isolate was more susceptible in vitro to teicoplanin than to vancomycin. Three of the staphylococcal isolates were resistant to methicillin. Pharmacokinetic studies demonstrated that after an initial drug-accumulation period, a single daily dose adequately maintained the teicoplanin concentrations in serum within therapeutic ranges. Teicoplanin also penetrated well into synovial fluid. The drug was well tolerated by either intravenous or intramuscular administration. The most significant adverse reaction was an urticarial rash which required discontinuation of therapy in one patient; a second patient experienced a modest decrease in high-frequency auditory threshold. Asymptomatic eosinophilia and mild elevation of serum transaminases were noted as well. The results of this study suggest that teicoplanin is a safe and effective new agent for treatment of serious infections caused by gram-positive organisms.