A prospective, open, and randomized study of right-sided endocarditis caused by Staphylococcus aureus in drug abuse patients is reported. The following parenteral treatments were compared. Group A patients were treated with 2 g of cloxacillin every 4 h and 1.5 mg of gentamicin per kg of body weight every 8 h for 2 weeks. Group B patients were treated with teicoplanin at 10 mg/kg/12 h on the 1st to 3rd days, 6 mg/kg/12 h on the 4th to 7th days, and 7 mg/kg/24 h on the 8th to 28th days. Drug abusers with bacteremia caused by S. aureus and suggestive signs of endocarditis were included. Clinical failures were observed in one patient in group A and in four of six patients in group B. Three patients in group B developed breakthrough bacteremia with teicoplanin-susceptible strains on days ؉6, ؉14, and ؉19. Serum teicoplanin levels and serum bactericidal titers showed a decrease in the 2nd week, when dosages received were 7 mg/kg/day. In conclusion, in treatment of right-sided endocarditis caused by S. aureus in drug abusers with teicoplanin, the use of dosages of 7 mg/kg/day is not recommended even if patients have received dosages of 12 mg/kg/day during the 1st week.Right-sided endocarditis caused by Staphylococcus aureus in parenteral drug abusers is more amenable to a benign treatment than left-sided endocarditis, particularly in the absence of extensive pulmonary embolization (4, 15).Results after 2 weeks of treatment with a combination of isoxazolyl penicillins and aminoglycosides are satisfactory in more than 90% of patients (6).Nonintravenous therapy of right-sided endocarditis in drug abusers will be a help in the management of these patients. Preliminary studies with an oral combination of ciprofloxacin and rifampin are encouraging (9); however, in vitro studies have found that this combination can be antagonistic (23).The more usual alternative is the use of glycopeptides: vancomycin and teicoplanin. Experience with vancomycin in endocarditis caused by S. aureus is unfavorable (22). On the other hand, two characteristics of teicoplanin are relevant in these patients: its special pharmacokinetics and its proven efficiency in endocarditis caused by gram-positive organisms (8,11,17,18,20).To evaluate the efficiency of teicoplanin in right-sided endocarditis caused by S. aureus in parenteral drug abusers, a comparative study was conducted with the following two parenteral treatments: cloxacillin-gentamicin for 2 weeks (group A) and teicoplanin for 4 weeks (group B). MATERIALS AND METHODSThis was a prospective, open, randomized (1 of group A:1 of group B), and parallel study.Parenteral drug abusers with the following findings were included: (i) two or more blood cultures with isolation of methicillin-susceptible S. aureus, (ii) community-acquired infection, (iii) tricuspid regurgitation murmur, and (iv) clinical or radiological findings of septic pulmonary embolization or evidence of rightsided vegetations in transthoracic ecocardiography.Patients were excluded from enrollment if any of the following criteria was...