A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals

Objective: To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients. Design: A randomized, open-labeled, comparative trial. Setting: Outpatient clinics. Patients: Seventy-four patients with HIV and symptomatic bacteremic M. avium infection. Interventions: Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. Main outcome measure: Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium. Results: No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups. Conclusions: The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.