Long-term outcomes of treatment of Mycobacterium avium complex bacteremia using a clarithromycin-containing regimen

Objectives: To describe the long-term outcomes of treatment of AIDS-related Mycobacterium avium complex (MAC) bacteremia using a standard clarithromycin-based regimen. Design: Retrospective study of patients with MAC bacteremia diagnosed between April 1992 and April 1995. Setting: An urban AIDS clinic Subjects: One hundred seventy-six consecutive patients with MAC bacteremia. Interventions: Clarithromycin 500 mg twice daily, ethambutol 800 or 1200 mg daily, and clofazimine 100 mg daily. Main outcome measures: Late treatment failure (defined as a positive blood culture more than 90 days after starting treatment), clarithromycin susceptibility of initial and treatment-failure isolates, DNA fingerprinting of isolates from treatment failures. Results: Two out of 176 (1.1%) baseline isolates were resistant to clarithromycin. One hundred and fifty-one patients were treated for MAC bacteremia, 144 (95%) with the standard regimen. Of the 117 patients who survived > 90 days after starting therapy, 25 (21%) met the criteria for late treatment failure. Of the 22 treatment-failure isolates available for susceptibility testing, 19 (86%) were resistant to clarithromycin. Therefore, 13% of patients treated using the standard regimen (19 out of 144) had treatment failure associated with the emergence of clarithromycin resistance. Using logistic regression, non-compliance was associated with treatment failure (P = 0.02). Fourteen out of the 17 (82%) evaluable paired isolates had identical DNA fingerprint patterns, whereas three pairs showed that a different strain of MAC was present at the time of treatment failure. Conclusions: Initial resistance to clarithromycin was rare during this period. However, late treatment failure associated with the emergence of clarithromycin resistance was relatively common during long-term follow-up. Most late treatment failures represented emergence of clarithromycin resistance in the initial strain.