Clarithromycin Resistance and Susceptibility Patterns ofMycobacterium aviumStrains Isolated During Prophylaxis for Disseminated Infection in Patients with AIDS

Abstract

A randomized, placebo-controlled trial was conducted to evaluate the efficacy of clarithromycin in the prevention of disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS; special attention was given to the development of clarithromycin resistance. The median time to documented MAC bacteremia was 199 days for placebo-treated patients, 217 days for clarithromycin-treated patients infected with clarithromycin-susceptible MAC, and 385 days for clarithromycin-treated patients infected with clarithromycin-resistant MAC. Most of the patients with clarithromycin-resistant isolates (91%) had a baseline CD4 T-cell count of õ20/mL, while these low counts occurred in only 25% of patients having clarithromycin-susceptible breakthrough isolates. The emergence of clarithromycin resistance did not affect the total period of survival. Resistance to clarithromycin in breakthrough MAC isolates emerges most likely when the patient is extremely immunodeficient at the time of initiation of the preventative therapy.

Mycobacterial Infections Caused by Nontuberculous Mycobacteria

“…80 Most of the M. avium clinical isolates (but not all) from newly diagnosed patients are susceptible to clarithromycin and azithromycin, and the MIC determination in this case has shown a very clear predictability value of drug susceptibility testing. 81,82 The situation with other available drugs is different. The isolates have shown a very broad range of susceptibility/resistance patterns, and from 30 to 75% of them, depending on the drug, were resistant even in the most favorable in vitro conditions, with MICs exceeding any possibility of being achieved in blood and tissues.…”