RELATIONSHIP OF ADVERSE EVENTS TO SERUM DRUG LEVELS IN PATIENTS RECEIVING HIGH-DOSE AZITHROMYCIN FOR MYCOBACTERIAL LUNG-DISEASE

We treated 39 elderly human immunodeficiency virus-noninfected patient s with Mycobacterium avium complex and/or Mycobacterium abscessus lung disease with azithromycin (600 mg daily), given initially as monother apy. Adverse events occurred in 33 of 39 patients (85%) receiving azit hromycin alone, most commonly gastrointestinal (GI) symptoms (32 of 39 , or 82%) and hearing impairment (10 of 39, or 26%). Twenty-four of 39 patients (62%) required a lower dose or withdrawal of the drug, The m ean serum level in patients who required a dose reduction because of h earing impairment was 0.8 +/- 0.4 mu g/mL, and that in patients whose reduction was necessitated by GI symptoms was 0.7 +/- 0.4 mu g/mL; in comparison, the mean serum level was 0.3 +/- 0.16 mu g/mL in patients with no adverse events (P =.004 and .003, respectively). Decreasing th e daily dose to 300 mg resulted in resolution of most adverse events. Serum levels with monotherapy were comparable to levels after the addi tion of other antituberculous drugs that included rifampin or rifabuti n. Thus, a 300-mg rather than 600-mg daily dose of azithromycin is bet ter tolerated by elderly patients, and serum levels appear unaffected by other antituberculous agents, including rifampin.