Therapeutic drug monitoring in patients with cystic fibrosis and mycobacterial disease.
Cystic fibrosis (CF) patients require higher dosages of many antibiotics. The relapse of tuberculosis in one CF patient, and the repeated growth of Mycobacterium avium-intracellulare in another, despite conventional therapy, raised the question of whether the serum levels of the antimycobacterial drugs were adequate. Antimycobacterial drug serum concentrations were assayed in 10 CF patients with pulmonary mycobacterial disease. Serum levels below the proposed target range were seen 2 h after drug intake in the initial four patients treated: for rifampicin in 2/3, ethambutol in 3/4 and for clarithromycin in 2/3 patients, despite standard dosages. Reassays after dose adjustment and assays in six other patients showed that adequate levels were not achieved 4 h after clarithromycin in 3/5, ethambutol in 1/5, ciproflaxacin in 1/2 and ofloxacin in 2/2 patients. The patient with relapse of tuberculosis and the patient with continuous growth of M. avium-intracellulare improved and became culture negative after dose adjustment. Low drug serum levels is one reason for therapy failure in cystic fibrosis patients with mycobacterial disease. Therapeutic drug monitoring is recommended.
Gilljam
M
M
Dept of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Göteborg, Sweden.
Berning
S E
SE
Peloquin
C A
CA
Strandvik
B
B
Larsson
L O
LO
D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D015270:Mycobacterium avium-intracellulare Infection / Q000097:blood / Q000188:drug therapy*; D011247:Pregnancy; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000188:drug therapy*
D000995:Antitubercular Agents; D004977:Ethambutol; D017291:Clarithromycin; D012293:Rifampin