Clarithromycin Significantly Increases Linezolid Serum Concentrations

Abstract

A 42-year-old male patient was admitted at our hospital for treatment of smear-positive pulmonary tuberculosis (TB). Drug sensitivity testing revealed extensively drug-resistant TB, and the isolate appeared only susceptible to cycloserine, linezolid, clarithromycin, and clofazimine. According to the WHO treatment guidelines for TB, the treatment regimen was composed of these four drugs, as no other options were available (11). Linezolid was the cornerstone of this regimen because of the high in vitro activity against Mycobacterium tuberculosis (MIC of 0.125 to 0.5 mg/liter) (1, 8). Linezolid is a toxic drug, and its labeled duration of administration is therefore limited to 28 days to prevent peripheral neuropathy and anemia. Dose reduction has been evaluated in TB patients as an attempt to reduce toxicity to allow prolonged treatment for 18 to 24 months (6, 7, 10). The serum linezolid concentration target in our hospital is to maintain an AUC (the area under the concentration-time curve over 24 h in the steady state)/MIC ratio of >100 and a percentage of time in excess of the MIC of 100%. These conditions are generally reached with a dosage of 300 mg twice daily (2). Serum drug concentrations are analyzed using a validated liquid chromatography-tandem mass spectrophotometry method (5). In this patient, we measured a considerable increase in the AUC of linezolid from 29 mg·h/liter to 108 mg·h/liter (Fig. ​(Fig.11).