Abstract
Background: Treatment outcome in Mycobacterium avium complex (MAC) lung disease is poor, with cure rates of 50-70%. To understand this, we retrospectively assessed the pharmacokinetics and MICs of key drugs in MAC disease treatment.
Methods: Pharmacokinetic and drug susceptibility data of all patients admitted at National Jewish Health, Denver, USA, in the January 2006-June 2010 period was retrieved from databases. Pharmacokinetic measurements were done by high performance liquid chromatography and gas chromatography. Isolates were identified as MAC by AccuProbe assays. MICs were determined by the BacTec460 macrodilution method; synergy between rifampicin and ethambutol was assessed.
Results: Pharmacokinetic data, median MICs and pharmacodynamic calculations are given in Table 1. Simultaneous use of rifampicin significantly lowered serum concentrations of macrolides (30-60%) and moxifloxacin (10-15%).
Average serum concentrations and pharmacokinetic calculations
Conclusions: Serum rifampicin, ethambutol and moxifloxacin concentrations attain effective levels in a minority of patients; rifampicin use exerts detrimental effects on pharmacokinetics of macrolides and moxifloxacin. This may partly explain the poor outcomes of MAC disease treatment.
- © 2012 ERS
