Pharmacokinetics of ertapenem in patients with multidrug-resistant tuberculosis

Abstract

Treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is becoming more challenging because of increased levels of drug resistance against second-line TB drugs. One promising group of antimicrobial drugs is carbapenems. Ertapenem is an attractive carbapenem for the treatment of MDR- and XDR-TB because its relatively long half-life enables once-daily dosing. A retrospective study was performed for all patients with suspected MDR-TB at the Tuberculosis Center Beatrixoord of the University Medical Center Groningen (Haren, the Netherlands) who received ertapenem as part of their treatment regimen between December 1, 2010 and March 1, 2013. Safety and pharmacokinetics were evaluated. 18 patients were treated with 1000 mg ertapenem for a mean (range) of 77 (5-210) days. Sputum smear and culture were converted in all patients. Drug exposure was evaluated in 12 patients. The mean (range) area under the concentration-time curve up to 24 h was 544.9 (309-1130) h mg L-1. The mean (range) maximum observed plasma concentration was 127.5 (73.9-277.9) mg L-1. In general, ertapenem treatment was well tolerated during MDR-TB treatment and showed a favourable pharmacokinetic/pharmacodynamic profile in MDR-TB patients. We conclude that ertapenem is a highly promising drug for the treatment of MDR-TB that warrants further investigation.