title: 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.
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy, Groningen, The Netherlands Both authors contributed equally.
authors.forename: Sander P
authors.initials: SP
authors.lastname: van Rijn
authors.affiliation: University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands Both authors contributed equally.
authors.forename: Richard
authors.initials: R
authors.lastname: van Altena
authors.affiliation: University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands.
authors.forename: Onno W
authors.initials: OW
authors.lastname: Akkerman
authors.affiliation: Radboud University Nijmegen Medical Center, Depts of Pulmonary Diseases and Medical Microbiology, Nijmegen, The Netherlands National Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
authors.affiliation: National Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Tridia
authors.initials: T
authors.lastname: van der Laan
authors.affiliation: University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands.
authors.forename: Wiel C M
authors.initials: WC
authors.lastname: de Lange
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy, Groningen, The Netherlands University of Groningen, University Medical Center Groningen, Section Pharmacotherapy and Pharmaceutical Care, Dept of Pharmacy, Groningen, The Netherlands.
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.affiliation: University of Groningen, University Medical Center Groningen, Depts of Internal Medicine and Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy, Groningen, The Netherlands j.w.c.alffenaar@umcg.nl.
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D000077727:Ertapenem; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D009426:Netherlands; D012189:Retrospective Studies; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D055815:Young Adult; D047090:beta-Lactams / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D000995:Antitubercular Agents; D047090:beta-Lactams; D000077727:Ertapenem