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J Antimicrob Chemother. 2017 Jul 1;72(7):2012-2019. doi: 10.1093/jac/dkx081.

Activity of faropenem with and without rifampicin against Mycobacterium tuberculosis: evaluation in a whole-blood bactericidal activity trial.

Author information

1
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
2
Singapore Clinical Research Institute, Singapore.
3
Dean's Office (BSL3 Core Facility), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4
Investigational Medicine Unit, National University Health System, Singapore.

Abstract

Background:

Faropenem has in vitro activity against Mycobacterium tuberculosis (Mtb) and shows synergy with rifampicin. We tested this in a whole-blood bactericidal activity (WBA) trial.

Methods:

We randomized healthy volunteers to receive a single oral dose of faropenem (600 mg) with amoxicillin/clavulanic acid (500/125 mg) ( n  =   8), rifampicin (10 mg/kg) ( n  =   14) or the combination rifampicin + faropenem + amoxicillin/clavulanic acid ( n  =   14). Blood was drawn at intervals to 8 h post-dose. Drug levels were measured using LC-tandem MS. WBA was measured by inoculating blood samples with Mtb and estimating the change in bacterial cfu after 72 h. Trial registration: ClinicalTrials.gov (NCT02393586).

Results:

There was no activity in the faropenem + amoxicillin/clavulanic acid group (cumulative WBA 0.02 Δlog cfu; P  =   0.99 versus zero change). There was a suggestion of a trend favouring the rifampicin + faropenem + amoxicillin/clavulanic acid group at 8 h (cumulative WBA -0.19 ± 0.03 and -0.26 ± 0.03 Δlog cfu in the rifampicin and rifampicin + faropenem + amoxicillin/clavulanic acid groups, respectively; P  =   0.180), which was significant in the first hour post-dose ( P  =   0.032). Faropenem C max and AUC were 5.4 mg/L and 16.2 mg·h/L, respectively, and MIC for Mtb H37Rv was 5-10 mg/L.

Conclusions:

Faropenem is not active when used alone, possibly due to inadequate plasma levels relative to MIC. However, there was a suggestion of modest synergy with rifampicin that may merit further testing in clinical trials.

PMID:
28333342
DOI:
10.1093/jac/dkx081
[Indexed for MEDLINE]

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