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Int J Infect Dis. 2016 Nov;52:23-28. doi: 10.1016/j.ijid.2016.08.027. Epub 2016 Sep 7.

Interactions of linezolid and second-line anti-tuberculosis agents against multidrug-resistant Mycobacterium tuberculosis in vitro and in vivo.

Author information

1
Department of Pharmacology, Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou District, Beijing, China.
2
Pharmacy of Beijing Chest Hospital affiliated to the Capital Medical University, No. 97 Beimachang, Tongzhou District, Beijing, China.
3
Pharmacy of Beijing Chest Hospital affiliated to the Capital Medical University, No. 97 Beimachang, Tongzhou District, Beijing, China. Electronic address: guozhenyong0425@sina.com.

Abstract

OBJECTIVES:

The objectives of this study were to evaluate the interactions between linezolid (LZD) and second-line anti-tuberculosis (TB) agents in susceptible and multidrug-resistant (MDR) TB in vitro, and to validate the in vitro results in a murine TB model.

METHODS:

The minimum inhibitory concentrations of LZD and seven second-line anti-TB drugs against H37Rv and three multidrug-resistant clinical isolates were determined by Alamar Blue assay, and the interaction patterns of LZD and the seven second-line anti-TB agents against the four isolates were studied using a dynamic checkerboard method. The activities of these combinations against Mycobacterium tuberculosis were evaluated in a murine model of TB.

RESULTS:

The combination of LZD + capreomycin exhibited partial synergism for three of four isolates, LZD + para-aminosalicylic acid exhibited partial synergism for two of four isolates, and LZD + levofloxacin and LZD + amikacin exhibited partial synergism for one of four isolates; all other combinations showed indifference or an additive effect in vitro. The activities of six combinations and the standard regimen rifampicin + isoniazid + pyrazinamide were investigated in a murine model of TB (infection with H37Rv). Significant reductions in colony-forming units (CFU) were found in LZD + capreomycin and LZD + clofazimine groups when the CFU in the lungs on day 0 (the day of beginning treatment) was compared with the CFU in the lungs after 2 months of treatment.

CONCLUSIONS:

These combinations of LZD and second-line anti-TB drugs were all active against MDR-TB with indifference or an additive effect, except LZD + capreomycin, which showed partial synergy.

KEYWORDS:

Interaction; Linezolid; Multidrug-resistant; Mycobacterium tuberculosis; Second-line anti-TB

PMID:
27613365
DOI:
10.1016/j.ijid.2016.08.027
[Indexed for MEDLINE]
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