In Vitro Activities of Fourteen Antimicrobial Agents Against Drug Susceptible and Resistant Clinical Isolates of Mycobacterium tuberculosis and Comparative Intracellular Activities Against the Virulent H37Rv Strain in Human Macrophages |
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Authors: | Nalin Rastogi Valérie Labrousse Khye Seng Goh |
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Institution: | (1) Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Morne Jolivière, B.P. 484, 97165-Pointe à Pitre Cedex, Guadeloupe, French West Indies , TS |
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Abstract: | Minimal inhibitory concentrations (MICs) of 14 first and second-line antituberculous drugs against drug-susceptible and drug-resistant
clinical isolates of Mycobacterium tuberculosis (including the multiple drug-resistant or MDR-TB isolates), as well as the type strain H37Rv, were determined radiometrically
by the Bactec 460-TB methodols. MICs (μg/ml) of all the fourteen drugs were within an extremely narrow range in case of susceptible
strains; isoniazid (0.02–0.04), rifampin (0.2–0.4), ethambutol and streptomycin (0.5–2.0), ethionamide (0.25–0.5), D-cycloserine
(25–75), capreomycin (1–2), kanamycin (2–4), amikacin (0.5–1.0), clofazimine (0.1–0.4), ofloxacin (0.5–1.0), ciprofloxacin
(0.25–1.0), and sparfloxacin (0.1–0.4). The activity of second-line drugs remained unaltered against MDR-TB isolates resistant
to routine first-line drugs. With peak serum level concentrations (Cmax), the intracellular killing of the virulent H37Rv
strain was studied in detail in cultured human macrophages. Based on an decreasing order of bactericidal activity, our results
showed the following spectrum of intracellular drug action: among the first-line drugs, rifampin > ethionamide = isoniazid
> ethambutol > streptomycin > D-cycloserine; among second-line drugs, clofazimine = amikacin > kanamycin = capreomycin; among
fluoroquinolones, sparfloxacin > ofloxacin > ciprofloxacin. On the other hand, contrary to atypical mycobacteria, the macrolide
drug clarithromycin was inactive against both extracellular and intracellular M. tuberculosis.
Received: 23 January 1996 / Accepted: 5 April 1996 |
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