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.
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 (microg/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.
Rastogi
N
N
Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Morne Jolivière, B.P. 484, 97165-Pointe à Pitre Cedex, Guadeloupe, French West Indies.
Labrousse
V
V
Goh
K S
KS
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D006801:Humans; D007613:Kanamycin Resistance; D008264:Macrophages / Q000382:microbiology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014376:Tuberculosis / Q000188:drug therapy*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D024841:Fluoroquinolones; D017291:Clarithromycin