Differences in Drug-Susceptibility Patterns between Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium chimaera Clinical Isolates: Prospective 8.5-Year Analysis by Three Laboratories
Mariana Fernández-PittolSara Batista-ArnauAngely RománLorena San NicolásLaura OliverOlga González-MorenoJosé Antonio MartínezRosanel Amaro-RodríguezNéstor SolerAmadeu GenéAraceli González-CuevasGriselda TudóJulián González-Martín
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Abstract:
Background: It has been suggested that Mycobacterium avium, Mycobacterium intracellulare, and M. chimaera have differential drug susceptibility patterns. We prospectively analyzed and compared the drug susceptibility patterns among these species over an 8.5-year period. Methods: A microdilution method (Slomyco®) was performed for drug susceptibility testing of 402 M. avium, 273 M. intracellulare, and 139 M. chimaera clinical isolates. Results: M. avium showed significantly higher resistance to moxifloxacin, ciprofloxacin, rifampicin, ethambutol, streptomycin, linezolid, cotrimoxazole, and clarithromycin. M. avium also showed higher minimum inhibitory concentrations (MIC) than M. intracellulare and M. chimaera against all drugs except ethionamide, to which M. intracellulare and M. chimaera showed greater resistance. Conclusions: Our series demonstrated differential drug resistance patterns among the most frequent M. avium complex species. M. avium was more resistant than M. intracellulare and M. chimaera versus eight antibiotics and showed greater MIC values to most of the antibiotics studied. These data suggest that knowledge of the local distribution and susceptibility profiles of these pathogens is essential for adequate clinical management.Keywords:
Broth microdilution
Ethionamide
Antimycobacterial
Nontuberculous Mycobacteria
Mycobacterium avium-intracellulare infection
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Pyrazinamide
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The results are presented of a single-blind trial of 3 and 4 drug combinations in 117 cases of advanced, previously treated pulmonary tuberculosis. Generally good response was noted, but best bacteriological control with 100% sputum culture conversion was obtained with rifampicin + ethambutol + ethionamide-with or without Hydronsan. This combination can be recommended whenever treat ment of polyresistant cases must be undertaken without sensitivity testing. S. Afr. Med. J., 46, 354 (1972). Our earlier studies' showed that rifampicin in combina tion with INH and/or ethambutol is superior to INH com bined with streptomycin or ethambutol in previously un treated pulmonary tuberculosis. We undertook the present study in an attempt to assess 3- and 4-drug regimens in previously treated patients.
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Antimycobacterial
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In vitro sensitivities to various drugs of a total of 106 strains of atypical mycobacteria were studied in modified Dubos Tween albumin liquid medium. Eight triple-drug combinations of antituberculous drugs were also evaluated in vitro for their potentiated activities. Minimal to moderate potentiation was demonstrated in the majority of the combination. From the results, the triple-drug combination--including rifampin, one of three aminoglycosides (streptomycin, kanamycin, viomycin), and either ethionamide or ethambutol--might be recommended for Mycobacterium kansasii infections. Against Mycobacterium avium-intracellulare infections, rifampin-kanamycin-ethionamide or rifampin-kanamycin-ethambutol might be the choice if we were to select any triple-drug regimen. None of the triple-drug regimens thus far tested on M. avium-intracellulare were active enough to recommend fully for clinical use. In vivo experimental chemotherapy of murine infection with Mycobacterium intracellulare (TMC 1469) on a five-drug regimen, kanamycin-rifampin-cycloserine-ethambutol-ethionamide, showed a moderate therapeutic effect but the infection was not eradicated.
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The central bacteriological laboratory of the Moscow Research-and-Practical Center for Tuberculosis Control studied the sensitivity of nontuberculous mycobacteria (NTM) to a number of antituberculous drugs (streptomycin, isoniazid, rifampicin, ethambutol, kanamycin, ethionamide, cycloserine, ofloxacin) by the absolute concentration method (after isolating the cultures on both solid and liquid nutrient media). A total of 160 cultures, including M. chelonae (n = 4), M. flavescense (n = 6), M. fortuitum (n = 34), M. avium complex (MAC) (n = 52), M. xenopi (n = 18), M. kansasii (n = 41), M. marinum (n = 2), M. malmoense (n = 1), M. simiae (n = 1), and M. gastri (n = 1), were explored. MAC was found to be resistant to streptomycin, isoniazid, rifampicin, ethambutol, and ethionamide in most cases, to ofloxacin in a nearly half of cases, to canamycin and cycloserine in a third of cases. In most cases, M. kansasii was sensitive not only to first-, but also second-line chemical drugs. M. xenopi was resistant to rifampicin in two thirds of cases and to streptomycin, isoniazid, ethambutol, and ethionamide in a half of cases. This species of NTM was more sensitive to kanamycin, cycloserine, and oflaxacin. In the majority of cases, M. fortuitum was resistant to streptomycin, isoniazid, rifampicin, ethambutol, ethionamide, kanamycin, and cycloserine and sensitive to ofloxacin.
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