In vitro antimycobacterial activities of newly synthesized benzoxazinorifamycins
Open Access
- 1 March 1991
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 35 (3), 542-547
- https://doi.org/10.1128/aac.35.3.542
Abstract
Newly synthesized rifamycin derivatives, KRM-1648, KRM-1657, KRM-1668, KRM-1686, and KRM-1687, having the chemical structures of 3'-hydroxy-5'-(4-alkylpiperazinyl)-benzoxazinorifamycins (alkyl residues: isobutyl, propyl, sec-butyl, sec-butyl [R configuration], and sec-butyl [S configuration], respectively), were studied for their in vitro antimycobacterial activities. Representative (KRM-1648) MICs for 90% of the strains tested, determined by the agar dilution method on 7H11 medium, of various pathogenic mycobacteria (9 species, 174 strains) were as follows (in micrograms per milliliter): Mycobacterium tuberculosis (rifampin [RMP]-susceptible strains), less than or equal to 0.0125; M. tuberculosis (RMP-resistant strains), 12.5; M. kansasii, 0.05; M. marinum, less than or equal to 0.0125; M. scrofulaceum, 0.1; M. avium, 1.56; M. intracellulare, 0.1; M. fortuitum, greater than 100; and M. chelonae subsp. abscessus and M. chelonae subsp. chelonae, greater than 100. These values are more than 64 times lower than those of RMP, except for the values against RMP-resistant M. tuberculosis (8 times lower) and those against rapid growers, including M. fortuitum and M. chelonae (the same as those of RMP). The other derivatives had similar levels of in vitro activity against these mycobacteria. When murine peritoneal macrophages in which M. intracellulare was phagocytosed in vitro were cultured in the presence of the benzoxazinorifamycins (1 microgram/ml), much more rapid killing of the organisms ingested in the macrophages was seen compared with when the same amount of RMP was added to the medium. The addition of benzoxazinorifamycins at the concentration of 0.05 micrograms/ml caused more marked suppression of intracellular growth of the organisms compared with addition of RMP. KRM-1648 and KRM-1657 inhibited intracellular growth of M. tuberculosis, and their efficacies were much greater than that of RMP.Keywords
This publication has 28 references indexed in Scilit:
- In vitro activities against mycobacteria of two longacting rifamycins, FCE22807 and CGP40/469A (SPAS-565)Tubercle, 1990
- Antibiotic Prophylaxis After Exposure to Antibiotic-Resistant Mycobacterium tuberculosisClinical Infectious Diseases, 1988
- Comparative in vitro and in vivo activity of rifabutin and rifampicin against mycobacterium avium complexTubercle, 1988
- In vitro properties of rifapentine (MDL473) relevant to its use in intermittent chemotherapy of tuberculosisTubercle, 1987
- Rifabutin (Ansamycin LM 427): A New Rifamycin-S Derivative for the Treatment of Mycobacterial DiseasesClinical Infectious Diseases, 1987
- Effect of Combined Clofazimine and Ansamycin Therapy on Mycobacterium avium--Mycobacterium intracellulare Bacteremia in Patients with AIDSThe Journal of Infectious Diseases, 1987
- Mycobacterial Infections in. AIDS Patients, with an Emphasis on the Mycobacterium avium ComplexClinical Infectious Diseases, 1986
- How macrophages kill tubercle bacilliJournal of Medical Microbiology, 1983
- Treatment of Disease Due to Mycobacterium intracellulareClinical Infectious Diseases, 1981
- Treatment of Pulmonary Disease Due to Mycobacterium kansasii: Recent Experience with RifampinClinical Infectious Diseases, 1981