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Activities of roxithromycin used alone and in combination with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine against Mycobacterium avium complex. 1994

N Rastogi, and K S Goh, and A Bryskier
Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Morne Jolivière, Pointe-à-Pitre, Guadeloupe, French West Indies.

Preliminary studies showed that roxithromycin possessed significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii and rare pathogens such as M. chelonae and M. fortuitum. In this investigation, radiometric MICs of roxithromycin, ethambutol, rifampin, amikacin, ofloxacin, and clofazimine for 10 clinical isolates of the M. avium complex (5 each from human immunodeficiency virus [HIV]-positive and HIV-negative patients) were determined. Roxithromycin MICs against all the isolates were below the reported maximum concentration of drug in serum at the routine pH of 6.8, and the MICs were further lowered by 1 to 2 dilutions at a pH of 7.4. In vitro enhancement of roxithromycin activity against all strains was further investigated by the previously established Bactec 460-TB method by combining the drugs at sub-MIC levels. Antibacterial activity of roxithromycin was enhanced in all 10 strains by ethambutol, in 3 strains each by rifampin and clofazimine, in 2 strains by amikacin, and in 1 strain by ofloxacin. In vitro screening of three-drug combinations showed that combinations of roxithromycin, ethambutol, and a third potential anti-M. avium drug (rifampin, amikacin, ofloxacin, or clofazimine) resulted in further enhancement of activity in 13 out of 20 drug combinations screened.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D002991 Clofazimine A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619) B-663,G-30,320,Lamprene,N,5-Bis(4-chlorophenyl)-3,5-dihydro-3-((1-methylethyl)imino)-2-phenazinamine,B 663,B663,G 30,320,G30,320
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004977 Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863) Dexambutol,EMB-Fatol,EMB-Hefa,Etambutol Llorente,Ethambutol Hydrochloride,Etibi,Miambutol,Myambutol,EMB Fatol,EMB Hefa,Hydrochloride, Ethambutol,Llorente, Etambutol
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000583 Amikacin A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics. A.M.K,Amikacin Sulfate,Amikacina Medical,Amikacina Normon,Amikafur,Amikalem,Amikason's,Amikayect,Amikin,Amiklin,Amukin,BB-K 8,BB-K8,Biclin,Biklin,Gamikal,Kanbine,Oprad,Yectamid,BB K 8,BB K8,BBK 8,BBK8,Medical, Amikacina,Normon, Amikacina,Sulfate, Amikacin
D012293 Rifampin A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160) Rifampicin,Benemycin,Rifadin,Rimactan,Rimactane,Tubocin
D015242 Ofloxacin A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION. DL-8280,DR-3355,Hoe-280,ORF-28489,Ofloxacin Hydrochloride,Ofloxacine,Ru-43280,Tarivid,DL 8280,DL8280,DR 3355,DR3355,Hoe 280,Hoe280,ORF 28489,ORF28489,Ru 43280,Ru43280
D015269 Mycobacterium avium Complex A complex that includes several strains of M. avium. M. intracellulare is not easily distinguished from M. avium and therefore is included in the complex. These organisms are most frequently found in pulmonary secretions from persons with a tuberculous-like mycobacteriosis. Strains of this complex have also been associated with childhood lymphadenitis and AIDS; M. avium alone causes tuberculosis in a variety of birds and other animals, including pigs. Battey Bacillus,MAIC,Mycobacterium avium-intracellulare,Mycobacterium avium-intracellulare Complex,Mycobacterium intracellulare,Nocardia intracellularis
D015575 Roxithromycin Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. Biaxsig,Claramid,Infectoroxit,MTW-Roxithromycin,Macrosil,RU 28965,RU 965,RU-28965,RU-965,Rotesan,Rotramin,Roxi 1A Pharma,Roxi Basics,Roxi TAD,Roxi-Puren,Roxi-Q,Roxi-Wolff,Roxi-paed 1A Pharma,Roxi-saar,Roxibeta,Roxigamma,Roxigrün,Roxihexal,Roxithro-Lich,Rulid,Rulide,roxi von ct,roxidura,RU28965,RU965

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