Activity of poloxamer CRL-1072 against drug-sensitive and resistant strains of Mycobacterium tuberculosis in macrophages and in mice.
The present experiments evaluated a new, highly refined poloxamer, CRL-1072, alone and in combination with antibiotics against drug-sensitive and -resistant organisms. In macrophage culture, CRL-1072 reduced the drug concentration inhibiting 99% of control growth of isoniazid (INH) from 10 to 0.15 mg/l (fractional inhibitory concentration=0.07) for a drug-resistant strain. CRL-1072 also increased the susceptibility of drug-resistant strains of Mycobacterium tuberculosis to INH, streptomycin, rifampicin, pyrazinamide, ethambutol, PAS, thiacetazone and ethionamide. Fractional inhibitory concentration values of <0.5 indicated significant synergistic activity. In studies of acute infection in mice, CRL-1072 was only weakly bacteriostatic when used as a single agent but increased the bactericidal activity of INH, streptomycin, rifampicin, pyrazinamide and clindamycin, but not that of ethambutol. CRL-1072 enhanced the bactericidal activity of streptomycin against a streptomycin resistant strain of M. tuberculosis in a murine infection.
Jagannath
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CytRx Corporation, 30092, Norcross, GA 30092, USA. jagannath@casper.meed.uth.tmc.edu
Emanuele
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MR
Hunter
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D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D020442:Poloxamer / Q000494:pharmacology*
D000995:Antitubercular Agents; D020442:Poloxamer