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.
Animals Antitubercular Agents