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 -res istant organisms. In macrophage culture, CRL-1072 reduced the drug concentr ation inhibiting 99% of control growth of isoniazid (INH) from 10 to 0.15 m g/l (fractional inhibitory concentration = 0.07) for a drug-resistant strai n. 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 concen tration values of <0.5 indicated significant synergistic activity. In studi es of acute infection in mice, CRL-1072 was only weakly bacteriostatic when used as a single agent but increased the bactericidal activity of INH, str eptomycin, rifampicin, pyrazinamide and clindamycin, but not that of ethamb utol. CRL-1072 enhanced the bactericidal activity of streptomycin against a streptomycin resistant strain of M. tuberculosis in a murine infection. (C ) 2000 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.