Experimental and clinical studies on Rifacinna--the new effective antituberculous drug (review).

A new rifamycin derivative 3-(4-cinnamyl-piperazinyl iminomethyl) rifamycin SV (T9) and its sodium salt (T11, Rifacinna((R))) were in vitro, in vivo, toxicologically and clinically investigated in comparison with rifampicin, rifapentine, rifabutin, rifalazil. Our experiments showed that Rifacinna exhibits excellent in vitro activity against Gram(+), Gram (-) aerobic, anaerobic pathogens and mycobacteria. Rifacinna is active against Staphylococcus, Streptococcus spp. including MRSA, with MIC90- 0.06-0.5 mg/L; against Gram(+), Gram (-) anaerobes with MIC90 0.5 - 1 mg/L; against Mycobacterium tuberculosis (MTB) with MIC90 0.062 mg/L; against MDR resistant MTB (25%-30 %) and Mycobacterium avium complex (MAC) strains with MICs 0.6-1.0 mg/L. It shows high intraphagocytic activity against MAC strains (0.06 0.125mg/L). Single daily dose 10 mg/kg provides complete erradication of mycobacteria in experimental generalized tuberculosis. Pharmacological studies established: excellent pharmacokinetic profile following single oral dose 10mg/kg Tmax 5-6 h, C(max) 5-9 mg/L, T1/2 33-34 h; low toxicity; no teratogenic and embryotoxic effects. The clinical study of Rifacinna shows higher therapeutic efficacy than Rifampicin in patients with infiltrative, disseminated and cavitary form of pulmonary tuberculosis, good tolerability and safety profile. Some of the recent patents related to the treatment of tuberculosis are discussed in this review article.

In vitro and in vivo activities of clarithromycin against the Mycobacterium avium complex.

Clarithromycin (CAM) was assessed for in vitro antimicrobial activity against various mycobacterial species. Except for Mycobacterium tuberculosis, CAM displayed MICs for test mycobacteria comparable to those of sparfloxacin (SPFX) but lower than those of rifampicin (RMP) and ofloxacin (OFLX). CAM at 0.25 mug/ml (1 MIC) exhibited bactericidal action against M. intracellulare growing in 7H9 medium and at 1 or 10 mug/ml (4 and 40 MIC, respectively) CAM displayed antimicrobial activity against the organism phagocytosed in murine macrophages, while RMP failed to manifest such an effect. When CAM was given s.c. or by gavage to mice infected i.v. with M. intracellulare at doses of 0.2 to 2 mg/mouse once daily, six times per week, it exhibited significant therapeutic efficacy in terms of decreased incidence of gross lung lesions and reduced bacterial loads in the lungs and spleen.