RESUMO
The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined. Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments. Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin. WCK 771 MIC50/90 values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid. WCK 771 MIC50/90 values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin. Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4 x MIC, as were the other quinolones tested. Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci. Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility.
Assuntos
Bacteriemia/tratamento farmacológico , Fluoroquinolonas/farmacologia , Pneumonia Pneumocócica/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Farmacorresistência Bacteriana , Fluoroquinolonas/uso terapêutico , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Pneumonia Pneumocócica/microbiologia , Resultado do TratamentoRESUMO
A new macrocyclic lactone antibiotic mathemycin B (1) was isolated from the fermentation broth of an Actinomycete sp. culture Y-8620959. The structure of 1 was elucidated by high-resolution MS and interpretation of 2D NMR results. Mathemycin B is active against a variety of phytopathogenic organisms.
