In vitro activity of novobiocin against multiresistant strains of Enterococcus faecium

Abstract

Sixty strains of vancomycin-and ampicillin-resistant Enterococcus faecium were evaluated for their susceptibilities to novobiocin in vitro. In Mueller-Hinton broth, novobiocin inhibited all strains when it was used at a concentration of 52 ,ug/ml and 40 of 60 strains when it was used at a concentration of <0.5 ,ug/ml. MICs were 8-to 16-fold higher in 50%o serum. Novobiocin alone resulted in 2-log-unit killing at 24 h. Combinations of novobiocin and a fluoroquinolone (either ciprofloxacin or ofloxacin) were additive and bactericidal for quinolone-susceptible strains in either broth or 50%o serum. Gentamicin did not affect novobiocin activity, and rifampin and doxycycline were antagonistic.

Biological Evaluation of Benzothiazole Ethyl Urea Inhibitors of Bacterial Type II Topoisomerases

“…Interestingly, compound A and compound B also did not display any apparent in vitro interaction with levofloxacin or novobiocin, both of which target the type II topoisomerases. Additivity and synergism between the coumarin drugs (novobiocin or coumermycin) and quinolones has been reported in in vitro assays with S. aureus, Enterococcus spp., and E. coli (40)(41)(42)(43). These divergent observations further support the inference that the mechanism of action and molecular interaction between compound A or compound B and GyrB/ParE are distinct from the interaction between novobiocin and GyrB/ParE.…”

Vancomycin-Resistant Enterococci

“…Novobiocin plus ciprofloxacin was found to be effective in a rabbit model of endocarditis (211). The combination of fluoroquinolones with novobiocin has also been investigated in other studies (103,150,211). Novobiocin was not bactericidal alone; however, upon addition of a fluoroquinolone, the combination was additive and bactericidal.…”

“…Clinical application of novobiocin was abandoned due to the emergence of resistance in staphylococci and the availability of newer, less toxic agents (200). In vitro data suggest that novobiocin is very active against VanA-or VanBtype vancomycin-resistant E. faecium strains, even if these strains are concomittantly resistant to penicillin and ampicillin (103). Novobiocin plus ciprofloxacin was found to be effective in a rabbit model of endocarditis (211).…”

Avaliação da sensibilidade a antimicrobianos de 87 amostras clínicas de enterococos resistentes à vancomicina

“…Agentes de várias classes, incluindo fluoroquinolonas, estreptograminas e novobiocina, em baixas concentrações, têm sido testados contra enterococos e têm demonstrado inibir o crescimento in vitro desse microrganismo 4 . A novobiocina, um derivado cumarínico diidroxiglicosilado, já foi utilizada previamente para o tratamento de infecções por microrganismos gram-positivos 18 . Devido à sua relativa toxicidade e à alta taxa de surgimento de resistência, ela foi gradativamente abandonada.…”

“…Para enterococos, no entanto, dados disponíveis até o momento não são suficientes para analisar sua eficácia e há trabalhos demonstrando apenas atividade modesta contra esses patógenos. Além disso, a ligação protéica dessa droga é muito alta, o que pode interferir na sua eficácia in vivo 18,19 . Uma outra classe de agentes antimicrobianos que demonstra atividade in vitro contra enterococos é o grupo das fluoroquinolonas.…”