title: β-Lapachone activity in synergy with conventional antimicrobials against methicillin resistant Staphylococcus aureus strains.
abstract: The aim of this study was to evaluate the antimicrobial activity of lapachol, α-lapachone, β-lapachone and six antimicrobials (ampicillin, amoxicillin/clavulanic acid, cefoxitin, gentamicin, ciprofloxacin and meropenem) against twelve strains of Staphylococcus aureus from which resistance phenotypes were previously determined by the disk diffusion method. Five S. aureus strains (LFBM 01, LFBM 26, LFBM 28, LFBM 31 and LFBM 33) showed resistance to all antimicrobial agents tested and were selected for the study of the interaction between β-lapachone and antimicrobial agents, busing checkerboard method. The criteria used to evaluate the synergistic activity were defined by the Fractional Inhibitory Concentration Index (FICI). Among the naphthoquinones, β-lapachone was the most effective against S. aureus strains. FICI values ranged from 0.07 to 0.5, suggesting a synergistic interaction against multidrug resistant S. aureus (MRSA) strains. An additive effect was observed with the combination β-lapachone/ciprofloxacin against the LFBM 33 strain. The combination of β-lapachone with cefoxitin showed no added benefit against LFBM 31 and LFBM 33 strains. This study demonstrated that, in general, β-lapachone combined with beta lactams antimicrobials, fluoroquinolones and carbapenems acts synergistically inhibiting MRSA strains.
authors.affiliation: Laboratório de Fisiologia e Bioquímica de Micro-organismos, Centro de Ciências Biológicas, Departamento de Antibióticos, Universidade Federal de Pernambuco, CEP-50670-901 Recife, Pernambuco, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Macedo
authors.forename: T
authors.initials: T
authors.lastname: Fernandes
authors.forename: L
authors.initials: L
authors.lastname: Silveira
authors.forename: A
authors.initials: A
authors.lastname: Mesquita
authors.forename: A A
authors.initials: AA
authors.lastname: Franchitti
authors.forename: E A
authors.initials: EA
authors.lastname: Ximenes
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D016106:Methicillin Resistance / Q000187:drug effects*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000382:microbiology*; D029663:Tabebuia / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D009285:Naphthoquinones; D002939:Ciprofloxacin; C014638:beta-lapachone
keywords: Anti-MRSA activity; Fractional Inhibitory Concentration Index; Naphthoquinones; β-Lapachone