title: Carnosic acid acts synergistically with gentamicin in killing methicillin-resistant Staphylococcus aureus clinical isolates.
abstract: BACKGROUND
  Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to different commonly used antibiotics, stressing the need for further strategies to treat this human pathogen with worldwide prevalence. The use of phytochemicals within the current pharmacology is a promising approach to enhance the antimicrobial activity of common antibiotics in the battle against these bacteria.
  
  
  OBJECTIVE
  The purpose of this study was to determine the antimicrobial effectiveness of carnosic acid, the major constituent of Rosmarinus officinalis L. leaves, in combination with gentamicin against multi-drug resistant MRSA clinical isolates obtained from pediatric patients with bacteremia.
  
  
  METHODS
  Anti-MRSA activity was studied using the broth microdilution assay and time-kill method. Combinations of subinhibitory concentrations of carnosic acid and gentamicin were examined using the checkerboard method.
  
  
  RESULTS
  Carnosic acid exhibited a good antibacterial activity against all multidrug-resistant MRSA clinical isolates tested, which are resistant to four up to nine antibiotics. In addition, the combination of carnosic acid with gentamicin not only decreased the minimal inhibitory concentration (MIC) of both by 4- to 5-fold, but also improved the bactericidal potency of the common antibiotic by 32- to 40-fold against both gentamicin-susceptible and gentamicin-resistant MRSA clinical isolates. A clear bactericidal synergistic activity between carnosic acid and gentamicin in killing multidrug-resistant MRSA clinical isolates with a fractional bactericidal concentration index (FBCI) of 0.28-0.35 was demonstrated.
  
  
  CONCLUSIONS
  Our findings show the potential use of carnosic acid in combination with gentamicin as a promising alternative for the control of healthcare-associated infections caused by multidrug-resistant MRSA.
authors.affiliation: Leloir Institute and Institute of Biochemistry Research of Buenos Aires-IIBBA-CONICET, Patricias Argentinas 435 (C1405BWE), Ciudad Autónoma de Buenos Aires C1405, Argentina.
authors.forename: Nicolás M
authors.initials: NM
authors.lastname: Vázquez
authors.affiliation: Service of Microbiology, Garrahan Pediatric Hospital, Combate de los Pozos 1881 (1245AAM), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Graciela
authors.initials: G
authors.lastname: Fiorilli
authors.affiliation: Integrative Medicine Group, Garrahan Pediatric Hospital, Combate de los Pozos 1881 (1245AAM), Ciudad Autónoma de Buenos Aires, Argentina; Maimónides University, Hidalgo 775 (1405BCK), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Cáceres Guido
authors.affiliation: Leloir Institute and Institute of Biochemistry Research of Buenos Aires-IIBBA-CONICET, Patricias Argentinas 435 (C1405BWE), Ciudad Autónoma de Buenos Aires C1405, Argentina; Maimónides University, Hidalgo 775 (1405BCK), Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: smorenocontar@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Moreno
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts; D027542:Rosmarinus / Q000737:chemistry; D013203:Staphylococcal Infections / Q000382:microbiology
chemical_list: D045784:Abietanes; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010936:Plant Extracts; C018381:salvin
keywords: Bactericidal activity; Carnosic acid; Gentamicin resistance; Methicillin-resistant Staphylococcus aureus; Rosmarinus officinalis L.; Synergy