Carnosic acid acts synergistically with gentamicin in killing methicillin-resistant Staphylococcus aureus clinical isolates.

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. 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. 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. 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. 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.

Vázquez NM ，Fiorilli G ，Cáceres Guido PA ，Moreno S ... -  《-》

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study.

Kuok CF ，Hoi SO ，Hoi CF ，Chan CH ，Fong IH ，Ngok CK ，Meng LR ，Fong P ... -  《-》

In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

Zuo GY ，Zhang XJ ，Han J ，Li YQ ，Wang GC ... -  《BMC Complementary and Alternative Medicine》

Synergism of coumarins from the Chinese drug Zanthoxylum nitidum with antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious therapeutic challenge in current clinic and new drug development. Natural coumarins have diverse bioactivities and the potential of resistance modifying effects. This study is to present in-depth evaluations of in vitro antimicrobial activities of four natural coumarins 5-geranyloxy-7-methoxycoumarin (Gm, 1), (5,7-dimethoxy-8-prenyloxycoumarin (artanin, Ar, 2)), isopimpinellin (Is, 3) and phellopterin (Ph, 4) from Zanthoxylum nitidum (Roxb.) DC. (Rutaceae) extracts, focusing on their potential restoration the activity of conventional antibacterial agents against clinical MRSA strains. Bioactivity-guided fractionation and spectral analyses were used to isolate the coumarins and identify the structures, respectively. The double broth microdilution method was used to assay the coumarins' alone activity. The classic checkerboard microdilution and dynamic time-killing methods were used to evaluate combinatory effects. The four plant coumarins Gm (1), Ar (2), Is (3) and Ph (4) were isolated and identified from Z. nitidum extracts. Coumarins 1-4 displayed promising inhibition against both MSSA and MRSA with minimal inhibitory concentrations (MICs) of 8-64µg/ml, but very weak against Gram-negative pathogen and yeast with MICs of 256 to ≥1024µg/ml. The geranyloxy and prenyloxy substitutions showed to be more active than the methoxy substitution on the coumarin skeletons. 1-4 also showing different extent of synergism with a total of eight conventional antibacterial agents, i.e. chloramphenicol (CL), gentamicin (CN), fosfomycin (FF), levofloxacin (LE), minocycline (MI), piperacillin/tazobactam (P/T), teicoplanin (TE) and vancomycin (VA) against ten clinical MRSA strains. Four to ten of the tested MRSA strains showed bacteriostatic synergy in the eleven combinations. The anti-MRSA modifying effects were related to different arrangement in the combinations with fractional inhibitory concentration indices (FICIs) from 0.187 to 1.125 and the three combinations CN (Is), CL (Ph) and MI (Gm) were the best ones. The enhancement of activity was also shown by 2-64 of dose reduction indices (DRIs) of the combined MICs, with VA (Ph) combination resulted the biggest DRI. The resistance of MRSA to antibacterial agents could be reversed in the combinations of CL (Gm or Ph), LE (Ph) and MI (Is) following the Clinical and Laboratory Standards Institute (CLSI) criteria. Six combinations P/T (Gm), TE (Ar), CN (Is), VA (Ph) and CL (Gm or Ph) also showed bactericidal synergy with Δlog10CFU/ml >2 at 24h incubation. The coumarins showed high potentiating effects of the antibacterial agents against multi-drug resistant SA. The resistance reversal effect of CL, LE and MI warrants further pharmacological investigation on combinatory therapy for the sake of fighting against MRSA infections.

Zuo GY ，Wang CJ ，Han J ，Li YQ ，Wang GC ... -  《-》

Investigation of the antibacterial activity and efflux pump inhibitory effect of co-loaded piperine and gentamicin nanoliposomes in methicillin-resistant Staphylococcus aureus.

Khameneh B ，Iranshahy M ，Ghandadi M ，Ghoochi Atashbeyk D ，Fazly Bazzaz BS ，Iranshahi M ... -  《-》