Planta Med 2008; 74(8): 840-846
DOI: 10.1055/s-2008-1074559
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

The Effects of Antibiotics Combined with Natural Polyphenols against Clinical Methicillin-Resistant Staphylococcus aureus (MRSA)

Rong-Dih Lin1 , 2 , Yi-Ping Chin3 , Wen-Chi Hou4 , Mei-Hsien Lee4
  • 1Department of Internal Medicine, Ho-Ping Branch, Taipei City Hospital, Taipei, Taiwan
  • 2School of Bio-resources Technology, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
  • 3Department of Microbiology and Immunology, Taipei Medical University, Taipei, Taiwan
  • 4Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
Further Information

Publication History

Received: August 13, 2007 Revised: May 2, 2008

Accepted: May 5, 2008

Publication Date:
10 June 2008 (online)

Abstract

Novel therapies are needed to address the public health problem posed by methicillin-resistant Staphylococcus aureus (MRSA). In this study, we determined the effects of combinations of antibiotics and plant polyphenols against 20 clinical isolates of MRSA. The in vitro activities of 10 antibiotics and 15 natural polyphenols against the isolates were evaluated by determining minimum inhibitory concentrations (MICs). All isolates were susceptible to vancomycin and resistant to rifampicin, while susceptibilities to ciprofloxacin varied. Among the 15 natural polyphenols, kaempferol (3,4′,5,7-tetrahydroxyflavone) and quercetin (3,3′,4′,5,7-pentahydroxyflavone) showed the lowest MICs. In checkerboard assays, combinations of rifampicin and either kaempferol or quercetin acted synergistically or partially synergistically against the clinical MRSA isolates. Rifampicin combined with kaempferol or quercetin exhibited good β-lactamase inhibitory effects (57.8 % and 75.8 %, respectively) against a representative isolate according to nitrocefin analysis. The study results and ready availability and low toxicity of plant polyphenols warrant further investigations on the therapeutic potential of combination therapies for MRSA infections.

Abbreviations

FIC:fractional inhibitory concentration

MIC:minimum inhibitory concentration

MRSA:methicillin-resistant Staphylococcus aureus

References

  • 1 Kluytmans-Vandenbergh M F, Kluytmans J A, Voss A. Dutch guideline for preventing nosocomial transmission of highly resistant microorganisms (HRMO).  Infection. 2005;  33 309-13
  • 2 Plosker G L, Figgitt D P. Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections.  Pharmacoeconomics. 2005;  23 945-64
  • 3 Dajani A S. Beta-lactam resistance: clinical implications for pediatric patients.  J Int Med Res. 2002;  30 (Suppl 1) 2A-9A
  • 4 Chattopadhyay D, Naik T N. Antivirals of ethnomedicinal origin: structure-activity relationship and scope.  Mini Rev Med Chem. 2007;  7 275-301
  • 5 Hatano T, Kusuda M, Inada K, Ogawa T O, Shiota S, Tsuchiya T. et al . Effects of tannins and related polyphenols on methicillin-resistant Staphylococcus aureus.  Phytochemistry. 2005;  66 2047-55
  • 6 Clifford M N. Diet-derived phenols in plasma and tissues and their implications for health.  Planta Med. 2004;  70 1103-14
  • 7 Ginsburg I. The role of bacteriolysis in the pathophysiology of inflammation, infection and post-infectious sequelae.  Apmis. 2002;  110 753-70
  • 8 Clinical and laboratory standards institute (CLSI) Performance standards for antimicrobial susceptibility testing; fifteenth informational supplement. CLSI document M100-S17. Approved Standards M2-A9 Wayne; 2007
  • 9 Alcaraz L E, Blanco S E, Puig O N, Tomas F, Ferretti F H. Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains.  J Theor Biol. 2000;  205 231-40
  • 10 Toyokawa M, Asari S, Nishi I, Horikawa M, Tsukamoto H, Sunada A. et al . In vitro combined effects of cefozopran/teicoplanin and cefozopran/vancomycin on methicillin-resistant Staphylococcus aureus.  J Chemother. 2003;  15 31-6
  • 11 Pitkala A, Salmikivi L, Bredbacka P, Myllyniemi A L, Koskinen M T. Comparison of tests for detection of beta-lactamase-producing staphylococci.  J Clin Microbiol. 2007;  45 2031-3
  • 12 Aqil F, Khan M S, Owais M, Ahmad I. Effect of certain bioactive plant extracts on clinical isolates of beta-lactamase producing methicillin resistant Staphylococcus aureus.  J Basic Microbiol. 2005;  45 106-14
  • 13 Xu H X, Lee S F. Activity of plant flavonoids against antibiotic-resistant bacteria.  Phytother Res. 2001;  15 39-43
  • 14 Rayner C, Munckhof W J. Antibiotics currently used in the treatment of infections caused by Staphylococcus aureus.  Intern Med J. 2005;  35 (Suppl 2) S3-16
  • 15 Aliprandis E, Ciralsky J, Lai H, Herling I, Katz H R. Comparative efficacy of topical moxifloxacin versus ciprofloxacin and vancomycin in the treatment of P. aeruginosa and ciprofloxacin-resistant MRSA keratitis in rabbits.  Cornea. 2005;  24 201-5
  • 16 Bernard F X, Sable S, Cameron B, Provost J, Desnottes J F, Crouzet J. et al . Glycosylated flavones as selective inhibitors of topoisomerase IV.  Antimicrob Agents Chemother. 1997;  41 992-8
  • 17 Sierra J M, Marco F, Ruiz J, Jimenez de Anta M T, Vila J. Correlation between the activity of different fluoroquinolones and the presence of mechanisms of quinolone resistance in epidemiologically related and unrelated strains of methicillin-susceptible and -resistant Staphylococcus aureus.  Clin Microbiol Infect. 2002;  8 781-90
  • 18 Constantinou A, Mehta R, Runyan C, Rao K, Vaughan A, Moon R. Flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships.  J Nat Prod. 1995;  58 217-25
  • 19 Mandell G L, Bennett J E, Dolin R. Mandell, Douglas, and Bennett’s principle and practice of infectious diseases, 6th edition.  Philadelphia: Elsevier. Inc.;  2005 455-6
  • 20 Capitano B, Quintiliani R, Nightingale C H, Nicolau D P. Antibacterials for the prophylaxis and treatment of bacterial endocarditis in children.  Paediatr Drugs. 2001;  3 703-18
  • 21 Yoshida T, Hatano T, Ito H. Chemistry and function of vegetable polyphenols with high molecular weights.  Biofactors. 2000;  13 121-5
  • 22 Fuda C C, Fisher J F, Mobashery S. Beta-lactam resistance in Staphylococcus aureus: the adaptive resistance of a plastic genome.  Cell Mol Life Sci. 2005;  62 2617-33
  • 23 Tai P W, Huang C H, Lin Q D, Huang Y Y. Molecular pattern and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus isolates at a teaching hospital in Northern Taiwan.  J Microbiol Immunol Infect. 2006;  39 225-30
  • 24 Boyle-Vavra S, Ereshefsky B, Wang C C, Daum R S. Successful multiresistant community-associated methicillin-resistant Staphylococcus aureus lineage from Taipei, Taiwan, that carries either the novel staphylococcal chromosome cassette mec (SCCmec) type VT or SCCmec type IV.  J Clin Microbiol. 2005;  43 4719-30

Mei-Hsien Lee

Graduate Institute of Pharmacognosy

School of Pharmacy

Taipei Medical University

250 Wu-Hsing Street

Taipei 110

Taiwan

Phone: +886/2/2736/1661 ext. 6151

Fax: +886/2/2735/7983

Email: Lmh@tmu.edu.tw