title: Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa: - Combination therapy against resistant bacteria.
abstract: OBJECTIVE
  Bacterial resistant infections have become a global health challenge and threaten the society's health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates ofStaphylococcus aureus(S. aureus) and the standard strain ofPseudomonas aeruginosa(P. aeruginosa).
  
  
  METHODS
  The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studiedin vitroby using a checkerboard method and calculating the fraction inhibitory concentration index (FICI).
  
  
  RESULTS
  The MICs of gentamicin against bacterial strains were in the range of 0.312 - 320 μg/mL. The MIC values of both types of catechins were 62.5 - 250 μg/ mL. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1). A combination of caffeine with gentamicin did not alter the MIC values of gentamicin.
  
  
  CONCLUSIONS
  The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates ofS. aureusand standardP. aeruginosastrains. Therefore, combinations of gentamicin with these natural compounds might be a promising approach to combat microbial resistance.
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bibi Sedigheh
authors.initials: BS
authors.lastname: Fazly Bazzaz
authors.affiliation: Students' Research Committee, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Sarabandi
authors.affiliation: Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Khameneh
authors.affiliation: Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinzadeh
keywords:  Pseudomonas aeruginosa;  Staphylococcus aureus;  catechins;  gentamicin;  methylxanthine; antimicrobial resistant