Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synergy between Phenothiazines and Oxacillin against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus

Sanaz Hadji-nejad¹, Mohammad Rahbar², Hadi Mehrgan¹

¹Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences; ²Health Reference Laboratories, Ministry of Health, Tehran, Iran.

For correspondence:- Hadi Mehrgan Email: hmehrgan75@yahoo.com Tel:+982188200068

Received: 1 October 2009 Accepted: 2 March 2010 Published: 24 June 2010

Citation: Hadji-nejad S, Rahbar M, Mehrgan H. Synergy between Phenothiazines and Oxacillin against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus. Trop J Pharm Res 2010; 9(3):243-249 doi: 10.4314/tjpr.v9i3.5

© 2010 The authors.
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Abstract

Purpose: To evaluate the antimicrobial and resistance-reversal activities of seven phenothiazine derivatives against one standard methicillin-sensitive and ten methicillin-resistant Staphylococcus aureus (MRSA) strains originating from human infections.

Methods: Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and oxacillin was investigated using Checkerboard (microbroth dilution) technique.

Results: We found that all S. aureus strains, regardless of their susceptibility to oxacillin, were inhibited by phenothiazines at a concentration of 8 - 256 µg/mL, with thioridazine being the most potent inhibitory agent. Phenothiazines at sub-inhibitory concentrations lowered the MIC of oxacillin from 256 to 2 µg/mL, which is a clinically significant level. The highest number of synergistic combinations, i.e., fractional inhibitory concentration (FIC) index less than 0.5, was seen with chlorpromazine and perphenazine. However, thioridazine reversed antibiotic resistance at a concentration as low as 4 µg/mL.

Conclusion: Although synergy was observed at concentrations higher than those that phenothiazines usually attain in vivo, the potential offered by non-antibiotics justifies further animal experiments as well as clinical trials to establish their clinical relevance.

Keywords: Methicillin-resistance, Staphylococcus aureus, Oxacillin; Phenothiazines, Non-antibiotics, Synergy