Synergy of a novel antibiotic adjuvant entity against multi drug resistant Methicillin-resistant Staphylococcus aureus and heterogeneous glycopeptide-intermediate Staphylococcus aureus

Abstract

Objective

In the present study, we investigated the appropriate ratio of vancomycin with l-arginine, a non antibiotic adjuvant (NAA) and ceftriaxone against some selected clinical isolates. Furthermore, having determined the ratio, in vitro susceptibility studies were conducted.

Methods

The in vitro interaction between vancomycin with l-arginine and ceftriaxone was carried out on the chosen strains using agar dilution checkerboard method and results were presented as fractional inhibitory concentration (FIC) index. Susceptibility studies were carried out according to Clinical and Laboratory Standards Institute methods.

Results

Results of our study revealed that vancomycin with l-arginine and ceftriaxone at ratio, showed the lowest FICs, <0.5, for all selected positive controls as well as clinical isolates. The synergy between vancomycin with l-arginine and ceftriaxone was also confirmed by broth dilution, agar diffusion and time kill curve methods. In broth dilution and agar diffusion methods, vancomycin with l-arginine and ceftriaxone produced 4–5 fold lower minimum inhibitory concentration (MIC) and demonstrated greater zone of inhibition (≥5 mm) when compared with individual ceftriaxone and vancomycin. Approximately 10⁴–10⁵ log of killing reduction was observed with vancomycin with l-arginine and ceftriaxone in time kill curve study.

Conclusion

This study suggests that vancomycin with l-arginine and ceftriaxone could be an alternative regimen in combating antibiotic resistance among MRSA and hGISA.