Abstract
The rise of antibiotic resistance in recent years poses a major challenge in the management of bacterial infections caused by Staphylococcus aureus (S. aureus), especially methicillin-resistant S. aureus (MRSA). The rising prevalence of reduced susceptibility of S. aureus to existing antibiotics warrants an immediate action to explore existing molecules alone or in combination with standard antibiotics. In the present study, we have evaluated the prowess of thymol as an adjuvant with oxacillin against MRSA clinical isolate MB-0628 along with its preliminary safety profile under in-vitro conditions. Thymol demonstrated a strong synergistic effect with oxacillin against MRSA clinical isolates as indicated by fractional inhibitory concentration index (FICI, falls below 0.5). Time-kill curves revealed strong bactericidal activity as thymol-oxacillin combination reduced the microbial burden to 3 Log10 CFU/mL after 24 h of treatment and the post-antibiotic effect was significantly prolonged, predicting the clinical efficacy of this combination against MRSA. In addition, the combination showed enhanced loss of intracellular content at OD260nm and OD562nm, indicating its effectiveness in disrupting bacterial cells. Scanning electron microscopy further validated the changes in bacterial cell morphology after alone versus combination treatment. Notably, the thymol in combination with oxacillin has shown no adverse effect on human fibroblast cells. In conclusion, thymol-oxacillin combination has potential to develop as a promising combination against MRSA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-024-01311-9.