Synergistic Effects of Clove Essential Oil, Eugenol, Isoeugenol Combined with Meropenem against MRSA, Acinetobacter Baumannii, Bacillus spp in Vitro.

Antibiotic resistance, particularly multidrug resistance (MDR), remains a major global health threat. Combining natural products with conventional antibiotics, such as meropenem (MRP), offers a promising approach to enhance antibacterial efficacy. Syzygium aromaticum (clove) (SAE) is rich in bioactive compounds, notably eugenol (EU) and isoeugenol (IEU), yet studies on their synergy with MRP against MRSA, Acinetobacter baumannii, and Bacillus spp. are limited. This study evaluated the antibacterial activity of SAE, EU, and IEU, alone and in combination with MRP, using MICs, FICI, isobolograms, and dose reduction index (DRI) of MRP. The SAE-MRP combination showed strong synergy against MRSA (DRI = 16) and Bacillus spp. (DRI = 33), with moderate synergy against A. baumannii (DRI = 4). EU-MRP showed the highest DRI against Bacillus spp. (33), followed by A. baumannii (8) and MRSA (4). IEU-MRP produced weaker effects, from additive activity against MRSA (DRI = 2) to synergy against Bacillus spp. (DRI = 8). These results highlight the potential of clove-derived compounds to enhance MRP efficacy, reduce antibiotic dosages, and support strategies to combat multidrug-resistant infections.