RESTORING ANTIBIOTIC SENSITIVITY IN RESISTANT BACTERIA THROUGH THE ADJUNCTIVE USE OF CLOVE PHYTOCHEMICALS

Abstract

The persistent emergence of multidrug-resistant (MDR) bacterial pathogens poses a critical threat to global public health, necessitating the exploration of adjunctive antimicrobial strategies. This systematic review investigates the synergistic interactions between Syzygium aromaticum (clove) and conventional antibiotics against clinically relevant MDR strains. Literature published between January 2010 and May 2025 was sourced from databases including PubMed, Scopus, Web of Science, and Google Scholar using PRISMA guidelines. A total of 68 peer-reviewed articles were screened, with 42 studies meeting the inclusion criteria for qualitative and quantitative synthesis. Findings reveal that clove extracts especially eugenol-rich essential oils exhibited significant synergy when co-administered with antibiotics such as ciprofloxacin, gentamicin, amoxicillin, and tetracycline. In 87.5% of the studies reviewed, combination therapy resulted in a reduction of minimum inhibitory concentrations (MICs) ranging from 2- to 16-fold against pathogens including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Time-kill assays and checkerboard methods were predominantly used to evaluate synergism, with 70% of studies reporting a fractional inhibitory concentration index (FICI) ≤ 0.5, indicative of strong synergistic interactions. Mechanistically, clove-derived phytochemicals disrupt bacterial cell membranes, inhibit efflux pumps, and suppress biofilm formation factors that contribute to antibiotic resistance. Despite promising in vitro outcomes, translational research remains limited. The review highlights the potential of S. aromaticum as a bioactive adjuvant in antimicrobial therapy and advocates for further in vivo validation and clinical trials to determine optimal dosages, delivery systems, and toxicity profiles. 

Keywords: Syzygium aromaticum, multidrug resistance, antibiotic synergy, eugenol, FICI, antimicrobial adjuvant