Synergistic Activity of Thymol with Commercial Antibiotics against Critical and High WHO Priority Pathogenic Bacteria

Abstract

The use of synergistic combinations between natural compounds and commercial antibiotics may be a good strategy to fight against microbial resistance, with fewer side effects on human, animal and environmental, health. The antimicrobial capacity of four compounds of plant origin (thymol and gallic, salicylic and gentisic acids) was analysed against 14 pathogenic bacteria. Thymol showed the best antimicrobial activity, with MICs ranging from 125 µg/mL (for Acinetobacter baumannii, Pasteurella aerogenes, and Salmonella typhimurium) to 250 µg/mL (for Bacillus subtilis, Klebsiella aerogenes, Klebsiella pneumoniae, Serratia marcescens, Staphylococcus aureus, and Streptococcus agalactiae). Combinations of thymol with eight widely used antibiotics were studied to identify combinations with synergistic effects. Thymol showed synergistic activity with chloramphenicol against A. baumannii (critical priority by the WHO), with streptomycin and gentamicin against Staphylococcus aureus (high priority by the WHO), and with streptomycin against Streptococcus agalactiae, decreasing the MICs of these antibiotics by 75% to 87.5%. The kinetics of these synergies indicated that thymol alone at the synergy concentration had almost no effect on the maximum achievable population density and very little effect on the growth rate. However, in combination with antibiotics at the same concentration, it completely inhibited growth, confirming its role in facilitating the action of the antibiotic. The time–kill curves indicated that all the combinations with synergistic effects were mainly bactericidal.

Enhancing Commercial Antibiotics with Trans-Cinnamaldehyde in Gram-Positive and Gram-Negative Bacteria: An In Vitro Approach

“…natural compound and commercial antibiotic both at their respective MICs when tested in combination [102].…”

“…On a 96-well plate (round bottom), wells were filled with: (i) commercial antibiotic solution at its MIC when tested alone (MIC alone ), (ii) commercial antibiotic solution at its MIC when tested in combination with the natural product (MIC comb ), (iii) natural compound solution at its MIC when tested alone, (iv) natural product solution at its MIC when tested in combination with the commercial antibiotic, and (v) solution made of natural compound and commercial antibiotic both at their respective MICs when tested in combination [ 102 ].…”

Essential Oils from Southern Italian Aromatic Plants Synergize with Antibiotics against Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis Cell Growth and Biofilm Formation

“…To test the type of interaction between EOs and antibiotics, the Fractional Inhibitor Concentration Index (FIC I ) was calculated using the following formula: FIC I = FIC EO + FIC antibiotic , with FIC EO = (MIC of EO in combination with antibiotic)/(MIC of EO alone), and FIC antibiotic = (MIC of antibiotic in combination with EO)/(MIC of antibiotic alone). The results were interpreted as total synergism when FIC I ≤ 0.5; 0.5 < FIC I ≤ 1 indicates additivity; 1 < FICI ≤ 4 no interaction; and FICI > 4 antagonistic [50,51]. The MIC gain of the antibiotics was calculated according to the following formula: MIC gain = MIC of antibiotic alone/MIC of antibiotic in combination.…”

DFT Studies of the Activity and Reactivity of Limonene in Comparison with Selected Monoterpenes

“…In the literature review presented above, in addition to limonene, pinene [14], cymene [9,10], and thymol [9] were mentioned. These natural compounds, similar to limonene, are obtained from plants [65][66][67] and are monoterpenes known for their unique aromatic, therapeutic properties [65,[67][68][69]. In turn, due to structural similarity, thymol is often discussed with menthol [70][71][72], a monoterpene resembling hydrogenated thymol, found, e.g., in mint [73], which also has numerous applications [74][75][76].…”