The use of eugenol in combination with cefotaxime and ciprofloxacin to combat ESBL‐producing quinolone‐resistant pathogenicEnterobacteriaceae

Abstract

Aim Emergence of extended‐spectrum beta‐lactamase (ESBL) producing with quinolone‐resistant (QR) pathogenic Enterobacteriaceae augmented the need to establish therapeutic options against them. Present study aimed towards determination of synergistic combination of eugenol (EG) with cefotaxime (CTX) and ciprofloxacin (CIP) to combat against this resistance and potentiation of antibacterial drugs by EG against these bacteria. Methods and Results Synergistic interaction between EG and CTX/CIP (FICI: 0·08–0·5) were observed among ESBL‐QR bacteria using checkerboard assay. Approximately, 2‐ to 1024‐fold minimum inhibitory concentration value reduction and 17‐ to 165 030‐fold dose reduction index strongly suggested synergistic interaction between EG and antibiotics. Cell viability assay showed reduction in log10 CFU per ml from 16·6 to 3·1 at synergistic concentration. Scanning electron microscopy further proved disruptive effect of EG on cell architecture. Eugenol and/or its combination also altered genes’ expressions that imparted antibiotic resistance by ~1·6 to ~1226 folds. Conclusions Reduced doses of antibiotics, bacterial morphological alterations, efflux pump down regulation, porin over expression and beta‐lactamase gene inhibition of ESBL‐QR bacteria by EG alone or in combination with CTX/CIP might have reversed antibiotic resistance profile of ESBL‐QR bacteria. Significance and Impact of the Study This study provided a molecular insight into action of EG and/with CTX and CIP, which might have potentiated antibiotic’s activity against ESBL‐QR bacteria.

Repurposing carvacrol, cinnamaldehyde, and eugenol as potential anti-quorum sensing agents against uropathogenic Escherichia coli isolates in Alexandria, Egypt

“…Combining these natural compounds with antibiotics constrains bacterial adaptation and restores antibiotic sensitivity by allowing the penetration of the latter [ 59 ]. Another reason for the synergetic effect is accounted to the ability of EG and CaRV to disrupt the bacterial cytoplasmic membrane, permeabilize the cell wall, enhance the expression of porins, and downregulate the efflux pumps, thus facilitating the uptake of the antibiotics [ 60 , 61 ]. Despite being terpenic components of essential oils, the effect of CaRV, CiNN, and EG vary due to the difference in their chemical structure, where the phenolic nature of CaRV and EG tend to exhibit a greater bactericidal effect when compared to aldehydes [ 62 ].…”

Antimicrobial activity of Syzygium aromaticum L. essential oil on extended-spectrum beta-lactamases-producing Escherichia coli

“…Most of the earlier studies reported inhibitory potential of herbal compounds against antibiotic-resistant ATCC strains, and there are not enough studies with antibiotic resistance clinical strains and their gene expression. Similarly, the antibacterial activity of clove compounds is well known: 1) eugenol on ESBL-QR E. coli (quinolone resistant) has demonstrated a synergistic interaction with cefotaxime, and ciprofloxacin (MIC = 0.91-7.34 µg/mL), and shrinkage of cell surfaces with reduced cytoplasm among in others ESBL-QR strains (Dhara and Tripathi 2020). And 2) caryophyllene as β-caryophyllene was able to alter membrane permeability and integrity of B. cereus, leading to membrane damage and intracellular content leakage, which eventually caused cell death (MIC = 2.5% -v/v-) (Moo et al 2020).…”

“…For kinetic curve the times measured were 0, 2, 4, 6, 8, 12 h with a decrease of bacteria except for MBC at 6 h until 24 h an increasing of bacteria survival in comparison with control outpatients in Tabriz, Iran could be carriers of ESBL-E. coli with resistant genes, 2% of blaSHV and 4% of blaTEM (Dizage 2019). However, the combination between natural compounds and antibiotics (i.e., eugenol-cefotaxime) represents an important management to suppress the synthesis at transcript level in antibiotic-resistant genes (i.e., acrB) (Dhara and Tripathi 2020). Therefore, EOSA could be a potential such as adjuvant to combat certain infections caused by multidrug-resistant bacteria (i.e., ESBL-E. coli).…”

Efflux Pump Inhibitors in Controlling Antibiotic Resistance: Outlook under a Heavy Metal Contamination Context

“…Moreover, eugenol was reported as having an inhibitory effect on NorA efflux pumps when combined with norfloxacin in S.aureus . Eugenol was also demonstrated to inhibit the arB gene with cefotaxim and ciprofloxacin in ESBL Enterobacteriaceae [ 65 , 66 ].…”