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. 2022 Jul 26;11(8):1002.
doi: 10.3390/antibiotics11081002.

Synergistic Action of AMX Associated with 1,8-Cineole and Its Effect on the ESBL Enzymatic Resistance Mechanism

Ahmed Amin Akhmouch  1 , Soukayna Hriouech  1 , Aouatef Mzabi  1 , Mariam Tanghort  1 , Hanane Chefchaou  1 , Adnane Remmal  1 , Najat Chami  1
Affiliations

Synergistic Action of AMX Associated with 1,8-Cineole and Its Effect on the ESBL Enzymatic Resistance Mechanism

Ahmed Amin Akhmouch et al. Antibiotics (Basel). .

Abstract

The purpose of the present study is twofold. First, it aims to evaluate the synergistic action of the ß-lactam antibiotic; AMX is associated with 1,8-cineole on six clinical isolates of ESBL-producing Escherichia coli and Klebsiella pneumoniae strains. Second, it aims to determine the effect this association has on the ESBL enzymatic resistance mechanism. The synergistic action of AMX/1,8-cineole was evaluated using partial inhibitory concentrations (PIC), determined by a microplate, a checkerboard and time-kill assays. The effect of AMX/1,8-cineole associations on the ESBL enzymatic resistance mechanism was evaluated using a new optimized enzymatic assay. This assay was based on the determination of the AMX antibacterial activity when combined with 1,8-cineole (at subinhibitory concentrations) in the presence or absence of the ß-lactamase enzyme toward a sensitive E. coli strain. The results of both checkerboard and time-kill assays showed a strong synergistic action between AMX and 1,8-cineole. The results of the enzymatic assay showed that the combination of AMX with 1,8-cineole notably influences the enzymatic resistance of the reaction by decreasing the affinity of the β-lactam antibiotic, AMX, to the β-lactamase enzyme. All obtained results suggested that the AMX/1,8-cineole association could be employed in therapy to overcome bacterial resistance to AMX while reducing the prevalence of resistance.

Keywords: 1,8-cineole; Escherichia coli; Klebsiella pneumomniae; amoxicillin; extended-spectrum beta-lactamases (ESBL); resistance; synergistic action.

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Conflict of interest statement

The authors declare that there are no conflict of interest related to this research paper.

Figures

Figure 1
Figure 1
Time–kill curve of control assay, AMX alone at MIC (open squares), 1,8-cineole alone at MIC (filled circles) and AMX/1,8-cineole in combination at MIC (open triangles) against the E. coli P956 strain. The values that include different letters are significantly different from each other at p < 0.05.
Figure 2
Figure 2
Time–kill curve of control assay, AMX alone at MIC (open squares), 1,8-cineole alone at MIC (filled circles) and AMX/1,8-cineole in combination at MIC (open triangles) against the E. coli P933 strain. The values that include different letters are significantly different from each other at p < 0.05.
Figure 3
Figure 3
Time–kill curve of control assay, AMX alone at MIC (open squares), 1,8-cineole alone at MIC (filled circles) and AMX/1,8-cineole in combination at MIC (open triangles) against the E. coli P7847 strain. The values that include different letters are significantly different from each other at p < 0.05.
Figure 4
Figure 4
Time–kill curve of control assay, AMX alone at MIC (open squares), 1,8-cineole alone at MIC (filled circles) and AMX/1,8-cineole in combination at MIC (open triangles) against the K. pneumoniae H1878 strain. The values that include different letters are significantly different from each other at p < 0.05.
Figure 5
Figure 5
Time–kill curve of control assay, AMX alone at MIC (open squares), 1,8-cineole alone at MIC (filled circles) and AMX/1,8-cineole in combination at MIC (open triangles) against the K. pneumoniae H2001 strain. The values that include different letters are significantly different from each other at p < 0.05.
Figure 6
Figure 6
Time–kill curve of control assay, AMX alone at MIC (open squares), 1,8-cineole alone at MIC (filled circles) and AMX/1,8-cineole in combination at MIC (open triangles) against the K. pneumoniae H1893 strain. The values that include different letters are significantly different from each other at p < 0.05.
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