Effects of Ethanolic Ruta Graveolens L. Extracts on In Vitro Postantibiotic Effect of Erythromycin in MLS-Resistant Staphylococci

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Abstract
Introduction. Ruta graveolens L. (R. graveolens) is a rich source of biologically active compounds with antimicrobial and antibiotic-potentiating properties; however, its impact on the duration of the postantibiotic effect (PAE) remains unclear. This study aimed to evaluate, in vitro, the PAE duration of erythromycin in staphylococcal strains with different MLS (macrolides, lincosamides, and streptogramin B) resistance phenotypes and to assess the impact of 70% and 90% ethanolic R. graveolens extracts on this parameter. Methods. Three control strains of staphylococcal skin isolates with different MLS resistance phenotypes, inducible (D), constitutive (Neg), and resistant (R), were used in this study. The minimum inhibitory concentrations of erythromycin and ethanolic R. graveolens extracts (70% and 90%) were determined using the broth microdilution method. Bacterial growth was monitored spectrophotometrically in microplates, and the lag phase, log phase, and PAE values were assessed. Results. The duration of the erythromycin PAE differed among staphylococcal strains exhibiting different MLS resistance phenotypes. The most extended PAE duration was observed in the tested strain with an inducible phenotype (7.3 ± 0.75 hours). An intermediate mean PAE duration (3.76 ± 0.4 hours) was observed for the strain with complete resistance to the MLS group of antibiotics. The erythromycin PAE was not detected in the strain with the Neg phenotype. Seventy percent R. graveolens extract modified the lag phase and prolonged the erythromycin PAE duration in a phenotype-dependent manner. In contrast, 90% R. graveolens extract did not show a potentiating effect compared to 70% R. graveolens extract. Conclusions. Combinations of erythromycin with subinhibitory concentrations of 70% R. graveolens extract modified the lag phase and prolonged erythromycin PAE in a resistance phenotype-dependent manner. The most pronounced effect of 70% R. graveolens extract was observed in strains with the D and R MLS resistance phenotypes. Moreover, 90% R. graveolens extract did not potentiate erythromycin activity against MLS-resistant staphylococci.

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