Post-antibiotic effect induced by an antibiotic combination: influence of altered susceptibility to individual components

Abstract

The impact of altered susceptibility of an organism to the components of an antibiotic combination on post-antibiotic effect (PAE) was studied. The baseline PAEs expressed by Pseudomonas aeruginosa ATCC 27853 were recorded following 1 h of exposure to piperacillin and gentamicin, alone and in combination. Similar PAE assessments were made after resistance to the individual antibiotics was induced over 0.5-2x of their respective MIC. Before any induction, the PAE produced by piperacillin alone was negligible and that by the combination was synergistic. After piperacillin resistance was induced, PAE exhibited by the beta-lactam remained negligible, and comparable PAEs were observed for gentamicin and the combination, suggesting an additive interaction with a dominant effect from gentamicin. When resistance was induced against gentamicin, progressively shorter PAE was expressed by the aminoglycoside alone and the combination at increasing levels of resistance. In addition, a measurable PAE was unexpectedly observed for piperacillin, whereas the interaction also became additive. In summary, the PAE expressed by the test combination was highly dependent on the status of gentamicin resistance. The resistance profile exhibited by the organism against individual antibiotics of the combination showed an impact on the type of interaction expressed.