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

Area of Science:

• Microbiology and Infectious Diseases
• Pharmacology and Therapeutics

Background:

• The post-antibiotic effect (PAE) is crucial for understanding antibiotic efficacy.
• Antibiotic combinations are vital for treating resistant bacterial infections.
• Bacterial susceptibility to antibiotics can change, impacting treatment outcomes.

Purpose of the Study:

• To investigate how altered bacterial susceptibility affects the post-antibiotic effect (PAE) of antibiotic combinations.
• To examine the impact of induced resistance to piperacillin and gentamicin on their combined PAE in Pseudomonas aeruginosa.

Main Methods:

• Measured baseline PAEs of Pseudomonas aeruginosa ATCC 27853 exposed to piperacillin and gentamicin, alone and combined.
• Assessed PAEs after inducing resistance to individual antibiotics (0.5-2x MIC).
• Analyzed changes in PAE and interaction type (synergistic, additive) with induced resistance.

Main Results:

• Baseline combination showed synergistic PAE; piperacillin alone had negligible PAE.
• Piperacillin resistance induction resulted in negligible beta-lactam PAE and additive interaction, dominated by gentamicin.
• Gentamicin resistance induction led to shorter PAEs for gentamicin and the combination, with unexpected measurable PAE for piperacillin and additive interaction.

Conclusions:

• The PAE of the piperacillin-gentamicin combination is highly dependent on the level of gentamicin resistance.
• Bacterial resistance profiles against individual antibiotics significantly influence the interaction type observed in combination therapy.
• Understanding resistance-mediated changes in PAE is critical for optimizing antibiotic combination strategies.