Comparison of methods for assessing synergic antibiotic interactions

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Relapsing infections pose treatment challenges.
• Assessing antimicrobial combination efficacy is crucial.
• Standardized methods for evaluating drug synergy are needed.

Purpose of the Study:

• To evaluate the potential of antimicrobial combination therapy for relapsing infections.
• To compare the synergy results from microtitre chequerboard and time-kill assays.
• To assess the reproducibility and predictive value of these methods.

Main Methods:

• Twenty-five combination microtitre chequerboard and time-kill curves were performed.
• Ten bacterial isolates (Burkholderia cepacia, Staphylococcus aureus, Klebsiella pneumoniae) from relapsing infections were used.
• Fractional Inhibitory Concentration (FIC) index and Fractional Bactericidal Concentration (FBC) index were calculated.

Main Results:

• No antagonism was observed between any drug combinations.
• Synergy was observed in 21 combinations by time-kill assay, more frequently at 24 hours.
• FIC index synergy predicted FBC index synergy in 67% of cases and time-kill synergy at 24 hours.
• Reproducibility of chequerboard assays was confirmed across multiple days.
• Good correlation was found between FIC and FBC indices, and FIC predicted time-kill synergy.

Conclusions:

• Combining chequerboard and time-kill assays yields reproducible results and good correlation.
• FIC index is a reliable indicator of synergistic bactericidal activity for potential combination therapies.
• Antimicrobial combinations are viable options for treating relapsing bacterial infections without antagonism.