Performance of the Fractional Maximal Effect Method: Comparative Interaction Studies of Ciprofloxacin and Protein Synthesis Inhibitors

Abstract

The performance of the recently developed Fractional Maximal Effect (FME) method was evaluated along with the conventional checkerboard technique and time-kill method. Ciprofloxacin in combination with tobramycin was tested against Escherichia coli and Pseudomonas aeruginosa and in combination with tetracycline, chloramphenicol, erythromycin against Escherichia coli. Two combinations, amoxicillin-tetracycline (antagonistic) and tobramycin-ticarcillin (synergistic), were included as reference interactions. The FME method unequivocally showed an antagonistic interaction between ciprofloxacin and all the protein synthesis inhibitors (PSIs) tested, while the other two methods yielded variable results. At a total FME (TFME) level of 1, the FME method demonstrated a similar degree of antagonism against ciprofloxacin by tetracycline, chloramphenicol, and erythromycin, and much lower by tobramycin. Internal consistency of the FME operation was demonstrated by the identical conclusions obtained at both TFME levels of 0.5 and 1. The FME method appears to be a practical alternative for resolving the inconsistencies observed in conventional methods of antibiotic combination testing.

Demonstration of In Vitro Antagonism between Fusidic Acid and Quinolones

“…The FME method demonstrated a similar degree of antagonism against ciprofloxacin by tetracycline, chloramphenicol and erythromycin, and a much lower level of inhibition by tobramycin. 12 Data from our study and from the study by Li et al 12 indicate that the antagonism between quinolones and fusidic acid might not arise from constitutional properties.…”

“…Li et al 12 showed unequivocally an antagonistic interaction between ciprofloxacin and all the protein synthesis inhibitors (PSIs) tested by the fractional maximal effect (FME) method, 11 while the same study yielded variable results with either the conventional checkerboard technique or the time-kill method. The FME method demonstrated a similar degree of antagonism against ciprofloxacin by tetracycline, chloramphenicol and erythromycin, and a much lower level of inhibition by tobramycin.…”