An In Vitro Investigation of Synergy or Antagonism between Antimicrobial Combinations against Isolates from Bacterial Keratitis

Abstract

To investigate antimicrobial combinations for synergy or antagonism against isolates of Staphylococcus aureus and Pseudomonas aeruginosa. Isolates were collected from cases of microbial keratitis from six centers in the United Kingdom. Minimum inhibitory concentrations (MICs) were determined by using E-test strips for 16 antimicrobials, including both current and potentially available agents. E-test strips were used to test selected antimicrobials in combination against a representative set of 10 S. aureus and 10 P. aeruginosa isolates. E-tests of the two antimicrobials were placed on sensitivity agar at right angles intersecting at their respective MICs. Antimicrobial combinations were classified as synergistic, additive, indifferent, or antagonistic, according to their fractional inhibitory concentration (FIC). The combinations meropenem and ciprofloxacin, meropenem and teicoplanin, moxifloxacin and teicoplanin, and ciprofloxacin and teicoplanin, gave the lowest mean FICs for S. aureus, with synergy or additivity being seen in 60% to 80% of isolates. The meropenem/ciprofloxacin combination gave the lowest mean FIC for P. aeruginosa isolates, with 90% showing an additive or synergistic effect. The other combinations elicited a predominantly indifferent response. No consistent antagonistic effect was observed with the combinations used. The combination of meropenem and ciprofloxacin was predominantly additive or synergistic for both S. aureus and P. aeruginosa. Teicoplanin combined with meropenem, ciprofloxacin, or moxifloxacin was also predominantly additive or synergistic against S. aureus.