Abstract
Purpose :
In the treatment of ocular infections such as conjunctivitis, keratitis and endophthalmitis, it is common practice to use more than one antibiotic to achieve broad spectrum coverage as well as overcome circulating antibiotic resistance. However, there is the potential for individual compounds to either potentiate or antagonize one another with respect to antimicrobial efficacy when used in combination. Thus, we studied drug-drug interactions using a suite of common ophthalmic antibiotics to aid clinicians in selecting appropriate combination therapies.
Methods :
Using standard in vitro microbiologic growth conditions, we measured the minimum inhibitory concentrations (MICs) of 8 ophthalmic antibiotics (vancomycin, tobramycin, gentamicin, moxifloxacin, polymyxin B/trimethoprim, ceftazidime, cefazoline and erythromycin) towards Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. Next, each drug was systematically tested in combination with each other using standard checkerboard Fractional Inhibitory Concentration (FIC) testing. The formula: [(MIC Drug A in combination/MIC Drug A alone) + (MIC Drug B in combination/MIC Drug B alone) = FICI] was used to classify drug-drug interactions as antagonistic (FICI>4), indifferent (FICI=1-4), additive (FIC=0.5-1) or synergistic (FIC<0.5).
Results :
56 combinations were evaluated for drug-drug interactions (28 in S. aureus and 28 in P. aeruginosa). Towards S. aureus, 19 combinations were indifferent (efficacy was similar alone or in combination). However, 8 combinations demonstrated additive activity (improved efficacy in combination), and 1 displayed synergistic activity (improved activity beyond what may be expected). Similarly, against P. aeruginosa, 20 combinations proved indifferent, 7 were additive and 1 was synergistic. No antibiotic drug combinations were found to be antagonistic towards either S. aureus or P. aeruginosa.
Conclusions :
Drug-drug interactions are well known in medicine yet have not been specifically studied with a relevant set of ophthalmic antibiotics. Our data suggest that while the majority of ophthalmic antibiotics had no change in efficacy when used alone vs in combination, there were combinations that displayed improved antimicrobial efficacy. These combinations may represent an improved treatment modality for ocular infections.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.