Infectious Keratitis Drug Combinations May Affect Treatment Efficacy

Infectious keratitis drug combinations have the potential to improve, reduce, or have no effect on improving outcomes in patients with the condition, according to a study published in Cornea.

Researchers used fractional inhibitory concentration testing in a standard checkerboard format to investigate the effects of infectious keratitis treatment efficacy resulting from combinations of ophthalmic antibiotics (n=9), antifungal agents (n=3), and antiacanthamoeba medications (n=2). Overall, the team included 36 antibiotic-antibiotic combinations, 26 antibiotic-antifungal combinations, and 18 antibiotic-antiacanthamoeba combinations. The investigators evaluated whether each combination demonstrated synergistic (improved efficacy beyond what might be predicted when in combination), antagonistic (decreased efficacy), additive (improved efficacy), or neutral efficacy toward treating staphylococcus aureus and pseudomonas aeruginosa.

“Given the diagnostic ambiguity that often exists at the time of clinical presentation, a common treatment strategy is to provide patients with a combination of topical antimicrobials to ensure broad antimicrobial coverage,” the study authors explain. “Currently, the approach of prescribing multiple ophthalmic antimicrobial agents assumes no, or minimal, relevant drug–drug interactions that could result in altered efficacy of one or more of the drugs in a treatment combination.”

Overall, a majority of treatment combinations did not affect the antimicrobial efficacy, the report shows. However, a combination of erythromycin plus polyhexamethylene biguanide demonstrated antagonism toward P. aeruginosa. Several infectious keratitis drug combinations showed improved treatment efficacy — 18 showed additive or synergistic activity toward S. aureus and 15 were additive or synergistic toward P. aeruginosa. A total of 4 combinations were additive or synergistic toward both bacteria.

“Faced with the need for immediate and intensive therapy to prevent vision loss in keratitis coupled with increasing antibiotic resistance, understanding how the efficacy of antimicrobial drugs may be altered when used in combination is critical for selecting the most appropriate and efficacious treatment modality,” according to the researchers.

Study limitations include a lack of in vivo assessments.