Antimicrobial concentrations in the cornea and aqueous humour: a meta-analysis

AimTo interpret the likely clinical susceptibility of isolates from microbial keratitis we performed a meta-analysis of published data that measured the concentrations of, topically applied, antimicrobials in the cornea or aqueous humour. We then correlated these values with the in vitro minimum inhibitory concentration (MIC). Methods and AnalysisWe searched PubMed to identify studies reporting aqueous and/or corneal concentrations of 53 topically applied ocular antimicrobials, spanning the following classes: beta-lactams, glycopeptides, aminoglycosides, chloramphenicol, lincosamides, macrolides, oxazolidinones, steroidal antimicrobials, tetracyclines, diaminopyrimidines, sulfonamides, lipopeptides and polymyxins. For each class, two clinicians independently screened the abstracts. For articles that met the inclusion criteria, data were extracted on participant species, antimicrobial concentration, dosing regimens, epithelial status, and measurement methods. Concentrations were standardised to mg/L. First quartile concentrations (EQ1) were extrapolated from the mean and standard deviation or calculated from the contained data where available. The data were tabulated to generate the EQ1 concentrations for the aqueous and cornea of each antimicrobial, stratified by applied concentration and dosing regimen. ResultsWe screened 7247 publications. Eighty-one publications were included in the meta-analysis, comprising data on the aqueous and/or corneal concentrations of twenty-eight antimicrobials. Bioassay was the most frequently used method for quantifying antimicrobial concentrations (25 studies), followed by liquid chromatography and fluorescence assays (18 studies each), mass spectrometry (12 studies), and radioactivity and colorimetric assays (three studies each). ConclusionWe provide a practical resource for clinicians to assess whether the expected EQ1 of an antimicrobial in the cornea is above the in vitro MIC of the pathogen. This reduces reliance on systemic break-point concentrations enabling evidence-based antimicrobial treatment decisions for microbial keratitis. KEY MESSAGESO_ST_ABSWhat is already known on the topicC_ST_ABSMicrobial keratitis (MK) is a major cause of preventable blindness worldwide. The susceptibility of an isolate is based on systemic breakpoint criteria that may not reflect corneal or aqueous concentrations following topical application. What this study addsWe provide a comprehensive and standardised resource of corneal and aqueous antimicrobial concentrations following topical application. This enables treatment decisions based on the minimal inhibitory concentrations (MIC) of the isolate and the expected tissue concentration of the antimicrobial for evidence-based management of MK. How this study might affect research, practice or policyThis study provides a practical resource linking in vitro antimicrobial MIC values to anticipated ocular drug concentrations, enabling more precise treatment of microbial keratitis, supporting research and the development of clinical guidelines.