Bacterial susceptibility to topical antimicrobials and clinical outcome in bacterial keratitis

PURPOSE. To investigate the relationship between the susceptibility of bacteria to topical antimicrobials and clinical outcome in microbial keratitis. METHODS. Clinical outcome data were collected from patients with microbial keratitis from whom a bacterium had been isolated during the period 2003 to 2006. The minimum inhibitory concentration (MIC) was determined for the isolates against 10 antimicrobials. The determinants of the primary clinical outcome, the ratio of healing time (closure of epithelial defect) to ulcer size (HT/UA), was analyzed in a general linear model. RESULTS. Complete clinical outcome and MIC data were available for 421 patients. Sixteen (4%) patients required enucleation and 23 (5%) surgical treatment; in 382 (91%) the ulcer healed with intensive topical antimicrobial therapy. There were significant correlations between HT/UA and organism type (P = 0.001), nearest distance of the ulcer to the limbus (0.02), and MIC of the first antimicrobial used or lowest MIC of combined therapy (P = 0.006). In a model including patients who received monotherapy with a fluoroquinolone who had no subsequent change in their treatment and whose ulcers healed without surgical intervention, there were significant linear associations between clinical outcome and MIC for Pseudomonas spp. (P = 0.047), Staphylococcus aureus (P = 0.04), and Enterobacteriaceae (P = 0.045), but not for Streptococcus spp. (P = 0.85) and coagulase-negative staphylococci (CNS) (P = 0.88). CONCLUSION. With fluoroquinolone monotherapy, there was significant association between the MIC of the antimicrobial prescribed and the clinical outcome with all bacteria except CNS and Streptococcus spp. The approach used in this study, if used prospectively, could allow topical breakpoint susceptibility concentrations to be determined for individual antimicrobial and bacterial combinations.