Can Serum Drops Containing Doxycycline Provide a Supplemental Anti-Bacterial Effect in the Treatment of Bacterial Keratitis?

PURPOSE: Systemic doxycycline has been prescribed to reduce inflammation and enhance corneal healing in bacterial keratitis. Topical autologous serum drops (ASD) containing doxycycline following oral supplementation may additionally confer an anti-bacterial effect. The potential of this supplementation was evaluated by determining the in vitro susceptibility of bacterial keratitis isolates to doxycycline. METHODS: The minimum inhibitory concentrations (MICs) of doxycycline against 100 bacterial keratitis isolates were determined using Etests. Twenty-seven Staphylococcus aureus, ten coagulase-negative Staphylococci, six Streptococcus pneumoniae, seven viridans group streptococci, seven other Gram-positive bacteria, nineteen Pseudomonas aeruginosa, eight Serratia marcescens, four Moraxella spp., two Haemophilus spp., and ten other Gram-negative bacteria isolates were tested. MICs of doxycycline were compared to a serum standard concentration of doxycycline (SSCD) of 4 µg/mL and concentrations that would be found in 50% and 20% serum component clinical preparations of ASD, corresponding to 50% SSCD (2 µg/mL) and 20% SSCD (0.8 µg/mL), respectively. MICs equal to or less than these values were used to deem a bacterial isolate susceptible. RESULTS: For Gram-positive bacteria, susceptibilities to SSCD, 50% SSCD, and 20% SSCD were 86%, 65%, and 60%, respectively. For Gram-negative bacteria, susceptibilities to SSCD, 50% SSCD, and 20% SSCD were 37.2%, 23.3%, and 11.6%, respectively. Chi-squared analyses comparing Gram-positive and Gram-negative susceptibilities showed significantly greater susceptibility of Gram-positive bacteria at all three tested MICs (<0.0001, <0.0001, <0.0001). CONCLUSIONS: Our data suggest that autologous serum drops containing theoretic concentrations of doxycycline may provide an additional anti-bacterial effect in the treatment of bacterial keratitis, especially for Gram-positive bacterial keratitis compared to Gram-negative bacterial keratitis.