Moxifloxacin and cholesterol combined treatment of pneumococcal keratitis.
OBJECTIVE
Compare the efficacy of treatment of pneumococcal keratitis with cholesterol, moxifloxacin, or a mixture of the two (moxifloxacin/cholesterol).


METHODS
New Zealand white rabbits were injected intrastromally with 10(6) colony-forming units (CFU) of a clinical keratitis strain of Streptococcus pneumoniae. Eyes were examined before and after treatment of topical drops every 2 hr from 25 to 47 hr post-infection (PI). Corneas were harvested to quantitate bacterial CFU, and myeloperoxidase (MPO) activity was measured at 48 hr PI. Eyes were extracted for histology. Minimal inhibitory concentrations (MICs) were determined for each compound.


RESULTS
Eyes treated with moxifloxacin/cholesterol had a significantly lower mean slit lamp examination (SLE) score than eyes treated with phosphate-buffered saline (PBS), moxifloxacin alone, or cholesterol alone (P ≤ 0.02). A significantly lower log(10) CFU was recovered from corneas treated with moxifloxacin/cholesterol and moxifloxacin alone as compared to corneas of eyes treated with PBS or cholesterol alone (P < 0.01). At 48 hr PI, significantly lower MPO activity was quantitated from eyes treated with moxifloxacin/cholesterol as compared to eyes treated with cholesterol or moxifloxacin alone (P ≤ 0.046). Eyes treated with moxifloxacin/cholesterol had fewer immune cells and less corneal destruction than eyes from all other treatment groups. The MIC for moxifloxacin alone was 0.125 μg/mL, and cholesterol alone was unable to inhibit growth at any of the concentrations tested. The MIC for moxifloxacin when combined with 1% cholesterol was 0.0625 μg/mL.


CONCLUSIONS
Treatment with a mixture of moxifloxacin and cholesterol significantly lowers the severity of infection caused by pneumococcal keratitis as compared to treatment with moxifloxacin alone, cholesterol alone, or PBS. This treatment mixture eradicates the bacteria in the cornea, unlike treatment with PBS or cholesterol alone. Using cholesterol with moxifloxacin as a treatment for bacterial keratitis could help lower the clinical severity of the infection.
Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Melissa E
ME
Sanders
Nathan A
NA
Tullos
Sidney D
SD
Taylor
Erin W
EW
Norcross
Lauren B
LB
King
Isaiah
I
Tolo
Mary E
ME
Marquart
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use*; D002784:Cholesterol / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D024841:Fluoroquinolones; D007634:Keratitis / Q000188:drug therapy* / Q000382:microbiology; D000077266:Moxifloxacin; D009195:Peroxidase / Q000378:metabolism; D011804:Quinolines / Q000627:therapeutic use*; D011817:Rabbits; D012720:Severity of Illness Index; D013234:Stem Cells / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002784:Cholesterol; D009195:Peroxidase; D000077266:Moxifloxacin