Moxifloxacin efficacy and vitreous penetration in a rabbit model of Staphylococcus aureus endophthalmitis and effect on gene expression of leucotoxins and virulence regulator factors.
Bacterial endophthalmitis is a serious complication of ocular surgery and of eye trauma; the leading causative organisms are Staphylococcus aureus strains. Tissue damage is due both to the host inflammatory response and to toxin synthesis by bacteria. Systemic treatment remains difficult because most antibiotics show poor ocular penetration. Moxifloxacin (MXF), a novel fluoroquinolone, was evaluated for its penetration into the vitreous of normal rabbit eyes and of eyes of rabbits infected for 24 h with methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA) following a single intravenous administration of 5 or 20 mg/kg. MXF penetration was rapid and efficient regardless of the dose, ranging from 28 to 52%. An inflammatory state of the vitreous significantly increased penetration after the 20-mg/kg dose, with penetration reaching 52%. Concentrations determined in the vitreous cavity following a 20-mg/kg administration showed a 3.5-fold decrease of the bacterial density within 5 h for MSSA (MIC, 0.125 micro g/ml) and a 1.6-fold decrease for MRSA (MIC, 4 micro g/ml) strains, respectively. By using a semiquantitative reverse transcription-PCR method, the expression of luk-PV and hlgCB, but not hlgA, encoding staphylococcal leukotoxins, was detected in the vitreous without MXF treatment. A slight decrease in the expression of leucotoxins and sarA, agr, and sigB virulence regulatory factors was observed 1 h following the administration of 5 mg of MXF per kg.
Bronner
Stéphane
S
Institut de Bactériologie, Faculté de Médecine, Université Louis Pasteur-Hôpitaux Universitaires de Strasbourg, F-67000 Strasbourg, France.
Jehl
François
F
Peter
Jean-Daniel
JD
Ploy
Marie-Cécile
MC
Renault
Corinne
C
Arvis
Pierre
P
Monteil
Henri
H
Prevost
Gilles
G
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001372:Aza Compounds; D009877:Endophthalmitis / Q000188:drug therapy*; D005098:Exotoxins / Q000235:genetics*; D005260:Female; D024841:Fluoroquinolones; D008297:Male; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D037521:Virulence Factors
D000890:Anti-Infective Agents; D001372:Aza Compounds; D005098:Exotoxins; D024841:Fluoroquinolones; D011804:Quinolines; D037521:Virulence Factors; C018579:leukotoxin; D000077266:Moxifloxacin