Efficacy of intravitreal administrations of linezolid in an experimental model of S. aureus-related endophthalmitis.
OBJECTIVE
To evaluate the efficacy of intravitreal administration of linezolid (LZD) in a rabbit model of Staphylococcus aureus endophthalmitis.


METHODS
Of 40 rabbits studied, 36 of them received 10(2) colony-forming units (CFU) of S. aureus in their right eye before being randomly assigned to the following groups: four groups of 8 animals received 24 hours after the bacterial inoculation, 1, 10, 30 mg of LZD (LZD 1, LZD 10, and LZD 30) or 1 mg of vancomycin (V1), respectively. Four other animals had a sham injection in their infected eye. The 4 remaining animals were used as negative controls. Clinical, bacterial, and histologic assessments were conducted at different endpoints. Animals were euthanized at day 8. The safety profile of intravitreal LZD was assessed by electroretinography in 5 more animals by comparing the recordings in eyes injected with 30 mg of LZD and contralateral control eyes injected with a solution of sterile saline water.


RESULTS
At day 5, the mean inflammatory clinical scores of Nussenblatt were 7.0 ± 1.0, 3.6 ± 0.7, and 3.1 ± 0.8, in the LZD 1, LZD 10, and LZD 30 groups and 3.4 ± 1.7 and 7.5 ± 0 in the V1 and BSS+ groups, respectively (P < 0.05, ANOVA). The corresponding mean bacterial counts in the vitreous (log 10 CFU/mL) were 6.2 ± 6.5, 3.5 ± 3.8, 0, 3.8 ± 4.2, and 7.8 ± 4.9, respectively (P < 0.05, ANOVA). A 30 mg dose of LZD sterilized all the eyes at day 5 and displayed the lowest (best) histologic score (1.5 ± 0.6). Residual LZD concentrations 24 hours after the administration were between 0.1 and 7.2 mg/L LZD 30 group. The half-time of linezolid in the vitreous was 2 hours. There were no differences in the electroretinogram recordings between control eyes and eyes injected with 30 mg of linezolid at days 1 and 14 after the intravitreal injection.


CONCLUSIONS
This is the first evidence of the effectiveness of linezolid for the treatment of experimental staphylococcal endophthalmitis. High ocular concentrations of LZD were needed to obtain a satisfactory bactericidal effect. Linezolid displayed a concentration-dependent killing activity in the eye. Such doses of intravitreal linezolid appeared to be safe for the retinal function.
Department of Microbiology, University of Strasbourg, 1 place de l’hopital, Strasbourg, France. mahers_fr@yahoo.fr
Maher
M
Saleh
Sophie
S
Lefèvre
Niyazi
N
Acar
Tristan
T
Bourcier
Luc
L
Marcellin
Gilles
G
Prévost
Audrey
A
Subilia
David
D
Gaucher
François
F
Jehl
D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004596:Electroretinography; D009877:Endophthalmitis / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D058449:Intravitreal Injections; D000069349:Linezolid; D023303:Oxazolidinones / Q000008:administration & dosage*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage; D014822:Vitreous Body / Q000187:drug effects / Q000382:microbiology
D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid