Treatment of experimental Staphylococcus epidermidis endophthalmitis with oral trovafloxacin.
OBJECTIVE
To investigate the ocular pharmacokinetics and efficacy of oral trovafloxacin, a novel fluoroquinolone antibiotic, in Staphylococcus epidermidis endophthalmitis.


METHODS
Albino rabbits (n = 20) were infected with an intravitreal inoculum of S epidermidis (1.0 x 10(8) colony-forming units [CFU/0.1 ml) and 24 hours later received a single oral dose of trovafloxacin (250 mg/kg). Serum and intraocular samples from infected and control (noninfected) eyes were obtained up to 24 hours after antibiotic administration for measurement of trovafloxacin levels. A second group of rabbits (n = 72) was infected intraocularly and randomized 24 hours later to oral trovafloxacin (250 mg/kg twice a day) for 6 days or no treatment (control). Treatment efficacy was assessed by vitreous culture, clinical examination, and histopathology.


RESULTS
Following a single dose of trovafloxacin, maximal vitreous levels were achieved at 8 hours in infected eyes, with a penetration ratio of 36%. Vitreous levels were greater than 15 times the minimum inhibitory concentration of the strain employed. In animals with established endophthalmitis, treated eyes were sterilized after 5 days (P = .0495) compared with control eyes, which autosterilized at 14 days. Clinical and histologic examination revealed significant amelioration of anterior segment inflammation in treated eyes, although severe destruction of posterior segment structures occurred in both groups after 6 days of therapy.


CONCLUSIONS
These data support trovafloxacin as a potential oral agent for treatment or prophylaxis of S epidermidis endophthalmitis, although retinal alterations that occur over the period required for vitreous sterilization suggest that it will not replace intravitreal therapy in established endophthalmitis.
Ng
E W
EW
Massachusetts Eye and Ear Infirmary, and the Department of Ophthalmology, Harvard Medical School 02114-3096, USA.
Samiy
N
N
Ruoff
K L
KL
Cousins
F V
FV
Hooper
D C
DC
von Gunten
S
S
D'Amico
D J
DJ
Baker
A S
AS
D000284:Administration, Oral; D000818:Animals; D000869:Anterior Eye Segment / Q000473:pathology; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D009877:Endophthalmitis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D024841:Fluoroquinolones; D008297:Male; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D012160:Retina / Q000473:pathology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013212:Staphylococcus epidermidis / Q000302:isolation & purification*; D014822:Vitreous Body / Q000378:metabolism / Q000382:microbiology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin