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Background: To compare the efficacy of intravenous (IV) imipenem (IPM) and a combination of IV ceftazidime (CAZ) and amikacin (AN) in the treatment of Staphylococcus aureus endophthalmitis in a rabbit model. Methods: Right eyes of 60 albino rabbits were injected with 1000 colony-forming units of S. aureus intravitreally. After 24 h, treatment with either IV IPM (37.5 mg/kg) every 8 h ( n=18) or IV CAZ (50 mg/kg) and AN (10 mg/kg) every 8 hours ( n=18) was begun and continued until the animals were killed at the indicated timepoints; 24 control animals received no treatment. The concentration of bacteria in the vitreous from six animals per group was determined microbiologically on days 2, 3, and 5 after infection, and histologic examination was performed on all eyes. Results: The number of eyes with positive cultures on day 5 was lower in the group that received IV IPM (2/6) compared with the IV CAZ/AN group (4/6) and the control group (6/6). For the culture-positive eyes, the bacterial concentrations were significantly lower for the IV IPM group compared with the IV CAZ/AN group on days 2 and 5 ( P<0.05 and P<0.0065, respectively), but not on day 3 ( P <0.8. Bacterial counts in both treatment groups were significantly lower than in the control group ( P<0.005). Eyes in all groups, however, showed severe intraocular inflammation. Conclusions: IV IPM is more effective than is IV CAZ/AN in reducing the number of bacteria in an animal model of S.aureus endophthalmitis. [ABSTRACT FROM AUTHOR]