Determination of nontoxic concentrations of piperacillin/tazobactam for intravitreal application. An electroretinographic, histopathologic and morphometric analysis.
BACKGROUND
To investigate the highest nontoxic intravitreal dose of piperacillin/tazobactam in rabbits.


METHODS
Forty New Zealand white albino rabbits were used in this study. The rabbits were divided into four equal groups (10 rabbits in each) and the right eyes were treated with 0.1 ml intravitreal injections of 1,000 microg piperacillin/tazobactam in group 1, 500 microg in group 2, 250 microg in group 3, and 100 microg in group 4. The left eyes served as controls and were injected with 0.1 ml of saline solution. Ganzfeld electroretinogram (ERG) was performed on all eyes before and after 4 weeks of intravitreal injections. Then, the rabbits were killed and the eyes were enucleated for histopathological evaluation of the retina. Retinal sections were evaluated by morphometric analyses on cell counts of ganglion cell layer and thickness of the various retinal layers.


RESULTS
Baseline ERGs were similar among the groups (p > 0.05). After 4 weeks of injection, there were a reduction of the b-wave amplitude and extension of the b-wave implicit time in photopic and scotopic ERGs in group 1 and group 2 when compared with controls (for each, p < 0.001). Intravitreal injection of 100 and 250 microg piperacillin/tazobactam did not cause any deterioration of the b-wave of ERGs throughout the follow-up period of 4 weeks (for each, p > 0.05). After morphometric analysis of retinal sections in all groups, there were no statistically significant differences in the mean number of surviving ganglion cells, thickness of the whole retina and the inner plexiform layer compared with controls (p > 0.05).


CONCLUSIONS
250 microg/0.1 ml piperacillin/tazobactam is the highest nontoxic dose to the normal retinas of adult albino rabbits as intravitreal injection. Piperacillin/tazobactam may be a new, potentially important drug in the treatment of endophthalmitis as it has a broad antimicrobial spectrum.
Ozkiriş
Abdullah
A
Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey. aozkiris@erciyes.edu.tr
Evereklioglu
Cem
C
Kontaş
Olgun
O
Oner
Ayşe Oztürk
AO
Erkiliç
Kuddusi
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007267:Injections; D009994:Osmolar Concentration; D010397:Penicillanic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage*; D011817:Rabbits; D012160:Retina / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D000078142:Tazobactam; D014822:Vitreous Body
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin