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We thank Doft et al for their useful and expert opinion.1 The choice of which agent to use to empirically treat Gram negative organisms implicated in endophthalmitis remains controversial. As amikacin has been proved to cause macular infarction, we think one should look at viable alternatives. Ceftazidime is already in widespread use in the United Kingdom and appears not only to have an excellent safety profile but also good clinical effect. Unfortunately, until we have proper in vivo and in vitro “head to head” comparison studies, it is difficult to know which is the more efficacious agent. As far as synergism is concerned, vancomycin and ceftazidime are usually not tested together because vancomycin acts on Gram positive organisms and ceftazidime is used primarily for Gram negative infections. However, there is one study that reported synergy between vancomycin and ceftazidime against Gram positive organisms.2
The study by Kwok and colleagues raises a concern that ceftazidime precipitation, as assessed by in vitro studies, may affect its action in vivo.3 The authors of our study have noticed temporary precipitants in vivo without apparent alteration of clinical effect (AR). Previous animal models do show that ceftazidime reaches intravitreal minimal inhibitory concentrations for common Gram negative microbes after a single intravitreal injection.4 Perhaps assay at the time of repeat injection, non-invasive confocal Raman spectroscopy of the anterior chamber, or further animal models may provide additional insight into ceftazidime pharmacokinetics and the phenomenon of ceftazidime precipitation so as to guide future therapeutic choice. Ultimately the decision lies with the treating surgeon, who should be aware of both the efficacy and safety profiles of the agents available. We still believe, with the evidence presented in our article,5 that ceftazidime currently represents the best agent for the treatment of Gram negative microbes in endophthalmitis.
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