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I read with great interest the letter by Doft et al1 suggesting amikacin to be a better alternative to ceftazidime, in response to the article by Galloway et al,2 that suggested the converse. I would like to suggest that ciprofloxacin is a better alternative to both these drugs. There are certain points that I would like to mention to support my statement.
(1) It has been shown that vancomycin and ceftazidime are incompatible upon mixing, with precipitate formation.3 In addition, Kwok et al have suggested ceftazidime to be relatively ineffective owing to its higher rate of precipitation in the vitreous at body temperature resulting in a free antibiotic concentration much less than the MIC90 of the organisms.4 Interestingly, in the study, ceftazidime was precipitated to a significant extent, especially when prepared in balanced salt solution plus (BSS Plus) rather than in normal saline (NS), with up to 88% loss in concentrations of the measurable free antibiotics. Such a low antibiotic concentration would be inadequate for the treatment of a potentially blinding disease like infective endophthalmitis. Hui et al, in an elegant study, measured the concentrations of vancomycin and ciprofloxacin in an equilibrium dialysis chamber by high performance liquid chromatography and fluorescence polarisation immunoassay.5 They did note that ciprofloxacin precipitates in vitreous, but to a much lesser extent than ceftazidime and, significantly, the remaining ciprofloxacin concentration was many times above the MIC90 of the drug against the common Gram negative bacteria encountered. This suggests that the problem of precipitation might not be so important in the use of intravitreal ciprofloxacin. The precipitation of ciprofloxacin was also found to be independent of the medium, which means that there is no need to avoid the use of BSS Plus during preparation of the ciprofloxacin for intravitreal injection or during intraocular surgery.
(2) Various studies have shown the efficacy of ciprofloxacin. Benz et al have shown that 92% of Gram negative organisms in culture proved endophthalmitis were susceptible to ciprofloxacin.6 In the Indian scenario too ciprofloxacin is considered to be a very dependable drug. In fact, 88.4% of even the Gram positive organisms in the series of Anand et al,7 were sensitive to ciprofloxacin. This is a significantly lower rate of resistance of Gram positive organisms to ciprofloxacin than that found in the ex vivo study. The series of post-traumatic endophthalmitis over a period of 2 years from our institute also shows 26 of the 39 isolates to be sensitive to ciprofloxacin and a hitherto unreported poor rate of susceptibility to ceftazidime (four out of the 39 isolates) (unpublished data).
(3) The intravitreal combination of choice for the initial empirical treatment of endophthalmitis could be vancomycin and ciprofloxacin. A certain amount of synergy could be expected with this combination, with vancomycin inhibiting the cell wall synthesis of the bacteria allowing ciprofloxacin to penetrate into the cell and inhibiting the DNA supercoiling. This synergy and the resultant greater bactericidal activity would be all the more important considering that there is no assistance from the body’s immune system in combating the intraocular infection. Although it has been proved to be non-toxic in animal models,8 this substitution of ceftazidime with ciprofloxacin of course, would necessitate further studies on the safety profile of intravitreal ciprofloxacin.