Dear Editor

I read with great interest the letter by Doft et al [1] 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 lesser than the MIC90 of the organisms [4]. Interestingly, in the study, ceftazidime precipitated to a significant extent, especially when prepared in balanced salt solution plus (BSS Plus) 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 precipitataion might not be so important in the usage 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 nor 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 EVS. The series of posttraumatic endophthalmitis over a period of two 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 (4 out of the 39 isolates); (unpublished data).

3. The intravitreal combination of choice for the initial empiric 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.

Vasumathy Vedantham MS, DNB, FRCS.

Correspondence to Dr.Vasumathy Vedantham, Consultant, Retina-Vitreous service, Aravind Eye hospital & PG Institute of Ophthalmology, 1, Anna Nagar, Madurai, Tamil Nadu, India-625020.

E-Mail: drvasumathy@yahoo.com.

References

(1) Doft BH, M Barza. Macular infarction after intravitreal amikacin. Br J Ophthalmol 2004;88: 850.

(2) Galloway G, Ramsay A, Jordan K, Vivian A. Macular infarction after intravitreal amikacin: mounting evidence against amikacin. Br J Ophthalmol 2002;86: 359-360.

(3) Lifshitz T, Lapid-Gortzak R, Finkelman Y, Klemperer I. Vancomycin and ceftazidime incompatibility upon intravitreal injection. Br J Ophthalmol 2000;84:117–118.

(4) Kwok AKH, Hui M, Pang CP, Chan RCY, Cheung SW, Yip CMS, Lam DSC, Cheng AFB. An in vitro Study of ceftazidime and vancomycin concentrations in various fluid media: implications for use in treating endophthalmitis. Invest Ophthalmol Vis Sci 2002;43: 1182–8.

(5) Hui M, Kwok AKH, Pang CP, Cheung SW, Chan RCY, Lam DSC, Cheng AFB. An in vitro study on the compatibility and precipitation of a combination of ciprofloxacin and vancomycin in human vitreous. Br J Ophthalmol 2004;88: 218-222.

(6) Benz MS, Scott IU, Flynn HW, et al. In vitro susceptibilities to antimicrobials of pathogens isolated from the vitreous cavity of patients with endophthalmitis. Invest Ophthalmol Vis Sci 2002;43:E-Abstract 4428.

(7) Anand AR, Therese KL, Madhavan HN. Spectrum of aetiological agents of postoperative endophthalmitis and antibiotic susceptibility of bacterial isolates. Indian J Ophthalmol 2000;48: 123-128.

(8) Hainsworth DP, Conklin JD, Bierly JR, Ax D, Ashton P. Intravitreal delivery of ciprofloxacin. J Ocul Pharmacol Ther1996;12: 183–91.