Vitreous and Aqueous Penetration of Orally Administered Gatifloxacinin Humans

We read with interest the intriguing study by Hariprasad et al.¹ Fourth-generation fluoroquinolones, such as gatifloxacin,certainly hold great potential in the treatment and prophylaxis of endophthalmitisand other ophthalmic infections. We applaud the authors for their study confirminggatifloxacin's significant penetration into ocular fluids. However, we takeissue with their discussion of moxifloxacin in the "Comment" section.

The authors specifically quote 2 articles to compare and contrast these2 relatively new fourth-generation fluoroquinolones.^{2 - 3} Theircomments regarding the article by Mather et al² attemptto convey an equivalency of gatifloxacin and moxifloxacin against ocular endophthalmitisisolates. Although in vitro susceptibility data from this study display anequal effectiveness of gatifloxacin and moxifloxacin (against all isolatesexcept resistant Staphylococcus epidermis species,against which moxifloxacin displayed greater effectiveness), the median MICvalues revealed a greater potency of moxifloxacin against all bacteria isolatestested, except 3 species, which displayed equal potency. These MIC data suggestthat a lower concentration of moxifloxacin, compared with gatifloxacin, isneeded to inhibit bacterial growth. Furthermore, Mather et al² conclude,"Concerning the fourth generations alone, our study suggests that moxifloxacinis more potent than gatifloxacin for gram-positive bacteria."

The authors also reference García-Sáenz et al,³ citing that the MIC₉₀ of moxifloxacinagainst Staphylococcus aureus is 2µg/mL, whichsuggests a relative ineffectiveness of this drug to treat the most commonpostcataract infecting organism. The authors thereafter state that "this isnot the case with gatifloxacin." However, the quoted MIC₉₀ valueis not original research by García-Sáenz and colleagues butrepresents a modified table from a review article⁴ analyzingin vitro activities of 6 fluoroquinolones (including both moxifloxacin andgatifloxacin) against a multitude of bacterial strains. Interestingly, gatifloxacinis reported in this same article⁴ to displayan identical MIC₉₀ of 2µg/mL against the S epidermis species tested. This finding calls into question the proposedsuperiority of gatifloxacin for S epidermis ocularinfections, as Hariprasad and colleagues seem to imply.

Various reports confirm the strong action of moxifloxacin against gram-positiveorganisms, including Staphylococcus epidermis.^{2 ,4 - 5} Although most S epidermis strains show susceptibility to these fourth-generationfluoroquinolones at a MIC₉₀ between 0.05 and 0.25 µg/mL,there seems to be a subgroup of isolates that have already acquired resistanceto earlier-generation fluoroquinolones and require levels between 2.0 and2.5 µg/mL to achieve inhibition. These higher MIC₉₀ valuesfor strains already resistant to earlier-generation fluoroquinolones are expected.

We agree with the authors that newer-generation fluoroquinolones shouldbe considered and further evaluated for their use in treating and preventingendophthalmitis and other ocular infections. We applaud their research, whichrepresents the first confirmation of significant vitreous penetration of afourth-generation fluoroquinolone. Although one study³ reporteda mean moxifloxacin aqueous level of 2.33 µg/mL after a single 400-mgoral dose (nearly double the level the authors obtained after 2 oral dosesof gatifloxacin in the present study), there are presently no reports evaluatingits vitreous penetration. Therefore, further studies are required to evaluatethe possible clinical use of oral moxifloxacin in the prophylaxis and treatmentof endophthalmitis and other ocular infections.

Correspondence: Dr Fuller, Department of Ophthalmology, Medical Collegeof Georgia, 1120 15th St, Augusta, GA 30912 (jfuller@gmail.com).