Azithromycin in the Management of Pythium insidiosum Keratitis

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To the Editor:
Pythium insidiosum causes destructive progressive keratitis that is nonresponsive to conventional treatment and has a poor outcome.1,2 In a recent study, Ramappa et al reported the first successful medical treatment of P. insidiosum keratitis (PIK) with combined therapy of topical azithromycin 1%, topical linezolid 0.2%, and oral azithromycin.3 Based on their study, we report the successful treatment of a 7-year-old boy with a combination therapy of topical and oral azithromycin and topical voriconazole.
The boy presented to us on May 2017, with a central corneal ulcer of 10-day duration (Figs. 1A, B). There was no history of ocular trauma or entry of foreign body. Light microscopic examination of 10% potassium hydroxide wet mount and Gram stain of corneal scrapings revealed aseptate fungal filaments. A diagnosis of fungal keratitis was made, and he was treated with 5% natamycin eye drops every half hour, 1% atropine eye drops 3 times daily and oral analgesics. Ten days later, as there was no improvement, 1% voriconazole eye drops every hour were added to the previous regimen. Despite this, the ulcer continued to progress (Fig. 1C, D). The ulcer was rescraped a week later. Direct light microscopy examination of the corneal scrapings revealed broad aseptate hyaline filaments with ribbon-like folds and right-angled bends (Fig. 1E–G). A presumed diagnosis of PIK was made. He was then treated with 1% azithromycin eye drops every 1 hour, 1% voriconazole eye drops every 1 hour, 1% atropine eye drops 3 times daily, oral azithromycin 250 mg once daily for 3 days each week, and oral analgesics. Topical 5% natamycin was discontinued. Cultures were negative. After rescraping, there was significant corneal thinning (Fig. 1H) that necessitated application of cyanoacrylate adhesive and a bandage contact lens to prevent corneal perforation. Soon after, the clinical condition improved (Fig. 1I). Oral azithromycin was discontinued after 4 weeks. Thirteen weeks after presentation, the cyanoacrylate adhesive was removed. A week later, the corneal surface had completely epithelialized. There was a dense vascularized stromal scar (Fig. 1J), and his vision was perception of hand movement close to his face. The child is awaiting penetrating keratoplasty.
Dense grayish-white stromal infiltrates with feathery margins and tentacle-like projections with subepithelial pinhead-shaped infiltrates are suggestive of PIK.1–3 These features were lacking at presentation in our patient and developed only later. Although aseptate fungal filaments were detected in the initial scrapings, unfamiliarity with the morphology and distinctive characteristics of P. insidiosum led to a delay in diagnosis.
The outcome of medical treatment of PIK is unsatisfactory.1,2 Recently, Ramappa et al reported the first successful medical treatment with combination therapy of oral and topical azithromycin and topical linezolid.3 Following this report, we treated our patient with topical and oral azithromycin. We continued using voriconazole because of our inability to isolate the microorganism in culture. We avoided linezolid for many reasons: the patient was already being treated with 2 antimicrobial agents; need for reconstituting the drug from parenteral preparations; frequent need to refill the prescription as the patient was being treated on an outpatient basis; and uncertainty about shelf life of the reconstituted eye drops in the hot tropical climate of the patient's home, which lacked a refrigerator.
A delay in starting appropriate antimicrobial therapy in our patient resulted in descemetocele formation (Fig. 1H). Although the prompt use of cyanoacrylate adhesive prevented corneal perforation, it, nevertheless, increased morbidity and the treatment period. However, the subsequent resolution of the stromal infiltrate, despite the presence of an overlying cyanoacrylate adhesive cap, indicated adequate penetrance of the topical antimicrobial agents.
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