Persistently culture positive acanthamoeba keratitis: in vivo resistance and in vitro sensitivity

Abstract

Purpose: To characterize the risk factors, clinical course, treatment outcome and the association between in vivo resistance and in vitro sensitivity for subjects with persistently culture-positive Acanthamoeba keratitis.

Design: Retrospective noncomparative case series.

Participants: Eleven subjects with repeatedly positive cultures for Acanthamoeba treated between January 1990 and December 2000, were reviewed. Only subjects with 2 or more positive cultures, availability of the clinical data, and availability of the last Acanthamoeba isolate were included in this study.

Methods: The medical records were analyzed, and the last isolate from each case was tested in vitro for the antiamoebic drugs used clinically: polyhexamethylene biguanide (PHMB), chlorhexidine, propamidine and hexamidine.

Main outcome measures: Risk factors, the clinical outcome and in vitro cysticidal drug sensitivity assay.

Results: Eleven subjects (11/180, 6.1%) had 2 or more positive cultures of whom 8 eyes of 8 subjects (8/180, 4.45%) were included in this study. Seven of eight (87%) subjects were diagnosed over 1 month from onset (late diagnosis). The most common presenting findings were diffuse stromal infiltrate (5/8, 62.5%), ring infiltrate (5/8, 62.5%), and corneal ulceration (3/8, 37.5%). The clinical course of the disease in all subjects consisted of recurrent episodes of corneal and scleral inflammation, with a mean duration of 13.4 +/- 9 months. All subjects received PHMB, and 5/8 (62.5%) chlorhexidine too; hexamidine was used in combination in 6/8 (75%), and propamidine in 1/8 (12.5%). All subjects had topical steroids, and 5/8 (62.5%) systemic immunosuppression. The disease resolved with corneal scarring in 3/8 (37.5%) subjects, corneal (or impending) perforation treated with therapeutic keratoplasty in 4/8 (50%), and enucleation in 1/8 (12.5%). Final visual acuity was 0.43 +/- 0.37. In vitro most isolates were resistant to propamidine, hexamidine was cysticidal in high concentrations, and PHMB and chlorhexidine had excellent sensitivity profiles.

Conclusions: In our large series of Acanthamoeba keratitis with a positive microbiologic diagnosis at presentation, nearly 5% developed recurrent episodes of corneal and scleral inflammation with viable Acanthamoeba in the cornea despite prolonged treatment with biguanides and/or diamidines. There was no correlation between in vitro drug sensitivities and the in vivo response for biguanides.