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

Ophthalmology. 2003 Aug;110(8):1593-600. doi: 10.1016/S0161-6420(03)00481-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acanthamoeba / drug effects*
  • Acanthamoeba / isolation & purification*
  • Acanthamoeba Keratitis / diagnosis
  • Acanthamoeba Keratitis / drug therapy
  • Acanthamoeba Keratitis / parasitology*
  • Adult
  • Amebicides / pharmacology*
  • Amebicides / therapeutic use
  • Animals
  • Benzamidines / pharmacology
  • Benzamidines / therapeutic use
  • Biguanides / pharmacology
  • Biguanides / therapeutic use
  • Chlorhexidine / pharmacology
  • Chlorhexidine / therapeutic use
  • Cornea / parasitology*
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parasitic Sensitivity Tests
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome


  • Amebicides
  • Benzamidines
  • Biguanides
  • polihexanide
  • hexamidine
  • propamidine
  • Chlorhexidine