title: Persistently culture positive acanthamoeba keratitis: in vivo resistance and in vitro sensitivity.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Retrospective noncomparative case series.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Cornea and External Disease Service, Moorfields Eye Hospital, London, UK.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Pérez-Santonja
authors.forename: Simon
authors.initials: S
authors.lastname: Kilvington
authors.forename: Reanne
authors.initials: R
authors.lastname: Hughes
authors.forename: Adnan
authors.initials: A
authors.lastname: Tufail
authors.forename: Melville
authors.initials: M
authors.lastname: Matheson
authors.forename: John K G
authors.initials: JK
authors.lastname: Dart
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects* / Q000302:isolation & purification*; D015823:Acanthamoeba Keratitis / Q000175:diagnosis / Q000188:drug therapy / Q000469:parasitology*; D000328:Adult; D000563:Amebicides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology / Q000627:therapeutic use; D001645:Biguanides / Q000494:pharmacology / Q000627:therapeutic use; D002710:Chlorhexidine / Q000494:pharmacology / Q000627:therapeutic use; D003315:Cornea / Q000469:parasitology*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D021261:Parasitic Sensitivity Tests; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000563:Amebicides; D001550:Benzamidines; D001645:Biguanides; C031233:polihexanide; C018961:hexamidine; C005555:propamidine; D002710:Chlorhexidine