title: Effect of low concentrations of benzalkonium chloride on acanthamoebal survival and its potential impact on empirical therapy of infectious keratitis.
abstract: OBJECTIVE
  The significant antiacanthamoebal effect of benzalkonium chloride, at or below concentrations used for preservation of common ophthalmic preparations, should be understood both when choosing empiric antibiotic therapy for infectious keratitis and when assessing the persistent rise in Acanthamoeba cases in the United States since 2003.
  
  
  OBJECTIVE
  To characterize the antiacanthamoebal efficacy of low concentrations of benzalkonium chloride (BAK) for drug preservation and therapeutic effect against Acanthamoeba.
  
  
  METHODS
  Experimental study with a review of the literature.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  A concentration of 10(4) trophozoites of 3 well-characterized clinical strains of Acanthamoeba were exposed at 0.5, 2.0, 3.5, 5.0, and 6.5 hours to BAK (0.001%, 0.002%, and 0.003%), moxifloxacin hydrochloride (0.5%), and moxifloxacin (0.5%) + BAK (0.001% and 0.003%) with hydrogen peroxide (3%) and amoeba saline controls.
  
  
  METHODS
  Amoeba survival was calculated using the most probable number method recorded as log kill values. The relationship of BAK concentration and exposure time as well as the relative effect of BAK and moxifloxacin on acanthamoebal survival were analyzed.
  
  
  RESULTS
  Amoebicidal activity of BAK is both time dependent and concentration dependent in pooled and strain-stratified analyses (P < .001). Moxifloxacin demonstrated no significant independent inhibitory effect or additive effect to BAK efficacy on acanthamoebal survival. The profound antiacanthamoebal effect of BAK, 0.003%, was similar to that of hydrogen peroxide for certain strains.
  
  
  CONCLUSIONS
  Low concentrations of BAK, previously demonstrated to concentrate and persist in ocular surface epithelium, exhibit significant antiacanthamoebal activity in vitro at or below concentrations found in commercially available ophthalmic anti-infectives. The unexplained persistence of the Acanthamoeba keratitis outbreak in the United States, clusters abroad, and clinical studies reporting resolution or modification of Acanthamoeba keratitis without specific antiacanthamoebal therapy suggests that other contributing factors should be considered, including changes in the formulations used for empirical therapy of presumed infectious keratitis occurring in the same period.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA. etu@uic.edu
authors.forename: Elmer Y
authors.initials: EY
authors.lastname: Tu
authors.forename: Megan E
authors.initials: ME
authors.lastname: Shoff
authors.forename: Weihua
authors.initials: W
authors.lastname: Gao
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Joslin
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects* / Q000254:growth & development*; D015823:Acanthamoeba Keratitis / Q000188:drug therapy* / Q000469:parasitology; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D001372:Aza Compounds / Q000008:administration & dosage; D001548:Benzalkonium Compounds / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D006790:Host-Parasite Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage; D000077266:Moxifloxacin; D021261:Parasitic Sensitivity Tests; D011804:Quinolines / Q000008:administration & dosage
chemical_list: D000981:Antiprotozoal Agents; D001372:Aza Compounds; D001548:Benzalkonium Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D006861:Hydrogen Peroxide; D000077266:Moxifloxacin