P58: Rare Outbreaks of Infections Associated with Pharmaceutical Products Contaminated with Eukaroytic Microorganisms

Acanthamoeba, Fusarium, Exserohilum, Paecilomyces, and Rhizopus are common in our environment. These eukaryotic microorganisms seldom cause disease, but as contaminants in certain pharmaceuticals have been associated with rare outbreaks of infection with serious adverse health and financial impacts. From 2004 to 2007, different over-the-counter contact lens disinfection solutions were recalled because of extrinsic contamination; one associated with 165 Fusarium keratitis cases and the other with 145 Acanthamoeba keratitis cases (incidences of infection <0.8). Non-compliance and formulations were mediating factors. Probable extrinsic contamination during reformulation of non-preserved methylprednisolone acetate associated with near 730 infections (100 identified with E. rostratum) and at least 53 deaths. This outbreak (Centers for Disease Control 2012-2013) was particularly devastating because of  injection of the drug and delayed onset of symptoms. The incidence of infection (about 14,000 patients) has been < 2%. Similarities among amoeba-, fungal- and human cells present problems for avoiding toxic reactions in therapy and preservation of pharmaceuticals. Moreover, the above contaminants under stress conditions produce resistant stages: cysts in the amoeba and chlamydoconidia in the fungi. These may permit survival and growth in preserved formulations. Antimicrobials targeted for unique properties, e.g., ergosterol in cell membranes and chitin or cellulose in cell walls offer promise. Host disposition, intended target of the drug and density of contaminant determine any significant health threat. Good Laboratory Practice in manufacturing, and education of the technical personnel need to be emphasized in preventing these rare drug-associated outbreaks.