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Treatment of Resistant Herpes Simplex Virus With Continuous-Infusion Acyclovir
Jeffrey P. Engel, MD;
Janet A. Englund, MD;
Courtney V. Fletcher, PharmD;
Edgar L. Hill, MS
JAMA. 1990;263(12):1662-1664.
Abstract
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Two patients with acquired immunodeficiency syndrome who developed severe ulcerative proctitis caused by herpes simplex virus type 2 that was resistant to acyclovir were successfully treated with 6 weeks of high-dose, continuousinfusion acyclovir sodium (1.5 to 2.0 mg/kg per hour). Viruses cultured from the lesions were resistant to acyclovir in vitro after the patients had received prolonged therapy with oral and intravenous acyclovir in traditional divided doses. Investigation into the mechanism of the acyclovir resistance revealed changes in the thymidine-kinase activity of both isolates. This viral enzyme phosphorylates acyclovir and is necessary for drug activation. The first patient's isolate was deficient of all thymidine-kinase activity, while the second patient's isolate had a thymidine kinase with altered substrate specificity for acyclovir. The continuous infusion was safe, well tolerated, and done in an outpatient setting with weekly clinic visits and monitoring of creatinine and acyclovir levels.
(JAMA. 1990;263:1662-1664)
Author Affiliations
From the Departments of Medicine (Dr Engel), Pediatrics (Dr Englund), and Laboratory Medicine and Pathology (Dr Englund), and the College of Pharmacy (Dr Fletcher), University of Minnesota, Minneapolis; and the Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, NC (Mr Hill). Dr Engel is now with the Department of Medicine, East Carolina University School of Medicine, Greenville, NC. Dr Englund is now with the Departments of Microbiology and Immunology and Pediatrics, Baylor College of Medicine, Texas Medical Center, Houston.
Footnotes
Reprint requests to the Department of Medicine, East Carolina University School of Medicine, Greenville, NC 27858-4354 (Dr Engel).
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