Abstract
Whenever a new antimicrobial drug has been used on a large scale in medical treatment, the selection pressure exerted by that drug has favored the emergence of drugresistant microbial variants. Failure of clinical treatment has often been the first indication of the emergence of drug resistance. Idoxuridine (5-iodo-2-deoxyuridine, IUDR) was the first drug employed on a significant scale in the United States for the treatment of a human viral infection, herpes simplex keratitis 1 . During the past 4 years ophthalmologists, observing patients with herpetic keratitis who failed to respond to IUDR treatment, have speculated as to the nature of this “resistance” and its possible increasing frequency.
Buthala 2 , Smith 3 and others 4 , 5 , 6 have studied the emergence of IUDR-resistant herpes simplex viruses (HSV) in cell culture. Repeated passage of HSV in medium containing IUDR promptly yielded strains that could replicate in the presence of IUDR up to 500 μg/ml. About 1 in 1000 or 1 in 10,000 particles appeared to be highly IUDR-resistant, and this resistance was stable on passage. On the other hand it has been reported 7 that some HSV strains are fully susceptible to IUDR in vitro yet are treatment-resistant in vivo, because they escape the action of the drug by rapidly progressing into the depths of the infected cornea. Therefore, it was of interest to determine whether HSV strains of increased resistance to IUDR could be isolated from patients whose herpetic keratitis had failed to respond to IUDR treatment. As a corollary we determined the influence of IUDR treatment on the frequency of HSV isolation from herpetic keratitis in patients, and made observations on IUDR resistance induced in HSV isolates in vitro and in herpetic keratitis of rabbits.
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