Background: In countries where the resistance of cytomegalovirus to ganciclovir has been studied, strains resistant to therapeutic doses of this drug have been isolated. When a change in treatment has been impossible the patient has shown bad clinical evolution. The aim of this study was to investigate the presence of these strains in our medium, observe whether the resistances appear in patients previously treated with ganciclovir and determine its implication in the evolution of cytomegalovirus infection.
Patients and methods: One hundred twenty-three stains of cytomegalovirus, isolated during the period 1990-1998, corresponding to the following 94 patients were studied: 17 breast feeding children of healthy parents who were negative controls (sensitive strains), 43 organ transplant recipients, 29 AIDS patients, 2 with other immunodeficiencies and 3 children with intrauterine infection. Seventeen patients were studied due to the insidious course of the infection despite treatment. The remaining were random. The technique used was that of growth inhibition of the strains seeded on different gradients of ganciclovir: 0, 1, 5, 10 and 20 microM. The inoculate consisted in a cellular suspension evaluated according to the degree of viral growth. The strains presenting an inhibitory doses 50% (ID 50%) greater than 10 microM were considered as resistant.
Results: Eighty-two strains presented an ID 50% lower than 5 microM, 24 from 5 to 10 microM and in the 17 remaining strains, corresponding to 12 patients, the ID 50% was greater than 10 microM. The evolution of these latter 12 patients with strains considered to be resistant to ganciclovir was of death in 8. All were immunodepressed and with a history of having previously received ganciclovir. Another currently has a chronic evolution and the three remaining patients, who presented better immunity, became cured. All patients has a chronic evolution and the three remaining patients, who presented better immunity, became cured. All patients had undergone previous treatment with ganciclovir except two: one patient with Wegener disease treated with acyclovir 15 days before, and the other was an infant of an HIV positive mother who had received the drug.
Conclusions: The presence of cytomegalovirus strains resistant to ganciclovir was confirmed in our patients. The previous use of ganciclovir and, in one case of acyclovir, appears to be implicated in the appearance of resistance. The evolution of the immunodepressed patients with infection by resistant strains was mortal except when their immunity was improved.