RESUMEN
Mutations in the human cytomegalovirus (CMV) UL97 protein kinase are the most common mechanism of ganciclovir (GCV) resistance in the clinical setting. A CMV strain with a previously unrecognized UL97 mutation N597D was identified in the blood of a heart transplant recipient who experienced a persistent CMV infection with high viral loads accompanying pain and fever while receiving valganciclovir (valGCV) therapy. The N597D mutation was transferred by mutagenesis to an antiviral sensitive CMV strain for analysis of antiviral susceptibility by standardized phenotypic assay. Recombinant phenotyping showed N597D conferred a less than twofold increase in GCV IC(50) compared to the sensitive control strain. Despite the presence of this mutation, valGCV eventually resolved the infection after 6 weeks of therapy. A subsequent CMV reactivation was also responsive to valganciclovir. This case illustrates the diversity of UL97 mutations in the codon segment 590-607 usually associated with GCV resistance, with some mutations producing minimal levels of resistance that do not preclude a therapeutic response to the drug. Accurate interpretation of genotypic test results ultimately requires experimental determination of the level of resistance conferred by newly discovered UL97 mutations.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Citomegalovirus/efectos de los fármacos , Citomegalovirus/genética , Ganciclovir/análogos & derivados , Mutación Missense , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Sangre/virología , Citomegalovirus/aislamiento & purificación , Ganciclovir/uso terapéutico , Trasplante de Corazón/efectos adversos , Humanos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Resultado del Tratamiento , Valganciclovir , Carga ViralRESUMEN
BACKGROUND: Severe refractory angina pectoris can occur in end-stage coronary artery disease despite maximal medical and revascularization therapy. Spinal cord stimulation is an under-utilized but well-established modality for the treatment of intractable angina pain. AIM: To illustrate the practical, beneficial and effective use of spinal cord stimulation as a treatment option for refractory angina in a local context. METHOD: A case series clinical audit of 11 patients with refractory angina treated with spinal cord stimulation over a one-year period was carried out. Baseline, three-month, six-month and two-year functional assessment data and subjective patient reports on their symptoms were evaluated. RESULTS: Spinal cord stimulation improves six-minute walk distance, exercise duration, New York Heart Association functional class, Likert score, and number of angina free days per week for at least one year over two years of follow-up. CONCLUSION: Spinal cord stimulation is an effective medium-term treatment option for refractory angina pectoris with significant benefits to functional parameters and patient symptoms. Spinal cord stimulation is an under-utilized but well-established modality for the treatment of intractable angina pain. We report a small case series clinical audit of patients who gained significant functional and symptomatic benefits from this treatment.