Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

Tuberculosis multirresistente en pacientes con SIDA a comienzos del milenio / Multidrug-resistant tuberculosis in AIDS patients at the beginning of the millennium

La tuberculosis multirresistente (TBMR) asociada al sida emergió durante los años 90 en varios países del mundo. En Argentina, el brote más importante se originó en el Hospital Muñiz y susconsecuencias persisten hasta ahora. Con el objeto de evaluar la situación de la TBMR en este hospital, analizamoslas características clínico-demográfico-epidemiológicas de los 53 pacientes masculinos con TBMR/sida internados por primera vez en el trienio 2001-2003 con relación al genotipo del polimorfismo de longitud de fragmentos de restricción (RFLP) IS6110 de los aislamientos. La edad promedio de los pacientes fue 32 años, 37 (70%) residían en el conurbano bonaerense, 36 (68%) eran usuarios de drogas ilícitas y 14 (26.4%) tenían antecedentes carcelarios. El 88% presentó grave inmunodepresión (CD4+<100/μl) y el 58.5% falleció. La mortalidadse asoció a baja adherencia al tratamiento y a comorbilidades, pero no a enfermedad por Mycobacteriumtuberculosis cepa “M”, causante del brote original. De los 40 casos analizados por RFLP, 29 (72.5%) conformaron clusters y 24 presentaban el genotipo “M”. La resistencia a 5 o 6 drogas resultó un indicador de enfermedad por esa cepa. El genotipo “M” se asoció significativamente a internaciones previas en el Hospital Muñiz oencarcelamiento. En síntesis, 14 años después de ocurrido el primer caso de TBMR/sida, se constata la persistenciay predominancia en el hospital de la cepa responsable del brote. Se requiere una intensificación de las medidas de control de la diseminación institucional de la tuberculosis para consolidar la tendencia decrecientede la TBMR observada en el país en la última década

Aids-related multidrug-resistant tuberculosis (MDRTB) emerged during the 90s in several countries aroundthe world. In Argentina, the most notorious outbreak was documented in the Hospital Muñiz, which is still undergoing its aftermaths. In order to evaluate the situation in this hospital regarding MDRTB, we analysed clinical,demographic and epidemiological traits of the 53 male MDRTB-aids patients admitted during 2001-2003 at award especially dedicated to their isolation. Patients’ mean age was 32 years, 70% lived in Buenos Aires suburbs. A history of illicit drug users or imprisonment was recorded in 68% and 26% of the patients, respectively.Severe immunodepression (CD4+ count <100/μl) was found in 88% of the patients and 58% died. Mortality wasassociated with non-adherence to treatment and co-morbidity, but not with the genotype of the “M” strain, responsible for the original outbreak. Of 40 cases available for restriction fragment length polymorphism (RFLP),29 (72.5%) resulted in cluster. RFLP patterns of 24 matched the “M” genotype. In this study, resistance to 5 or 6 drugs was found to be an indicator of disease due to the “M” strain. The “M” genotype associated significantlyto previous admission at the Hospital Muñiz or imprisonment. In brief, 14 years after the detection of the firstMDRTB-aids case, we report here the persistence and predominance of the original outbreak strain at the hospital.Stronger TB infection control measures are urgently needed in hospitals and jails in order to strengthenthe declining trend of the MDRTB observed in our country towards the end of the last decade

Multiple isolates from Aids patients: aspects of an analysis by a genotypic marker and antimicrobial susceptibilities variations

Twenty-one Mycobacterium avium multisolates, from ten human immunodeficiency virus-infected patients, were typed by restriction fragment length polymorphism using as marker the IS1245 and characterized by minimum inhibitory concentration for nine different antibiotics. Two out of four patients harboring multisolates with different fingerprint profile, were therefore considered as having a polyclonal infection, since their isolates were taken from sterile site. This result confirms that polyclonal infection caused by M. avium occurs with a nonnegligenciable frequency. Analyzing the multisolates susceptibility profile of each patient it was observed that most of them were infected with strains having appreciably different antimicrobial susceptibility patterns, no matter what the genotypic pattern of the strains was. These results have strong implication for the treatment of the patients.