Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens.

BACKGROUND AND OBJECTIVE: Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI) -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens. METHODS: This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). RESULTS: A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI95, 76.8-81.8) and 91.5% (CI95, 89.6-93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. CONCLUSION: Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.

Brote de bacteriemia por Burkholderia cepacia en una unidad de hemodiálisis de Cádiz, 2014 / An outbreak of Burkholderia cepacia bacteremia in a hemodialysis unit, Cadiz, 2014

INTRODUCCIÓN: En enero de 2014 se conoció la existencia de un posible brote de bacteriemia por Burkholderia cepacia en un centro concertado de hemodiálisis en La Línea de la Concepción (Cádiz). Se inició una investigación para determinar la causa del brote y establecer medidas de control. MÉTODOS: Se realizó un análisis descriptivo de los pacientes afectados por bacteriemia por Burkholderia cepacia desde noviembre de 2013 hasta febrero de 2014 y de las posibles características comunes entre cada uno de ellos. Se tomaron muestras de diferentes zonas y superficies buscando el origen el brote. Se realizó estudio de tipificación molecular mediante electroforesis en gel de campo pulsado (Spel PFGE) y análisis mediante MLST en centro de referencia para determinar la similitud genética de las cepas aisladas. RESULTADOS: En el periodo de estudio se aisló la bacteria en los hemocultivos de 7 pacientes, en 3 muestras de sellado (líquido endoluminal) de catéteres (2 de ellos fueron también casos) y en 4 muestras de botes de clorhexidina. Los pacientes eran coincidentes en 2 de los 6 turnos de diálisis. La edad media de los casos fue de 67 años. El 57% fueron mujeres. Se analizó la relación clonal entre casos y una muestra ambiental y resultaron ser idénticos genéticamente (clon ST653). CONCLUSIONES: Se confirmó la presencia de un brote de Burkholderia cepacia con 7 casos entre pacientes que estaban siendo hemodializados. El brote fue debido a una misma cepa con una fuente probablemente común y una transmisión secundaria de persona a persona

INTRODUCTION: In January 2014 a possible outbreak of Burkholderia cepacia bacteremia occurred in a hemodialysis center situated in La Linea de la Concepción (Cadiz). An investigation was begun to confirm the outbreak, identify the source, and implement control measures. METHODS: A descriptive analysis was performed to describe the characteristics of the patients affected with Burkholderia cepacia bacteremia from November 2013 to February 2014. Environmental samples were taken. A molecular typing study was performed using pulsed field gel electrophoresis (SpeI PFGE) and MLST analysis in order to determine the genetic similarity between the isolates. RESULTS: The bacterium was isolated from blood cultures of 7 patients during the study period. Three of the samples (2 of which were also cases) were endoluminal fluid from catheter locks, and 4 chlorhexidine bottle samples. The patients were coincident in 2 of the 6 work shifts. The mean age of the cases was 67 years of whom 57% were women. Human samples and an environmental sample was analyzed and found to be genetically identical (ST653 clone). CONCLUSIONS: The analysis confirmed the outbreak of Burkholderia cepacia, with 7 cases among the patients of the hemodialysis center. The outbreak was due to the same strain, probably a common source and secondary transmission from person to person

[An outbreak of Burkholderia cepacia bacteremia in a hemodialysis unit, Cadiz, 2014]. / Brote de bacteriemia por Burkholderia cepacia en una unidad de hemodiálisis de Cádiz, 2014.

INTRODUCTION: In January 2014 a possible outbreak of Burkholderia cepacia bacteremia occurred in a hemodialysis center situated in La Linea de la Concepción (Cadiz). An investigation was begun to confirm the outbreak, identify the source, and implement control measures. METHODS: A descriptive analysis was performed to describe the characteristics of the patients affected with Burkholderia cepacia bacteremia from November 2013 to February 2014. Environmental samples were taken. A molecular typing study was performed using pulsed field gel electrophoresis (SpeI PFGE) and MLST analysis in order to determine the genetic similarity between the isolates. RESULTS: The bacterium was isolated from blood cultures of 7 patients during the study period. Three of the samples (2 of which were also cases) were endoluminal fluid from catheter locks, and 4 chlorhexidine bottle samples. The patients were coincident in 2 of the 6 work shifts. The mean age of the cases was 67 years of whom 57% were women. Human samples and an environmental sample was analyzed and found to be genetically identical (ST653 clone). CONCLUSIONS: The analysis confirmed the outbreak of Burkholderia cepacia, with 7 cases among the patients of the hemodialysis center. The outbreak was due to the same strain, probably a common source and secondary transmission from person to person.

Predictors of early mortality in very elderly patients with bacteremia: a prospective multicenter cohort.

OBJECTIVES: The proportion of very elderly people in the population is increasing, and infectious diseases in this patient group may present with specific characteristics. The objective of this study was to investigate the outcome predictors of bacteremia among the very elderly. METHODS: This was a multicenter prospective cohort study of bloodstream infections (BSI) in patients ≥ 80 years old in 15 hospitals in Spain. The outcome variables were 14-day and 30-day mortality. Multivariate analysis was performed. RESULTS: One hundred and twenty episodes were included. Mortality was 22% (n = 26) on day 14 and 28% (n = 34) on day 30. In the univariate analysis, the variables associated with mortality were neutropenia, recent surgery, Pitt score ≥ 2, intensive care unit (ICU) admission, severe sepsis or shock, and abdominal, unknown, and respiratory tract sources. In the multivariate analysis, variables associated with mortality on day 14 were high-risk source (abdominal, unknown, and respiratory tract sources; odds ratio (OR) 7.9, 95% confidence interval (CI) 1.8-33.9), Pitt score ≥ 2 (OR 5.6, 95% CI 1.3-23.3), inadequate empirical treatment (OR 11.24, 95% CI 1.6-80.2), and severe sepsis or shock at presentation (OR 5.3, 95% CI 1.4-20.7); the interaction between empiric treatment and high-risk source was significant. On day 30, mortality was independently related to a high-risk source (OR 2.92, 95% CI 1.1-7.5) and presentation with severe sepsis or shock (OR 3.81, 95% CI 1.2-12.4). CONCLUSIONS: Presentation with severe sepsis or shock and a high-risk source of BSI were independent predictors of 14-day and 30-day mortality. Inadequate empirical treatment was also a predictor of early mortality in patients with a high-risk source.

Clinical and virological efficacy of etravirine plus two active Nucleos(t)ide analogs in an heterogeneous HIV-infected population.

UNLABELLED: Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01437241.