[Lessons learned in the Covid-19 pandemic: Novel approaches to respiratory disease prevention] / Lecciones aprendidas en la pandemia de Covid-19: Nuevas perspectivas en prevención de enfermedades respiratorias.

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Corrigendum to Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial [EClinicalMedicine 37 (2021) 100,959]".

[This corrects the article DOI: 10.1016/j.eclinm.2021.100959.].

Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial.

BACKGROUND: There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARS-CoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma. METHODS: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884. FINDINGS: 45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59-77) versus untreated controls (42% IQR 31-73) (p = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed. INTERPRETATION: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19. FUNDING: This work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Budget impact analysis of using procalcitonin to optimize antimicrobial treatment for patients with suspected sepsis in the intensive care unit and hospitalized lower respiratory tract infections in Argentina.

BACKGROUND: Inappropriate antibiotic use represents a major global threat. Sepsis and bacterial lower respiratory tract infections (LRTIs) have been linked to antimicrobial resistance, carrying important consequences for patients and health systems. Procalcitonin-guided algorithms may represent helpful tools to reduce antibiotic overuse but the financial burden is unclear. The aim of this study was to estimate the healthcare and budget impact in Argentina of using procalcitonin-guided algorithms to guide antibiotic prescription. METHODS: A decision tree was used to model health and cost outcomes for the Argentinean health system, over a one-year duration. Patients with suspected sepsis in the intensive care unit and hospitalized patients with LRTI were included. Model parameters were obtained from a focused, non-systematic, local and international bibliographic search, and validated by a panel of local experts. Deterministic and probabilistic sensitivity analyses were performed to analyze the uncertainty of parameters. RESULTS: The model predicted that using procalcitonin-guided algorithms would result in 734.5 [95% confidence interval (CI): 1,105.2;438.8] thousand fewer antibiotic treatment days, 7.9 [95% CI: 18.5;8.5] thousand antibiotic-resistant cases avoided, and 5.1 [95% CI: 6.7;4.2] thousand fewer Clostridioides difficile cases. In total, this would save $422.4 US dollars (USD) [95% CI: $935;$267] per patient per year, meaning cost savings of $83.0 [95% CI: $183.6;$57.7] million USD for the entire health system and $0.4 [95% CI: $0.9;$0.3] million USD for a healthcare provider with 1,000 cases per year of sepsis and LRTI patients. The sensitivity analysis showed that the probability of cost-saving for the sepsis patient group was lower than for the LRTI patient group (85% vs. 100%). CONCLUSIONS: Healthcare and financial benefits can be obtained by implementing procalcitonin-guided algorithms in Argentina. Although we found results to be robust on an aggregate level, some caution must be used when focusing only on sepsis patients in the intensive care unit.

[Candidemia: characteristics in elderly patients]. / Candidemia: características en los adultos mayores.

BACKGROUND: Candidemia is a nosocomial bloodstream infection and an important cause of comorbidity and mortality. Elderly patients present the highest rates of candidemia but data about this population is scarce. AIMS: To describe characteristics of candidemia in elderly patients, to identify risk factors associated with mortality and to evaluate the usefulness of a predictive score. METHODS: A retrospective observational study of candidemia in elderly patients from a tertiary care hospital was carried out. We analyzed all Candida bloodstream infections during an eight-year period in patients older than 60 years. RESULTS: Fifty-nine episodes were included. Diabetes was the most frequent comorbidity. Most candidemia were catheter related infections (45%). Only 17% of patients had a Candida score > 2.5. Overall mortality at 48 hours was 20%, and at 15 days was 49%. Mortality-related factors were shock, assisted mechanical ventilation, thrombocytopenia, renal failure and leukocytosis (p range < 0.0001-0.006). On multivariate analysis septic shock was independently associated with mortality (HR 4.02 [CI 95% 1.18-13.72] p = 0.026). CONCLUSIONS: Nearly half of patients with candidemia died during the first fifteen days. Shock, assisted mechanical ventilation, thrombocytopenia, renal failure, and leukocytosis were factors associated with mortality. The predictive score was not useful in this population.

Consenso Argentino intersociedades de Infección Urinaria 2018-2019 - Parte II / Argentine Intersociety Consensus on Urinary Infection 2018-2019 - Part II

La segunda parte del Consenso Argentino Intersociedades de Infección Urinaria incluye el análisis de situaciones especiales. En pacientes con sonda vesical se debe solicitar urocultivo solo cuando hay signo-sintomatología de infección del tracto urinario, antes de instrumentaciones de la vía urinaria o como control en pacientes post-trasplante renal. El tratamiento empírico recomendado en pacientes sin factores de riesgo es cefalosporinas de tercera generación o aminoglucósidos. Las infecciones del tracto urinario asociadas a cálculos son siempre consideradas complicadas. En caso de obstrucción con urosepsis, deberá realizarse drenaje de urgencia por vía percutánea o ureteral. En pacientes con stents o prótesis ureterales, como catéteres doble J, el tratamiento empírico deberá basarse en la epidemiología, los antibióticos previos y el estado clínico. Antes del procedimiento de litotricia extracorpórea se recomienda pesquisar la bacteriuria y, si es positiva, administrar profilaxis antibiótica según el antibiograma. Cefalosporinas de primera generación o aminoglúcosidos son opciones válidas. Se recomienda aplicar profilaxis antibiótica con cefalosporinas de primera generación o aminoglúcosidos antes de la nefrolitotomía percutánea. La biopsia prostática trans-rectal puede asociarse a complicaciones infecciosas, como infecciones del tracto urinario o prostatitis aguda, principalmente por Escherichia coli u otras enterobacterias. En pacientes sin factores de riesgo para gérmenes multirresistentes y urocultivo negativo se recomienda realizar profilaxis con amikacina o ceftriaxona endovenosas. En pacientes con urocultivo positivo, se realizará profilaxis según antibiograma, 24 horas previas a 24 horas post-procedimiento. Para el tratamiento dirigido de la prostatitis post-biopsia trans-rectal, los carbapenémicos durante 3-4 semanas son el tratamiento de elección.

The second part of the Inter-Society Argentine Consensus on Urinary Tract Infection (UTI) includes the analysis of special situations. In patients with urinary catheter, urine culture should be requested only in the presence of UTI symptomatology, before instrumentation of the urinary tract, or as a post-transplant control. The antibiotics recommended for empirical treatment in patients without risk factors are third-generation cephalosporins or aminoglycosides. UTIs associated with stones are always considered complicated. In case of obstruction with urosepsis, an emergency drainage should be performed via a percutaneous nefrostomy or ureteral stenting. In patients with stents or ureteral prostheses, such as double J catheters, empirical treatment should be based on epidemiology, prior antibiotics, and clinical status. Before the extracorporeal lithotripsy procedure, bacteriuria should be investigated and antibiotic prophylaxis should be administered in case of positive result, according to the antibiogram. First generation cephalosporins or aminoglycosides are valid alternatives. The use of antibiotic prophylaxis with first-generation cephalosporins or aminoglycosides before percutaneous nephrolithotomy is recommended. Transrectal prostatic biopsy can be associated with infectious complications, such as UTI or acute prostatitis, mainly due to Escherichia coli or other enterobacteria. In patients without risk factors for multiresistant bacteria and negative urine culture, prophylaxis with intravenous amikacin or ceftriaxone is recommended. In patients with positive urine culture, prophylaxis will be performed according to the antibiogram, from 24 hours before to 24 hours post-procedure. For the targeted treatment of post-transrectal biopsy prostatitis, carbapenems for 3-4 weeks are the treatment of choice.

Candidemia: características en los adultos mayores / Candidemia: characteristics in elderly patients

Resumen Introducción: La candidemia es una micosis sistémica asociada a los cuidados de la salud de elevada morbimortalidad. Los adultos mayores presentan las tasas más altas y la información en esta población es escasa. Objetivos: Describir las características de las candidemias en los adultos mayores, identificar factores asociados a mortalidad y evaluar la utilidad de un score predictor. Métodos: Estudio retrospectivo de las candidemias en adultos mayores en un hospital de la ciudad de Buenos Aires. Se analizaron todos los episodios en pacientes mayores de 60 años en un período de ocho años. Resultados: Se incluyeron 59 episodios. La co-morbilidad más frecuente fue diabetes mellitus. El principal sitio de origen fue infección asociada a catéter (45%). Sólo 17% presentó un Candida score mayor a 2,5. La mortalidad global a las 48 h fue 20% y a 15 días 49%. Las variables asociadas a mortalidad fueron: shock, asistencia respiratoria mecánica (ARM), plaquetopenia, insuficiencia renal y leucocitosis (rango p < 0,0001-0,006). En el análisis multivariado el shock fue la única variable independiente asociada a mortalidad (HR 4,02 [IC 95% 1,18-13,72], p = 0,026). Conclusiones: La mitad de los adultos mayores con candidemia falleció en los primeros 15 días. Shock, ARM, plaquetopenia, insuficiencia renal y leucocitosis fueron factores asociados a mortalidad. El score predictor de uso habitual no fue útil en esta población.

Abstract Background: Candidemia is a nosocomial bloodstream infection and an important cause of comorbidity and mortality. Elderly patients present the highest rates of candidemia but data about this population is scarce. Aims: To describe characteristics of candidemia in elderly patients, to identify risk factors associated with mortality and to evaluate the usefulness of a predictive score. Methods: A retrospective observational study of candidemia in elderly patients from a tertiary care hospital was carried out. We analyzed all Candida bloodstream infections during an eight-year period in patients older than 60 years. Results: Fifty-nine episodes were included. Diabetes was the most frequent comorbidity. Most candidemia were catheter related infections (45%). Only 17% of patients had a Candida score > 2.5. Overall mortality at 48 hours was 20%, and at 15 days was 49%. Mortality-related factors were shock, assisted mechanical ventilation, thrombocytopenia, renal failure and leukocytosis (p range < 0.0001-0.006). On multivariate analysis septic shock was independently associated with mortality (HR 4.02 [CI 95% 1.18-13.72] p = 0.026). Conclusions: Nearly half of patients with candidemia died during the first fifteen days. Shock, assisted mechanical ventilation, thrombocytopenia, renal failure, and leukocytosis were factors associated with mortality. The predictive score was not useful in this population.

[Argentine Intersociety Consensus on Urinary Infection 2018-2019 - Part II]. / Consenso Argentino Intersociedades de Infección Urinaria 2018-2019 - Parte II.

The second part of the Inter-Society Argentine Consensus on Urinary Tract Infection (UTI) includes the analysis of special situations. In patients with urinary catheter, urine culture should be requested only in the presence of UTI symptomatology, before instrumentation of the urinary tract, or as a post-transplant control. The antibiotics recommended for empirical treatment in patients without risk factors are third-generation cephalosporins or aminoglycosides. UTIs associated with stones are always considered complicated. In case of obstruction with urosepsis, an emergency drainage should be performed via a percutaneous nefrostomy or ureteral stenting. In patients with stents or ureteral prostheses, such as double J catheters, empirical treatment should be based on epidemiology, prior antibiotics, and clinical status. Before the extracorporeal lithotripsy procedure, bacteriuria should be investigated and antibiotic prophylaxis should be administered in case of positive result, according to the antibiogram. First generation cephalosporins or aminoglycosides are valid alternatives. The use of antibiotic prophylaxis with first-generation cephalosporins or aminoglycosides before percutaneous nephrolithotomy is recommended. Transrectal prostatic biopsy can be associated with infectious complications, such as UTI or acute prostatitis, mainly due to Escherichia coli or other enterobacteria. In patients without risk factors for multiresistant bacteria and negative urine culture, prophylaxis with intravenous amikacin or ceftriaxone is recommended. In patients with positive urine culture, prophylaxis will be performed according to the antibiogram, from 24 hours before to 24 hours post-procedure. For the targeted treatment of post-transrectal biopsy prostatitis, carbapenems for 3-4 weeks are the treatment of choice.

La segunda parte del Consenso Argentino Intersociedades de Infección Urinaria incluye el análisis de situaciones especiales. En pacientes con sonda vesical se debe solicitar urocultivo solo cuando hay signo-sintomatología de infección del tracto urinario, antes de instrumentaciones de la vía urinaria o como control en pacientes post-trasplante renal. El tratamiento empírico recomendado en pacientes sin factores de riesgo es cefalosporinas de tercera generación o aminoglucósidos. Las infecciones del tracto urinario asociadas a cálculos son siempre consideradas complicadas. En caso de obstrucción con urosepsis, deberá realizarse drenaje de urgencia por vía percutánea o ureteral. En pacientes con stents o prótesis ureterales, como catéteres doble J, el tratamiento empírico deberá basarse en la epidemiología, los antibióticos previos y el estado clínico. Antes del procedimiento de litotricia extracorpórea se recomienda pesquisar la bacteriuria y, si es positiva, administrar profilaxis antibiótica según el antibiograma. Cefalosporinas de primera generación o aminoglúcosidos son opciones válidas. Se recomienda aplicar profilaxis antibiótica con cefalosporinas de primera generación o aminoglúcosidos antes de la nefrolitotomía percutánea. La biopsia prostática trans-rectal puede asociarse a complicaciones infecciosas, como infecciones del tracto urinario o prostatitis aguda, principalmente por Escherichia coli u otras enterobacterias. En pacientes sin factores de riesgo para gérmenes multirresistentes y urocultivo negativo se recomienda realizar profilaxis con amikacina o ceftriaxona endovenosas. En pacientes con urocultivo positivo, se realizará profilaxis según antibiograma, 24 horas previas a 24 horas post-procedimiento. Para el tratamiento dirigido de la prostatitis post-biopsia trans-rectal, los carbapenémicos durante 3-4 semanas son el tratamiento de elección.

Infecciones postneuroquiróºrgicas: Puesta al día y recomendaciones intersociedades / Post-neurosurgical infections. Update and intersociety recommendations

Las infecciones asociadas a procedimientos neuroquiró;ºrgicos son complicaciones graves que contribuyen a la morbimortalidad de los pacientes neurocríticos, así como tambín a la prolongació;n de la estancia en la UTI y/o en el hospital. El diagnó;stico es complejo ya que no se dispone de gold standard y se apoya en la sospecha clínica, las alteraciones físico-químicas del líquido cefalorraquídeo y el aislamiento microbiano. El tratamiento debe ser precoz y guiado por la epidemiología local. La duració;n dependerá del microorganismo causal, su sensibilidad y la disponibilidad de tratamientos antibió;ticos efectivos en el sitio de la infecció;n. La implementació;n de medidas de prevenció;n con evidencia demostrada minimiza el riesgo de infecció;n. Esta puesta al día intersociedades SADI-SATI presenta datos epidemioló;gicos (internacionales y locales), mó;©todos diagnó;sticos, tratamiento, y pautas de prevenció;n, considerando las publicaciones más relevantes de los ó;ºltimos aó;±os sobre el tema.

Infections associated with neurosurgical procedures are serious complications that contribute to the morbidity and mortality of neurocritical patients, as well as to the prolongation of the stay in the ICU and the hospital. The diagnosis is complex since there is no gold standard, so it is based on clinical suspicion, CSF physical-chemical examination, and microbial isolation. Treatment should be initiated early, guided by local epidemiology. The duration will depend on the causative microorganism, its sensitivity and the availability of antibiotic treatments that are effective at the site of infection. The implementation of preventive measures with proven efficacy minimizes the risk of infection. This SADI-SATI intersociety update reviews relevant data recently published on this area at the national at international level regarding epidemiology, diagnostic methodologies, therapeutic approaches, and prevention guidelines.

Infecciones asociadas a catéteres venosos centrales: Actualización y recomendaciones intersociedades / Central venous catheter related infections. Inter-Societies update and recommendations

Representantes de la Sociedad Argentina de Infectología (SADI) y la Sociedad Argentina de Terapia Intensiva (SATI) se reunieron para trabajar en la elaboración de recomendaciones concretas de diagnóstico, tratamiento y prevención de las infecciones asociadas a catéteres venosos centrales (IAC). La metodología utilizada fue el análisis de la bibliografía publicada en los últimos 10 años complementada con la opinión de expertos y datos locales. En este documento se pretende ofrecer herramientas básicas de optimización de diagnóstico sobre la base de criterios clínicos y microbiológicos, orientar acerca de los esquemas antibióticos empíricos y dirigidos, la posología y la administración de antibióticos en pacientes críticos, y promover las medidas efectivas para reducir el riesgo de IAC. Asimismo, se ofrece un algoritmo de diagnóstico y tratamiento para uso en la actividad asistencial y consideraciones sobre la dosificación de antibióticos. Este trabajo conjunto de infectólogos e intensivistas pone en evidencia la preocupación por el manejo de las IAC y la importancia de velar por la mejora en las prácticas cotidianas. A través de esta recomendación se establecen pautas locales para optimizar el diagnóstico, el tratamiento y la prevención de las IAC con el objeto de disminuir la morbimortalidad, los días de internación, los costos y la resistencia antimicrobiana.

Representatives of the Argentine Society of Infectious Diseases (SADI) and the Argentine Society of Intensive Therapy (SATI) joined together to issue specific recommendations for the diagnosis, treatment, and prevention of intravascular catheter related infections (CRI). The methodology used was the analysis of the literature published in the last 10 years, complemented with the opinion of experts and local data. This document aims to promote effective measures to reduce the risk of CRI and to offer basic tools for diagnosis optimization based on clinical and microbiological criteria, orientation on empirical and targeted antibiotic schemes, posology, and administration of antibiotics in critical patients. It also offers a diagnostic and treatment algorithm for use in the care activity, as well as considerations on the dosage of antibiotics. The joint work of both societies highlights the concern for the management of CRI and the importance of ensuring improvement in daily practices. Through this recommendation, local guidelines are established to optimize the diagnosis, treatment and prevention of CRI in order to reduce morbidity and mortality, days of hospitalization, costs, and antimicrobial resistance.

[Central venous catheter related infections. Inter-Societies update and recommendations]. / Infecciones asociadas a catéteres venosos centrales. Actualización y recomendaciones intersociedades.

Representatives of the Argentine Society of Infectious Diseases (SADI) and the Argentine Society of Intensive Therapy (SATI) joined together to issue specific recommendations for the diagnosis, treatment, and prevention of intravascular catheter related infections (CRI). The methodology used was the analysis of the literature published in the last 10 years, complemented with the opinion of experts and local data. This document aims to promote effective measures to reduce the risk of CRI and to offer basic tools for diagnosis optimization based on clinical and microbiological criteria, orientation on empirical and targeted antibiotic schemes, posology, and administration of antibiotics in critical patients. It also offers a diagnostic and treatment algorithm for use in the care activity, as well as considerations on the dosage of antibiotics. The joint work of both societies highlights the concern for the management of CRI and the importance of ensuring improvement in daily practices. Through this recommendation, local guidelines are established to optimize the diagnosis, treatment and prevention of CRI in order to reduce morbidity and mortality, days of hospitalization, costs, and antimicrobial resistance.

Enterobacterias portadoras de KPC en un hospital universitario / KPC-producing Enterobacteriaceae in a university hospital

La resistencia a carbapenemes en enterobacterias representa una situación de alto impacto clínico debido a las limitadas opciones terapéuticas disponibles para el tratamiento de las infecciones causadas por estos microorganismos multirresistentes que cursan con altas tasas de morbilidad y mortalidad. En nuestro país, en los últimos 5 años, se observó la diseminación de aislamientos de Klebsiella pneumoniae portadores de carbapenemasa de tipo KPC pertenecientes al ST258, clon diseminado mundialmente. En nuestro hospital la incidencia de episodios fue aumentando, especialmente la infección del sitio quirúrgico y las bacteriemias. En el último bienio se observó la diseminación del mecanismo de resistencia a otras enterobacterias y probablemente a otros secuenciotipos de K pneumoniae con mayor sensibilidad a antibióticos no ß-lactámicos. Se hace necesario instaurar las correctas medidas de prevención y control para evitar la diseminación de estos patógenos.

The presence of carbapenem -resistant Enterobacteriaceae in clinical settings represents a concerning issue due to the limited therapeutic options available for the treatment of the infections caused by these multi-drug resistant bacteria which usually have high mortality rates. The spread of Klebsiella pneumoniae isolates belonging to ST258 was observed in the last 5 years in our country. In our hospital the number of episodes has grown with the years and the most prevalent infections were the surgical site and bacteremia. In the last 2 years KPC spread to other Enterobacteriaceae and probably to other STs in K pneumoniae which showed different susceptibility patterns to non ß-lactamic antimicrobials. We believe that it is vital to install the appropriate measures to prevent and control the dissemination of these microorganisms.