Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

[Guidelines for management of community-acquired pneumonia in adults]. / Neumonía adquirida de la comunidad en adultos. Recomendaciones sobre su atención.

Community-acquired pneumonia in adults is a common cause of morbidity and mortality particularly in the elderly and in patients with comorbidities. Most episodes are of bacterial origin, Streptococcus pneumoniae is the most frequently isolated pathogen. Epidemiological surveillance provides information about changes in microorganisms and their susceptibility. In recent years there has been an increase in cases caused by community-acquired meticillin resistant Staphylococcus aureus and Legionella sp. The chest radiograph is essential as a diagnostic tool. CURB-65 score and pulse oximetry allow stratifying patients into those who require outpatient care, general hospital room or admission to intensive care unit. Diagnostic studies and empirical antimicrobial therapy are also based on this stratification. The use of biomarkers such as procalcitonin or C-reactive protein is not part of the initial evaluation because its use has not been shown to modify the initial approach. We recommend treatment with amoxicillin for outpatients under 65 year old and without comorbidities, for patients 65 years or more or with comorbidities amoxicillin-clavulanic/sulbactam, for patients hospitalized in general ward ampicillin-sulbactam with or without the addition of clarithromycin, and for patients admitted to intensive care unit ampicillin-sulbactam plus clarithromycin. Suggested treatment duration is 5 to 7 days for outpatients and 7 to 10 for those who are hospitalized. During the influenza season addition of oseltamivir for hospitalized patients and for those with comorbidities is suggested.

Understanding the Burden of Respiratory Syncytial Virus in Older Adults in Latin America: An Expert Perspective on Knowledge Gaps.

Respiratory syncytial virus (RSV) is a significant global health concern and major cause of hospitalization, particularly among infants and older adults. The clinical impact of RSV is well characterized in infants; however, in many countries, the burden and risk of RSV in older populations are overlooked. In Latin America, there are limited data on RSV epidemiology and disease management in older adults. Therefore, the impact of RSV in this region needs to be addressed. Here, current insights on RSV infections in older populations in Latin America, including those with underlying health conditions, are discussed. We also outline the key challenges limiting our understanding of the burden of RSV in Latin America in a worldwide context and propose an expert consensus to improve our understanding of the burden of RSV in the region. By so doing, we aim to ultimately improve disease management and outcomes of those at risk and to alleviate the impact on healthcare systems.A graphical plain language summary is available with this article.

[Inter-society consensus for the management of respiratory infections: acute bronchitis and chronic obstructive pulmonary disease]. / Consenso Intersociedades para el manejo de infecciones respiratorias: bronquitis aguda y enfermedad pulmonar obstructiva crónica.

The Argentine Society for Infectious Diseases and other national societies issued updated practical guidelines for the management of acute bronchitis (AB) and reactivations of chronic obstructive pulmonary disease (COPD) with the aim of promoting rational use of diagnostic and therapeutic resources. AB is a condition characterized by inflammation of the bronchial airways which affects adults and children without underlying pulmonary disease. It is usually caused by a virus. The diagnosis is based on clinical findings after community acquired pneumonia has been ruled out. Treatment of AB is mainly symptomatic. Antibiotics should be used in immune-compromised hosts, patients with chronic respiratory or cardiac diseases and in the elderly with co-morbidities. Reactivation of COPD is defined as an acute change in the patient's baseline clinical situation beyond normal day to day variations, with an increase in dyspnea, sputum production and/or sputum purulence, warranting a change in medication. An increase in one symptom is considered a mild exacerbation, two as moderate, and the presence of three symptoms is considered a severe exacerbation. An infectious agent can be isolated in sputum in 50 to 75% of COPD reactivations. Moderate and severe episodes must be treated with antibiotics, amoxicillin/ beta-lactamase inhibitor, macrolides and fluoroquinolones are first choice drugs.

[Human monkeypox: epidemiological and clinical characteristics of a series of cases]. / Viruela símica humana: características epidemiológicas y clínicas de una serie de casos.

INTRODUCTION: Monkeypox It is a zoonotic disease. The etiologic agent is the monkeypox virus. Since January 1, 2022, monkeypox cases have been reported to the World Health Organization (WHO) in 110 Member States across 6 WHO regions. METHODS: The present work is a descriptive-observational-retrospective cohort in the first instance, and prospective at the end, where the epidemiological characteristics, clinical presentation and complications collected by telephone call on day 28, are described 75 patients diagnosed with monkeypox, confirmed by RT-PCR (corresponding to 7% of the cases reported in Argentina). It was developed between July 12, 2022 and October 6, 2022. RESULTS: The affected population was entirely cisgender men, 70 (93.3%) identified as men who have sex with men (MSM). Fifty-one (68%) were co-infected with HIV, 50 (98%) were receiving ART. All patients presented mucocutaneous manifestations. The rash manifested with a variety of lesions: papular, vesicular, and pustular. In 26 (44.1%) the systemic symptoms presented prior to the appearance of the rash, being the increase in body temperature the most frequent. Thirty-four (45.3%) of the patients reported some complication, with proctitis being the most frequent followed by penile edema. Sequelae were observed in 40 (53.3%), the most frequent being skin scars. CONCLUSION: In this case series we were able to observe mostly mild symptoms, with anogenital lesions being the most frequent clinical presentation. The presence of sequelae, the social and emotional impact of this disease make a multidisciplinary approach necessary.

Introducción: Es una enfermedad zoonótica cuyo agente etiológico es el virus de la viruela símica. Desde el 1 de enero de 2022, se han notificado casos de viruela símica a la Organización Mundial de la Salud (OMS) en 110 Estados Miembros en las 6 regiones de la OMS. Métodos: El presente trabajo es un estudio observacional descriptivo de cohorte retrospectivo en primera instancia, y prospectivo al final, donde se describen las características epidemiológicas, la presentación clínica, y las complicaciones recabadas mediante llamado telefónico al día 28 en 75 pacientes con diagnóstico de viruela símica confirmado por RT-PCR (correspondientes al 7% de los casos notificados en Argentina). Fue desarrollado entre el 12 de julio de 2022 y el 6 de octubre de 2022. Resultados: La población afectada fue en su totalidad hombres cisgénero, 70 (93.3%) identificados como hombres que tienen sexo con hombres (HSH). Cincuenta y uno (68%) estaban coinfectados con HIV, 50 (98%) estaban recibiendo TARV. Todos los pacientes presentaron manifestaciones mucocutáneas. El exantema se manifestó con variedad de lesiones: papulares, vesiculares y pustulosas. En 26 (44.1%) los síntomas sistémicos se presentaron previos a la aparición del exantema, siendo el aumento de la temperatura corporal el más frecuente. Treinta y cuatro (45.3%) de los pacientes reportaron alguna complicación, siendo la proctitis la más frecuente seguida por edema de pene. Se observaron secuelas en 40 (53.3%), siendo la más frecuente las cicatrices cutáneas. Conclusión: En esta serie de casos pudimos observar mayormente cuadros leves, siendo las lesiones anogenitales la presentación clínica más frecuente. La presencia de secuelas, el impacto social y emocional de esta enfermedad hacen necesario un enfoque multidisciplinario.

[Comparative analysis of clinical characteristics, evolution and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID Study)]. / Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (Registro ECCOVID).

INTRODUCTION: Clinical features and outcomes of SARSCoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. METHODS: Multicenter and prospective registry of patients =18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. RESULTS: A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized patients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hospitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hospitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. CONCLUSION: Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 during the second wave in Argentina were more seriously ill and had a higher mortality.

Introducción: Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos: Registro multicéntrico y prospectivo de pacientes = 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolución a 30 días. Resultados: Se incluyeron un total de 1691 pacientes (primera ola n = 809, segunda ola n = 882). Los pacientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospitalización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p < 0,001) y presentaron mayor mortalidad (11% vs. 26%, p < 0.001). Comparando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión: Comparados con los pacientes internados durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

[Consensus guidelines for the management of upper respiratory tract infections]. / Consenso sobre diagnóstico y tratamiento de infecciones de vías respiratorias altas.

Upper respiratory tract infections are the most common source of antibiotic prescriptions. Acute pharyngitis is caused mainly by viruses, viral cases can be distinguished from acute streptococcal pharyngitis using Centor clinical epidemiological criteria, by rapid antigen tests or throat culture. Treatment of choice for streptococcal infection is penicillin V given in two daily doses. In children, acute otitis media (AOM) is the infection for which antibiotics are most often prescribed. Predominant causative pathogens include Streptococcus pneumoniae, Haemophilus influenzae non-type b and Moraxella catarrhalis. Diagnosis is based on history, physical examination and otoscopic exam. Antibiotic treatment should be initiated promptly in all children<2 years of age, and in older children presenting bilateral AOM, otorrhoea, co-morbidities or severe illness. In Argentina, amoxicillin is the drug of choice given the low penicillin resistance rates for S. pneumoniae. In children who fail amoxicillin therapy, amoxicillin/clavulanate provides better coverage against beta-lactamase producing H. influenzae and M. catarrhalis. Rhinosinusitis is caused mainly by viruses, secondary bacterial complication occurs in less than 5% of cases. Diagnosis is based on physical examination and additional studies are not usually required. Acute bacterial sinusitis is caused by the same pathogens that cause AOM and amoxicillin is the drug of choice.

Monkeypox: Another Sexually Transmitted Infection?

Monkeypox virus is a zoonotic DNA virus (Poxviridae family), identified in 1958 in Asian monkeys (mostly Macaca fascicularis) in a polio vaccine research animal facility in Copenhagen, Denmark [...].

A global perspective on improving patient care in uncomplicated urinary tract infection: expert consensus and practical guidance.

OBJECTIVES: Uncomplicated urinary tract infections (uUTIs) are a common problem in female patients. Management is mainly based on empirical prescribing, but there are concerns about overtreatment and antimicrobial resistance (AMR), especially in patients with recurrent uUTIs. METHODS: A multidisciplinary panel of experts met to discuss diagnosis, treatment, prevention, guidelines, AMR, clinical trial design and the impact of COVID-19 on clinical practice. RESULTS: Symptoms remain the cornerstone of uUTI diagnosis, and urine culture is necessary only when empirical treatment fails or rapid recurrence of symptoms or AMR is suspected. Specific antimicrobials are first-line therapy (typically nitrofurantoin, fosfomycin, trimethoprim/sulfamethoxazole and pivmecillinam, dependent on availability and local resistance data). Fluoroquinolones are not first-line options for uUTIs primarily due to safety concerns but also rising resistance rates. High-quality data to support most non-antimicrobial approaches are lacking. Local AMR data specific to community-acquired uUTIs are needed, but representative information is difficult to obtain; instead, identification of risk factors for AMR can provide a basis to guide empirical antimicrobial prescribing. The COVID-19 pandemic has impacted the management of uUTIs in some countries and may have long-lasting implications for future models of care. CONCLUSION: Management of uUTIs in female patients can be improved without increasing complexity, including simplified diagnosis and empirical antimicrobial prescribing based on patient characteristics, including a review of recent antimicrobial use and past pathogen resistance profiles, drug availability and guidelines. Current data for non-antimicrobial approaches are limited. The influence of COVID-19 on telehealth could provide an opportunity to enhance patient care in the long term.

Safety and effectiveness of RBD-specific polyclonal equine F(ab´)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: A retrospective cohort study.

BACKGROUND: Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population. METHODS: We conducted a retrospective cohort study at "Hospital de Campaña Escuela-Hogar" (HCEH) in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. FINDINGS: Subsequent clinical records of 446 non-exposed (Controls) and 395 exposed (EPIC) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95% CI: 0.46-0.96) P = 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n = 379), OR 0.58 (95% CI 0.39 to 0.85) P = 0.005. Overall and serious adverse events were not significantly different between groups. CONCLUSIONS: In this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.

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.

Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study.

BACKGROUND: Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina. METHODS: Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). RESULTS: A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27). CONCLUSIONS: This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

[Updated acute community-acquired pneumonia in adults: Guidelines for initial antimicrobial therapy based on local evidence from the South American Working Group (ConsenSur II)]. / Neumonía aguda adquirida en la comunidad en adultos: Actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II).

Community-acquired pneumonia (CAP) in adults is probably one of the infections affecting ambulatory patients for which the highest diversity of guidelines has been written worldwide. Most of them agree in that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of comorbidities and the etiologic pathogen. Nevertheless, a great variability may be noted among the different countries in the selection of the primary choice in the antimicrobial agents, even for the cases considered as at a low-risk class. This fact may be due to the many microbial causes of CAP and specialties involved, as well as the different health-care systems effecting on the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations regardless of the local data, probably because of the scarcity of such data. This is the reason why we have developed a guideline for the initial treatment of CAP by 2002 upon the basis of several local evidences in South América (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity índex (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the región, such as community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and Legionella spp; new evidences on the performance of the rapid test for the etiologic diagnosis in CAP have been reported (eg. urinary Legionella andpneumococcus antigens); new therapeutic considerations needs to be approached (i.e. dosage reformulation, duration of treatment, emergence of novel antibiotics and clinical impact of combined therapy). Like in the first versión of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II.

Systematic review on respiratory syncytial virus epidemiology in adults and the elderly in Latin America.

OBJECTIVES: The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America. METHODS: A systematic literature search was carried out in Medline, Scielo, Lilacs, and Cochrane Library. The search strategy aimed at retrieving studies focusing on RSV prevalence, burden, risk factors, and the routine clinical practice in the prevention and management of RSV infections in Latin American countries. Only articles published between January 2011 and December 2017 were considered. RESULTS: Eighteen studies were included. Percentages of RSV detection varied highly across included studies for adult subjects with respiratory infections (0% to 77.9%), influenza-like illness (1.0% to 16.4%) and community-acquired pneumonia (1.3% to 13.5%). Considerable percentages of hospitalization were reported for RSV-infected adults with influenza-like illness (40.9% and 69.9%) and community-acquired pneumonia (91.7%). CONCLUSIONS: Recent RSV data regarding adult populations in Latin America are scarce. RSV was documented as a cause of illness in adults and the elderly, being identified in patients with acute respiratory infections, influenza-like illness and community-acquired pneumonia. The studies suggest that RSV infections may be a significant cause of hospitalization in adult populations in Latin America, including younger adults.

[Impact of low-grade viremia on the risk of virological failure in patients with HIV-1 infection on antiretroviral therapy]. / Impacto de la viremia de bajo grado en el riesgo de fallo virológico en pacientes con infección por VIH-1.

BACKGROUND: Viral loads (VL) between 20-200 copies/mL are considered low-grade viral loads (LGVL). Its clinical implications and management have not been defined. AIM: To evaluate the impact of LGVL on the risk of subsequent development of virological failure (VF). METHODS: Patients ≥ 18 years, with HIV-1 infection who had VL < 20 copies/mL for at least six months and/or in two consecutive samples under antiretroviral therapy (ART) were included, between January 1st, 2009 and December 31, 2019. Follow-up of the VLs was carried out stratifying them in VL < 20 copies/mL, LGVL (20-50 copies/mL and 51-200 copies/mL) and VF. Median follow-up 25 months (IQR 15-31). RESULTS: 1,416 patients were included who reached VL < 20 copies/ml under ART, 797 patients remained with CV < 20 copies/mL during follow-up, 144 patients had VL between 21-50 copies/mL, 384 between 51-200 copies/mL and 91 had VF without previous LGVL. Out of 528 patients who had LGVL, 110 failed, risk 3.45 times higher than those who had no previous LGVL. Risk 3.27 times higher of VF for those who had LGVL between 51-200 copies/mL compared to 20-50 copies/mL. DISCUSSION: The study allows to relate the LGVL with VF. This association was observed more frequently with LGVL between 51-200 copies/mL.

Highlights of an Expert Advisory Board on Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AE-COPD) in Latin America.

Background: Chronic obstructive pulmonary disease (COPD) is a preventable and usually progressive lung disease that affects millions of people worldwide and is the sixth leading cause of death in the Americas. Viral and bacterial respiratory tract infections and air pollution may cause acute exacerbations of COPD (AE-COPD) ranging from mild, moderate to severe. The greatest proportion of the overall COPD burden on the health system is due to disease exacerbations. There is limited evidence regarding the etiology and burden of AE-COPD in Latin America (LATAM). Methods: To respond to this gap in evidence, an Advisory Board with regional pneumologists and infectious disease experts was convened in September 2018 in Panama City, Panama, to: 1) review the burden of AE-COPD in LATAM; 2) evaluate the etiology of AE-COPD in LATAM; and 3) assess and compare the local/regional guidelines to confirm the etiology, characterize, and manage AE-COPD. Results: The results of the meeting showed that there is a high prevalence of AE-COPD in LATAM countries, limited evidence on etiology data, and discrepancies in the case definitions and symptomology (ie, severity) classifications used in LATAM. Conclusion: The Advisory Board discussions further resulted in recommendations for future research on the impact on the epidemiology and burden of disease, on establishing standardized AE-COPD case definition guidelines, and on studying the etiology of both moderate and severe AE-COPD cases.

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

The Argentine Society of Infectious Diseases and other scientific societies have updated these recommendations based on data on urinary tract infections in adults obtained from a prospective multicenter study conducted in Argentina during 2016-2017. Asymptomatic bacteriuria should be treated only in pregnant women, who should also be systematically investigated; the antibiotics of choice are nitrofurantoin, amoxicillin, clavulanic/amoxicillin, cephalexin and trimethoprim-sulfamethoxazole. In procedures involving injury to the urinary tract with bleeding, it is recommended to request urine culture and, in the presence of bacteriuria, antimicrobial treatment according to sensitivity should be prescribed from immediately before up to 24 hours after the intervention. In women, cystitis can be treated with nitrofurantoin, cephalexin or fosfomycin, while trimethoprim-sulfamethoxazole and fluoroquinolones are not recommended; pyelonephritis can be treated with ciprofloxacin, cefixime or cephalexin in ambulatory women or ceftriaxone, cefazolin or amikacin in those who are hospitalized. In men, urinary tract infections are always considered complicated; nitrofurantoin or cephalexin are recommended for 7 days, alternatively fosfomycin should be given in a single dose. In men, ciprofloxacin, ceftriaxone or cefixime are suggested for pyelonephritis on ambulatory treatment whereas ceftriaxone or amikacin are recommended for hospitalized patients. Acute bacterial prostatitis can be treated with ceftriaxone or gentamicin. Fluoroquinolones were the choice treatment for chronic bacterial prostatitis until recently; they are no longer recommended due to the increasing resistance and recent concerns regarding the safety of these drugs; alternative antibiotics such as fosfomycin are to be considered.

La Sociedad Argentina de Infectología y otras sociedades científicas han actualizado estas recomendaciones utilizando, además de información internacional, la de un estudio multicéntrico prospectivo sobre infecciones del tracto urinario del adulto realizado en Argentina durante 2016-2017. La bacteriuria asintomática debe ser tratada solo en embarazadas, a quienes también se las debe investigar sistemáticamente; los antibióticos de elección son nitrofurantoína, amoxicilina, amoxicilina-clavulánico, cefalexina y trimetoprimasulfametoxazol. Ante procedimientos que impliquen lesión con sangrado del tracto urinario se recomienda solicitar urocultivo para pesquisar bacteriuria asintomática, y, si resultara positivo, administrar antimicrobianos según sensibilidad desde inmediatamente antes hasta 24 horas luego de la intervención. En mujeres, la cistitis puede ser tratada con nitrofurantoina, cefalexina, o fosfomicina y no se recomienda usar trimetoprima-sulfametoxazol o fluoroquinolonas; en pielonefritis puede emplearse ciprofloxacina, cefixima o cefalexina si el tratamiento es ambulatorio o ceftriaxona, cefazolina o amikacina si es hospitalario. En los hombres, las infecciones del tracto urinario se consideran siempre complicadas. Se recomienda tratamiento con nitrofurantoina o cefalexina por 7 días, o bien monodosis con fosfomicina. Para la pielonefritis en hombres se sugiere ciprofloxacina, ceftriaxona o cefixima si el tratamiento es ambulatorio y ceftriaxona o amikacina si es hospitalario. Se sugiere tratar las prostatitis bacterianas agudas con ceftriaxona o gentamicina. En cuanto a las prostatitis bacterianas crónicas, si bien su tratamiento de elección hasta hace poco fueron las fluoroquinolonas, la creciente resistencia y ciertas dudas sobre la seguridad de estas drogas obligan a considerar el uso de alternativas como fosfomicina.

Treatment of Community-Acquired Pneumonia in Immunocompromised Adults: A Consensus Statement Regarding Initial Strategies.

BACKGROUND: Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. RESEARCH QUESTION: There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. STUDY DESIGN AND METHODS: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. RESULTS: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. INTERPRETATION: This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

[High prevalence of hypovitaminosis D in HIV-infected persons attending an outpatient clinic, Buenos Aires city]. / Alta prevalencia de hipovitaminosis D en personas infectadas con HIV atendidas en un centro ambulatorio de la ciudad de Buenos Aires.

Hypovitaminosis D is frequent worldwide. In Argentina, according to studies conducted between 1987 and 2015, prevalence was > 40% in the general population. In people living with HIV it may vary between 20 and 90%, but the prevalence in our environment is not known. Our objective was to determine the prevalence of hypovitaminosis D in a cohort of adults with HIV infection in the city of Buenos Aires. We analyzed retrospectively medical records of 814 HIV positive subjects older than 18 years with at least one determination of vitamin D. The median age was 44 years (interquartile range 21-80), 746 (91.6%) were men, and 813 (99.9%) were on antiretroviral treatment. Univariate and multivariate analyses were performed to determine the association of hypovitaminosis D with CD4 values, viral load for HIV, and antiretroviral therapy. The present study shows that, in our environment, hypovitaminosis D is very common in people with HIV infection. Although it does not reveal evidence of a relationship with viral load for HIV, immune status, or antiretroviral treatment, the systematic search for hypovitaminosis D is mandatory in this population, taking into account its high frequency and the increased risk of osteopenia, osteoporosis and fractures, as described in people with HIV.

La hipovitaminosis D es frecuente en el mundo. Según estudios realizados entre 1987 y 2015, en Argentina la prevalencia fue > 40%. En personas con infección por HIV variaría entre 20 y 90%, pero en nuestro medio no se conoce con precisión. Nuestro objetivo fue determinar la prevalencia de hipovitaminosis D en una cohorte de adultos con infección por HIV asistidos en forma ambulatoria en la ciudad de Buenos Aires. Se analizaron retrospectivamente las historias clínicas de 814 sujetos mayores de 18 años HIV positivos con al menos una determinación de vitamina D. La mediana de edad fue 44 años (rango intercuartílico 21-80), 746 (91.6%) eran hombres y 813 (99.9%) recibían tratamiento antirretroviral. Se realizó análisis uni y multivariado para determinar asociación entre hipovitaminosis D y valores de CD4, carga viral para HIV y terapia antirretroviral. La prevalencia de hipovitaminosis D fue 79.7% (insuficiencia 34.2%, deficiencia 45.5%). No se encontró asociación con el uso de efavirenz o inhibidores de la proteasa (p = 0.86 en ambos casos), con el recuento de linfocitos CD4, ni con la carga viral plasmática (p = 0.81 y 0.74, respectivamente). El presente estudio muestra que, en nuestro medio, la hipovitaminosis D es muy frecuente en personas con infección por HIV. Aun cuando no revela evidencia de relación con carga viral para HIV, estado inmune, ni tratamiento antirretroviral, es necesaria la búsqueda sistemática de hipovitaminosis D en esta población, en vista de la alta frecuencia de osteopenia y osteoporosis y el mayor riesgo de fracturas descripto en personas HIV positivas.