Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

[Etiology and antimicrobial resistance of uncomplicated urinary tract infections]. / Etiología y resistencia a antimicrobianos de la infección no complicada del tracto urinario.

Uncomplicated urinary tract infections rank among the most frequent bacterial infections in women in the outpatient setting and represent a major cause of antimicrobial prescription. The aims of this study were to assess frequencies and antimicrobial resistance of current uropathogens causing uncomplicated urinary tract infection. In a prospective multicenter study, patients were recruited in ambulatory settings of four participating hospitals between June 2011 and December 2013. We analyzed 138 patients that met clinical and bacteriological diagnostic criteria. The mean age was 28 years. Cystitis was defined in 70% (n: 97) and pyelonephritis in 30% (n: 41). Frequencies of isolated microorganisms were: Escherichia coli 70% (n: 97), Staphylococcus saprophyticus 17% (n: 24), Proteus spp. 7% (n: 10), Klebsiella spp. 4% (n: 5), Enterococcus spp. and Pseudomonas aeruginosa 1 (0.7%) each. The antimicrobial resistance was: ampicillin-sulbactam 37% (n: 51) cephalexin 28% (n: 39), trimethoprim/sulfamethoxazole 22% (n: 31), nitrofurantoin 12% (n: 17), gentamicin 7% (n: 10) and ciprofloxacin 5% (n: 7). The levels of resistance found for ampicillin-sulbactam, trimethoprim/sulfamethoxazole and cephalexin were higher than those previously reported in Argentina. A better knowledge of the etiology and local antimicrobial susceptibility allows the design of more adequate guidelines for empirical treatment.

[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.

[Clinical features and outcome of community-acquired methicillin-resistant Staphylococcus aureus pneumonia]. / Características clínicas y pronóstico de la neumonía adquirida en la comunidad causada por Staphylococcus aureus resistente a la meticilina.

INTRODUCTION: The aim of this study is to describe the epidemiological and clinical features, treatment and prognosis of community-acquired pneumonia (CAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) in two different geographic regions where community-acquired MRSA (CA-MRSA) infections have different frequencies. METHODS: Observational study of patients admitted to two hospitals (one in Argentina, the other in Spain) between March 2008 and June 2012. RESULTS: We documented 16 cases of CAP caused by MRSA. MRSA accounted for 15 of 547 (2.7%) cases of CAP in Hospital Rodolfo Rossi and 1 of 1258 (0,08%) cases at the Hospital Universitari de Bellvitge (P ≤ .001). Most patients were young and previously healthy. Multilobar infiltrates, cavitation and skin and soft tissue involvement were frequent. All patients had positive blood cultures. Five patients required admission to the intensive care unit. Early mortality (≤ 48 hours) was 19%, and overall mortality (≤ 30 days) was 25%. CONCLUSION: CAP caused by MRSA causes high morbidity and mortality rates. It should be suspected in areas with a high prevalence of CA-MRSA infections, and especially in young and healthy patients who present with multilobar pneumonia with cavitation. Mortality is mainly related to septic shock and respiratory failure and occurs early in most cases.

Characteristics of endemic human coronavirus infections during times of COVID-19 pandemic.

INTRODUCTION: After the implementation of mitigation strategies during the COVID-19 pandemic, the incidence of respiratory viruses, including human coronaviruses (HCoV), experienced a significant decrease. The aim of this study is to characterize the epidemiology and clinical aspects of HCoV infections in ambulatory adults during COVID-19 pandemic times. METHODS: descriptive, prospective, longitudinal study performed in a private hospital in La Plata, Buenos Aires, Argentina between November 2020 and October 2022; 458 outpatient adults with upper respiratory tract infections (URTI) were studied undergoing clinical and microbiological follow-up. RESULTS: 44 (9.6%) subjects were positive by multiplex PCR for HCoV. 14 of them for 229E (31.8%), 13 for OC43 (29.5%), 11 for HKU-1 (25.1%) and 6 for NL63 (13.6%). A repeated PCR was positive for the same HCoV in 19 (57%) of 33 patients on day 3-5. No hospitalizations or deaths were reported. DISCUSSION: Endemic HCoV caused a significant proportion of URTI among outpatient adults during COVID-19-related restrictions times. An alternating pattern of circulation between alfa-HCoV and beta-HCoV was observed.

Introducción: Tras la implementación de estrategias de mitigación durante la pandemia de COVID-19, la incidencia de virus respiratorios, incluyendo los coronavirus humanos (HCoV), disminuyó significativamente. El objetivo de este estudio es caracterizar la epidemiología y los aspectos clínicos de las infecciones por HCoV en adultos ambulatorios durante la pandemia de COVID-19. Métodos: estudio descriptivo, prospectivo, longitudinal, realizado en un hospital privado de La Plata, Buenos Aires, Argentina, entre noviembre de 2020 y octubre de 2022. Se estudiaron 458 pacientes adultos ambulatorios con infecciones del tracto respiratorio superior (ITRS) bajo seguimiento clínico y microbiológico. Resultados: 44 (9.6%) sujetos fueron positivos por PCR multiplex para HCoV. Se detectaron 14 229E (31.8%), 13 OC43 (29.5%), 11 HKU-1 (25.1%) y 6 NL63 (13.6%). Una segunda PCR fue positiva para el mismo HCoV en 19 (57 %) de 33 pacientes en los días 3-5. No se reportaron hospitalizaciones ni muertes. Discusión: los HCoV endémicos causaron una proporción significativa de ITRS entre pacientes adultos ambulatorios durante los tiempos de restricciones relacionados con COVID-19. Se observó un patrón alternante de circulación entre alfa-HCoV y beta-HCoV.

[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.

[Impact of population mobility on the behavior of respiratory viruses during the COVID-19 pandemic]. / Impacto de la movilidad poblacional en el comportamiento de virus respiratorios durante la pandemia COVID-19.

INTRODUCTION: During the SARS-CoV-2 pandemic, Argentina population suffered from significant changes in population mobility due to non-pharmaceutical interventions. The aim of this study was to describe the impact of the mobility restrictions to the rates of positivity and diversity among different respiratory viruses. METHODS: Retrospective analytical study performed at Instituto Médico Platense in La Plata that included 458 patients with nasopharyngeal swab to search for respiratory pathogens by multiplex PCR. Changes in mobility were studied using "Community Mobility Reports", data set developed by Google and publicly available. RESULTS: Community mobility had significant correlation with the percentages of viral test positivity (p = < 0.01; R2=0.89) and viral diversity (p = 0.04; R2 = 0.78). DISCUSSION: Non-pharmaceutical interventions established to contain SARS-CoV-2 spread had a significant impact in the circulation patterns of other respiratory viruses.

Introducción: Durante la pandemia de SARS-CoV-2 en Argentina se implementaron intervenciones no farmacológicas que produjeron cambios en la movilidad de la población. El objetivo de este estudio fue relacionar los porcentajes de positividad y la diversidad viral con la movilidad poblacional durante parte del período de restricciones. Métodos: Estudio retrospectivo analítico realizado en el Instituto Médico Platense durante los años 2020 a 2022 que incluyó 458 pacientes a los que se les tomó un hisopado nasofaríngeo para la búsqueda de patógenos respiratorios por PCR multiplex. Se analizaron los cambios en la movilidad de la población utilizando los "Informes de Movilidad Local", herramienta desarrollada por Google, cuyos datos son de público acceso. Resultados: La movilidad poblacional se correlacionó significativamente con el porcentaje de positividad de las muestras (p = <0.01; R2 = 0.89) y la diversidad viral (p = 0.04; R2 = 0.78). Discusión: Las intervenciones no farmacológicas destinadas a limitar la propagación del SARS-CoV-2 tuvieron efecto en la circulación de otros virus respiratorios, hallándose mayor porcentaje de positividad y diversidad a medida que las mismas disminuyeron su grado de restricción.

Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza.

BACKGROUNDAntibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A.METHODSTo probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays.RESULTSInfluenza-specific FcγR-binding antibodies were elevated in Flu-IVIG-infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody.CONCLUSIONThese detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies.TRIAL REGISTRATIONClinicalTrials.gov NCT02287467.FUNDINGFunding for this research was provided by subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.

[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.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19. Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality. Results: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41- 0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo). Conclusions: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality. Trial registration: ClinicalTrials.gov ( NCT04593940 ).

Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care. Methods: We conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality. Results: A total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99-1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05-1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39-0.90). No differences in risk of serious adverse events including secondary infections. Conclusions: Infliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28- day mortality compared with standard of care. Trial registration: ClinicalTrials.gov ( NCT04593940 ).

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.

[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.

Nephrotoxicity associated with the use of intravenous colistin.

We retrospectively assessed the renal toxicity associated with the use of intravenous colistin. Fifty-four patients with multidrug-resistant Acinetobacter infections were included. At the end of therapy 6/54 patients (11%) suffered renal impairment. Renal impairment associated with the use of colistin is less frequent than initially reported.

Safety, Resistance, and Efficacy Results from a Phase IIIb Study of Conventional- and Double-Dose Oseltamivir Regimens for Treatment of Influenza in Immunocompromised Patients.

INTRODUCTION: Immunocompromised patients infected with influenza exhibit prolonged viral shedding and higher risk of resistance. Optimized treatment strategies are needed to reduce the risk of antiviral resistance. This phase IIIb, randomized, double-blind study (NCT00545532) evaluated conventional-dose or double-dose oseltamivir for the treatment of influenza in immunocompromised patients. METHODS: Patients with primary or secondary immunodeficiency and influenza infection were randomized 1:1 to receive conventional-dose oseltamivir (75 mg adolescents/adults [≥ 13 years]; 30-75 mg by body weight in children [1-12 years]) or double-dose oseltamivir (150 or 60-150 mg, respectively), twice daily for an extended period of 10 days. Nasal/throat swabs were taken for virology assessments at all study visits. Co-primary endpoints were safety/tolerability and viral resistance. Secondary endpoints included time to symptom alleviation (TTSA) and time to cessation of viral shedding (TTCVS). RESULTS: Of 228 patients enrolled between February 2008 and May 2017, 215 (199 adults) were evaluable for safety, 167 (151 adults) for efficacy, and 152 (138 adults) for resistance. Fewer patients experienced an adverse event (AE) in the conventional-dose group (50.5%) versus the double-dose group (59.1%). The most frequently reported AEs were nausea, diarrhea, vomiting, and headache. Fifteen patients had post-baseline resistance, more commonly in the conventional-dose group (n = 12) than in the double-dose group (n = 3). In adults, median TTSA was similar between arms, while median TTCVS was longer with conventional dosing. CONCLUSIONS: Oseltamivir was well tolerated, with a trend toward better safety/tolerability for conventional dosing versus double dosing. Resistance rates were higher with conventional dosing in this immunocompromised patient population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00545532. FUNDING: F. Hoffmann-La Roche Ltd.

Characteristics of endemic human Coronavirus infections during times of COVID-19 pandemic / Características de las infecciones causadas por Corona virus humanos endémicos durante la pandemia COVID-19

Abstract Introduction : After the implementation of mitigation strategies during the COVID-19 pandemic, the incidence of respiratory viruses, including human coronaviruses (HCoV), experienced a significant decrease. The aim of this study is to characterize the epidemiology and clinical aspects of HCoV infections in ambulatory adults during COVID-19 pandemic times. Methods : descriptive, prospective, longitudinal study performed in a private hospital in La Plata, Buenos Aires, Argentina between November 2020 and October 2022; 458 outpatient adults with upper respiratory tract infections (URTI) were studied undergoing clinical and microbiological follow-up. Results : 44 (9.6%) subjects were positive by multiplex PCR for HCoV. 14 of them for 229E (31.8%), 13 for OC43 (29.5%), 11 for HKU-1 (25.1%) and 6 for NL63 (13.6%). A repeated PCR was positive for the same HCoV in 19 (57%) of 33 patients on day 3-5. No hospitalizations or deaths were reported. Discussion : Endemic HCoV caused a significant pro portion of URTI among outpatient adults during COVID- 19-related restrictions times. An alternating pattern of circulation between alfa-HCoV and beta-HCoV was observed.

Resumen Introducción : Tras la implementación de estrate gias de mitigación durante la pandemia de COVID-19, la incidencia de virus respiratorios, incluyendo los coronavirus humanos (HCoV), disminuyó significati vamente. El objetivo de este estudio es caracterizar la epidemiología y los aspectos clínicos de las infecciones por HCoV en adultos ambulatorios durante la pandemia de COVID-19. Métodos : estudio descriptivo, prospectivo, longitudi nal, realizado en un hospital privado de La Plata, Buenos Aires, Argentina, entre noviembre de 2020 y octubre de 2022. Se estudiaron 458 pacientes adultos ambulatorios con infecciones del tracto respiratorio superior (ITRS) bajo seguimiento clínico y microbiológico. Resultados : 44 (9.6%) sujetos fueron positivos por PCR multiplex para HCoV. Se detectaron 14 229E (31.8%), 13 OC43 (29.5%), 11 HKU-1 (25.1%) y 6 NL63 (13.6%). Una segunda PCR fue positiva para el mismo HCoV en 19 (57 %) de 33 pacientes en los días 3-5. No se reportaron hospitalizaciones ni muertes. Discusión : los HCoV endémicos causaron una pro porción significativa de ITRS entre pacientes adultos ambulatorios durante los tiempos de restricciones rela cionados con COVID-19. Se observó un patrón alternante de circulación entre alfa-HCoV y beta-HCoV.

Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes.

BACKGROUND: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. METHODS: Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. RESULTS: Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). CONCLUSIONS: At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.

Impacto de la movilidad poblacional en el comportamiento de virus respiratorios durante la pandemia COVID-19 / Impact of population mobility on the behavior of respira tory viruses during the COVID-19 pandemic

Resumen Introducción : Durante la pandemia de SARS-CoV-2 en Argentina se implementaron intervenciones no farma cológicas que produjeron cambios en la movilidad de la población. El objetivo de este estudio fue relacionar los porcentajes de positividad y la diversidad viral con la movi lidad poblacional durante parte del período de restricciones. Métodos : Estudio retrospectivo analítico realizado en el Instituto Médico Platense durante los años 2020 a 2022 que incluyó 458 pacientes a los que se les tomó un hisopado nasofaríngeo para la búsqueda de patóge nos respiratorios por PCR multiplex. Se analizaron los cambios en la movilidad de la población utilizando los "Informes de Movilidad Local", herramienta desarrollada por Google, cuyos datos son de público acceso. Resultados : La movilidad poblacional se correlacionó significativamente con el porcentaje de positividad de las muestras (p = <0.01; R2 = 0.89) y la diversidad viral (p = 0.04; R2 = 0.78). Discusión : Las intervenciones no farmacológicas destinadas a limitar la propagación del SARS-CoV-2 tuvieron efecto en la circulación de otros virus respi ratorios, hallándose mayor porcentaje de positividad y diversidad a medida que las mismas disminuyeron su grado de restricción.

Abstract Introduction : During the SARS-CoV-2 pandemic, Ar gentina population suffered from significant changes in population mobility due to non-pharmaceutical interventions. The aim of this study was to describe the impact of the mobility restrictions to the rates of positivity and diversity among different respiratory viruses. Methods : Retrospective analytical study per formed at Instituto Médico Platense in La Plata that included 458 patients with nasopharyngeal swab to search for respiratory pathogens by multiplex PCR. Changes in mobility were studied using "Community Mobility Reports", data set developed by Google and publicly available. Results : Community mobility had significant cor relation with the percentages of viral test positiv ity (p = < 0.01; R2=0.89) and viral diversity (p = 0.04; R2 = 0.78). Discussion : Non-pharmaceutical interventions estab lished to contain SARS-CoV-2 spread had a significant impact in the circulation patterns of other respiratory viruses.

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) / Comparative analysis of clinical characteristics, evolu tion and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID STUDY)

Resumen 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 evolu ción a 30 días. Resultados : Se incluyeron un total de 1691 pacien tes (primera ola n = 809, segunda ola n = 882). Los pa cientes 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 hospi talización, 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 presen taron mayor mortalidad (11% vs. 26%, p < 0.001). Compa rando 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 interna dos durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Abstract Introduction : Clinical features and outcomes of SARS-CoV-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 pa tients 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 hos pitalization, 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 hos pitalization, 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 dur ing the second wave in Argentina were more seriously ill and had a higher mortality.