Update on diagnosis and treatment of fungal meningitis: lessons from recent outbreaks.

PURPOSE OF REVIEW: Recently, fungal meningitis outbreaks have occurred in association with neuraxial and epidural anesthesia in immunocompetent patients. Herein, we describe the course of those outbreaks, their diagnosis, treatment, prognosis, and lessons learned. RECENT FINDINGS: Two outbreaks of Fusarium solani meningitis during 2022-2023 were associated with epidural anesthesia in two distant cities in Mexico (Durango and Matamoros). The initial etiological agent identification was delayed due to insensitivity of cultures. A Fusarium solani qPCR was validated and positive in 38% cerebrospinal fluid (CSF) samples from Durango, while BD-Glucan allowed early diagnosis of the index case in Matamoros. Antifungal treatment with voriconazole and liposomal amphotericin B (L-AmB) was recommended. Overall mortality was 51%. Once the cause was confirmed, some patients received fosmanogepix. SUMMARY: Fungal meningitis outbreaks due to filamentous fungi are usually associated with direct epidural inoculation. They result in severe presentations and high mortality. Early diagnosis should be suspected, BD-Glucan CSF testing screening is recommended. Aggressive antifungal treatment based on antifungal susceptibility testing should be administered as early as possible. The advent of molecular diagnostic methods and new antifungal drugs may allow for timely diagnosis and treatment, increasing the chances of survival.

Clinical and Microbiological Characteristics of Febrile Neutropenia During Induction Chemotherapy in Adults With Acute Leukemia.

BACKGROUND: Few studies regarding infectious causes of febrile neutropenia (FN) in Mexico are available. AIMS: We aimed to describe clinical and microbiological characteristics of FN episodes during induction chemotherapy in adults with acute leukemia. METHODS AND RESULTS: This retrospective cohort from a Mexican tertiary care center included adults with newly diagnosed acute leukemia between January 2014, and December 2018. Clinical and microbiological characteristics were summarized using descriptive statistics. Univariate analyses for associations between clinical characteristics and FN and/or death were made; logistic regression analysis was performed to assess relationships with FN. Kaplan-Meier survival estimates were modeled for antimicrobial prophylaxis and FN. Ninety-five patients were included. Median age was 28 (IQR 20-43), 49 (52%) were males, and 74 (78%) developed FN (74/95). Among these, 98% had an identified source of infection (73/74) and 65% had >1. Common infections were urinary tract infection (24%), bacterial sinusitis (20%), and bacterial pneumonia (19%). Gram-negatives were the most frequently isolated microorganisms (69%), followed by Gram-positives (21%), and fungi (9%). Antimicrobial prophylaxis was inversely associated with FN (aOR = 0.07, CI 0.008-0.060, p = 0.02). Invasive fungal diseases were associated with 30-day mortality (aOR = 9.46, 95% CI 1.66-54.05). CONCLUSION: Infections caused 98% of the FN episodes. Gram-negative bacteria are the most common pathogens.

Histoplasmosis Beyond Human Immunodeficiency Virus (HIV): Clinical Characteristics and Outcomes in a Non-HIV Population.

Histoplasmosis is an endemic and invasive mycosis caused by Histoplasma capsulatum. We conducted a retrospective study comparing immunosuppressed patients without human immunodeficiency virus (HIV) with a historical cohort of people with HIV and histoplasmosis. We included 199 patients with proven or probable histoplasmosis, of which 25.1% were people without HIV. Diabetes mellitus, chronic kidney disease, hematologic neoplasms, rheumatologic diseases, and transplantations were more frequent among people without HIV (P < .01). Forty-four percent of immunocompromised patients without HIV died within the first 6-week period following their diagnosis. A high suspicion index for histoplasmosis should be kept in immunosuppressed patients.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients to prevent hospitalization or death during the Omicron era: a propensity score-matched study.

Background: Even though worldwide death rates from coronavirus disease 2019 (COVID-19) have decreased, the threat of disease progression and death for high-risk groups continues. Few direct comparisons between the available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals have been made. Objective: We aimed to compare two SARS-CoV-2 antivirals (nirmatrelvir/ritonavir and remdesivir) against all-cause hospitalization or death. Design: This is a propensity score-matched cohort study. Methods: We included all high-risk outpatients with COVID-19 in a tertiary referral center in Mexico City from 1 January 2022 to 31 July 2023. The primary outcome was all-cause hospitalization or death 28 days after symptom onset. The secondary outcome was COVID-19-associated hospitalization or death 28 days after symptom onset. Logistic regression analysis for characteristics associated with the primary outcome and a multi-group comparison with Kaplan-Meier survival estimates were performed. Results: Of 1566 patients analyzed, 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. The median age was 60 years (interquartile range: 46-72), 62.5% were female and 97.8% had at least one comorbidity. The use of nirmatrelvir/ritonavir was associated with an absolute risk reduction of 8.8% and a relative risk reduction of 90% for all-cause hospitalization or death. The use of remdesivir was associated with an absolute risk reduction of 6.4% and a relative risk reduction of 66% for all-cause hospitalization or death. In multivariable analysis, both antivirals reduced the odds of 28-day all-cause hospitalization or death [nirmatrelvir/ritonavir odds ratio (OR) 0.08 - 95% confidence interval (CI): 0.03-0.19, remdesivir OR 0.29 - 95% CI: 0.18-0.45]. Conclusion: In high-risk COVID-19 outpatients, early antiviral treatment with nirmatrelvir/ritonavir or remdesivir was associated with lower 28-day all-cause hospitalization or death.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients In this study, we included high-risk non-hospitalized patients with confirmed mild COVID-19. We compared those who received antiviral treatment (nirmatrelvir/ritonavir or remdesivir) against those who only received symptomatic treatment. The aim was to detect differences in hospitalization or death 28 days after symptom onset. We analyzed 1566 patients: 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. Most patients were female and over 60 years old. The most common comorbidities were chronic hypertension (44%), diabetes mellitus (26%), and autoimmune diseases (25%); systemic immunosuppression was registered in 35% of patients. Hospitalization or death 28 days after symptom onset occurred in 168 patients (136 in the symptomatic treatment group, 27 in the remdesivir group, and 5 in the nirmatrelvir/ritonavir group). Considering multiple variables like age, sex, comorbidities, and previous vaccination, both antivirals significantly reduced the odds of hospitalization or death (nirmatrelvir/ritonavir odds ratio 0.08, 95% confidence interval 0.03-0.19; remdesivir odds ratio 0.29, 95% confidence interval 0.18-0.45).

Cephalotin Versus Dicloxacillin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteraemia: A Retrospective Cohort Study.

BACKGROUND: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia. METHODS: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality. RESULTS: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic. CONCLUSIONS: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.

Histoplasma capsulatum prosthetic joint infection.

Immunocompromised patients are at risk of opportunistic infections. This is a 67-year-old woman with systemic sclerosis and knee osteoarthritis who underwent left total knee arthroplasty in 2009. In 2018 she underwent surgery for presumed aseptic loosening. Inflammation and purulent fluid were found; implant was removed and replaced with a static spacer. Three weeks later, H. capsulatum was isolated. She was successfully treated with itraconazole for 18 months; cultures on revision spacer replacement surgery were negative.

Predictors of Poor Outcomes in Young Non-Comorbid Patients with COVID-19.

Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objectives: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV. (Rev Invest Clin. 2022;74(5):268-75).

Prevention of COVID-19 superspreading events in buses boarded by presymptomatic cases.

INTRODUCTION: COVID-19 superspreader events have occurred when symptomatic individuals without wearing face masks boarded buses. OBJECTIVE: To report the risk of superspreader events when presymptomatic individuals boarded buses to-gether with unvaccinated passengers, but with non-pharmacological preventive interventions being maintained. METHODS: Prospec-tive study of health personnel transported in buses to a COVID-19 vaccination center for two weeks. Open windows, correct use of face masks and exclusion of symptomatic individuals were mandatory. Prospective surveillance identified workers with COVID-19 within 14 days after vaccination. Each asymptomatic passenger of buses where cases were identified was monitored for a similar time period. Voluntary screening results were available for workers who were tested in the month before or after vaccination. RESULTS: 1,879 workers boarded 65 buses. On-board time ranged from three to eight hours. Twenty-nine cases of COVID-19 and four asymptomatic cases were identified among 613 passengers of 21 buses. Median time between vaccina-tion and COVID-19 symptoms onset was six days. One case of suspected transmission on a bus was identi-fied. CONCLUSIONS: Strict nonpharmacological preventive interventions substantially reduced the risk of COVID-19 super-spreader events in buses boarded by presymptomatic individuals.

ANTECEDENTES: Ha ocurrido superpropagación de COVID-19 cuando individuos sintomáticos sin uso de cubrebocas abordaron autobuses. OBJETIVO: Reportar el riesgo de superpropagación cuando individuos presintomáticos abordaron autobuses junto con pasajeros no vacunados pero se mantuvieron intervenciones preventivas no farmacológicas. MATERIAL Y MÉTODOS: Estudio prospec­tivo de personal de salud transportado durante dos semanas en autobuses a un centro de vacunación contra COVID-19. Fue obligatorio llevar ventanas abiertas, uso correcto de cubrebocas y exclusión de personas con síntomas. La vigilancia prospectiva identificó a trabajadores con COVID-19 los 14 días siguientes a la vacunación. Cada pasajero asintomático de autobuses donde se detectaron casos fue vigilado durante un periodo de tiempo similar. Los resultados de tamizaje voluntario estuvieron disponibles para los trabajadores que se realizaron prueba el mes previo o el siguiente a la vacunación. RESULTADOS: 1879 trabajadores abordaron 65 autobuses. El tiempo a bordo varió de tres a ocho horas. Veintinueve casos de COVID-19 y 4 casos asintomáticos fueron identificados entre 613 pasajeros de 21 autobuses. La mediana de tiempo entre la vacunación y el inicio de síntomas en casos de COVID-19 fue de seis días. Fue identificado un caso de transmisión sospechada en autobús. CONCLUSIONES: Las intervenciones preventivas no farmacológicas estrictas redujeron sustancialmente el riesgo de superpropagación de COVID-19 en autobuses ocupados por individuos presintomáticos.

Early Outpatient Treatment With Remdesivir in Patients at High Risk for Severe COVID-19: A Prospective Cohort Study.

Background: Early treatment of coronavirus disease 2019 (COVID-19) with remdesivir in high-risk patients, including those with immunosuppression of different causes, has not been evaluated. The objective of this study was to assess the clinical effectiveness of early remdesivir treatment among patients with mild to moderate COVID-19 at high risk of progression. Methods: This prospective cohort comparative study was conducted in a tertiary referral center in Mexico City. Patients with mild to moderate COVID-19 at high risk for progression were treated with an ambulatory 3-day course of remdesivir. The primary efficacy composite outcome was hospitalization or death at 28 days after symptom onset. A Cox proportional hazards regression model was used to identify associations with the primary outcome. Results: From December 1, 2021, to April 30, 2022, a total of 196 high-risk patients were diagnosed with COVID-19, of whom 126 were included in this study (43%, 54/126, received remdesivir; 57%, 72/126, did not receive remdesivir). Baseline clinical characteristics were similar between groups; autoimmune diseases (39/126), solid organ transplant (31/126), and malignant neoplasms (24/126) were the most common immunocompromising conditions. Diabetes mellitus was strongly associated with the primary outcome in both groups. Prior severe acute respiratory syndrome coronavirus 2 infection or vaccination was not independently associated with COVID-19 progression. Treatment with remdesivir significantly reduced the odds of hospitalization or death (adjusted hazard ratio, 0.16; 95% CI, 0.06-0.44; P < .01). Conclusions: Early outpatient treatment with remdesivir significantly reduces hospitalization or death by 84% in high-risk, majority immunosuppressed patients with Omicron variant COVID-19.

Predictors of poor outcomes in young non-comorbid patients with COVID-19

ABSTRACT Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objective: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV.

Prevención de eventos de superpropagación de COVID-19 en autobuses que transportaron pacientes presintomáticos / Prevention of COVID-19 superspreader events in buses boarded by presymptomatic patients

Resumen Introducción: Ha ocurrido superpropagación de COVID-19 cuando individuos sintomáticos sin uso de cubrebocas abordaron autobuses. Objetivo: Reportar el riesgo de superpropagación cuando individuos presintomáticos abordaron autobuses junto con pasajeros no vacunados, pero se mantuvieron intervenciones preventivas no farmacológicas. Métodos: Estudio prospectivo de personal de salud transportado durante dos semanas en autobuses a un centro de vacunación contra COVID-19. Fue obligatorio llevar ventanas abiertas, uso correcto de cubrebocas y exclusión de personas con síntomas. La vigilancia prospectiva identificó a trabajadores con COVID-19 los 14 días siguientes a la vacunación. Cada pasajero asintomático de autobuses donde se detectaron casos fue vigilado durante un periodo similar. Los resultados de tamizaje voluntario estuvieron disponibles para los trabajadores que se realizaron prueba el mes previo o el siguiente a la vacunación. Resultados: 1879 trabajadores abordaron 65 autobuses. El tiempo a bordo varió de tres a ocho horas. Veintinueve casos de COVID-19 y cuatro casos asintomáticos fueron identificados entre 613 pasajeros de 21 autobuses. La mediana de tiempo entre la vacunación y el inicio de síntomas de COVID-19 fue de seis días. Fue identificado un caso de transmisión sospechada en autobús. Conclusiones: Las intervenciones preventivas no farmacológicas estrictas redujeron sustancialmente el riesgo de superpropagación de COVID-19 en autobuses ocupados por individuos presintomáticos.

Abstract Introduction: COVID-19 superspreader events have occurred when symptomatic individuals without wearing face masks boarded buses. Objective: To report the risk of superspreader events when presymptomatic individuals boarded buses together with unvaccinated passengers, but with non-pharmacological preventive interventions being maintained. Methods: Prospective study of health personnel transported in buses to a COVID-19 vaccination center for two weeks. Open windows, correct use of face masks and exclusion of symptomatic individuals were mandatory. Prospective surveillance identified workers with COVID-19 within 14 days after vaccination. Each asymptomatic passenger of buses where cases were identified was monitored for a similar time period. Voluntary screening results were available for workers who were tested in the month before or after vaccination. Results: 1,879 workers boarded 65 buses. On-board time ranged from three to eight hours. Twenty-nine cases of COVID-19 and four asymptomatic cases were identified among 613 passengers of 21 buses. Median time between vaccination and COVID-19 symptoms onset was six days. One case of suspected transmission on a bus was identified. Conclusions: Strict nonpharmacological preventive interventions substantially reduced the risk of COVID-19 superspreader events in buses boarded by presymptomatic individuals.

Geotrichum spp: An overlooked and fatal etiologic agent in immunocompromised patients. A case series from a referral center in Mexico.

Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.

Outbreak of NDM-1-Producing Escherichia coli in a Coronavirus Disease 2019 Intensive Care Unit in a Mexican Tertiary Care Center.

Emergency department areas were repurposed as intensive care units (ICUs) for patients with acute respiratory distress syndrome during the initial months of the coronavirus disease 2019 (COVID-19) pandemic. We describe an outbreak of New Delhi metallo-ß-lactamase 1 (NDM-1)-producing Escherichia coli infections in critically ill COVID-19 patients admitted to one of the repurposed units. Seven patients developed infections (6 ventilator-associated pneumonia [VAP] and 1 urinary tract infection [UTI]) due to carbapenem-resistant E. coli, and only two survived. Five of the affected patients and four additional patients had rectal carriage of carbapenem-resistant E. coli. The E. coli strain from the affected patients corresponded to a single sequence type. Rectal screening identified isolates of two other sequence types bearing blaNDM-1. Isolates of all three sequence types harbored an IncFII plasmid. The plasmid was confirmed to carry blaNDM-1 through conjugation. An outbreak of clonal NDM-1-producing E. coli isolates and subsequent dissemination of NDM-1 through mobile elements to other E. coli strains occurred after hospital conversion during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This emphasizes the need for infection control practices in surge scenarios. IMPORTANCE The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios.

Tracheal Aspirate Galactomannan Testing in COVID-19-Associated Pulmonary Aspergillosis.

Among critically ill patients, COVID-19-associated pulmonary aspergillosis (CAPA) is a challenging complication. The recommended diagnostic methods for this disease are bronchoalveolar lavage (BAL) culture and galactomannan (GM) testing, which were not widely available during the pandemic. There is scarce information regarding GM testing in other respiratory specimens. Our objective was to compare the agreement of GM between BAL and tracheal aspirate (TA) samples. We selected patients with COVID-19 and those with suspected CAPA who were admitted in the intensive care unit (ICU). GM was routinely done in BAL. We performed GM in TA samples and compared the results. The agreement was evaluated with Cohen's Kappa coefficient. GM was considered positive when an OD index ≥ 1 in BAL and ≥ 2 in TA were found. Probable CAPA was considered when the ECMM/ISHAM criteria were met. A descriptive analysis of clinical characteristics and mortality was made. We included 20 patients with suspected CAPA from 54 patients with critical COVID-19, of which 5 (9%) met the probable category. Aspergillus fumigatus was the most frequent isolate. We found moderate agreement between BAL and TA GM (Kappa = 0.47, p = 0.01, 95% CI.04-0.9), whereas TA GM had 75% sensitivity (95% CI 19.4-99.4%), 81.2% specificity (95% CI 54.4-95.9%), 50% positive predictive value (95% CI 23.8-76.3%),] and 92.8% negative predictive value (95% CI 70.1-98.6%), and 80% accuracy (95% CI 56.3-94.3%). Lastly, three (60%) patients with CAPA died during hospitalization compared to 40% (6/15) without CAPA (p = 0.4). In conclusion, a moderate agreement between TA GM and BAL was found. Therefore, TA testing may aid in ruling out CAPA due to high negative predictive value when bronchoscopies are unavailable.

Outcomes of patients with severe and critical COVID-19 treated with dexamethasone: a prospective cohort study.

Dexamethasone implementation for COVID-19 management represented a milestone but data regarding its impact and safety have not been consistently reproduced. We aimed to evaluate in-hospital mortality before and after the implementation of corticosteroid treatment (CS-T) for severe and critical COVID-19. We conducted a cohort study that included patients admitted with severe and critical COVID-19. The primary outcome was death during hospitalization. Secondary outcomes included the length of stay (LOS), need for invasive mechanical ventilation (IMV), time to IMV initiation, IMV duration, and development of hospital-acquired infections (HAIs). Bivariate, multivariate, and propensity-score matching analysis were performed. Among 1540 patients, 688 (45%) received CS-T. Death was less frequent in the CS-T group (18 vs 31%, p < .01). Among patients on IMV, death was also less frequent in the CS-T group (25 vs 55%, p < .01). The median time to IMV was longer in the CS-T group (5 vs 3 days, p < .01). HAIs occurred more frequently in the CS-T group (20 vs 10%, p < .01). LOS, IMV, and IMV duration were similar between groups. Multivariate analysis revealed an independent association between CS-T and lower mortality (aOR 0.26, 95% CI 0.19-0.36, p < .001). Propensity-score matching analysis revealed that CS-T was independently associated with lower mortality (aOR 0.33, 95% CI 0.22-0.50, p < .01). Treatment with corticosteroids was associated with reduced in-hospital mortality among patients with severe and critical COVID-19, including those on IMV.

Large-scale screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) among healthcare workers: Prevalence and risk factors for asymptomatic and pauci-symptomatic carriers, with emphasis on the use of personal protective equipment (PPE).

Healthcare workers (HCWs) not fulfilling the coronavirus disease 2019 (COVID-19) case definition underwent severe acute respiratory coronavirus virus 2 (SARS-CoV-2) screening. Risk of exposure, adherence to personal protective equipment (PPE), and symptoms were assessed. In total, 2,000 HCWs were screened: 5.5% were positive for SARS-CoV-2 by polymerase chain reaction (PCR). There were no differences in PPE use between SARS-CoV-2-positive and -negative HCWs (adherence, >90%). Nursing and kitchen staff were independently associated with positive SARS-CoV-2 results.

Effect of Tocilizumab in Mortality among Patients with Severe and Critical Covid-19: Experience in a Third-Level Medical Center.

BACKGROUND: Trials evaluating safety and efficacy of tocilizumab in coronavirus disease 19 (COVID-19) show contradictory results. OBJECTIVE: The objective of the study was to evaluate the effect of tocilizumab in hospital mortality among patients with severe COVID-19 in a third-level medical center. METHODS: This prospective cohort study included patients with severe and critical COVID-19. Primary outcome was death during hospitalization. Secondary outcomes included invasive mechanical ventilation (IMV), days on IMV, ventilator-free days (VFDs), length of hospital stay (LOS), and development of hospitalacquired infections (HAIs). Bivariate, multivariate, and propensity score matching analysis were performed. RESULTS: During the study period, 99/794 (12%) patients received tocilizumab. Male patients, health care workers, and patients with increased inflammatory markers received tocilizumab more frequently. No difference in hospital mortality was observed between groups (34% vs. 34%, p = 0.98). Tocilizumab was not independently associated with mortality. No significant treatment effects were observed in propensity score analysis. IMV was more frequent (46% vs. 11%, p < 0.01) and LOS was longer (12 vs. 7 days, p < 0.01) in the tocilizumab group, reflecting increased severity. Although HAIs were more frequent in the tocilizumab group (22% vs. 10%, p < 0.01), no difference was seen after adjusting for IMV (38% vs. 40%, p = 0.86). CONCLUSIONS: In our study, tocilizumab was not associated with decreased hospital mortality among patients with severe COVID-19.

COVID-19: WHAT'S NEXT?

Since December 2019, when severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China, this virus and the resulting disease, coronavirus disease (COVID-19), has spread worldwide. What has occurred in this year and a half goes beyond anything we have dealt with, as humankind, in the past two centuries, perhaps obscured only by war. An incredible number of articles, whether scientific or in the press, have been published, making it impossible to discern between what is biological and what is social in nature. Here, we aim to reflect on the basic structure of the virus and associate its behavior to that of determining factors of the human condition that may be modifiable soon. Needless to say, we find our effort clearly incomplete, and that both scientific and social aspects regarding COVID-19 or any other pandemic encountered in the future, will be constantly changing, from their beginning to their end.

Surge in Ventilator-Associated Pneumonias and Bloodstream Infections in An Academic Referral Center Converted to Treat COVID-19 Patients

Background: Healthcare-associated infections (HAIs) are important adverse events that must be prevented. Objective: The objective of the study was to report and study possible changes in HAI rates as well as their causes after the COVID-19 hospital surge capacity response (HSCR) in an academic referral center. Methods: This was a before-after observational study. The Infection Prevention and Control (IPC) program (prospective surveillance, prevention bundles, antibiotic stewardship, continuing education, and feedback) was transiently disrupted after the start of HSCR (March 2020). HAI rates were compared before (January 2019-February 2020) and after (April-July 2020) HSCR, and plausible predisposing factors in affected patients were compared. Results: An increase in the HAI rate from 6.2 to 11.8 cases/1000 patient-days was noted between periods due to increases in ventilator-associated pneumonia and bloodstream infection (BSI) rates. More critically ill patients were admitted during HSCR, and use of invasive devices increased. Prone positioning and infusion of muscle relaxants became commonplace. The nurse-to-patient ratio in the intensive care unit decreased, and 4 h shifts were introduced to avoid fatigue. The BSI rate decreased after the IPC program with additional measures was reintroduced in May 2020. Conclusions: The strain on the workforce and modifications to the IPC program very possibly underlay the findings. IPC programs continue to be essential during the pandemic.

Isolation of Rhizopus microsporus and Lichtheimia corymbifera from tracheal aspirates of two immunocompetent critically ill patients with COVID-19.

We describe two fatal cases of COVID-19 in which Rhizopus microsporus and Lichtheimia corymbifera were cultured from endotracheal aspirate samples. Both patients had no underlying comorbidities other than obesity. Despite antifungal therapy, both cases developed septic shock and progressive refractory hypoxemia without evidence of other underlying infections. It is unclear whether isolation of these fungal organisms represents invasive disease or corresponds to an epiphenomenon of critical illness. Yet, patients suffering from COVID-19 may be at risk of superinfection from a broader range of fungal organisms than previously thought.