Differences in nosocomial infections in patients on VV-ECMO for COVID-19 and influenza

Objectives: In COVID-19 associated acute respiratory distress syndrome (ARDS) requiring VV-ECMO, ventilator-associated-pneumonia (VAP), pulmonary aspergillosis and viral reactivations are observed frequently, but there is only little knowledge on incidence, onset and causative pathogens. This study analyzes frequency of VAP, pulmonary aspergillus infections, and viral reactivations in a large cohort of patients with ARDS treated with VV-ECMO due to either COVID-19 or Influenza. Method(s): Retrospective analysis of all consecutively patients at the University Hospital Regensburg requiring VVECMO due to COVID-19 (March 2020 and May 2022) or Influenza (May 2012 and December 2022). VAP was diagnosed according to current guidelines. Pulmonary Aspergillosis met criteria of probable COVID-associated Aspergillosis according to current guidelines. Result(s): 147 patients (age (median [IQR]) 55.3 [48.7 - 61.7], SOFA at VV-ECMO initiation 9 [8 - 12], 23 [14 - 38] days on VV-ECMO) suffering from COVID-19 and 72 influenza patients (age 55.3 [46 - 61.3], SOFA at VV-ECMO initiation 13 [10 - 15], 16 [10 - 23] days on VV-ECMO) were included in the analysis. Pulmonary superinfections were more frequent in COVID-19 than in influenza (VAP: 61% vs. 39%, pulmonary Aspergillosis: 33% vs. 22%, CMV reactivation: 19% vs. 4%, HSV reactivation: 49% vs. 26%.) The first episode of VAP in COVID-19 and Influenza was detected 2 days [1 - 15] after and 1 day (-3 - 22) before ECMO initiation, respectively. First VAP-episode in COVID-19 were mainly caused by Klebsiella spp. (29%,), Staphylococcus aureus (27%) and E. coli (11%). Further VAP-episodes (30% in COVID-19) and relapses of VAP were mainly caused by Klebsiella spp. (53%, 64%, respectively). In Influenza, VAP was mainly caused by Staphylococcus aureus (28%) and Streptococcus pneumoniae(28%), further VAP episodes were not observed. Conclusion(s): Superinfections were common in patients treated with VV-ECMO and occur more frequently in COVID-19 ARDS compared to Influenza. VAP occurs early and may significantly contribute to the need of VV-ECMO. Therefore, a meticulous routine microbiologic workup is advisable. The observed differences in the spectrum of secondary infectious agents in COVID19 compared to Influenza are not understood yet.

Repurposing Methylene Blue for the Management of COVID-19: Prospects, Paradox, and Perspective

COVID-19 onslaught has led to widespread morbidity and mortality globally. Another major concern, especially in developing countries like India, has been the development of fungal superinfection and colonization of other pathogens in hospitalized COVID-19 patients. Even though an armamentarium of repurposed, antiviral, anticytokine, and antifungal drugs is available to manage the disease progression, no single drug and/or therapy has provided positive clinical outcomes with efficacy and affordability. Therefore, it is imperative to explore innovative approaches for standalone treatment and/or adjunct therapeutic regimes based on our current understanding of disease prognosis. Low-income and emerging economies have less resources to protect themselves against the COVID-19-induced health and economic crisis. With the continuously evolving nature of coronavirus, a cost-effective strain independent mechanism that could be delivered easily even in a nonhealthcare setting is an urgent need of the hour. Methylene blue appears an apt candidate as it is an FDA-approved safe drug that is economically viable and easily available. Since MB has a long-standing history of being used in clinical setup for diverse medical applications and possesses intrinsic anti-inflammatory, anticytokine, and antifungal properties, this study analyzes prospects of its use in the management of COVID-19. Paradox and prospects of MB applications for the management of COVID-19, with or without fungal superinfections, are also discussed. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Frequency of antibiotic prescribing in adults hospitalized for SARS-CoV-2 in a high complexity institution in Santiago de Cali, Colombia.

Objective: To determine the frequency of antibiotic use and to know which clinical and socio-demographic variables were related to the probability of suffering infections associated with COVID-19. Method(s): Adults hospitalized for COVID-19 who received one or more antibiotics during hospitalization were evaluated. We performed a descriptive analysis of variables in the general population' bivariate analysis in two groups (documented vs. suspected infection) and multivariate logistic regression of factors associated with mortality. Result(s): It was determined that 60.4% of adults hospitalized for COVID-19 received antibiotics. Coinfection was documented in 6.2% and superinfection in 23.3%. Gram-negative germs were reported in 75.8% of cultures, fungi in 17.8% and gram-positive in 14.2%. Variables such as age, comorbidities, ICU, anemia, steroids, mechanical ventilation, hemofiltration were statistically significantly related to documented infection. High-flow cannula was associated as a protective factor. Overall mortality was 43.9%, 57.8% in the first group and 38.1% in the second (p=0.002). Conclusion(s): There is a considerable frequency of antibiotic use in subjects hospitalized for COVID-19, particularly related to relevant findings of bacterial superinfection, in those with comorbidities, such as diabetes mellitus, immunosuppression, anemia and fragility, in whom the behavior of the disease is more severe and lethal.Copyright © 2023 Asociacion Colombiana de Infectologia. All rights reserved.

Use of novel oxygenated right ventricular assist device hybrid ECLS for adolescents with refractory hypoxemic respiratory dailure due to Covid-19 pneumonia

Objectives: To describe institutional experience using Oxygenated Right Ventricular Assist Device (OxyRVAD) Hybrid ECLS for adolescents with respiratory failure due to SARS-CoV-2 pneumonia. Method(s): Between September and December 2021, 44 Covid-19+ patients were admitted to our regional Pediatric Intensive Care Unit (PICU), including 4 adolescents who required Extracorporeal life support (ECLS) due to refractory hypoxemia. Two patients were initially cannulated onto Veno-Venous (VV) ECLS and converted to Oxy-RVAD ECLS due to refractory hypoxemia;the others were cannulated directly onto Oxy-RVAD ECLS. Two patients had observed right ventricular (RV) dysfunction or failure on echocardiography. Cannulations were performed in the cardiac catheterization suite by an interventional cardiologist using percutaneous technique under fluoroscopy. Circuit construction was varied and included the use of a dedicated RVAD cannula or standard cannula used for VA/VV ECLS. All patients were connected to Cardiohelp systems with built in centrifugal pumps and oxygenators. Result(s): Two patients were initially placed on VV-ECLS and converted to Oxy-RVAD ECLS days into their course due to severe, refractory hypoxemia with one having improvement in hypoxemia after the conversion. Two patients received renal replacement therapy (RRT) without complications, the others did not have indications for renal support. Two patients underwent tracheostomy on ECMO though none were able to separate from mechanical ventilation. Three patients survived to discharge. No incidents of circuit air or clotting were noted. The patient with the longest ECLS run required one circuit change and was the only patient to develop a superinfection: a successfully-treated fungal infection. All patients were mobilized on ECLS to sitting in a chair;one was able to ambulate. Conclusion(s): Oxy-RVAD hybrid ECLS can be used to effectively support adolescents with severe respiratory disease from conditions associated with RV dysfunction. Pediatric providers can collaborate with adult critical care colleagues to use novel methods to support these patients. RRT can also be used with this circuit. While more experience and data on this modality is needed, Oxy-RVAD ECLS should be considered in patients with severe RV dysfunction and associated refractory hypoxemia. (Figure Presented).

Leading Pathogens Involved in Co-Infection and Super-Infection with COVID-19: Forensic Medicine Considerations after a Systematic Review and Meta-Analysis.

The COVID-19 pandemic raised concerns about the potential for co-infection or over-infection with other respiratory infections, as they can complicate the diagnosis, treatment and prognosis of the disease. This is also a challenge for forensic pathologists, who may come across cases where the presence of co-infection or over-infection is suspected or confirmed, and it is important that they take this into account when determining the cause of death. The aim of this systematic review is to analyse the prevalence of each specific pathogen co-infecting or over-infecting patients with SARS-CoV-2 infection. In total, 575 studies were selected from the Scopus and Pub-Med online databases and 8 studies were included in a meta-analysis. Male gender, advanced age and nursing home care are risk factors associated with the development of co-infection, whereas age, tachypnoea, hypoxaemia and bacterial infection are predictors of mortality. Overall, however, having a SARS-CoV-2 infection does not represent a real risk for the development of co-infections/super-infections.

Global Access to Antimicrobials and Enhanced Emergence of Amr in Covid-19 Era

Of the major global public health issues of the 21st century, antimicrobial resistance (AMR) is still emerging as one of the leading threats, given its significant health, economic and security ramifications. Optimizing the use of antimicrobials through antimicrobial stewardship programs/efforts is a fundamental aspect in increasing clinical outcomes, via cost-effective treatments, as well as in reducing AMR. On the other hand, studies have shown that limited access to antimicrobials was not the answer in several settings. Accordingly, a combined approach of ensuring adequate global access to and appropriate use of antimicrobials was found to be a better response/action plan to the AMR problem. In addition to its serious health, economic and social implications, Covid-19 pandemic was a catalyst for AMR. Several AMR national action plans were affected by the prioritization of COVID-19 emergency, whereby activities and resources were diverted and channeled towards responding to the pandemic and AMR stewardship programs were not being reinforced. Additionally, the increased access to and use of antimicrobials to treat Covid-19 patients further fuelled AMR. Studies assessing the impact of the pandemic on AMR reported that antibiotic treatment was received by up to 70% of the hospitalized Covid-19 patients and among the latter high prevalence of AMR was reported during the first 18 months of the pandemic. Reasons underlying the increased prescribing of antimicrobials by the physicians treating Covid-19 patients included, suspected bacterial/fungal coinfection or superinfection, insufficient knowledge of the natural course of the respiratory illness and misdiagnosing cases due to the resemblance between the symptoms of SARS-Cov2 infection and that of bacterial pneumonia or other respiratory infection.Copyright © 2023

Use of Novel Oxygenated Right Ventricular Assist Device Hybrid ECLS for Adolescents with Refractory Hypoxemic Respiratory Failure due to Covid-19 Pneumonia

Objective: To describe institutional experience using Oxygenated Right Ventricular Assist Device Oxy-RVAD) Hybrid ECLS for adolescents with respiratory failure due to SARS-CoV-2 pneumonia. Method(s): Between September and December 2021, 44 Covid-19+ patients were admitted to our regional Pediatric Intensive Care Unit (PICU) including 4 adolescents who required Extracorporeal life support (ECLS) due to refractory hypoxemia. Two patients were initially cannulated onto Veno-Venous (VV) ECLS and converted to Oxy-RVAD ECLS due to refractory hypoxemia;the others were cannulated directly onto Oxy-RVAD ECLS. Two patients had observed right ventricular dysfunction (RV) or failure on echocardiography. Cannulations were performed in the cardiac catheterization suite by an interventional cardiologist using percutaneous technique under fluoroscopy. Circuit construction was varied and included the use of a dedicated RVAD cannula or standard cannula used for VA/VV ECLS. All patients were connected to CardiohelpTM systems with built-in centrifugal pumps and oxygenators. Result(s): Two patients were initially placed on VV-ECLS and converted to Oxy-RVAD ECLS days into their course due to severe, refractory hypoxemia with one having improvement in hypoxemia after the conversion. Two patients were cannulated directly to Oxy-RVAD ECLS support. Two patients received renal replacement therapy (RRT) without complications, the others did not have indications for renal support. Two patients underwent tracheostomy on ECMO though none were able to separate from mechanical ventilation. Three patients survived to discharge. No incidents of circuit air or clotting were noted. The patient with the longest ECLS run required one circuit change and was the only patient to develop a superinfection: a successfully-treated fungal infection. All patients were mobilized on ECLS to sitting in a chair;one was able to ambulate. Conclusion(s): Oxy-RVAD hybrid ECLS can be used to effectively support adolescents with severe respiratory disease from conditions associated with RV dysfunction. Pediatric providers can collaborate with adult-focused colleagues to use novel methods to support these patients. RRT can also be used with this circuit. While more experience and data on this modality is needed, Oxy-RVAD ECLS should be considered in patients with severe RV dysfunction and associated refractory hypoxemia.

Acute care treatment of COVID-19 pneumonia with acute respiratory failure

Treatment of COVID-19 patients and their extreme numbers represented an unprecedented challenge for the intensive care system in healthcare facilities throughout the Czech Republic, a country particularly affected by the new coronavirus SARS-CoV-2 pandemic. A steep increase in the need for intensive care placed an excess burden on bed and staff capacity. For a severe and critical course of COVID-19, bilateral pneumonia with acute hypoxemic respiratory failure is pathognomonic. In the intensive care setting, COVID-19 therapy is primarily symptomatic, supporting failing respiratory function to gain time needed to restore it and to repair the lungs. The aggressiveness and comprehensiveness of respiratory support depend on the severity of failure, ranging from simple oxygen therapy, to non-invasive support and mechanical ventilation, to extracorporeal support. By contrast, specific COVID-19 therapy is directly targeted against SARS-CoV-2 or modulates the organism's response to the virus. Primary, virus-induced lung injury may be secondarily complicated by coinfection or superinfection, most commonly bacterial, increasing the severity and lethality of the disease. Therefore, anti-infective therapy is crucial for the prognosis and outlook of intensive care COVID-19 patients. Among nosocomial infections com-plicating COVID-19, ventilator-associated pneumonia (developing in mechanically ventilated patients) is particularly important and challenging, and so are issues related to bacterial resistance and rational antibiotic therapy.Copyright © 2021, Trios spol. s.r.o.. All rights reserved.

Covid-19 Associated Hepatitis in Children (Cah-C) during the Rise of Delta Variant in India: A New Covid-19 Complication or a Superinfection

Intro: While the pediatric population has largely remained free of severe COVID- 19, in some situations SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). Recently, cases of hepatitis in children have caused tremendous worry across the globe, we describe a unique presentation from 2021, subsequent to asymptomatic infection of SARS-CoV-2, a unique form of severe hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The clinical presentations, temporal association, and viral parameters of CAH-C cases, and contrast to that of MIS-C cases are presented here. Method(s): As a retrospective and follow-up case-control study we reviewed all children within 14 years presenting with "sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice. After performing all routine tests among them, those lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis (A-E) or previous underlying liver disease, and (b) multi-system involvement", being unique such cases were classified as CAH-C, and are described here. Finding(s): Among 475 children who tested positive, 37/47 cases had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers, 100% positivity for SARS-CoV-2 antibodies, and uneventful recovery. The remaining 10/47 having MIS-C had protracted illness, multiple system involvement, required admission to critical care, and a mortality rate of 30%. Among controls, only 26/50 (52%) had SARS-CoV-2 antibodies. Discussion(s): During the pandemic, various COVID-19 complications have been observed posing safety concerns, where our study identified a unique form of acute hepatitis in children designated as CAH-C. Conclusion(s): With the emergence of newer variants, including the Delta variant which predominated the second wave of infections in India and spread worldwide with changing presentations and complications, CAH-C is such new entity in children. It needs early identification and differentiation from other emerging syndromes during the ongoing pandemic for preventing adversities through timely intervention.Copyright © 2023

Secondary infections in critically ill patients with COVID-19: effects of intravenous IgM-enriched immunoglobulin therapy

Introduction: Critically ill patients with severe COVID-19 have an increased risk of bacterial and fungal superinfections due to a dysregulated immune response characterized by lymphopenia and low immunoglobulins levels. The intravenous immunoglobulins are involved in pathogen/toxin scavenging and inhibition of inflammatory mediators gene transcription with anti-apoptotic effects on immune system cells. This research aimed to describe the effects of intravenous IgM-enriched immunoglobulins in COVID-19 patients with sepsis due to secondary infections and low IgM levels. Method(s): We performed an observational retrospective study, including patients admitted to our intensive care unit (ICU) between March 2020 and February 2021 with severe COVID-19 and sepsis due to a superinfection (known or suspected) treated with intravenous IgM-enriched immunoglobulins. We collected demographic data and comorbidities. We noted hemodinamic data, antimicrobial and adiuvant therapies, laboratory results at ICU admission (T0), at the beginning (T1) and at the end (T2) of the IgM-enriched immunoglobulins infusion and at ICU discharge (T3). Result(s): In our cohort of 36 patients (Table 1) the prevalence of documented secondary infections was 83%. We observed a significant reduction of leukocytes from T0 to T3 (10.4 [8.3-14.5] x 103/ mmc vs 7.1 [4.8-11.2] x 103/ mmc, p < 0.01) and the SOFA score from T0 to T2 (7 [6-19] vs 5 [3-7], p < 0.01) and from T0 to T3 (7 [6-10] vs 4 [2-9], p < 0.01);from T1 to T2 (7 [6-9] vs 5 [3-7], p < 0.01) and from T1 to T3 (7 [6-9] vs 4 [2-9], p < 0.01). Cardiovascular SOFA showed a statistically significant reduction from T1 to T2 (4 [3-4] vs 0 [0-3], p < 0.01). Conclusion(s): The IgM-enriched immunoglobulins could improve organ function, as evidenced by the reduction of the SOFA score. Although the latest Surviving Sepsis Campaign guidelines suggest against using of IgM-enriched immunoglobulins, our study supports its use as an adjunctive therapy in COVID-19 patients with septic shock.

Characterization of secondary bacterial and fungal infections in ICU hospitalized patients with COVID-19: retrospective observational study

Introduction: We aimed to describe the incidence, risk factors, and clinical outcomes of bacterial and fungal co-infections and superinfections in intensive care patients with COVID-19 in a retrospective observational study. Method(s): A retrospective cohort of intensive care patients with confirmed SARS-CoV-2 by PCR was analysed from January to March 2021. This was contrasted to a control group of influenza-positive patients admitted during 2012-2022. Patient demographics, microbiology and clinical outcomes were analysed. Result(s): A total of 70 patients with confirmed SARS-CoV-2 were included;6 (8.6%) of 70 had early bacterial isolates identified rising to 42 (60%) of 70 throughout admission. Blood cultures, respiratory samples, and urinary samples were obtained from 66 (94.3%), 18 (25.7%) and 61 (87.1%) COVID-19 patients. Positive blood culture was identified in 13 patients (18.6%). Bacteraemia resulting from respiratory infection was confirmed in 3 cases (all ventilator-associated). Line-related bacteraemia was identified in 9 patients (6 Acinetobacter baumannii, 4 Enterococcus spp. and 1 Pseudomonas aeruginosa and 1 Micrococcus lylae). No concomitant pneumococcal, Legionella or influenza co-infection was detected. Invasive fungal infections with Aspergillus spp. were identified in 2 cases. Pneumococcal coinfections (7/68;10.3%) were identified in the control group of confirmed influenza infection;clinically relevant bacteraemias (6/68;8.8%), positive respiratory cultures (15/68;22.1%). The rate of hospital- acquired infections was 51.4% for COVID-19 and 27.9% for influenza. Longer intensive care stay, type 2 diabetes, obesity and hematologic diseases were independent risk factors for superinfections in the COVID-19 cohort. Conclusion(s): Respiratory coinfections occurred in influenza but not in COVID-19 patients. The rate of hospital-acquired infections (51.4% for COVID-19;27.9% for influenza) was unexpectedly high in both groups.

Sars-CoV-2 in critical immunocompromised patients. Evolution and prognosis

Introduction: In this study, we share the results of immunosuppressed patients who suffered from acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonia managed in our ICU. Method(s): We tracked all patients admitted to ICU of a Tertiary Hospital diagnosed with severe SARS-COV2 pneumonia from March 1, 2020 to January 31, 2022. The definition of Immunocompromised patient is based on history of transplantation, active neoplasia, autoimmune diseases or HIV. Collected data includes: sex, age, type of immunosuppression, vaccination, mechanical ventilation, ECMO VV, incidence of superinfections and mortality. Result(s): From a cohort of 425 patients, 55 met the inclusion criteria. 33% were women and 67% male. The average age was 58 years for women and 62 years for men. Out of these patients, 27% had solid organ transplants. 40% suffered from neoplasic disease. 27% had autoimmune diseases and were under treatment with immunosuppressants. 3 had HIV. Only the 29% had received at least 1 dose of COVID 19 vaccine. 80% required orotracheal intubation. 3.64% (2) required Veno-Venous ECMO. 61% presented bacterial superinfection, with the most frequent germs being Pseudomonas aeruginosa and Enterococcus. 36% had viral superinfection, being cytomegalovirus the most frequent one. 32% had fungal superinfection, mainly by Aspergillus fumigatus. 27% did not suffer any superinfection. 40% of the total sample died. After logistic regression, in our model (AUC 83,4% (Se 57.1%, Sp 87.9%), we identified need of intubation as independent variable of mortality (OR 27,06 IC95% 1.76-415.55, p = 0.018). Conclusion(s): Immunocompromised patients with ARDS secondary to COVID-19 pneumonia present high mortality, with statistically significant difference when mechanical ventilation is needed. The most frequently isolated germs causing superinfection in this group of patients are bacterias. We believe that this group of patients require special care in our ICU units and an in-depth analysis and study to optimize their prognosis.

Lung cavitation as a rare complication of severe COVID-19: report of 3 cases

Introduction: Lung cavitation is a rare radiological finding of COVID- 19 pneumonia associated with unfavorable outcome. Its pathogenesis is unclear and it is characterized by diffuse alveolar damage, intra-alveolar hemorrhage and necrosis of parenchymal cells. Method(s): We retrospectively reviewed the radiological findings of COVID-19 patients admitted to our ICU during the pandemic in order to identify the development of lung cavitary lesions. Result(s): From 11/2020 until 10/2022 1000 patients were admitted to our COVID-19 ICU (92% on invasive mechanical ventilation). According to our data there were three cases of lung cavity formation. The first case was a 78 years male with history of hypertension. Chest CT (Day26) showed a 11.6 cm cavity in the right middle lobe (Fig. 1). The second case was a 52 year old female with history of diabetes mellitus, obesity, hypertension and rheumatoid arthritis. Follow up chest CT (D29) revealed progressive development of multiple bilateral cavitary lesions. The third case was a 61 year old male with no medical history, who developed (D17) multiple cavitary lesions in both lower lobes, concomitant with left-sided pulmonary embolism. The presence of other well defined etiologies of cavitary lesions such as mycobacterial and fungal infections as well as neoplasmatic or autoimmune diseases had been widely excluded. However, since pulmonary cavitation is a late complication of severe COVID disease, we cannot overlook the fact that all patients suffered from superinfections by XDR Acinetobacter baumanii and/or Klebsiella pneumonia, as most of our patients with prolonged length of stay. Moreover, two of the three patients developed pneumothorax. All patients finally died. Conclusion(s): Although bacterial co-infection does not allow absolute association between cavitary formation and coronavirus disease, it seems that destructive triggers, such as bacteria or mechanical ventilation, may aggravate COVID underlying lung lesions leading to cavitation.

Co-infections and antimicrobial use in hospitalized patients with moderate-severe COVID-19

Introduction/Aim: Coinfection in COVID-19 has been reported internationally, however, data on prevalence and outcomes in Australia is lacking. This study aimed to determine the prevalence and microbiology of coinfections, associated antimicrobial use, and outcomes in hospitalised patients with moderate-severe COVID-19 admitted to the Sunshine Coast University Hospital (SCUH). Method(s): A retrospective observational cohort study of adult patients admitted to the SCUH from February to July 2022 with moderate-severe COVID-19 was conducted. Demographics, comorbidities, laboratory, microbiological and radiological results, antimicrobial use, and hospital length of stay were collected. All-cause 30-day mortality and ICU admission were also collected, and incidence rate ratios (IRR) were calculated. Result(s): Sixty-six patients (57% male;median age 78.3) were captured. 13 coinfections occurred in 11 (16.7%) patients. Microbiological testing was performed in 94% of patients;respiratory viral PCR in 78.8%, blood cultures in 69.7%, sputum cultures in 25.8%, urinary antigens in 13.6% and atypical serology in 12.1%. Bacterial pathogens were most prevalent (53.8% of coinfections), whilst viral and fungal infections accounted for 30.8% and 15.4%, respectively. The most common pathogens were Streptococcus pneumoniae, Pseudomonas aeruginosa and influenza A. Most patients (74.2%) received empirical antibiotic therapy (mean = 5.5 days), with similar rates of use between those with coinfection (66.7%) and those without (75.9%). Overall patient mortality was 10.6%, with coinfections demonstrating a higher 30-day mortality (IRR = 2.0). Coinfected patients were seven times more likely to experience ICU admission (IRR = 7.5) compared to patients without coinfections. Conclusion(s): The prevalence of confirmed coinfection in hospitalised patients with moderate-severe COVID 19 was low;however, antimicrobial use was high. Importantly, patients with coinfections were twice as likely to die, and seven times more likely to be admitted to ICU. This study indicates the importance of developing improved diagnostic tools to identify coinfection and to help guide appropriate antimicrobial use.

Mortality in patients with COVID-19-related ARDS treated with venovenous extracorporeal membrane oxygenation: a retrospective observational study

Introduction: Venovenous extracorporeal membrane oxygenation (VV ECMO) is a technique that provides blood oxygenation and CO2 removal, allowing a protective ventilation strategy until the resolution of respiratory failure. A delay in ECMO initiation could worsen the outcome and prolong the duration of treatment. The study aims to describe the incidence of mortality in our intensive care unit (ICU) in patients with severe COVID-19-related acute respiratory distress syndrome (ARDS) treated with VV ECMO. Method(s): We performed an observational retrospective study, including patients with severe COVID-19-related ARDS admitted to our ICU and treated with VV ECMO between February 2020 and February 2022. We collected data on demographic characteristics, comorbidities, mechanical ventilation, therapies, laboratory results, VV ECMO and ICU mortality. SOFA score, SAPS II and Charlson Comorbidity Index were calculated at ICU admission. Result(s): The average age of our cohort of 60 patients was 54.4 +/- 7.7 years and 51 (85%) were males. The mean value of the SOFA score at ICU admission was 7 +/- 2.3 points, and the median value of the SAPS II score was 41 [31-48] points. The incidence of mortality in the whole cohort was 48.3%. The differences between the two groups of patients, Survivors and Non-survivors, are presented in Table 1. Through a multivariate logistic regression model we found that age (OR 1.09 [95% CI 1.00-1.19], p = 0.03) and lymphocytes (OR 0.09 [95% CI 0.01-0.59], p = 0.01) were significantly associated with ICU mortality. Mechanical ventilation before ECMO placement higher than 10 days and superinfections at ICU admission were not significantly associated with the outcome in the same model. Conclusion(s): In patients with COVID-19-related ARDS treated with VV ECMO, advanced age and lymphopenia at ICU admission are risk factors for ICU mortality. A longer duration of mechanical ventilation before ECMO placement and traditional ICU prognostic scores seem not to be relevant for the prognosis.

COVID-19 association with multidrug-resistant bacteria superinfections: Lessons for future challenges.

The future waves of COVID 19 infections will continue to raise serious problems in patients with severe forms of the disease. Bacterial infections associated with SARS-CoV-2 disease may complicate the progress of hospitalized patients with COVID-19. The present study aimed to evaluate the etiological spectrum of superinfection in adult patients with COVID-19 and to investigate the correlation between superinfection with multidrug-resistant (MDR) bacteria and serum procalcitonin (PCT). A total of 82 COVID-19 hospitalized patients with COVID-19 and bacterial superinfection were included. The superinfections were classified into early infections (3-7 days from admission) and late infections (>7 days from admission). Bacterial superinfection etiological spectrum, MDR bacteria profile and levels of serum PCT were studied. The most frequently isolated bacteria were Klebsiella pneumoniae, Acinetobacter baumannii and Enterococcus spp. MDR bacteria were involved in 73.17% of COVID-19 patients with bacterial superinfections. Most MDR bacteria superinfections (73.52%) occurred in the late infection period. Klebsiella pneumoniae, Enterococcus spp. and Methicillin-resistant Staphylococcus aureus were the most common MDR bacteria identified in late infections after hospitalization in 20.43, 4.30 and 4.30% of all infections, respectively. Serum PCT values were significantly higher in patients with MDR bacteria superinfection compared with patients with sensitive bacteria superinfection (P=0.009). The principal findings of the present study were the high prevalence of superinfection with MDR bacteria among the COVID-19 patients with bacterial superinfections and the presence of a statistically significant association between serum PCT levels and the presence of superinfection with MDR bacteria. The most effective way to fight against microbial resistance to antibiotics, whether it occurs independently or overlaps with viral infections, is to pursue a national policy for the rational use of antibiotics.

Anti-Inflammatory Therapy of Infections

Anti-inflammatory treatment of infections is challenging due to the heterogeneity of etiologic agents and complex immune interactions. Nevertheless, anti-inflammatory medications are commonly used in infections to reduce unpleasant symptoms and to modify host response. They may play a fundamental role in managing infection with over-inflammation by decreasing inflammatory organ damage, e.g., COVID-19. However, by its inherent inhibition of immune functions, they might also contribute to the development of serious bacterial infections. Moreover, reducing a patient's symptoms and signs may provide a false sense of security and delay diagnosing threatening infections. © 2022 Elsevier Inc. All rights reserved.

Acute exantematic pustulosis generalized by meropenem, differential diagnosis with COVID

Case report We present the case of a 63-year- old man with two consecutive admissions, due to COVID19 infection and subsequent bacterial superinfection. Three days after the second admission (04/28), and 43 days from the beginning of the infection an assessment by dermatology and allergology is then requested. The patient had generalized erythematous maculopapular rash in the trunk, back, groin and limbs. On the left side and back, pustular lesions not focused on follicles were also added, with a fever of 37.7degreeC. There were no oral and genital lesions. No psoriasis. The drugs used during the present and previous admissions were reviewed. Previous admission (04/04-22/ 20): Linezolid, ciprofloxacin, meropenem 04/13-22, piperacillin/tazobactam, hydroxychloroquine, azithromycin, ceftriaxone. Upon discharge amoxicillin/acid clavulanic. Present admission (04/25) Cutaneous reaction 04/28. 04/25: meropenem, paracetamol, enoxaparin, insulin, omeprazole, venlafaxine. 04/26: Darbepoetin, furosemide, mycophenolate in single dose. 04/27: Linezolid, macrogol, Clopidogrel, Magnesium, Calcitriol. Medical records: DM type 2, liver transplantation due to HCV cirrhosis, HCV recurrence, uninodular hepatocarcinoma, advanced CKD, secondary hyperparathyroidism, multiple neurological antecedents. We performed a detailed study. We hypothesized with a pharmagological/ drug reaction with several drugs possibly involved and our main suspicion was an allergic reaction to beta-lactams. Biopsy: Subcorneal pustules, basal spongiosis and presence in the superficial dermis of edema and an inflammatory infiltrate with abundant neutrophils. No fungi. Findings compatible with clinical diagnosis of generalized acute exanthematic pustulosis (PEGA). Immunohistochemical study Covid19. (Jimenez Diaz Foundation) Finely granular positivity in endothelium and more coarse in sweaty epithelium. Neutrophilic superficial inflammatory component with presumably spure staining. ACe-2 (positive external control) is not detected. The patient presents a EuroSCAR score of 9, sum of the clinic and the pathological anatomy, and therefore defined diagnosis. Clinical diagnosis: PEGA secondary to meropenem. Conclusion(s): We present the case of a PEGA by meropenem, not very often described in the literature. We highlight the importance of differential diagnosis with viral infections. Skin tests, especially epicutaneous tests, are key to the diagnosis. (Figure Presented).

A Retrospective Assessment of Sputum Samples and Antimicrobial Resistance in COVID-19 Patients.

Data on bacterial or fungal pathogens and their impact on the mortality rates of Western Romanian COVID-19 patients are scarce. As a result, the purpose of this research was to determine the prevalence of bacterial and fungal co- and superinfections in Western Romanian adults with COVID-19, hospitalized in in-ward settings during the second half of the pandemic, and its distribution according to sociodemographic and clinical conditions. The unicentric retrospective observational study was conducted on 407 eligible patients. Expectorate sputum was selected as the sampling technique followed by routine microbiological investigations. A total of 31.5% of samples tested positive for Pseudomonas aeruginosa, followed by 26.2% having co-infections with Klebsiella pneumoniae among patients admitted with COVID-19. The third most common Pathogenic bacteria identified in the sputum samples was Escherichia coli, followed by Acinetobacter baumannii in 9.3% of samples. Commensal human pathogens caused respiratory infections in 67 patients, the most prevalent being Streptococcus penumoniae, followed by methicillin-sensitive and methicillin-resistant Staphylococcus aureus. A total of 53.4% of sputum samples tested positive for Candida spp., followed by 41.1% of samples with Aspergillus spp. growth. The three groups with positive microbial growth on sputum cultures had an equally proportional distribution of patients admitted to the ICU, with an average of 30%, compared with only 17.3% among hospitalized COVID-19 patients with negative sputum cultures (p = 0.003). More than 80% of all positive samples showed multidrug resistance. The high prevalence of bacterial and fungal co-infections and superinfections in COVID-19 patients mandates for strict and effective antimicrobial stewardship and infection control policies.

Early Bacterial Coinfections in Patients Admitted to the ICU With COVID-19 or Influenza: A Retrospective Cohort Study.

Previous findings suggest that bacterial coinfections are less common in ICU patients with COVID-19 than with influenza, but evidence is limited. OBJECTIVES: This study aimed to compare the rate of early bacterial coinfections in ICU patients with COVID-19 or influenza. DESIGN SETTING AND PARTICIPANTS: Retrospective propensity score matched cohort study. We included patients admitted to ICUs of a single academic center with COVID-19 or influenza (January 2015 to April 2022). MAIN OUTCOMES AND MEASURES: The primary outcome was early bacterial coinfection (i.e., positive blood or respiratory culture within 2 d of ICU admission) in the propensity score matched cohort. Key secondary outcomes included frequency of early microbiological testing, antibiotic use, and 30-day all-cause mortality. RESULTS: Out of 289 patients with COVID-19 and 39 patients with influenza, 117 (n = 78 vs 39) were included in the matched analysis. In the matched cohort, the rate of early bacterial coinfections was similar between COVID-19 and influenza (18/78 [23%] vs 8/39 [21%]; odds ratio, 1.16; 95% CI, 0.42-3.45; p = 0.82). The frequency of early microbiological testing and antibiotic use was similar between the two groups. Within the overall COVID-19 group, early bacterial coinfections were associated with a statistically significant increase in 30-day all-cause mortality (21/68 [30.9%] vs 40/221 [18.1%]; hazard ratio, 1.84; 95% CI, 1.01-3.32). CONCLUSIONS AND RELEVANCE: Our data suggest similar rates of early bacterial coinfections in ICU patients with COVID-19 and influenza. In addition, early bacterial coinfections were significantly associated with an increased 30-day mortality in patients with COVID-19.