Diagnosis of bacterial infection in patients with COVID-19: is it a simple task? (literature review)

Diagnosing bacterial infection in patients with novel coronavirus infection (COVID-19) is not an easy task. Available data suggest that bacterial infection in patients with COVID-19 is rare and occurs in less than 10% of cases. At the same time, data of individual studies and systematic reviews indicate that more than 70% of patients with COVID-19 receive mainly empirical antimicrobial therapy with broad-spectrum antibiotics often before the diagnosis of COVID-19 has been verified. Therefore, this widespread empirical use of antibiotics is not supported by data on the need for their use. The article discusses the literature data on the significance of commonly accepted methods for diagnosing bacterial infection, with an emphasis on laboratory presence/absence tests. In everyday practice, the likelihood of bacterial coinfection in patients with COVID-19 is assessed by clinical presentation of the disease and the results of standard laboratory tests and imaging methods. However, when viral respiratory infection develops, this approach does not always allow to diagnose bacterial coinfection with sufficient significance. This issue may be handled by available modern test systems, the use of a combination of signs or additional laboratory criteria (for example, procalcitonin), and the analysis of the overall clinical presentation by the doctor using knowledge about patient risk groups. © 2023 Siberian State Medical University. All rights reserved.

Potential role of Pancreatic Stone Protein (PSP) as early marker of bacterial infection in COVID-19 patients

Background: Sepsis is a life-threatening condition that needs immediate diagnosis and treatment to maximize the chances of survival. Bacterial superinfection is a severe and frequent complication among COVID-19 patients and its diagnosis is challenging. Previous reports suggested that Pancreatic Stone Protein (PSP) may be a predictive biomarker for sepsis in critically ill patients. We report a case series of three COVID- 19 patients admitted to our intensive care unit (ICU) with risk of sepsis. Method(s): We daily monitored PSP, procalcitonin (PCT), and C-reactive protein (CRP) levels in three COVID- 19 patients admitted to our ICU. Microbiological sampling and antibiotic treatment were performed according to the ward organization and in case of clinical suspects for infection. Positive cultures and antibiotic treatment were retrieved from clinical charts and patients were followed from ICU admission up to a maximum of 20 days. Result(s): Patient 1 (male, 55 years-old, overweight, no other comorbidity) was admitted to the ICU in treatment with Ceftriaxone then interrupted on day 7. On day 2 he was intubated and piperacillin/tazobactam was started on day 12 for suspected hospital acquired pneumonia. PSP levels markedly increased on day 10 with no significant changes in CRP and PCT levels. On day 13 a positive bronchospirate for Klebsiella pneumoniae was found. Similarly, patient 2 (male, 70 years-old, mild emphysema and diabetes) was admitted to ICU without antibiotic and with a PSP level of 287 ng/ml. His conditions rapidly worsened in severe septic shock requiring intubation. CRP markedly raised 48-72 hours after PSP with only mild increase of PCT. Patient 3 (male, 78 years-old, no comorbidities) was admitted to ICU with high levels of PSP and piperacillin/tazobactam therapy was started. After 48-72 hours CRP levels increased with no significant changes of PCT. A positive bronchospirate for Ps. aeruginosa was collected on day 3. Conclusion(s): Our findings suggest a potential role of PSP as early biomarker of sepsis in critically ill COVID-19 patients. Daily PSP monitoring may anticipate an appropriate treatment of COVID-19 patients with a septic complication in comparison with the actual laboratory markers. Further studies are needed to confirm our hypothesis.

Diagnosis of bacterial infection in patients with COVID-19: is it a simple task? (literature review)

Diagnosing bacterial infection in patients with novel coronavirus infection (COVID-19) is not an easy task. Available data suggest that bacterial infection in patients with COVID-19 is rare and occurs in less than 10% of cases. At the same time, data of individual studies and systematic reviews indicate that more than 70% of patients with COVID-19 receive mainly empirical antimicrobial therapy with broad-spectrum antibiotics often before the diagnosis of COVID-19 has been verified. Therefore, this widespread empirical use of antibiotics is not supported by data on the need for their use. The article discusses the literature data on the significance of commonly accepted methods for diagnosing bacterial infection, with an emphasis on laboratory presence / absence tests. In everyday practice, the likelihood of bacterial coinfection in patients with COVID-19 is assessed by clinical presentation of the disease and the results of standard laboratory tests and imaging methods. However, when viral respiratory infection develops, this approach does not always allow to diagnose bacterial coinfection with sufficient significance. This issue may be handled by available modern test systems, the use of a combination of signs or additional laboratory criteria (for example, procalcitonin), and the analysis of the overall clinical presentation by the doctor using knowledge about patient risk groups.

Development of warm autoimmune hemolytic anemia after initiation of Ruxolitinib in a patient with STAT1 gain-of-function mutation

Introduction: STAT1 gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis (CMC) and a broad spectrum of infectious, inflammatory, and vascular manifestations. The Janus Kinase inhibitor ruxolitinib has been used successfully for CMC and autoimmune phenomena. We describe a case of warm autoimmune hemolytic anemia (WAIHA) in a patient with STAT1 GOF disease after initiating ruxolitinib. Case report: A 36-year-old man with STAT1 c.850G>A (p.Glu284Lys) mutation presented with CMC as well as recurrent viral and bacterial infections, lymphadenopathy, enteritis, nodular regenerative hyperplasia (NRH) and splenomegaly. Immune workup confirmed a combined immunodeficiency with hypogammaglobulinemia and T-cell lymphopenia. Ruxolitinib was initiated at 5 mg twice daily (due to pre-existing thrombocytopenia) with up titration over 3 months to 20 mg twice daily. He improved with weight gain, increased energy, resolution of chronic anemia, and improved lymphadenopathy and splenomegaly on imaging. Serum CXCL9 only minimally decreased from 4660 pg/ml to 3990 pg/ml. Soon after reaching ruxolitinib 20 mg twice daily, he developed JC viremia, prompting dose reduction to 15 mg BID. Within two weeks, he developed a non-COVID upper respiratory tract infection followed by fatigue, shortness of breath with ambulation, and dark urine. Emergency evaluation revealed warm antibody positive hemolytic anemia with a hemoglobin of 5 g/dL, and worsened thrombocytopenia. He was treated with blood transfusions, pulse steroids, and high-dose IVIG with stabilization but continued hemolysis. Due to the JC viremia, there was concern to give rituximab with increased PML risk. Bone marrow showed trilineage hematopoiesis, a mild increase in megakaryocytes and RBC precursors, and a loss of B-cell progenitors with retention of mature B cells. His B and T lymphocyte numbers had increased since prior to ruxolitinib, with a predominance of Tfh1-cells (58.7% of total Tfh-cells). He was started on sirolimus with a slow taper of prednisone with continued stable hemoglobin and platelets, and resolution of hemolysis after 3 months. Conclusion(s): To our knowledge, this is the first case of a STAT1 GOF patient developing WAIHA while receiving ruxolitinib therapy. Treatment choices were complicated by the risks of PML. Sirolimus combined with ruxolitinib allowed wean of corticosteroid and subsequent resolution of hemolysis.Copyright © 2023 Elsevier Inc.

Characteristics and Clinical Implications of Anti-IFN-alpha cytokine antibodies in partial Recombinase Activating Gene Deficiency patients before and during the COVID-19 Pandemic

Introduction: With the onset of the COVID-19 pandemic, there was increased attention on anti- IFN-alpha autoantibodies and its correlation with severe clinical outcomes in a large group of patients. However, this correlation has not been extensively investigated in patients with partial Recombinase Activating Gene Deficiency (pRD) who are known to have increased prevalence of anti- IFN-alpha autoantibodies. Therefore, there is a need to assess the presence of anti- IFN-alpha antibodies in pRD patients before and after the COVID-19 pandemic and explore the relationship between anti- IFN-alpha antibody presence and clinical outcomes. Method(s): Sera was collected from the whole blood after informed consent and Enzyme-Linked Immunosorbent Assay was conducted to confirm the presence of IgG-specific anti- IFN-alpha autoantibodies. Positive samples were determined as OD values above 3 standard deviations of the healthy donor OD mean. Result(s): Our cohort included both adult (n = 13) and pediatric (n = 9) patients with variants in RAG1 and RAG2. Eleven patients (50%) out of the 22 showed elevated anti- IFN-alpha autoantibodies levels. Five patients (23%) were defined as low positive for anti- IFN-alpha autoantibodies, and 6 patients had no autoantibody titers. Of the 22 patients, 16 were symptomatic with infectious and non-infectious complications including recurrent viral and/or bacterial infections, autoimmune cytopenias, and lymphoproliferation. Ten (63%) of the symptomatic patients demonstrated high anti-IFN-alpha autoantibodies titers. Of the 11 patients with no or low neutralizing anti- IFN-alpha autoantibodies levels, 5 were asymptomatic. In temporal comparison, 16 samples were collected pre-COVID-19 pandemic;8 samples were collected during the pandemic, 2 of which belonged to patients with samples collected before and during the pandemic. In the pre-pandemic cohort, 66% had anti- IFN-alpha autoantibodies. Conversely, during the COVID-19 pandemic, 89% had anti- IFN-alpha autoantibodies. Of note, one patient who had neutralizing anti- IFN-alpha autoantibodies remained positive both before and during the pandemic despite HSCT. Patient also had a SARS-CoV-2 infection in summer of 2022 with a mild clinical course. Conclusions & Next Steps: We observed persistence of anti-IFN-alpha autoantibodies in our cohort post-pandemic and even post-HSCT. It is unclear whether the presence of anti-cytokine antibodies are risk factor for severe COVID-19.Copyright © 2023 Elsevier Inc.

Mortality in adults with COVID-19: experience of the Intensive Care Unit of a Third Level Hospital in Paraguay

Introduction: Several factors may influence mortality in patients hospitalized with COVID-19. Objective: This research aimed to determine mortality and associated factors in adults with COVID-19 hospitalized in the intensive care unit of a Third Level Hospital in Paraguay. Methodology: Observational, descriptive of crossassociation, cross-sectional, and retrospective study. We included medical records of adult patients, of both sexes, who had a confirmed diagnosis (by antigen and/or PCR test) of SARS-CoV-2 infection and who were hospitalized in the intensive care unit of a Third Level General Hospital in Paraguay. Results: We included 116 patients, 54% of whom were male. The mean age was 57 ± 12.9 years. Of participants, 51% had hypertension and 29% diabetes mellitus. Mechanical ventilation was required in 85% of the patients. Of ventilated patients, 75% had a fatal outcome. A statistically significant association was found between the presence of bacterial infections and hemodialysis requirement and fatal outcome (p=0.0074 and p=0.00011, respectively). The mean age of the deceased patients was 59.5 years, while the group of patients discharged from the intensive care unit had a mean age of 54.2 years. The difference between these ages in relation to death was significant, with a p<0.05. Discussion: Overall mortality due to COVID-19 was more than 6 per 10 patients, being higher in those patients with ventilation. Those patients who presented bacterial superinfection or required hemodialysis during hospitalization had a worse outcome compared to patients who did not present this type of complications. © 2023, Faculty of Medical Sciences, Santa Rosa del Aguaray Branch, National University of Asuncion. All rights reserved.

The Effect of FOXP3+Regulatory T Cells on Infectious and Inflammatory Diseases

CD4+CD25+FOXP3+regulatory T cells (Tregs) contribute to the maintenance of immune homeostasis and tolerance in the body. The expression levels and functional stability of FOXP3 control the function and plasticity of Tregs. Tregs critically impact infectious diseases, especially by regulating the threshold of immune responses to pathogenic microorganisms. The functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth, which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.Copyright © 2021. All rights reserved.

Secondary Infections in Patients with Extremely Severe COVID-19 During ECMO Therapy.

Up to 70% of patients hospitalized for COVID-19 need respiratory support, up to 10% need high-flow oxygen therapy, non-invasive and invasive ventilation. However, standard methods of respiratory support are ineffective in 0.4-0.5% of patients. In case of potentially reversible critical refractory respiratory failure that patients may require ECMO. Management of patients with extremely severe COVID-19 associates with numerous clinical challenges, including critical illness, multiple organ dysfunction, blood coagulation disorders, requiring prolonged ICU stay and care, use of multiple pharmacotherapies including immunosuppressive drugs. Pharmacological suppression of immunity is associated with a significant increase in the risk of secondary bacterial and fungal infections. Currently, data on epidemiology of secondary infections in patients with COVID-19 undergoing ECMO is limited. Aim. To study the prevalence and etiology of secondary infections associated with positive blood cultures in patients with extremely severe COVID-19 requiring ECMO. Materials and methods. A single-center retrospective non-interventional epidemiological study including 125 patients with extremely severe COVID-19 treated with ECMO in April 2020 to December 2021. Results. Out of 700 blood culture tests performed in 125 patients during the study, 250 tests were positive confirming bacteremia/fungemia. Isolated pathogens varied depending on the duration of ECMO: gram-positive bacteria (primarily coagulase-negative staphylococci) dominated from the initiation of ECMO support;increased duration of ECMO associated with an increasing the proportion of pathogens common in ICU (Klebsiella pneumoniae and/or Acinetobacter baumannii with extensively drug resistant and pan-drug resistant phenotypes, and vancomycin-resistant Enterococcus faecium). When ECMO lasted more than 7-14 days, opportunistic pathogens (Candida species, Stenotrophomonas maltophilia, Providencia stuartii, non-diphtheria corynebacteria, Burkholderia species and others) prevailed as etiological agents. Conclusion. Longer duration of ECMO resulted in increasing the rates of infectious complications. In patients undergoing ECMO for more than 14 days, the microbiological landscape becomes extremely diverse, which hampers choosing an empirical antimicrobial therapy. Since potential pathogens causing secondary infections in patients during ECMO are difficult to predict, rapid identification of rare opportunistic pathogens and their sensitivity profile, followed by targeted administration of antimicrobials, seems most beneficial.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

Investigation on Bacterial Infection, IL-17 and Some Biomarkers with Related to Covid-19 Patients' Outcome

Since it has been a global pandemic for the past three years, the coronavirus disease 2019, or COVID-19, has spread to all parts of the world. It first appears as pneumonia, which can progress to severe respiratory failure and has as its major hallmark a systemic inflammatory immune response brought on by an increased production of cytokines that causes a cytokine storm. Bacterial co-infections raise the risk of morbidity and mortality in COVID-19 patients. The current study was conducted to investigate the impact of bacterial co-infection, IL-17, D-dimer, fer-ritin and CRP in Covid-19 pneumonia outcome. Four mL of blood samples were collected from 120 patients attending to AL-Amal hospital and Al-Sader medical city, Najaf/Iraq, from July 2021-January 2022;1.5 mL of blood kept in tube containing 3.2% sodium citrate to estimation D-dimer by Minivides and 2.5 mL in plane tube to separate serum that used to detect IL-17, ferritin and CRP. Patient divided into Critical 33 (27.5%), sever 42 (35%) and Mild/Moderate (M/M) 45 (37.5%), In addition to 60 apparently healthy subjects as controls group. The result indicated that a significant increase (p < 0.05) in mean serum level of IL-17 in patients compare to healthy group, and the mean critical and server cases higher than M/M cases (101.79, 74.83, and 27.65) pg/mL. The results founded that most bacterial co-infection within critical and sever cases with 22(44%) and 26 (52%) respectively while M/M cases were 2(4%) only. Finally the results founded an elevated number of leukocyte, higher neutrophil and higher infection-related biomarkers (S. ferritin, D-dimer, and CRP) especially in critical cases (18.5+/- 2.62, 88.42+/-12.6, 738.68+/-154.41, 5.76+/-2.75, and 122.85+/-35.39) respectively. In conclusion the level of IL-17, ferritin and D-dimer highly increased in Covid patients that correlated with severity of Covid pneumonia so by this biomarkers can recognized between two types of patients. Secondary bacterial infection increased progressive state of patients.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study.

INTRODUCTION: The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study. METHODS: The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up. RESULTS: Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age. CONCLUSION: We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up. TRIAL REGISTRATION: BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832. PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

Placing Antimicrobial Resistance in the Context of Competing Public Health Priorities in Sub-Saharan Africa, a Perspective from Malawi

Antimicrobial resistance is a major threat to human health that is predicted to impact most heavily on sub-Saharan Africa, however there is a lack of clinical outcome data from drug-resistant infections in this setting. There are reasons to expect the COVID-19 pandemic to have both positive and negative impacts on AMR in Africa. We have recruited a series of prospective longitudinal cohorts from Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi and the surrounding communities in the Southern Region of Malawi. The data from these cohorts has been used to describe the aetiology of febrile illness, the burden of antimicrobial resistance in this setting and the distribution of extended spectrum beta-lactamase producing bacteria in humans, animals and the environment. Amongst a cohort of patients presenting to QECH unwell with febrile illness, 67% were living with human immunodeficiency virus (HIV). We identified a diagnosis in 145 of 225 (64%) participants, most commonly tuberculosis (TB;34%) followed by invasive bacterial infections (17%), arboviral infections (13%), and malaria (9%). In a second cohort with drug resistant infection, resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1.44, 95% CI 1.02-2.04), longer hospital stays (1.5 days, 1.0-2.0) and decreased probability of discharge alive (HR 0.31, 0.22-0.45). In the community cohorts, a paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites and ESBL-Enterobacterales were isolated from 41.8% of human stool, 29.8% of animal stool and 66.2% of river water samples and was associated with the wet season, living in urban areas, advanced age and in household-animal interactions. Life threatening febrile illness is common in Blantyre however, diagnostics are few, however the COVID-19 pandemic has led to rapid expansion of diagnostic capacity. We are, however frequently treating the wrong bugs with ceftriaxone, further there was significant expansion of azithromycin demand and usage during the pandemic. Current management of sepsis has not been optimised and ceftriaxone use is promoting carriage of ESBL bacteria out of the hospital and ESBL E. coli and K. pneumoniae are ubiquitous in the community, where environmental hygiene infrastructure and community antimicrobial stewardship are critically lacking.Copyright © 2023

Experience of Baricitinib in a Real-World Population with Efficacy and Side Effects: A South London Regional Analysis

Background/Aims Baricitinib is the most common Janus Kinase inhibitor (JAKi) used in the treatment of rheumatological conditions. Whilst randomised controlled trials have demonstrated the efficacy and safety profile of baricitinib, real-world data on the experience of JAKi use in clinical practice is lacking. The aim of this analysis was to evaluate baricitinib use in a real-world patient population in South London. Methods We looked at two rheumatology departments in South London (St George's Hospital;a tertiary teaching centre and Kingston Hospital;a district general hospital). All patients prescribed baricitinib between January 2017 to June 2022 were included. A retrospective assessment of electronic patient notes was performed to evaluate disease activity (determined by DAS-28 scores at baseline, 3-6 months and presently);adverse effects including side effects, rates of and reasons for discontinuation;and prescribing practice, including previous use of other biological disease modifying anti-rheumatic drugs (bDMARDs). Baseline data including age, gender, co-morbidities and rheumatological diagnoses were also included. Results 233 patients were included in this evaluation, with seropositive rheumatoid arthritis being the most common diagnosis (58%) and with a significant female population (87%). Baricitinib improved average DAS-28 scores from 5.75 (range 3.57-8.3) at baseline to 3.23 (range 0.28-7.49) at 3-6 months post-baricitinib, with the most recent DAS-28 score of 2.90 (range 0.56-6.77). Rates of adverse effects were low as shown in Table 1. Baricitinib was discontinued in 60/233 patients, with average duration to discontinuation of 9.5 months. The most common reasons for discontinuation were: ineffective disease control (28/60), recurrent bacterial infection (5/60), deranged liver function (3/60) and venous thromboembolism (2/60). Eight patients died whilst taking baricitinib. Where documented, the causes of death were Covid-19 (4/8) and malignancy (1/8). 110 out of 233 patients had received other bDMARDs before starting baricitinib. Documented reasons for baricitinib choice over tumour necrosis factor inhibitors (TNFi) included: previous lack of response to TNFi (89/233), contra-indication to TNFi (11/233) and preference of oral route (10/ 233). Conclusion Our real-world study of JAKi use shows that baricitinib is efficacious in the treatment of rheumatological conditions. Moreover, baricitinib is well tolerated, with low rates of adverse effects and subsequent discontinuation. (Table Presented).

Antibiotic Stewardship Strategies to Limit Inappropriate Antibiotic Use and Reduce Multi-Drug Resistant Pathogens during Covid-19 Pandemic

Antibiotics have been extensively used in COVID-19 patients without a clear indication. COVID-19 pneumonia is associated with a mortality up to 20% varying by country with the number of global deaths over 5 million. Antibiotics have been extensively used in COVID-19 patients in intensive care units (ICUs) without a clear indication. According to a previous study, the frequency of bacterial pneumonia in COVID-19 patients was 6.9%, while >70% of patients received antibiotics. This is likely due to the clinical findings of COVID-19 pneumonia overlapping with those of bacterial pneumonia and the lack of reliable indicators of bacterial infection. Strategies that distinguish bacterial from viral pneumonia are desirable. In this session, I will discuss the impact of inappropriate antibiotic use during pandemic as well as the strategy to limit inappropriate antibiotic use as well as multi-drug resistant pathogen during COVID-19 pandemic among COVID-19 and non-COVID-19 populations.Copyright © 2023

Scientific debrief: cirrhosis

Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.

Explaining COVID-19-Related Concepts in Singapore: A Minimal Language Approach

After COVID-19 reportedly emerged in Wuhan, China, in late 2019 and spread across the world, governments everywhere were quick to impose mandatory preventive measures, such as safe distancing. However, many people ignored such measures, in some cases breaking the law. While some did it willfully, others probably did it out of ignorance;ignorant of what certain instructional keywords mean and/or of the gravity of the situation. This problem has to do with public communication and is especially acute in a country like Singapore, where many people (the locally-called ‘aunties' and ‘uncles') have not gone through much formal education and lack the intellectual means to understand technical ideas. In this paper, a method of making important, technical ideas accessible to the general public using a ‘minimal language' approach is showcased. However, it is argued that ‘minimal language' explanations need to be culture-specific to a certain extent, as they depend on the needs of the local community. This paper uses ‘Minimal English' (which can be fairly accurately translated to other ‘minimal languages' such as ‘Minimal Chinese') to explain a virus to the Singapore community. The ‘scripts' or explanations are functional in nature and include aspects of meaning and implications in the local context. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Bacterial Infectious Diseases in the Covid-19 Era

The outbreak of SARS-CoV-2 in December 2019 in China quickly spread to the rest of the world. By March 2020, the World Health Organization declared the COVID-19 pandemic, and several mitigation strategies were implemented worldwide, highlighting social distancing, quarantine and the use of face masks. Since then, many studies have reported the impact of these interventions on the occurrence of other infectious diseases, especially bacterial infectious diseases disseminated through airborne. Invasive infections with respiratory bacterial pathogens, such as Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Bordetella pertussis, Chlamydia pneumoniae and Mycoplasma pneumoniae have had a marked decline in several countries of the world. Low- and middle-income (LMIC) and high-income countries (HIC) were at different seasons of the year when COVID-19 started and interventions were implemented, but long-lasting consequences of seasonal differences are yet to be elucidated. In this session, we aim to describe the impact of COVID-19 and related intervention strategies in bacterial infectious diseases between LMIC and HIC;determine whether and how the onset of COVID-19 pandemic has changed the broader scenario of infectious diseases;and envision future and emerging infectious diseases in the post-pandemic world.Copyright © 2023

Fungal And Bacterial Sinusitis In Covid-19 Era, A Comprehensive Narrative Review

Generally, infection with respiratory tract viruses leads to secondary infections in which bacteria and fungi play an important role. One of the important secondary infections related to Covid-19 is sinusitis. Due to the complications of fungal and bacterial sinusitis, it is important to know the most substantive factors that predispose people to these diseases. Covid-19 treatment solutions and excessive use of steroids and immune system of infected people are effective in causing invasive fungal sinusitis related to COVID-19. Findings show that uncontrolled blood sugar levels are also effective in sinusitis. Corona virus affects immune system. The severe inflammatory response causes an increase in cytokines and a decrease in specific immune system function in these patients and causes a prolongation of disease period and sinus tissue inflammation. Clinically, fungal and bacterial sinusitis are very similar. In this article, the aspects of corona disease and subsequent bacterial and fungal sinusitis were discussed. According to available data, a high percentage of patients with SARS-CoV-2 infection have fungal sinusitis after disease. Bacterial sinusitis is generally not as common as acute viral rhinosinusitis and affects more women than men. By attacking and causing tissue inflammation and then using corticosteroids to reduce immune response, Covid-19 provides conditions for opportunistic fungi. Often items like allergies or an acute illness like covid-19 can affect immune system. Oral corticosteroids can cause serious side effects if used long-term, so their use is recommended only when necessary and to treat severe symptoms. [ FROM AUTHOR] Copyright of Journal of Pharmaceutical Negative Results is the property of ResearchTrentz and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)