Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care.

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

Critically ill children with SARS-COV-2 Omicron infection at a national children medical center, Guangdong, China.

BACKGROUND: SARS-CoV-2 infection is described as asymptomatic, mild, or moderate disease in most children. SARS-CoV-2 infection related death in children and adolescents is rare according to the current reports. COVID-19 cases increased significantly in China during the omicron surge, clinical data regarding pediatric critical patients infected with the omicron variant is limited. In this study, we aim to provide an overview of the clinical characteristics and outcomes of critically ill children admitted to a national children's medical center in Guangdong Province, China, during the outbreak of the omicron variant infection. METHODS: We conducted a retrospective study from November 25, 2022, to February 8, 2023, which included 63 critically ill children, under the age of 18, diagnosed with SARS-CoV-2 infection. The patients were referred from medical institutions of Guangdong province. The medical records of these patients were analyzed and summarized. RESULTS: The median age of patients was 2 years (Interquartile Range, IQR: 1.0-8.0), sex-ratio (male/female) was 1.52. 12 (19%) patients (age ≥ 3 years) were vaccinated. The median length of hospital stay was 14 days (IQR: 6.5-23) in 63 cases, and duration of fever was 5 days (IQR: 3-8.5), pediatric intensive care unit (PICU) stay was 8 days (IQR 4.0-14.0) in 57 cases. 30 (48%) cases had clear contact history with family members who were infected with SARS-CoV-2. Three children who tested positive for SARS-CoV-2 infection did not show any abnormalities on chest imaging examination. Out of the total patients, 33 (52%) had a bacterial co-infection, with Staphylococcus aureus being the most commonly detected bacterial pathogen. Our cohort exhibited respiratory and nervous system involvement as the primary features. Furthermore, fifty (79%) patients required mechanical ventilation, with a median duration of 7 days (IQR 3.75-13.0). Among these patients, 35 (56%) developed respiratory failure, 16 (25%) patients experienced a deteriorating progression of symptoms and ultimately succumbed to the illness, septic shock was the most common condition among these patients (15 cases), followed by multiple organ failure in 12 cases, and encephalopathy identified in 7 cases. CONCLUSION: We present a case series of critically ill children infected with the SARS-CoV-2 omicron variant. While there is evidence suggesting that Omicron may cause less severe symptoms, it is important to continue striving for measures that can minimize the pathogenic impact of SARS-CoV-2 infection in children.

Bacterial co-infection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Understanding the proportion of patients with COVID-19 who have respiratory bacterial co-infections and the responsible pathogens is important for managing COVID-19 effectively while ensuring responsible antibiotic use. OBJECTIVE: To estimate the frequency of bacterial co-infection in COVID-19 hospitalized patients and of antibiotic prescribing during the early pandemic period and to appraise the use of antibiotic stewardship criteria. METHODS: Systematic review and meta-analysis was performed using major databases up to May 5, 2021. We included studies that reported proportion/prevalence of bacterial co-infection in hospitalized COVID-19 patients and use of antibiotics. Where available, data on duration and type of antibiotics, adverse events, and any information about antibiotic stewardship policies were also collected. RESULTS: We retrieved 6,798 studies and included 85 studies with data from more than 30,000 patients. The overall prevalence of bacterial co-infection was 11% (95% CI 8% to 16%; 70 studies). When only confirmed bacterial co-infections were included the prevalence was 4% (95% CI 3% to 6%; 20 studies). Overall antibiotic use was 60% (95% CI 52% to 68%; 52 studies). Empirical antibiotic use rate was 62% (95% CI 55% to 69%; 11 studies). Few studies described criteria for stopping antibiotics. CONCLUSION: There is currently insufficient evidence to support widespread empirical use of antibiotics in most hospitalised patients with COVID-19, as the overall proportion of bacterial co-infection is low. Furthermore, as the use of antibiotics during the study period appears to have been largely empirical, clinical guidelines to promote and support more targeted administration of antibiotics in patients admitted to hospital with COVID-19 are required.

From Co-Infections to Autoimmune Disease via Hyperactivated Innate Immunity: COVID-19 Autoimmune Coagulopathies, Autoimmune Myocarditis and Multisystem Inflammatory Syndrome in Children.

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two of many measures of increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis and multisystem inflammatory syndrome in children (MIS-C). This paper integrates currently disparate measures of innate hyperactivation in severe COVID-19 and its autoimmune complications, and relates these to SARS-CoV-2 activation of innate immunity. Aggregated data include activation of Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) receptors, NOD leucine-rich repeat and pyrin-domain-containing receptors (NLRPs), retinoic acid-inducible gene I (RIG-I) and melanoma-differentiation-associated gene 5 (MDA-5). SARS-CoV-2 mainly activates the virus-associated innate receptors TLR3, TLR7, TLR8, NLRP3, RIG-1 and MDA-5. Severe COVID-19, however, is characterized by additional activation of TLR1, TLR2, TLR4, TLR5, TLR6, NOD1 and NOD2, which are primarily responsive to bacterial antigens. The innate activation patterns in autoimmune coagulopathies, myocarditis and Kawasaki disease, or MIS-C, mimic those of severe COVID-19 rather than SARS-CoV-2 alone suggesting that autoimmunity follows combined SARS-CoV-2-bacterial infections. Viral and bacterial receptors are known to synergize to produce the increased inflammation required to support autoimmune disease pathology. Additional studies demonstrate that anti-bacterial antibodies are also required to account for known autoantigen targets in COVID-19 autoimmune complications.

Evaluation of bacterial agents isolated from endotracheal aspirate cultures of Covid-19 general intensive care patients and their antibiotic resistance profiles compared to pre-pandemic conditions.

BACKGROUND: Early reports have shown that critically ill patients infected with SARS-CoV-2 have a high prevalence of nosocomial pneumonia, particularly ventilator-associated pneumonia (VAP). METHOD: In the present study, we determined the bacterial agents isolated from endotracheal aspirate (ETA) cultures of Covid-19 general intensive care patients and evaluated the antibiotic resistance profiles of common bacterial agents compared to the pre-pandemic period. RESULTS: While a total of 119 significant growths with polymicrobial growths were detected in the ETA cultures of 73 (7.5%) of 971 patients hospitalized in the intensive care unit before the pandemic, 87 significant growths were detected in the ETA cultures of 67 (11.1%) of 602 patients hospitalized in the Covid-19 intensive care unit (ICU) after the pandemic. While 61 (83.6%) of patients in the ICU died before the pandemic, 63 (94.0%) of patients in the Covid-19 ICU died after the pandemic. In terms of age, gender, and mortality, there was no significant difference between the two ICUs (p > 0.05). Before the pandemic, the mean length of stay in the ICU was 33.59 ± 32.89 days, and after the pandemic, it was 13.49 ± 8.03 days. This was a statistically significant difference (p < 0.05). Acinetobacter baumannii (28.5%), Klebsiella pneumoniae (22.6%), Pseudomonas aeruginosa (15.9%), Staphylococcus aureus (6.7%), Escherichia coli (7.5%), Candida spp. (5.0%) were the most prevalent causal microorganisms discovered in pre-pandemic ICU ETA samples, whereas A. baumannii (54.0%), K. pneumoniae (10.3%), P. aeruginosa (6.8%), E. faecium (8%), and Candida spp.(13.7%) were the most common causative microorganisms detected in Covid-19 ICU ETA samples. Except for tigecycline, antibiotic resistance rates in A. baumannii strains increased following the pandemic. Only tobramycin showed a significant difference in the increase of resistance among these antibiotics (p = 0.037). The rate of tigecycline resistance, on the other hand, was 17.6% before the pandemic and 2.2% afterward (p < 0.05). After the pandemic, increased resistance of K. pneumoniae strains to colistin, meropenem, ertapenem, amoxicillin-clavulanic acid, piperacillin-tazobactam, ciprofloxacin, tigecycline, and cefepime antibiotics was observed. However, these increases were not statistically significant. Except for imipenem, antibiotic resistance rates in P. aeruginosa strains increased following the pandemic. The increase in resistance of ceftazidime and levofloxacin was statistically significant (p < 0.05). CONCLUSION: As a result, the Covid-19 pandemic requires intensive care follow-ups at an earlier age and with a more mortal course. Although the length of stay in the intensive care unit has been shortened, it is observed that this situation is observed due to early mortality. In P. aeruginosa strains, a significant difference was detected in the resistance increase of the ceftazidime and levofloxacin (p < 0.05) and with the exception of tigecycline, antibiotic resistance rates in A. baumannii strains increased following the pandemic. Only tobramycin showed a significant difference in the increase of resistance among these antibiotics (p = 0.037). Secondary infections in patients create more difficult treatment processes due to both Covid-19 and increasing antibiotic resistance today.

Predictive model for bacterial co-infection in patients hospitalized for COVID-19: a multicenter observational cohort study.

OBJECTIVE: The aim of our study was to build a predictive model able to stratify the risk of bacterial co-infection at hospitalization in patients with COVID-19. METHODS: Multicenter observational study of adult patients hospitalized from February to December 2020 with confirmed COVID-19 diagnosis. Endpoint was microbiologically documented bacterial co-infection diagnosed within 72 h from hospitalization. The cohort was randomly split into derivation and validation cohort. To investigate risk factors for co-infection univariable and multivariable logistic regression analyses were performed. Predictive risk score was obtained assigning a point value corresponding to ß-coefficients to the variables in the multivariable model. ROC analysis in the validation cohort was used to estimate prediction accuracy. RESULTS: Overall, 1733 patients were analyzed: 61.4% males, median age 69 years (IQR 57-80), median Charlson 3 (IQR 2-6). Co-infection was diagnosed in 110 (6.3%) patients. Empirical antibiotics were started in 64.2 and 59.5% of patients with and without co-infection (p = 0.35). At multivariable analysis in the derivation cohort: WBC ≥ 7.7/mm3, PCT ≥ 0.2 ng/mL, and Charlson index ≥ 5 were risk factors for bacterial co-infection. A point was assigned to each variable obtaining a predictive score ranging from 0 to 5. In the validation cohort, ROC analysis showed AUC of 0.83 (95%CI 0.75-0.90). The optimal cut-point was ≥2 with sensitivity 70.0%, specificity 75.9%, positive predictive value 16.0% and negative predictive value 97.5%. According to individual risk score, patients were classified at low (point 0), intermediate (point 1), and high risk (point ≥ 2). CURB-65 ≥ 2 was further proposed to identify patients at intermediate risk who would benefit from early antibiotic coverage. CONCLUSIONS: Our score may be useful in stratifying bacterial co-infection risk in COVID-19 hospitalized patients, optimizing diagnostic testing and antibiotic use.

Differentiating influenza from COVID-19 in patients presenting with suspected sepsis.

There is a need for a quick assessment of severely ill patients presenting to the hospital. The objectives of this study were to identify clinical, laboratory and imaging parameters that could differentiate between influenza and COVID-19 and to assess the frequency and impact of early bacterial co-infection. A prospective observational cohort study was performed between February 2019 and April 2020. A retrospective cohort was studied early in the COVID-19 pandemic. Patients suspected of sepsis with PCR-confirmed influenza or SARS-CoV-2 were included. A multivariable logistic regression model was built to differentiate COVID-19 from influenza. In total, 103 patients tested positive for influenza and 110 patients for SARS-CoV-2, respectively. Hypertension (OR 6.550), both unilateral (OR 4.764) and bilateral (OR 7.916), chest X-ray abnormalities, lower temperature (OR 0.535), lower absolute leukocyte count (OR 0.857), lower AST levels (OR 0.946), higher LDH (OR 1.008), higher ALT (OR 1.044) and higher ferritin (OR 1.001) were predictive of COVID-19. Early bacterial co-infection was more frequent in patients with influenza (10.7% vs. 2.7%). Empiric antibiotic usage was high (76.7% vs. 84.5%). Several factors determined at presentation to the hospital can differentiate between influenza and COVID-19. In the future, this could help in triage, diagnosis and early management. Clinicaltrial.gov Identifier: NCT03841162.

Informing antimicrobial management in the context of COVID-19: understanding the longitudinal dynamics of C-reactive protein and procalcitonin.

BACKGROUND: To characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making. METHODS: Longitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital. RESULTS: CRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p < 0.0001) and in those who died (day 8: 226 vs 152 mg/L, p < 0.0001) but only after day 7 of COVID-related symptom onset. Failure for CRP to reduce in the first week of hospital admission was associated with significantly higher odds of death. PCT concentrations were higher in patients with COVID-19 and positive microbiology or in those who died, although these differences were not statistically significant. CONCLUSIONS: Both the absolute CRP concentration and the trajectory during the first week of hospital admission are important factors predicting microbiology culture positivity and outcome in patients hospitalised with COVID-19. Further work is needed to describe the role of PCT for co-infection. Understanding relationships of these biomarkers can support development of risk models and inform optimal antimicrobial strategies.

Bacterial coinfections and secondary infections in COVID-19 patients from a tertiary care hospital of northern India: Time to adhere to culture-based practices.

OBJECTIVE: Bacterial co-pathogens are common in various viral respiratory tract infections, leading to increased disease severity and mortality. Still, they are understudied during large outbreaks and pandemics. This study was conducted to highlight the overall burden of these infections in COVID-19 patients admitted to our tertiary care hospital, along with their antibiotic susceptibility patterns. MATERIAL AND METHODS: During the six-month study period, clinical samples (blood samples, respiratory samples, and sterile body fluids, including cerebrospinal fluid [CSF]) of COVID-19 patients with suspected bacterial coinfections (at presentation) or secondary infections (after 48 hours of hospitalization) were received and processed for the same. RESULTS: Clinical samples of 814 COVID-19 patients were received for bacterial culture and susceptibility. Out of the total patient sample, 75% had already received empirical antibiotics before the samples were sent for analysis. Overall, 17.9% of cultures were positive for bacterial infections. Out of the total patients with bacterial infection, 74% (108/146) of patients had secondary bacterial infections (after 48 hours of hospitalization) and 26% (38/146) had bacterial coinfections (at the time of admission). Out of the 143 total isolates obtained, the majority (86%) were gram-negative organisms, of which Acinetobacter species was the commonest organism (35.6%), followed by Klebsiella pneumoniae (18.1%). The majority (50.7%) of the pathogenic organisms reported were multidrug resistant. CONCLUSION: The overall rate of secondary bacterial infections (SBIs) in our study was lower (7.9%) than reported by other studies. A rational approach would be to adhere to the practice of initiating culture-based guidance for antibiotics and to restrict unnecessary empirical antimicrobial therapy.

Bacterial co-infections with SARS-CoV-2.

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.

Sialic acid-dependent interaction of group B streptococci with influenza virus-infected cells reveals a novel adherence and invasion mechanism.

Group B streptococci (GBS) contain a capsular polysaccharide with side chains terminating in α2,3-linked sialic acids. Because of this linkage type, the sialic acids of GBS are recognised by lectins of immune cells. This interaction results in a dampening of the host immune response and thus promotes immune evasion. As several influenza A viruses (IAV) use α2,3-linked sialic acid as a receptor determinant for binding to host cells, we analysed whether GBS and influenza viruses can interact with each other and how this interaction affects viral replication and bacterial adherence to and invasion of host cells. A co-sedimentation assay revealed that viruses with a preference for α2,3-linked sialic acids bind to GBS in a sialic acid-dependent manner. There is, however, a large variation in the efficiency of binding among avian influenza viruses of different subtypes as shown by a hemagglutination-inhibition assay. A delay in the growth curve of IAV indicated that GBS has an inhibitory effect on virus replication. On the other hand, both the adherence and invasion efficiency of GBS were enhanced when the cells were pre-infected by IAV with appropriate receptor specificity. Our results suggest that GBS infection may result in a more severe disease when patients are co-infected by influenza viruses. This co-infection mechanism may have relevance also to other human diseases, as there are more bacterial pathogens with α2,3-linked sialic acids and human viruses binding to this linkage type.

Community-acquired bacterial co-infection predicts severity and mortality in influenza-associated pneumonia admitted patients.

BACKGROUND: Influenza is frequently complicated by bacterial co-infection, causing additional hospitalization and mortality. We determined the incidence, risk factors and outcomes of patients with influenza-associated community-acquired bacterial co-infection. METHOD: This was a retrospective, observational study. Influenza was diagnosed using the polymerase chain reaction. Co-infection had to be confirmed using standard bacteriological tests. The primary endpoint was presence of community-acquired co-infection, and the secondary endpoint was in-hospital mortality. RESULTS: During the 8 influenza seasons from 2010 to 2018, of the 209 influenza-associated pneumonia admitted patients, 41 (19.6%) were identified with community-acquired bacterial co-infections and Staphylococcus aureus was the predominant strain. Compared with patients without co-infection, patients with co-infection had similar demographic characteristics and co-morbidities, obtained a higher APACHE II score and a higher SOFA score, and had higher ratio of sepsis shock, invasive mechanical ventilation, and ICU requirement. In-hospital mortality independently associated with bacterial co-infection (adjusted hazard ratio (aHR) 2.619; 95%CI 1.252-5.480; p = 0.011); in subgroup S. aureus (aHR 6.267; 95%CI 2.679-14.662; p < 0.001) and other pathogens (aHR 2.964; 95%CI 1.160-7.577; p = 0.023); and in subgroup positive findings in bloodstream (aHR 7.420; 95%CI 2.712-20.302; p < 0.001) and positive findings in other site (aHR 3.427; 95%CI 1.514-7.757; p = 0.003). CONCLUSION: Community-acquired bacterial co-infection was frequent in influenza-associated pneumonia, without risk factor identified yet. Bacterial co-infection was likely to predict severity, and was an independent risk factor for in-hospital mortality. Co-infection of Staphylococcus aureus with influenza was identified as a lethal synergism, and should be targeted when developing clinical antibiotic strategies.

Bacterial Co-infections in HIV/AIDS-positive Subjects: A Systematic Review and Meta-analysis.

BACKGROUND: Bacterial infections are the most common complications in people with HIV/AIDS. There has been no previous report on the prevalence of bacterial co-infections in Iranian HIV/AIDS-positive subjects. AIM: To evaluate the frequency of bacterial infections in hospitalized HIV/AIDS-infected patients in Iran. MATERIALS AND METHODS: Based on PRISMA guidelines, a computerized search in related data banks using relevant keywords was performed in both Persian and English languages for articles that were published until March 10, 2017. A total of 1118 original articles were systematically reviewed to identify eligible studies on the prevalence of bacterial co-infections in HIV/AIDS-infected patients from Iran. After screening for inclusion and exclusion criteria, we extracted data from 28 eligible articles for the meta-analysis. RESULTS: The overall bacterial infection rate among Iranian HIV/AIDS-positive individuals was estimated to be 48.6%. Gastrointestinal disorders (59.5%) were the most frequent bacterial infections in this group of patients followed by bacterial lymphadenopathy (38.9%), TB infection (38.2%), bacterial pneumonia (31.2%), brucellosis (26.3%), skin infections (13.3%) and sexually transmitted infections (9.7%). The prevalence of other bacterial infections including endocarditis, sepsis and Staphylococcus aureus (S. aureus) were 10%, 9.1%, and 6.9%, respectively. CONCLUSION: The prevalence of a wide spectrum of bacterial co-infections, especially endemic infections, in Iranian HIV/AIDS-infected patients, is alarming and calls for urgent need to improve the currently applied diagnostic and preventive methods. In addition, timely treatment of these infections is pivotal to decrease the morbidity and mortality rates in HIV/AIDS-infected patients.

Paramyxovirus Infection: Mortality and Morbidity in a Pediatric Intensive Care Unit.

OBJECTIVES: We investigated mortality and morbidity of patients admitted to a pediatric intensive care unit (PICU) with paramyxovirus infection. METHODS: A retrospective study between October 2002 and March 2015 of children with a laboratory-confirmed paramyxovirus infection was included. RESULTS: In all, 98 (5%) PICU admissions were tested positive to have paramyxovirus infection (respiratory syncytial virus = 66, parainfluenza = 27 and metapneumovirus = 5). The majority of admissions were young patients (median age 1.05 years). Bacteremia and bacterial isolation in any site were present in 10% and 28%, respectively; 41% were mechanically ventilated, and 20% received inotropes. The three respiratory viruses caused similar mortality and morbidity in the PICU. Fatality (seven patients) was associated with malignancy, positive bacterial culture in blood, the use of mechanical ventilation, inotrope use, lower blood white cell count and higher C reactive protein (p = 0.02-0.0005). Backward binary logistic regression for these variables showed bacteremia (odds ratio [OR]: 31.7; 95% CI: 2.3-427.8; p = 0.009), malignancy (OR: 45.5; 95% CI: 1.4-1467.7; p = 0.031) and use of inotropes (OR: 15.0; 95% CI: 1.1-196.1; p = 0.039) were independently associated with non-survival. March and July appeared to be the two peak months for PICU hospitalizations with paramyxovirus infection. CONCLUSIONS: Infections with paramyxoviruses account for 5% of PICU admissions and significant morbidity. Patient with premorbid history of malignancy and co-morbidity of bacteremia are associated with non-survival. March and July appeared to be the two peak months for PICU admissions with paramyxoviruses.

Pseudomonas aeruginosa Cif protein enhances the ubiquitination and proteasomal degradation of the transporter associated with antigen processing (TAP) and reduces major histocompatibility complex (MHC) class I antigen presentation.

Cif (PA2934), a bacterial virulence factor secreted in outer membrane vesicles by Pseudomonas aeruginosa, increases the ubiquitination and lysosomal degradation of some, but not all, plasma membrane ATP-binding cassette transporters (ABC), including the cystic fibrosis transmembrane conductance regulator and P-glycoprotein. The goal of this study was to determine whether Cif enhances the ubiquitination and degradation of the transporter associated with antigen processing (TAP1 and TAP2), members of the ABC transporter family that play an essential role in antigen presentation and intracellular pathogen clearance. Cif selectively increased the amount of ubiquitinated TAP1 and increased its degradation in the proteasome of human airway epithelial cells. This effect of Cif was mediated by reducing USP10 deubiquitinating activity, resulting in increased polyubiquitination and proteasomal degradation of TAP1. The reduction in TAP1 abundance decreased peptide antigen translocation into the endoplasmic reticulum, an effect that resulted in reduced antigen available to MHC class I molecules for presentation at the plasma membrane of airway epithelial cells and recognition by CD8(+) T cells. Cif is the first bacterial factor identified that inhibits TAP function and MHC class I antigen presentation.

Antimicrobial Resistance in Qatar: Prevalence and Trends before and Amidst the COVID-19 Pandemic.

Antimicrobial resistance (AMR) is a global healthcare challenge with substantial morbidity, mortality, and management costs. During the COVID-19 pandemic, there was a documented increase in antimicrobial consumption, particularly for severe and critical cases, as well as noticeable travel and social restriction measures that might influenced the spectrum of AMR. To evaluate the problem, retrospective data were collected on bacterial infections and antimicrobial susceptibility patterns in Qatar before and after the pandemic from 1 January 2019 to 31 December 2021, covering 53,183 pathogens isolated from reported infection episodes. The findings revealed a significant resistance pattern for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EBC), carbapenem-resistant Enterobacteriaceae (CR-EBC), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), ciprofloxacin-resistant Salmonella and methicillin-resistant Staphylococcus aureus (MRSA). For correlation with social restrictions, ESBL-EBC and MRSA were positively correlated with changing patterns of international travel (ρ = 0.71 and 0.67, respectively; p < 0.05), while CRPA was moderately correlated with the number of COVID-19 hospitalized patients (ρ = 0.49; p < 0.05). CREBC and CRPA respiratory infections were associated with hospitalized patients (OR: 3.08 and 2.00, respectively; p < 0.05). The findings emphasize the challenges experienced during the COVID-19 pandemic and links to international travel, which probably will influence the local epidemiology of AMR that needs further surveillance and control strategies.

Antimicrobial Use during the SARS-CoV-2 Pandemic in a Greek Tertiary University Hospital.

In cases of SARS-CoV-2 hospitalization, despite low bacterial co-infection rates, antimicrobial use may be disproportionately high. Our aim was to quantify such usage in COVID-19 patients and identify factors linked to increased antibiotic use. We retrospectively studied patients with SARS-CoV-2 infection who were hospitalized at our institution during the pandemic. In the initial two waves of the pandemic, antimicrobial use was notably high (89% in the first wave and 92% in the second), but it decreased in subsequent waves. Elevated procalcitonin (>0.5 µg/mL) and C-reactive protein (>100 mg/L) levels were linked to antibiotic usage, while prior vaccination reduced antibiotic incidence. Antimicrobial use decreased in the pandemic, suggesting enhanced comprehension of SARS-CoV-2's natural course. Additionally, it was correlated with heightened SARS-CoV-2 severity, elevated procalcitonin, and C-reactive protein levels.

Bacterial co-infections and secondary infections and their antimicrobial resistance in Covid-19 patients during the second pandemic wave.

Background: COVID-19 pneumonia with an unusual outbreak is considered a new, global public health threat. Microbiological characterization of co-infections in patients with COVID-19 is important, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and the antimicrobial resistance of the causative pathogens. Method: From January to December 2020, we tested 1,301 patients who were COVID-19 positive. We received clinical samples (blood, respiratory and sterile body fluids) of COVID-19 patients who were suspected to have bacterial co-infections. Samples were processed and antimicrobial susceptibility testing was performed based on the CLSI recommendation. Demographic, clinical, laboratory and outcome data of those with positive cultures were collected. Result: A total of 1301 COVID-19 patients (568 from the COVID ward and 733 from ICU) were admitted to the Covid care ward of a tertiary care hospital. 363 samples were sent for culturing and testing antibiotic susceptibility, of which 131 (36%) were found to be culture-positive (90 from ICUs, 41 from wards). Out of the 143 total isolates thus obtained from 131 samples, the majority (62.2%) were Gram-negative bacteria, and most of them were (70.8%) multidrug resistant. Discussion: Bacterial co-infection in patients with COVID-19 is more commonly reported in the severely ill hospitalized individuals (58%), particularly in the ICU (73.3%) setting. In terms of mortality, almost half of co-infected patients died (51.1%). In most of them, the cause of death was found to be sepsis with post-COVID ARDS (58%). Conclusion: Co-infection in COVID-19 patients may affect the outcome in terms of increasing the hospital stay.

High mortality of patients with severe pneumonia caused by respiratory syncytial virus, August 2021-June 2023, Taiwan.

Among the 14 patients with respiratory syncytial virus pneumonia, the majority (n = 8, 57.1 %) were older than 65 years and had health care-associated pneumonia (57.1 %). Over 70 % (n = 10) of them exhibited bacterial co-infection, with a high proportion (64.3 %) requiring mechanical ventilation. The hospital mortality rate was 50 %.