Lower respiratory tract delivery, airway clearance, and preclinical efficacy of inhaled GM-CSF in a postinfluenza pneumococcal pneumonia model.

Inhaled granulocyte/macrophage colony-stimulating factor (GM-CSF) shows promise as a therapeutic to treat viral and bacterial pneumonia, but no mouse model of inhaled GM-CSF has been described. We sought to 1) develop a mouse model of aerosolized recombinant mouse GM-CSF administration and 2) investigate the protection conferred by inhaled GM-CSF during influenza A virus (IAV) infection against secondary bacterial infection with pneumococcus. To assess lower respiratory tract delivery of aerosolized therapeutics, mice were exposed to aerosolized fluorescein (FITC)-labeled dextran noninvasively via an aerosolization tower or invasively using a rodent ventilator. The efficiency of delivery to the lower respiratory tracts of mice was 0.01% noninvasively compared with 0.3% invasively. The airway pharmacokinetics of inhaled GM-CSF fit a two-compartment model with a terminal phase half-life of 1.3 h. To test if lower respiratory tract levels were sufficient for biological effect, mice were infected intranasally with IAV, treated with aerosolized recombinant mouse GM-CSF, and then secondarily infected with Streptococcus pneumoniae. Inhaled GM-CSF conferred a significant survival benefit to mice against secondary challenge with S. pneumoniae (P < 0.05). Inhaled GM-CSF did not reduce airway or lung parenchymal bacterial growth but significantly reduced the incidence of S. pneumoniae bacteremia (P < 0.01). However, GM-CSF overexpression during influenza virus infection did not affect lung epithelial permeability to FITC-dextran ingress into the bloodstream. Therefore, the mechanism of protection conferred by inhaled GM-CSF appears to be locally mediated improved lung antibacterial resistance to systemic bacteremia during IAV infection.

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.

Microorganisms associated with respiratory syncytial virus pneumonia in the adult population.

Respiratory syncytial virus (RSV) has been recognized as responsible for severe respiratory illness in adults, especially in the elderly. While pneumonia is commonly observed during RSV infection, the burden and epidemiology of bacterial superinfection is poorly understood. The aim of this study was to identify microorganisms associated with RSV-positive pneumonia in adults. A retrospective study was conducted during three consecutive winters (October to April 2013-2016) in the University Hospital of Lyon, France. During RSV circulation periods, a systematic RSV screening was performed by reverse-transcription PCR on all respiratory samples collected from adults. Records of RSV-positive patients were subsequently analyzed to identify radiologically confirmed pneumonia cases. Bacteria were identified by standard bacteriology cultures or urinary antigen screening and classified as potentially causative of pneumonia if quantification was above the specific threshold as defined by the European Manual of Clinical Microbiology. Overall, 14,792 adult respiratory samples were screened for RSV detection by PCR. In total, 292 had a positive RSV detection (2.0%) among which 89 presented with pneumonia including 27 bacterial superinfections (9.3%) with Streptococcus pneumonia, Haemophilus influenza, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis. Most patients were elderly (55.6%) and patients with comorbidities (77.8%). A more severe outcome was observed for RSV-bacteria-associated pneumonia compared with RSV pneumonia: length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). In conclusion, we did not observe major differences in the epidemiology of bacterial superinfections in RSV-positive pneumonia compared to reports on post-influenza pneumonia.

[Nosocomial pneumonia from a radiological perspective]. / Nosokomiale Pneumonie aus radiologischer Sicht.

Due to the high morbidity and mortality, nosocomial pneumonia represents a serious risk in hospitalized patients. The increased risk of infections with multidrug-resistant (MDR) pathogens makes a timely diagnosis and prompt therapy indispensable. A newly occurring or progressive infiltrate in any patient who has been hospitalized for more than 48 h should be viewed with suspicion. In contrast to community acquired pneumonia (CAP), radiography plays a limited role in the diagnosis of hospital-acquired pneumonia (HAP). This is partly due to the technical challenges in imaging of patients who are in a lying position as well as the numerous other possible differential diagnoses. Careful analysis of the various radiological features, such as temporal progression, distribution and appearance can help to narrow down the differential diagnoses. In the absence of a single gold standard, clinical features and appropriate radiological features in addition to cultures obtained from respiratory secretions can help to maximize the diagnostic efficacy and expedite the treatment with appropriate antibiotic therapy.

Clinical Characteristics of Influenza-Associated Pneumonia of Adults: Clinical Features and Factors Contributing to Severity and Mortality.

Background: Pneumonia is a major complication of influenza that contributes to mortality. Clinical characteristics and factors of influenza virus contributing to the severity and mortality of pneumonia have not been fully elucidated. Objective: The objective was to clarify clinical characteristics and factors contributing to the severity and mortality of influenza-associated pneumonia (flu-p). Methods: We retrospectively analyzed patients with flu-p. Results: From December 1999 to March 2016, 210 patients with a median age of 69 (range, 17 to 92) years with flu-p based on positive rapid antigen tests, increased antibody titers of paired sera, or positive results of reverse transcription polymerase chain reaction were admitted to our institution. A multivariate analysis found that advanced age (≥ 65 years), pneumonia subtypes (unclassified), diabetes mellitus, and acute kidney injury complicated with flu-p were independent factors associated with disease severity, whereas pneumonia subtypes (mixed viral and bacterial pneumonia and unclassified), healthcare-associated pneumonia, acute kidney injury complicated with flu-p, and severity on admission (severe) were independent factors associated with non-survival. Conclusion: The clinical characteristics of flu-p are varied, and the contribution of several factors to the severity and mortality of flu-p suggest their importance in either preventing flu-p or managing flu-p after it develops.

Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia.

BACKGROUND: The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP. METHODS: Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns. RESULTS: Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients. CONCLUSIONS: Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.

The role of viral, host, and secondary bacterial factors in influenza pathogenesis.

Influenza A virus infections in humans generally cause self-limited infections, but can result in severe disease, secondary bacterial pneumonias, and death. Influenza viruses can replicate in epithelial cells throughout the respiratory tree and can cause tracheitis, bronchitis, bronchiolitis, diffuse alveolar damage with pulmonary edema and hemorrhage, and interstitial and airspace inflammation. The mechanisms by which influenza infections result in enhanced disease, including development of pneumonia and acute respiratory distress, are multifactorial, involving host, viral, and bacterial factors. Host factors that enhance risk of severe influenza disease include underlying comorbidities, such as cardiac and respiratory disease, immunosuppression, and pregnancy. Viral parameters enhancing disease risk include polymerase mutations associated with host switch and adaptation, viral proteins that modulate immune and antiviral responses, and virulence factors that increase disease severity, which can be especially prominent in pandemic viruses and some zoonotic influenza viruses causing human infections. Influenza viral infections result in damage to the respiratory epithelium that facilitates secondary infection with common bacterial pneumopathogens and can lead to secondary bacterial pneumonias that greatly contribute to respiratory distress, enhanced morbidity, and death. Understanding the molecular mechanisms by which influenza and secondary bacterial infections, coupled with the role of host risk factors, contribute to enhanced morbidity and mortality is essential to develop better therapeutic strategies to treat severe influenza.

[INTENSIVE THERAPY OF THE PATIENT WITH VIRAL-BACTERIAL PNEUMONIA, PROLONGED VENTILATION (137 DAYS) AND TRACHEOESOPHAGEAL FISTULA].

A case of successful therapy of the patient with viral and bacterial pneumonia, prolonged ventilation (137 days) and tracheoesophagealfistula presented. The possibility of optimizing the gas exchange in the lungs by selecting appropriate modes of mechanical ventilation with the use ofproportional assist ventilation of the lungs (PVVL or PAV +), rather than suppressing patient's own attempts is shown.

Influenza-induced type I interferon enhances susceptibility to gram-negative and gram-positive bacterial pneumonia in mice.

Suppression of type 17 immunity by type I interferon (IFN) during influenza A infection has been shown to enhance susceptibility to secondary bacterial pneumonia. Although this mechanism has been described in coinfection with gram-positive bacteria, it is unclear whether similar mechanisms may impair lung defense against gram-negative infections. Furthermore, precise delineation of the duration of type I IFN-associated susceptibility to bacterial infection remains underexplored. Therefore, we investigated the effects of preceding influenza A virus infection on subsequent challenge with the gram-negative bacteria Escherichia coli or Pseudomonas aeruginosa and the temporal association between IFN expression with susceptibility to Staphylococcus aureus challenge in a mouse model of influenza and bacterial coinfection. Here we demonstrate that preceding influenza A virus led to increased lung E. coli and P. aeruginosa bacterial burden, which was associated with suppression of type 17 immunity and attenuation of antimicrobial peptide expression. Enhanced susceptibility to S. aureus coinfection ceased at day 14 of influenza infection, when influenza-associated type I IFN levels had returned to baseline levels, further suggesting a key role for type I IFN in coinfection pathogenesis. These findings further implicate type I IFN-associated suppression of type 17 immunity and antimicrobial peptide production as a conserved mechanism for enhanced susceptibility to both gram-positive and gram-negative bacterial coinfection during influenza infection.

Etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in Norway.

BACKGROUND: Despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (CAP) is still not well described. We applied polymerase chain reaction (PCR) and conventional methods to describe etiology of CAP in hospitalized adults and evaluated their respective diagnostic yields. METHODS: 267 CAP patients were enrolled consecutively over our 3-year prospective study. Conventional methods (i.e., bacterial cultures, urinary antigen assays, serology) were combined with nasopharyngeal (NP) and oropharyngeal (OP) swab samples analyzed by real-time quantitative PCR (qPCR) for Streptococcus pneumoniae, and by real-time PCR for Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordetella pertussis and 12 types of respiratory viruses. RESULTS: Etiology was established in 167 (63%) patients with 69 (26%) patients having ≥1 copathogen. There were 75 (28%) pure bacterial and 41 (15%) pure viral infections, and 51 (19%) viral-bacterial coinfections, resulting in 126 (47%) patients with bacterial and 92 (34%) patients with viral etiology. S. pneumoniae (30%), influenza (15%) and rhinovirus (12%) were most commonly identified, typically with ≥1 copathogen. During winter and spring, viruses were detected more frequently (45%, P=.01) and usually in combination with bacteria (39%). PCR improved diagnostic yield by 8% in 64 cases with complete sampling (and by 15% in all patients); 5% for detection of bacteria; 19% for viruses (P=.04); and 16% for detection of ≥1 copathogen. Etiology was established in 79% of 43 antibiotic-naive patients with complete sampling. S. pneumoniae qPCR positive rate was significantly higher for OP swab compared to NP swab (P<.001). Positive rates for serology were significantly higher than for real-time PCR in detecting B. pertussis (P=.001) and influenza viruses (P<.001). CONCLUSIONS: Etiology could be established in 4 out of 5 CAP patients with the aid of PCR, particularly in diagnosing viral infections. S. pneumoniae and viruses were most frequently identified, usually with copathogens. Viral-bacterial coinfections were more common than pure infections during winter and spring; a finding we consider important in the proper management of CAP. When swabbing for qPCR detection of S. pneumoniae in adult CAP, OP appeared superior to NP, but this finding needs further confirmation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01563315 .

[EFFECTIVENESS OF FULLERENE-(TRIS-AMINOCAPRONIC ACID) HYDRATE IN THE MODEL OF EXPERIMENTAL VIRAL-BACTERIAL PNEUMONIA OF MICE].

AIM: Study the effectiveness of the substance and various drug formulations of fullerene-(tris-aminocapronic acid) hydrate (FTAAH onwards) in the model of experimental viral-bacterial pneumonia of mice. MATERIALS AND METHODS: BALB/c mice were infected with influenza virus A/California/04/2009 and subsequently infected with Staphylococcus aureus. The animals were treated after viral infection with the substance and various drug forms of FTAAH, as well as comparative preparations--oseltamivir and arbidol. Therapy effectiveness was evaluated by clinical indicators (survival, lifespan, animal mass decrease reduction), virological (virus titer), microbiological (density of bacteria in lungs) parameters, confirmed by pathomorphological characteristics of lungs. RESULTS: FTAAH therapy in injectable form was effective in the model of a combined viral-bacterial pneumonia of mice by all the studied criteria: treatment increased mice survival, reduced the decrease of their body weight, resulted in a reduction of virus titers and density of bacteria in lungs, that correlated with the data from morphological study and signs of bronchopneumonia resolution in mice. FTAAH therapy in rectal form depended on animal infection schemes, as well as preparation dose, increasing with its increase. CONCLUSION: FTAAH substance is effective in the model of experimental viral-bacterial pneumonia of mice.

Thoracic diseases associated with HIV infection in the era of antiretroviral therapy: clinical and imaging findings.

The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has entered its 4th decade. Since the introduction of combination antiretroviral therapy (ART) in 1996, the number of AIDS-related deaths has plateaued worldwide. Today, owing to the effectiveness of ART, the HIV-infected population is aging and HIV infection has become a chronic illness. Non-AIDS comorbidities are increasing, and the spectrum of HIV-related thoracic diseases is evolving. In developed countries, bacterial pneumonia has become more common than Pneumocystis pneumonia. Its imaging appearance depends on the responsible organism, most commonly Streptococcus pneumoniae. Mycobacterium tuberculosis continues to be a major threat. Its imaging patterns vary depending on CD4 count. Primary lung cancer and Hodgkin lymphoma are two important non-AIDS-defining malignancies that are increasingly encountered at chest imaging. Human herpesvirus 8, also known as Kaposi sarcoma-associated herpesvirus (KSHV), is strongly linked to HIV-related diseases, including Kaposi sarcoma, multicentric Castleman disease, KSHV inflammatory cytokine syndrome, and primary effusion lymphoma. Immune reconstitution inflammatory syndrome is a direct complication of ART whose manifestations vary with the underlying disease. Given the high rate of smoking among HIV-infected patients, chronic obstructive pulmonary disease is another important cause of morbidity and mortality. A high degree of suspicion is required for the early diagnosis of pulmonary arterial hypertension and lymphocytic interstitial pneumonia, given their nonspecific manifestations. Finally, multilocular thymic cyst manifests as a cystic anterior mediastinal mass. Recognition of the clinical and radiologic manifestations of these less traditional HIV-related diseases can expedite diagnosis and treatment in the ART era.

Pneumonia in solid organ transplant recipients: a prospective multicenter study.

BACKGROUND: Pneumonia frequently affects solid organ transplant (SOT) recipients, with high morbidity and mortality. However, the few studies on pneumonia in this population are mainly retrospective, single-center, and long-term studies, or include patients with only one type of SOT or a specific etiology. We performed a point prevalence study to investigate epidemiology, diagnosis, therapy, and outcome of pneumonia in an unselected SOT population. METHODS: Italian and Spanish transplant centers were invited to report on all SOT recipients with pneumonia treated during 2 separate weeks (1 each in February and June 2012). RESULTS: In total, 35 centers (18 in Italy, 17 in Spain) agreed to participate and collected 54 cases. The incidence of pneumonia was 10.1 episodes/1000 recipients/year. Pneumonia was classified as late (>6 months) in 70.4% of cases. Pneumonia was also classified as community-acquired (CAP), healthcare-associated (HCAP), and hospital-acquired (HAP) pneumonia in 40.7%, 38.9%, and 20.4% of cases, respectively. An attempt to microbiological diagnosis (≥1 sample) was made in 94.4% of patients, with a diagnostic yield of 60.7%. Causative agents included bacteria (87.1%), virus (29%), and fungi (6.4%). A multidrug-resistant bacterium was isolated in 18.2%, 40%, and 100% of patients with CAP, HCAP, and HAP (P = 0.007), respectively. Overall, 11.1% of patients were admitted to the intensive care unit, 3.7% developed graft rejection, and graft function deteriorated in 18.5%. In-hospital mortality was 1.9%. CONCLUSION: Pneumonia remains a frequent problem in SOT recipients, although it occurs later in patients who are in better physical health. Therefore, harmful pathogens and worse outcome are less common than previously thought.

Influence of prior pandemic A(H1N1)2009 virus infection on invasion of MDCK cells by community-associated methicillin-resistant Staphylococcus aureus.

Secondary bacterial pneumonia due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a highly publicized cause of death associated with influenza. In this study, we performed the gentamicin-killing assay using Madin-Darby canine kidney (MDCK) cells and MRSA strains to investigate whether prior infection from pandemic A(H1N1)2009 virus (A[H1N1]pdm09) lead to increased invasion of MDCK cells by MRSA. We found that the invasion rate of two MRSA strains (ATCC BAA-1680 [USA 300] and ATCC BAA-1699 [USA 100]) into intact MDCK cell monolayers was 0.29 ± 0.15% and 0.007 ± 0.002%, respectively (p < 0.01, n ≥ 3). In addition, the relative invasion rate of both ATCC BAA-1680 and ATCC BAA-1699 was significantly increased by prior A(H1N1)pdm09 infection of MDCK monolayers from 1 ± 0.28 to 1.38 ± 0.02 and from 1 ± 0.24 to 1.73 ± 0.29, respectively (p < 0.01). These results indicate that ATCC BAA-1680 displays much stronger invasiveness of MDCK cells than ATCC BAA-1699, although invasion of both strains was increased by prior A(H1N1)pdm09 infection. In conclusion, this study provided the first evidence that prior A(H1N1)pdm09 infection facilitates the invasion of MDCK cells by MRSA, presumably due to cellular injury caused by the virus.

Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice.

Staphylococcus aureus is a significant cause of hospital and community acquired pneumonia and causes secondary infection after influenza A. Recently, patients with hyper-IgE syndrome, who often present with S. aureus infections of the lung and skin, were found to have mutations in STAT3, required for Th17 immunity, suggesting a potential critical role for Th17 cells in S. aureus pneumonia. Indeed, IL-17R(-/-) and IL-22(-/-) mice displayed impaired bacterial clearance of S. aureus compared with that of wild-type mice. Mice challenged with influenza A PR/8/34 H1N1 and subsequently with S. aureus had increased inflammation and decreased clearance of both virus and bacteria. Coinfection resulted in greater type I and II IFN production in the lung compared with that with virus infection alone. Importantly, influenza A coinfection resulted in substantially decreased IL-17, IL-22, and IL-23 production after S. aureus infection. The decrease in S. aureus-induced IL-17, IL-22, and IL-23 was independent of type II IFN but required type I IFN production in influenza A-infected mice. Furthermore, overexpression of IL-23 in influenza A, S. aureus-coinfected mice rescued the induction of IL-17 and IL-22 and markedly improved bacterial clearance. These data indicate a novel mechanism by which influenza A-induced type I IFNs inhibit Th17 immunity and increase susceptibility to secondary bacterial pneumonia.

Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung.

Influenza viral infection is well-known to predispose to subsequent bacterial superinfection in the lung but the mechanisms have remained poorly defined. We have established a murine model of heterologous infections by an H1N1 influenza virus and Staphylococcus aureus. We found that indeed prior influenza infection markedly increased the susceptibility of mice to secondary S. aureus superinfection. Severe sickness and heightened bacterial infection in flu and S. aureus dual-infected animals were associated with severe immunopathology in the lung. We further found that flu-experienced lungs had an impaired NK cell response in the airway to subsequent S. aureus bacterial infection. Thus, adoptive transfer of naive NK cells to the airway of prior flu-infected mice restored flu-impaired antibacterial host defense. We identified that TNF-alpha production of NK cells played an important role in NK cell-mediated antibacterial host defense as NK cells in flu-experienced lungs had reduced TNF-alpha expression and adoptive transfer of TNF-alpha-deficient NK cells to the airway of flu-infected mice failed to restore flu-impaired antibacterial host defense. Defected NK cell function was found to be an upstream mechanism of depressed antibacterial activities by alveolar macrophages as contrast to naive wild-type NK cells, the NK cells from flu-infected or TNF-alpha-deficient mice failed to enhance S. aureus phagocytosis by alveolar macrophages. Together, our study identifies the weakened NK cell response in the lung to be a novel critical mechanism for flu-mediated susceptibility to bacterial superinfection.

Dysregulated macrophage-inflammatory protein-2 expression drives illness in bacterial superinfection of influenza.

Influenza virus infection is a leading cause of death and disability throughout the world. Influenza-infected hosts are vulnerable to secondary bacterial infection, however, and an ensuing bacterial pneumonia is actually the predominant cause of influenza-attributed deaths during pandemics. A number of mechanisms have been proposed by which influenza may predispose to superinfection with an unrelated or heterologous pathogen, but the subsequent interaction between the host, virus, and bacteria remains an understudied area. In this study, we develop and examine a novel model of heterologous pulmonary infection in which an otherwise subclinical Bordetella parapertussis infection synergizes with an influenza virus infection to yield a life-threatening secondary pneumonia. Despite a profound pulmonary inflammatory response and unaltered viral clearance, bacterial clearance was significantly impaired in heterologously infected mice. No deficits were observed in pulmonary or systemic adaptive immune responses or the viability or function of infiltrating inflammatory cells to explain this phenomenon, and we provide evidence that the onset of severe pulmonary inflammation actually precedes the increased bacterial burden, suggesting that exacerbated inflammation is independent of bacterial burden. To that end, neutralization of the ELR(+) inflammatory chemokine MIP-2 (CXCL2/GRO-beta) attenuated the inflammation, weight loss, and clinical presentation of heterologously infected mice without impacting bacterial burden. These data suggest that pulmonary inflammation, rather than pathogen burden, is the key threat during bacterial superinfection of influenza and that selective chemokine antagonists may be a novel therapeutic intervention in cases of bacterial superinfection of influenza.

[Zoflox, an antibacterial drug, in treatment of infectious pathologic processes in the lower respiratory tract complicating acute respiratory viral infection in elderly patients].

Clinical trial of Zoflox, an antimicrobial drug, was performed in complex therapy of elderly outpatients with acute pneumonia complicating acute respiratory viral infection. Among the outpatients there were elderly subjects with hepatic insufficiency. The drug showed to be efficient and safety when used in a middle therapeutic dose of 400 mg twice a day daily for 10-14 days.

Automated detection of COVID-19 through convolutional neural network using chest x-ray images.

The COVID-19 epidemic has a catastrophic impact on global well-being and public health. More than 27 million confirmed cases have been reported worldwide until now. Due to the growing number of confirmed cases, and challenges to the variations of the COVID-19, timely and accurate classification of healthy and infected patients is essential to control and treat COVID-19. We aim to develop a deep learning-based system for the persuasive classification and reliable detection of COVID-19 using chest radiography. Firstly, we evaluate the performance of various state-of-the-art convolutional neural networks (CNNs) proposed over recent years for medical image classification. Secondly, we develop and train CNN from scratch. In both cases, we use a public X-Ray dataset for training and validation purposes. For transfer learning, we obtain 100% accuracy for binary classification (i.e., Normal/COVID-19) and 87.50% accuracy for tertiary classification (Normal/COVID-19/Pneumonia). With the CNN trained from scratch, we achieve 93.75% accuracy for tertiary classification. In the case of transfer learning, the classification accuracy drops with the increased number of classes. The results are demonstrated by comprehensive receiver operating characteristics (ROC) and confusion metric analysis with 10-fold cross-validation.

Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT).

BACKGROUND AND OBJECTIVES: Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/µL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections. METHODS: Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected. RESULTS: IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/µL (IL-2 arm) and 463cells/µL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/µL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively. CONCLUSIONS: Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration.