Secondary Bacterial Respiratory Infections Research Articles

Resilience of swine nasal microbiota to influenza A virus challenge in a longitudinal study

Influenza A virus (IAV) is an important contributing pathogen of porcine respiratory disease complex (PRDC) infections. Evidence in humans has shown that IAV can disturb the nasal microbiota and increase host susceptibility to bacterial secondary infections. Few, small-scale studies have examined the impact of IAV infection on the swine nasal microbiota. To better understand the effects of IAV infection on the nasal microbiota and its potential indirect impacts on the respiratory health of the host, a larger, longitudinal study was undertaken to characterize the diversity and community composition of the nasal microbiota of pigs challenged with an H3N2 IAV. The microbiome of challenged pigs was compared with non-challenged animals over a 6-week period using 16S rRNA gene sequencing and analysis workflows to characterize the microbiota. Minimal changes to microbial diversity and community structure were seen between the IAV infected and control animals the first 10 days post-IAV infection. However, on days 14 and 21, the microbial populations were significantly different between the two groups. Compared to the control, there were several genera showing significant increases in abundance in the IAV group during acute infection, such as Actinobacillus and Streptococcus. The results here highlight areas for future investigation, including the implications of these changes post-infection on host susceptibility to secondary bacterial respiratory infections.

Profile of Secondary Bacterial Respiratory Infections in H1N1 Patients Admitted in a Tertiary Care Centre - A Four-year Retrospective Study.

H1N1 is known to cause periodic seasonal flu in the Indian subcontinent since 2009. The clinical course and the underlying immunity of the host contribute to the development of secondary bacterial infections in the infected patients. This study aims to analyze the secondary bacterial infections in confirmed H1N1 cases admitted in our hospital (from 2015 to 2018) with respect to the comorbidities, complications, associated bacteria with its antibiotic susceptibility pattern, and the outcome of such episodes. Data of 164 patients admitted in a tertiary care hospital with H1N1 was extracted from medical records using a semi-structured case report form. Data were entered and analyzed with SPSS version 17. A p-value of <0.05 was considered statistically significant. Most patients were aged above 40 years with female preponderance. In our study, 42% of patients had comorbidities. Only 14 (8.53%) had secondary bacterial infection confirmed by culture. Klebsiella pneumoniae and Acinetobacter baumannii were the most common bacteria that were isolated. They were treated based on the culture reports. There was no mortality in patients with a secondary bacterial infection. The early start of the antiviral agents and adherence to the antibiotic policy of the hospital contributed to lower secondary bacterial infections and zero mortality.

Recommendations for antibacterial therapy in adults with COVID-19 – an evidence based guideline

ScopeThe Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). MethodsWe performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions addressed by the guideline and RecommendationsWe assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.

The inflammasome potentiates influenza/Staphylococcus aureus superinfection in mice.

Secondary bacterial respiratory infections are commonly associated with both acute and chronic lung injury. Influenza complicated by bacterial pneumonia is an effective model to study host defense during pulmonary superinfection due to its clinical relevance. Multiprotein inflammasomes are responsible for IL-1β production in response to infection and drive tissue inflammation. In this study, we examined the role of the inflammasome during viral/bacterial superinfection. We demonstrate that ASC-/- mice are protected from bacterial superinfection and produce sufficient quantities of IL-1β through an apoptosis-associated speck-like protein containing CARD (ASC) inflammasome-independent mechanism. Despite the production of IL-1β by ASC-/- mice in response to bacterial superinfection, these mice display decreased lung inflammation. A neutrophil elastase inhibitor blocked ASC inflammasome-independent production of IL-1β and the IL-1 receptor antagonist, anakinra, confirmed that IL-1 remains crucial to the clearance of bacteria during superinfection. Delayed inhibition of NLRP3 during influenza infection by MCC950 decreases bacterial burden during superinfection and leads to decreased inflammatory cytokine production. Collectively, our results demonstrate that ASC augments the clearance of bacteria, but can also contribute to inflammation and mortality. ASC should be considered as a therapeutic target to decrease morbidity and mortality during bacterial superinfection.

Equine influenza in Brazil

O vírus da influenza equina (EIV) (H3N8 e H7N7) é o agente causador da influenza equina, ou gripe equina. O subtipo viral H7N7 é considerado como mundialmente extinto desde 1980. Os animais afetados têm sintomas respiratórios característicos que podem ser agravados por uma infecção respiratória bacteriana secundária causando grandes prejuízos no ramo equestre. No Brasil, os surtos da EI têm sido relatados desde 1963 e desde então vem sendo efetuados estudos sobre a presença de anticorpos hemaglutinantes contra os subtipos virais nos equídeos brasileiros. O presente artigo tem o objetivo de apresentar um histórico sobre o surgimento do EIV no mundo e no Brasil destacando os estudos conduzidos no Brasil até o momento acerca da infecção pelo EIV nos equídeos brasileiros.

A study on the immune response of horses bred against respiratory diseases vaccination in Jeju island

Viral respiratory infections are common in horses, notably equine herpesvirus infection and equine influenza, which primarily initiate secondary bacterial respiratory infections such as strangles caused by Streptococcus equi equi. A decline in the production of stallions has been associated with these respiratory diseases leading to adverse financial implications. This study investigated the antibody responses against respiratory diseases in horses from Jeju Island a year after vaccination. A low level of equine herpesvirus type 1 (EHV-1) (11.36%) antibodies was detected from stallions, however a high level of EHV-4 (95.84%) antibodies was detected from horses without vaccination against this infection suggesting that EHV-4 is ubiquitous in this horse population. In case of equine influenza, ranch stallions showed low positive rate (12.06%) whereas stallions from Subtropical Livestock Research Institute displayed higher positive rate (81.32%). Antibody responses against equine influenza and strangles revealed positive rates of 26.32% and 55.12%, respectively. These findings may draw attention towards the importance of developing an improved disease prevention and/or immunization program that will effectively control respiratory diseases in horses.

Stress significantly increases mortality following a secondary bacterial respiratory infection

A variety of mechanisms contribute to the viral-bacterial synergy which results in fatal secondary bacterial respiratory infections. Epidemiological investigations have implicated physical and psychological stressors as factors contributing to the incidence and severity of respiratory infections and psychological stress alters host responses to experimental viral respiratory infections. The effect of stress on secondary bacterial respiratory infections has not, however, been investigated. A natural model of secondary bacterial respiratory infection in naive calves was used to determine if weaning and maternal separation (WMS) significantly altered mortality when compared to calves pre-adapted (PA) to this psychological stressor. Following weaning, calves were challenged with Mannheimia haemolytica four days after a primary bovine herpesvirus-1 (BHV-1) respiratory infection. Mortality doubled in WMS calves when compared to calves pre-adapted to weaning for two weeks prior to the viral respiratory infection. Similar results were observed in two independent experiments and fatal viral-bacterial synergy did not extend beyond the time of viral shedding. Virus shedding did not differ significantly between treatment groups but innate immune responses during viral infection, including IFN-γ secretion, the acute-phase inflammatory response, CD14 expression, and LPS-induced TNFα production, were significantly greater in WMS versus PA calves. These observations demonstrate that weaning and maternal separation at the time of a primary BHV-1 respiratory infection increased innate immune responses that correlated significantly with mortality following a secondary bacterial respiratory infection.

Successful treatment of parapneumonic empyema after H1N1 infection in a heart transplant recipient

Pandemic influenza A H1N1 virus is likely to cause severe disease in patients who have received solid organs transplants. In these patients pneumonia is the most frequent clinical feature. Parapneumonic empyema (PPE) may represent the evolution of secondary bacterial respiratory infections. To our knowledge this is the first reported case of PPE during H1N1 influenza A in an adult heart transplanted patient. The patient was treated successfully with surgical empyemectomy and lung decortication, broad-spectrum antibiotics and oseltamivir. Eradication of influenza was obtained in the fifth postoperative day.

Bench-to-bedside review: Bacterial pneumonia with influenza - pathogenesis and clinical implications

Seasonal and pandemic influenza are frequently complicated by bacterial infections, causing additional hospitalization and mortality. Secondary bacterial respiratory infection can be subdivided into combined viral/bacterial pneumonia and post-influenza pneumonia, which differ in their pathogenesis. During combined viral/bacterial infection, the virus, the bacterium and the host interact with each other. Post-influenza pneumonia may, at least in part, be due to resolution of inflammation caused by the primary viral infection. These mechanisms restore tissue homeostasis but greatly impair the host response against unrelated bacterial pathogens. In this review we summarize the underlying mechanisms leading to combined viral/bacterial infection or post-influenza pneumonia and highlight important considerations for effective treatment of bacterial pneumonia during and shortly after influenza.

Abrupt Weaning Significantly Increases Mortality Following a Secondary Bacterial Respiratory Infection

Secondary bacterial respiratory infections are a major cause of mortality in fall-weaned feedlot calves, and epidemiological studies implicate a variety of stressors as significant contributing factors. Experimental studies have identified stressors that may compromise pulmonary defense mechanisms but there is no evidence that these functional changes alter respiratory disease outcome. We used a model of combined viral and bacterial respiratory disease to determine if nutritional and psychological stressors (abrupt weaning; AW) altered respiratory disease mortality. Mortality was doubled in AW calves challenged with Mannheimia haemolytica four days after a primary bovine herpesvirus-1 (BHV-1) respiratory infection, when compared to calves adapted to weaning (pre-conditioned; PC) for two weeks prior to respiratory challenge. Reduced survival time and decreased lung pathology in the AW group suggested death was due to an acute systemic reaction. Viral shedding did not differ significantly between the two treatment groups. AW calves and all calves developing fatal pneumonia had significantly elevated interferon (IFN)-y levels in nasal secretions and increased systemic proinflammatory responses. Analysis of blood leukocytes revealed significantly increased CD14 and TLR4 gene expression in animals with fatal pneumonia. These analyses support the conclusion that stress enhanced innate immune responses to viral infection without altering the level of BHV-1 infection. These studies provide the first quantitative evidence that stress associated with abrupt weaning contributes significantly to fatal bovine respiratory disease.

Biomarkers for Prediction of Bovine Respiratory Disease Outcome

Fatal bovine respiratory disease (BRD) is frequently the result of a primary viral and a secondary bacterial respiratory infection. In cattle, BRD causes more than half of feedlot deaths and has a major impact on financial losses in the cattle industry in North America. It is, therefore, very important to understand the mechanism of this complex disease process as well to predict and identify BRD susceptible cattle to enhance treatment efficacy. We recently established the value of using combinatorial omics approaches to identify candidate biomarkers associated with stress responses, a factor that can increase the severity of BRD. The objective of the present investigation was to experimentally recreate fatal BRD and to use a combinatorial analysis of proteomic, metabonomic, and elemental profiles in serum samples to determine if multimethod analysis of these biomarkers could predict disease outcome. The proteomic studies revealed that changes in the serum proteome were significant on day 4 postviral infection when compared to preinfection (day 0) serum samples. Proteomic studies identified a group of acute phase proteins (haptoglobin and apolipoprotein AI), which could be linked to a primary viral respiratory infection, but there was no significant association observed with fatal BRD. In contrast, metabonomic and elemental analyses identified candidate biomarkers for viral infection (glucose, LDL, valine, phosphorous, and iron) and disease outcome (lactate, glucose, iron). While multivariate analysis of proteomic and metabolite profiles did not discriminate between animals that survived or died postsynergic viral-bacterial infection by analyzing preinfection (day 0) serum samples, analysis of serum elemental profiles prior to infection was, however, predictive of BRD outcome. Furthermore, discriminant analyses of all three methodologies used to profile serum (collected on day 4 postviral but prior to bacterial infection) revealed differential trends between animals that survived or died following synergic viral-bacterial infection. Thus, a combinatorial approach using proteomic, metabonomic, and elemental analyses of serum samples revealed that multimethod analysis could discriminate between the complex biological responses to secondary bacterial respiratory infection and predict disease outcome.

Study of secondary bacterial respiratory infections associated with the common cold syndrome

Study of secondary bacterial respiratory infections associated with the common cold syndrome

Canine respiratory disease in an animal facility. Viral and bacteriological survey.

Canine morbidity and mortality due to respiratory disease has impeded medical investigation for many years and continues to be the major obstacle to consistent chronic survival of dogs undergoing research studies. The organism responsible for the majority of contagious respiratory infections in laboratory dogs has been believed to be viral, most frequently the distemper virus. Other viruses, such as canine herpes, hepatitis, and adenovirus, may also initiate respiratory infections but less commonly. Little attention has been directed to secondary bacterial respiratory infections which frequently follow mild canine viral infections. These bacterial infections appear to be much more likely to cause morbidity and mortality than do primary viral infections. The present investigation was undertaken to survey viral and bacterial flora from the respiratory tracts of dogs newly admitted to the UCLA Animal Facility. An antibiotic sensitivity analysis from each bacterial culture was carried out in order to develop a rational antibiotic