Clinical presentations and diagnostic approaches of pediatric necrotizing tracheobronchitis with influenza A virus and Staphylococcus aureus co-infections.

In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB's clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.

VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation): protocol for a multicenter randomized open-label trial of watchful waiting versus antimicrobial therapy for ventilator-associated tracheobronchitis.

BACKGROUND: Ventilator-associated tracheobronchitis is a common condition among invasively ventilated patients in intensive care units, for which the best treatment strategy is currently unknown. We designed the VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation) trial to assess whether a watchful waiting antibiotic treatment strategy is noninferior to routine antibiotic treatment for ventilator-associated tracheobronchitis regarding days free of mechanical ventilation. METHODS: VATICAN is a randomized, controlled, open-label, multicenter noninferiority trial. Patients with suspected ventilator-associated tracheobronchitis without evidence of ventilator-associated pneumonia or hemodynamic instability due to probable infection will be assigned to either a watchful waiting strategy, without antimicrobial administration for ventilator-associated tracheobronchitis and prescription of antimicrobials only in cases of ventilator-associated pneumonia, sepsis or septic shock, or another infectious diagnosis, or to a routine antimicrobial treatment strategy for seven days. The primary outcome will be mechanical ventilation-free days at 28 days, and a key secondary outcome will be ventilator-associated pneumonia-free survival. Through an intention-to-treat framework with a per-protocol sensitivity analysis, the primary outcome analysis will address noninferiority with a 20% margin, which translates to a 1.5 difference in ventilator-free days. Other analyses will follow a superiority analysis framework. CONCLUSION: The VATICAN trial will follow all national and international ethical standards. We aim to publish the trial in a high-visibility general journal and present it at critical care and infectious disease conferences for dissemination. These results will likely be immediately applicable to the bedside upon trial completion and will provide information with a low risk of bias for guideline development.

Severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus co-infection in an immunocompetent patient.

PURPOSE AND METHOD: Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus (MRSA) co-infection in an immunocompetent patient. CASE PRESENTATION: We described a 36-year-old man with initial symptoms of cough, rigors, muscle soreness and fever. His status rapidly deteriorated two days later and he was intubated. Bronchoscopy demonstrated severe necrotizing tracheobronchitis, and CT imaging demonstrated multiple patchy and cavitation formation in both lungs. Next-generation sequencing (NGS) and bronchoalveolar lavage fluid (BALF) culture supported the co-infection of influenza B and MRSA. We also found T lymphocyte and NK lymphocyte functions were extremely suppressed during illness exacerbation. The patient was treated with antivirals and antibiotics including vancomycin. Subsequent bronchoscopy and CT scans revealed significant improvement of the airway and pulmonary lesions, and the lymphocyte functions were restored. Finally, this patient was discharged successfully. CONCLUSION: Necrotizing tracheobronchitis should be suspected in patients with rapid deterioration after influenza B infection. The timely diagnosis of co-infection and accurate antibiotics are important to effective treatment.

Antibiotics for Pediatric Patients With Laryngotracheobronchitis in Korea: A Nationwide Study Based on Administrative Data.

BACKGROUND: Antimicrobial resistance (AMR) is an important global public health concern in adults and children. Laryngotracheobronchitis (croup) is a common acute respiratory infection (ARI) among children, most often caused by a virus, and should not be treated with antibiotics. Reducing the usage of unnecessary antibiotics in ARI using an antimicrobial stewardship program (ASP) is an effective measure against AMR in children. This study investigates the antibiotic prescription pattern in pediatric patients with laryngotracheobronchitis in Korea. Our results will be useful to improve the ASP. METHODS: The data were obtained from the government agency Health Insurance Review and Assessment Service. We analyzed outpatient prescriptions issued to children ≤ 5 years of age with a first-listed diagnosis code for laryngotracheobronchitis, i.e., International Classification of Disease, 10th Revision, code J050 (croup), J040 (laryngitis), or J041 (tracheitis), during 2017-2020. For each prescription, demographic information and information about medical facilities visited (type of hospital, specialty of physician, location of hospital) were extracted. The overall antibiotic prescription rate was subsequently estimated, and multivariable analysis was conducted to determine the associated factors of antibiotic prescription. Prescribed antibiotics were described and classified into extended-spectrum penicillins, cephalosporin, and macrolides. RESULTS: Of 2,358,194 prescriptions reviewed, 829,172 (35.2%) contained antibiotics. In the multivariable analysis, management in a hospital was the strongest factor associated with antibiotic prescription (adjusted odds ratio [aOR], 22.33; 95% confidence interval [CI], 20.87-23.89; P < 0.001), followed by management in a clinic (aOR, 12.66; 95% CI, 11.83-13.54; P < 0.001) and management in a general hospital (aOR, 8.96; 95% CI, 8.37-9.59; P < 0.001). Antibiotic prescription was also significantly associated with patients who were ≤ 2 years of age, managed by a pediatric specialist, and treated at a hospital located in a non-metropolitan region. Overall, extended-spectrum penicillins were the most frequently prescribed (18.6%) antibiotics, followed by cephalosporins (9.4%) and macrolides (8.5%). CONCLUSION: The results of our study suggest that ASPs need to focus on physicians in hospitals, clinics, general hospitals, and pediatric specialties. Providing education programs to these groups to increase awareness of AMR and appropriate antibiotics use could be effective ASP policy and may help to reduce unnecessary prescriptions of antibiotics for laryngotracheobronchitis among pediatric patients and therefore potentially AMR in children in Korea.

A case report and review of the literature on swine hemorrhagic tracheitis syndrome in a Portuguese farm.

Background: Respiratory diseases, including the multifactorial "swine respiratory disease complex," have a significant impact on swine production. Recently, a condition manifesting primarily in the trachea, known as hemorrhagic tracheitis syndrome (HTS), has been described in pigs. HTS is characterized by severe coughing and high mortality in finishing pigs. Case Description: This report presents the first case of HTS in an adult male pig from a Portuguese farm. The animal died without any previous clinical signs. Necropsy revealed significant thickening of the trachea. Fibrinous necrotic hemorrhagic tracheitis was identified through histopathological analysis, but no bacterial infectious agents were detected during microbiological examination. Conclusion: This case underscores the need for comprehensive research, including systematic necropsies and histopathological assessments, to understand the actual prevalence of the disease, elucidate the etiology, and develop effective interventions for HTS in swine productions.

Outcomes associated with ventilator-associated events (VAE), respiratory infections (VARI), pneumonia (VAP) and tracheobronchitis (VAT) in ventilated pediatric ICU patients: A multicentre prospective cohort study.

OBJECTIVES: An objective categorization of respiratory infections based on outcomes is an unmet clinical need. Ventilator-associated pneumonia and tracheobronchitis remain used in clinical practice, whereas ventilator-associated events (VAE) are limited to surveillance purposes. RESEARCH METHODOLOGY/DESIGN: This was a secondary analysis from a multicentre observational prospective cohort study. VAE were defined as a sustained increase in minimum Oxygen inspired fraction (FiO2) and/or Positive end-expiratory pressures (PEEP) of ≥ 0.2/2 cm H2O respectively, or an increase of 0.15 FiO2 + 1 cm H20 positive end-expiratory pressures for ≥ 1 calendar-day. SETTING: 15 Paediatric Intensive Care Units. MAIN OUTCOME MEASURES: Mechanical ventilation duration, intensive care and hospital length of stay; (LOS) and mortality. RESULTS: A cohort of 391 ventilated children with an age (median, [Interquartile Ranges]) of 1 year[0.2-5.3] and 7 days[5-10] of mechanical ventilation were included. Intensive care and hospital stays were 11 [7-19] and 21 [14-39] days, respectively. Mortality was 5.9 %. Fifty-eight ventilator-associated respiratory infections were documented among 57 patients: Seventeen (29.3 %) qualified as ventilator-associated pneumonia (VAP) and 41 (70.7 %) as ventilator-associated tracheobronchitis (VAT). Eight pneumonias and 16 tracheobronchitis (47 % vs 39 %,P = 0.571) required positive end-expiratory pressure or oxygen increases consistent with ventilator-associated criteria. Pneumonias did not significantly impact on outcomes when compared to tracheobronchitis. In contrast, infections (pneumonia or tracheobronchitis) following VAEs criteria were associated with > 6, 8 and 15 extra-days of ventilation (16 vs 9.5, P = 0.001), intensive care stay (23.5 vs 15; P = 0.004) and hospital stay (39 vs 24; P = 0.015), respectively. CONCLUSION: When assessing ventilated children with respiratory infections, VAE apparently is associated with higher ventilator-dependency and LOS compared with pneumonia or tracheobronchitis. IMPLICATIONS FOR PRACTICE: Incorporating the modification of ventilatory settings for further categorization of the respiratory infections may facilitate therapeutic management among ventilated patients.

Transcriptomics reveals shared immunosuppressive landscapes in ventilator-associated lower respiratory tract infections (VA-LRTI) patients.

BACKGROUND: Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection. RESEARCH DESIGN AND METHODS: A prospective observational study in five medical ICUs to evaluate immunological alterations of patients with VA-LRTI. Immunological gene expression profiles in the blood using whole transcriptome microarrays in the first 24 hours following diagnosis. The area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of mRNA levels to differentiate VA-LRTI and lack of infection. A principal component analysis (PCA) was employed for analyzing the impact of each genetic expression footprint variable in explaining the variance of the cohort. RESULTS: There was overlapping between the three classes of patients encompassing gene expression levels of 8 genes (i.e. HLA, IL2RA, CD40LG, ICOS, CCR7, CD1C, CD3E). HLA-DRA was equally low among VAT and VAP patients characterizing immune depression, and significantly lower than the control group. CONCLUSIONS: Our findings suggest that VAP and VAT are not so different regarding gene expression levels suggesting a degree of immunosuppression. Our results indicate a state of immunoparalysis in respiratory infections in critically ill patients.

Protection Efficacy of the Infectious Laryngotracheitis (ILT) Serva CEO Vaccine Strain in Broiler Chickens Under Different Vaccination Coverage Conditions.

Mass vaccination against infectious laryngotracheitis virus (ILTV) in drinking water can result in variable initial vaccine take. Partial initial vaccine coverage of 20% with an Australian ILT vaccine (A20) previously resulted in significant protection against virulent ILTV challenge. This follow-up study used the international Serva ILT vaccine strain in a factorial design testing four levels of vaccination coverage (0%, 10%, 20%, or 100% of chicks eye-drop vaccinated with the live vaccine at 7 days of age) and three levels of ILTV challenge (no challenge or challenge at 7 or 21 days postvaccination [DPV]). The increase in ILTV load in choanal cleft swabs detected by qPCR after challenge was significantly reduced by 20% and 100% but not by 10% vaccination coverage. Vaccination reduced weight gain in unchallenged birds. Daily weight gain of birds was not affected by ILTV challenge at 7 DPV in any group, but following challenge at 21 DPV, it was significantly reduced in unvaccinated and 10% vaccinated groups relative to 20% and 100% vaccinated groups. Vaccination of 20% of the chickens provided substantial but incomplete protection (protective index range 44%-70%) against the severity of clinical signs and mortality following challenge while 10% vaccination coverage provided limited or no protection. Clinical signs were more severe and appeared earlier following challenge at 21 DPV than at 7 DPV. Within the vaccination treatments, eye-drop-vaccinated birds were better protected than their in-contact cohorts. In conclusion, partial vaccination of 20%, but not 10% of chickens, induced substantial protection against subsequent challenge. However, the attendant risks of reduced protection against early challenge and the possible reversion to virulence of vaccine virus when transmitted to unvaccinated chickens make it essential that 100% initial vaccine take be the goal of mass vaccination programs.

Eficacia protectora de la cepa vacunal CEO Serva del virus de la laringotraqueítis infecciosa (ILT) en pollos de engorde bajo diferentes condiciones de cobertura vacunal. La vacunación masiva contra el virus de la laringotraqueítis infecciosa (ILTV) en el agua de bebida puede resultar en una cobertura vacunal inicial variable. La cobertura vacunal inicial parcial del 20 % con una vacuna ILT australiana (A20) previamente resultó en una protección significativa contra el desafío virulento con el virus de la laringotraqueítis. Este estudio de seguimiento utilizó la cepa de la vacuna vacunal internacional Serva ILT en un diseño factorial para probar cuatro niveles de cobertura de vacunación (0 %, 10 %, 20 % o 100 % de pollitos vacunados por gota ocular con la vacuna viva a los siete días de edad) y tres niveles de desafío con el virus de la laringotraqueítis (sin desafío o con desafío a los 7 o 21 días después de la vacunación [DPV]). El aumento en la carga viral en hisopos de la hendidura coanal detectados por qPCR después del desafío se redujo significativamente con cobertura de vacunación del 20% y 100%, pero no con el 10%. La vacunación redujo el aumento de peso en las aves no desafiadas. La ganancia diaria de peso de las aves no se vio afectada por el desafío con el virus de la laringotraqueítis a los siete días después de la vacunación en ningún grupo, pero después del desafío a los 21 días después de la vacunación, se redujo significativamente en los grupos no vacunados y con cobertura del 10% en comparación con los grupos con cobertura del 20% y 100%. La vacunación del 20 % de los pollos brindó una protección sustancial pero incompleta (con un rango de índice de protección del 44 % al 70 %) contra la severidad de los signos clínicos y la mortalidad después del desafío, mientras que la cobertura de vacunación del 10 % brindó protección limitada o nula. Los signos clínicos fueron más graves y aparecieron más temprano después del desafío a los 21 días después de la vacunación en comparación con el desafío a los siete días después de la vacunación. Dentro de los tratamientos de vacunación, las aves vacunadas con gota ocular estaban mejor protegidas que sus cohortes en contacto. En conclusión, la cobertura de vacunación parcial del 20%, pero no del 10% de los pollos, indujo una protección sustancial contra el desafío posterior. Sin embargo, los riesgos concomitantes de una protección reducida contra el desafío temprano y la posible reversión a la virulencia del virus vacunal cuando se transmite a pollos no vacunados hacen que sea esencial que la cobertura vacunal inicial del 100% sea el objetivo de los programas de vacunación masiva.

Pathogenesis of Bohle iridovirus infection in Krefft's freshwater turtle hatchlings (Emydura macquarii krefftii).

Ranaviruses have been detected in over 12 families of reptiles including many genera of turtles, tortoises, and terrapins, but the pathogenesis of these infections is still poorly understood. Krefft's river turtle hatchlings (N = 36; Emydura macquarii krefftii) were inoculated intramuscularly with Bohle iridovirus (BIV, Ranavirus, isolate) or saline, and euthanized at 9 timepoints (3 infected and 1 control per timepoint) over a 24-day period. Samples of lung, liver, kidney, and spleen were collected for quantitative polymerase chain reaction (PCR); internal organs, skin, and oral cavity samples were fixed for histopathological examination. The earliest lesions, at 8 days postinoculation (dpi), were lymphocytic inflammation of the skin and fibrinoid necrosis of regional vessels at the site of inoculation, and mild ulcerative necrosis with lymphocytic and heterophilic inflammation in the oral, nasal, and tongue mucosae. Fibrinonecrotic foci with heterophilic inflammation were detected in spleen and gonads at 16 dpi. Multifocal hepatic necrosis, heterophilic inflammation, and occasional basophilic intracytoplasmic inclusion bodies were observed at 20 dpi, along with ulcerative lymphocytic and heterophilic tracheitis and bronchitis. Tracheitis, bronchitis, and rare bone marrow necrosis were present at 24 dpi. Of the viscera tested for ranaviral DNA by PCR, the liver and spleen had the highest viral loads throughout infection, and thus appeared to be major targets of viral replication. Testing of whole blood by qPCR was the most-effective ante-mortem method for detecting ranaviral infection compared with oral swabs. This study represents the first time-dependent pathogenesis study of a ranaviral infection in turtles.

Late relapse of ulcerative colitis presenting as tracheobronchitis: a case report.

BACKGROUND: Lung involvement in inflammatory bowel diseases usually follows colitis. However, the time to lung involvement onset varies depending on the case, and pulmonary lesions are usually not parallel to exacerbations of the colitis. CASE PRESENTATION: A 67-year-old Asian woman with a 38-year history of ulcerative colitis presented to our hospital with a complaint of prolonged dry cough for 2 months. The colitis had remained quiescent for > 35 years with low-dose salazosulfapyridine treatment. Chest computed tomography indicated circumferential thickening of the tracheal wall, while bronchoscopy examination revealed widespread erythematous edema and diffuse narrowing of the bronchial lumen. Biopsy of the bronchial mucosa showed submucosal lymphocytic infiltration. She was diagnosed with ulcerative-colitis-related tracheobronchitis and successfully treated with corticosteroids. CONCLUSIONS: Tracheobronchitis, in our case, occurred despite the longest remission period previously reported. Careful follow-up is necessary for the early recognition and treatment of pulmonary disease in patients with ulcerative colitis, regardless of the disease duration and long-term remission of colitis.

Evaluation of barometric whole-body plethysmography for therapy monitoring in cats with feline lower airway disease.

OBJECTIVES: Feline lower airway disease (FLAD) is a common respiratory condition in cats. Traditionally, response to therapy is monitored only by evaluation of clinical signs and radiographic examination of the lungs. Barometric whole-body plethysmography (BWBP) is considered a non-invasive, well-tolerated form of measuring airway reactivity in cats. The aim of the study was to assess pulmonary function testing by BWBP for non-invasive evaluation of response to therapy in cats with FLAD and to investigate whether BWBP parameters correlate with clinical severity. MATERIAL AND METHODS: The prospective study included 25 client-owned cats, diagnosed with FLAD on the basis of their medical history, clinical signs, radiographic findings, and bronchoalveolar lavage fluid (BALF) examination. At three time points (day 0, 14, and 60), a standardised owner questionnaire, a clinical examination and BWBP measurements were carried out. Results of the questionnaire and the clinical examination were evaluated using a clinical 12-point score. Individual therapy was administered to all patients after diagnosis, based on the severity of disease and compliance of the cat. RESULTS: The total clinical score significantly improved over the entire study period (p<0.001). Significant improvement was detected for the frequency of coughing (p = 0.009), respiratory distress (p = 0.001), lung auscultation findings (p = 0.002), and general condition and appetite (p = 0.045). The BWBP parameter Penh, an indicator of bronchoconstriction, improved significantly under initial therapy between day 0 and 14 (p = 0.009). A significant correlation between Penh and the severity of auscultation findings was seen on day 0 (r = 0.40; p = 0.013). CONCLUSION: The study supports the role of Penh as a non-invasive parameter for monitoring initial treatment response in cats with FLAD. Further studies are needed to address whether other BWBP parameters might be suitable for non-invasive therapy monitoring of FLAD. Clinical evaluation is always essential in cats with FLAD to evaluate treatment response.

Necrotizing Tracheitis Complicated by Tracheal Wall Perforation.

Necrotizing tracheitis is a rare condition, mainly seen in immunocompromised patients, that may lead to pseudomembrane formation, airway obstruction and in severe cases, tracheal perforation. We present a case of a 32-year-old male with poorly controlled diabetes who presented with productive cough, dysphagia, and respiratory distress. Bronchoscopy revealed extensive tracheal necrosis along a 4-5 cm segment of cartilaginous trachea and was complicated by tracheal perforation with false passage into the anterior mediastinum. Once the airway was re-established, a multidisciplinary team discussed options for definitive airway management, including tracheal reconstruction, pulmonary stent, or tracheostomy. Ultimately, a distal XLT tracheostomy was placed. Microbiology specimens of the tracheal tissue were positive for Actinomyces. The patient was started on long-term antibiotics and diabetes management. At three-month follow-up, the trachea was patent with near complete mucosalization of the previously necrotic segment. An area of proximal tracheal stenosis was successfully managed with a customized tracheal T-tube. In conclusion, this is a case of necrotizing tracheitis complicated by tracheal perforation. Successful treatment required a multidisciplinary team for airway management as well as medical treatment of immunocompromising risk factors and antimicrobial therapy. This enabled timely healing of the trachea and a durable airway.