The Incidence of Laryngotracheal Stenosis in Neonates With a History of Ventilator-Associated Pneumonia.

OBJECTIVES/HYPOTHESIS: Neonatal patients requiring prolonged intubation are susceptible to both infection and laryngotracheal stenosis (LTS). This study investigated the effect of ventilator-associated pneumonia (VAP) on the development of LTS in neonates. STUDY DESIGN: Retrospective case-control study. METHODS: The incidence of LTS in neonates with VAP was compared with the incidence of LTS in matched intubated controls without VAP. Patients were treated at a tertiary-care medical center from 2004 to 2014. Eligible patient records were assessed for the development of LTS. Demographics, medical comorbidities, infection characteristics, and treatment variables were compared using unpaired t test or χ2 test. Statistical significance was set a priori at P < .05. RESULTS: When comparing the VAP patients with matched non-VAP controls, we found no significant differences in the incidence of LTS (VAP vs. non-VAP, 8.3% vs. 6.7%; P = .73). In subgroup analysis of the VAP cohort, LTS and non-LTS patients demonstrated similar VAP organisms on broncho-alveolar lavage (Klebsiella pneumoniae, Pseudomonas aeroginosa, Escherichia coli, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Enterobacter). Additionally, within the VAP cohort, LTS and non-LTS patients showed similar gestational age (LTS vs. non-LTS, 31.3 days vs. 28.1 days; P = .22), birth weight (LTS vs. non-LTS, 1.6 kg vs. 1.2 kg; P = .33), and similar intubation duration (LTS vs. non-LTS, 37.8 days vs. 27.5 days; P = .52). CONCLUSIONS: In this neonatal cohort, VAP was not associated with an increased incidence of LTS. Given severity of the burden of LTS on the healthcare system, multi-institutional longitudinal investigation into contributing risk factors for neonatal LTS is warranted. LEVEL OF EVIDENCE: NA Laryngoscope, 130:2252-2255, 2020.

Laryngotracheal Microbiota in Adult Laryngotracheal Stenosis.

Laryngotracheal stenosis is an obstructive respiratory disease that leads to voicing difficulties and dyspnea with potential life-threatening consequences. The majority of incidences are due to iatrogenic etiology from endotracheal tube intubation; however, airway scarring also has idiopathic causes. While recent evidence suggests a microbial contribution to mucosal inflammation, the microbiota associated with different types of stenosis has not been characterized. High-throughput sequencing of the V4 region of the16S rRNA gene was performed to characterize the microbial communities of 61 swab samples from 17 iatrogenic and 10 adult idiopathic stenosis patients. Nonscar swabs from stenosis patients were internal controls, and eight swabs from four patients without stenosis represented external controls. Significant differences in diversity were observed between scar and nonscar samples and among sample sites, with decreased diversity detected in scar samples and the glottis region. Permutational analysis of variance (PERMANOVA) results revealed significant differences in community composition for scar versus nonscar samples, etiology type, sample site, groups (iatrogenic, idiopathic, and internal and external controls), and individual patients. Pairwise Spearman's correlation revealed a strong inverse correlation between Prevotella and Streptococcus among all samples. Finally, bacteria in the family Moraxellaceae were found to be distinctly associated with idiopathic stenosis samples in comparison with external controls. Our findings suggest that specific microbiota and community shifts are present with laryngotracheal stenosis in adults, with members of the family Moraxellaceae, including the known pathogens Moraxella and Acinetobacter, identified in idiopathic scar. Further work is warranted to elucidate the contributing role of bacteria on the pathogenesis of laryngotracheal stenosis.IMPORTANCE The laryngotracheal region resides at the intersection between the heavily studied nasal cavity and lungs; however, examination of the microbiome in chronic inflammatory conditions of the subglottis and trachea remains scarce. To date, studies have focused on the microbiota of the vocal folds, or the glottis, for laryngeal carcinoma, as well as healthy larynges, benign vocal fold lesions, and larynges exposed to smoking and refluxate. In this study, we seek to examine the structure and composition of the microbial community in adult laryngotracheal stenosis of various etiologies. Due to the heterogeneity among the underlying pathogenesis mechanisms and clinical outcomes seen in laryngotracheal stenosis disease, we hypothesized that different microbial profiles will be detected among various stenosis etiology types. Understanding differences in the microbiota for subglottic stenosis subtypes may shed light upon etiology-specific biomarker identification and offer novel insights into management approaches for this debilitating disease.

The presence of staphylococcal superantigens in nasal swabs and correlation with activity of granulomatosis with polyangiitis in own material.

OBJECTIVES: Nasal carriage of Staphylococcus aureus and its superantigens (SAg) seem to be a risk factor disease exacerbation in granulomatosis with polyangiitis (GPA). We investigated the association between the presence of SAg in nasal swabs and activity of disease in GPA patients also taking into account correlation with an antimicrobial treatment. METHODS: In a prospective study of a total of 150 GPA patients hospitalised in the period 2009-2016, nasal swabs were examined for the presence of Staphylococcus aureus and SAg. Subsequently, the association with disease activity was assessed. RESULTS: Of 362 Staphylococcus aureus-positive nasal swab cultures from 115 of the 150 patients, the presence of at least one SAg in 126 samples (34.8%) from 56 patients (48.7%) was found. Among the 17 patients with limited to subglottic stenosis (SGS) disease, SAg were detected in 6 cases (35.3%). We did not find a significant correlation between the presence of SAg and disease activity (p=0.986), although when individual SAg were analysed separatively, SED and TSST-1 were more frequently present in active disease. Additionally, the results of the analysis demonstrated a protective effect of trimethoprim/sulfamethoxazole (T/S) treatment (0R 0.52, p<0.0092) in GPA patients. Interestingly, GPA limited to SGS appeared as an unfavourable factor associated with disease activity (0R 1.84, p=0.05). CONCLUSIONS: The association between staphylococcal SAg in nasal swabs and GPA activity is not evident. Multiple mechanisms that may lead to disease activation still need to be investigated.

Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species.

OBJECTIVES/HYPOTHESIS: Idiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown. Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens. METHODS: Utilizing 30 human iSGS, 20 intubation-related tracheal stenosis (iLTS), and 20 healthy control specimens, we applied molecular, immunohistochemical, electron microscopic, immunologic, and Sanger-sequencing techniques. RESULTS: With unbiased culture-independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that, rather than Mycobacterium tuberculosis, a variant member of the Mycobacterium tuberculosis complex or a closely related novel mycobacterium is present in iSGS specimens. CONCLUSION: These studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention. LEVEL OF EVIDENCE: NA Laryngoscope, 127:179-185, 2017.

Treatment of severe forms of paracoccidioidomycosis: is there a role for corticosteroids?

Despite their immunosuppressive effects, corticosteroids have long been used as adjunct therapy (aCST) in the treatment of infectious diseases. The rationale is that in certain infections it is necessary to decrease the exacerbated host's inflammatory response, which can otherwise result in tissue damage and organ dysfunction. In fact, a major concern in treating paracoccidioidomycosis (PCM) is the host's intense inflammatory response to Paracoccidioides brasiliensis, which can be further intensified by antifungal therapy. Depending on its localization, this immunological phenomenon may be life threatening or result in permanent sequels, as is the case for some patients with cerebral or laryngeal involvement. However, the literature on aCST in paracoccidioidomycosis treatment is scarce and as a result we present our recent experience in the management of four patients with severe PCM manifestations, i.e., cerebral paracoccidioidal granuloma, laryngeal stenosis, compressive abdominal mass, and exacerbated inflammatory response with tissue destruction. In addition to the antifungal therapy, these patients required aCST, which probably promoted their clinical improvement and/or prevented serious complications. We suggest that aCST: (a) can potentially help in the management of selected cases of severe forms of PCM, particularly when there is a risk of acute complications, and (b) that it can be used safely provided that the risk-benefit ratio is carefully weighed. Well-controlled, prospective studies of aCST in the treatment of severe cases of paracoccidioidomycosis are needed to better define its role in the management of PCM.

Biofilm accumulation on endotracheal tubes following prolonged intubation.

OBJECTIVE: To demonstrate that patients who have been intubated for prolonged periods of time will have an increased likelihood of developing bacterial biofilm on their endotracheal tubes. METHODS: We collected endotracheal tubes from patients at the time of extubation, and analysed representative sections with scanning electron microscopy for morphologic evidence of biofilms. RESULTS: From September 2007 to September 2008, 32 endotracheal tubes were analysed with electron microscopy. Patients who had been intubated for 6 days or longer had a significantly higher percentage of endotracheal tubes that exhibited bacterial biofilms, compared with patients intubated for less than 6 days (88.9 versus 57.1 per cent, p = 0.0439). CONCLUSIONS: Longer duration of intubation is associated with a higher incidence of bacterial biofilm. Further research is needed to link the presence of bacterial biofilms to acquired laryngotracheal damage.

[Characteristics of microflora of laryngeal mucosa in healthy subjects and patients with cicatrical stenosis of the larynx].

The authors present data on the occurrence, density, and species composition of microorganisms isolated from pharyngeal mucosa of 40 healthy subjects and 55 patients with cicatrical stenosis of the larynx. The total density of microbial populations in control subjects was estimated at 2,672+/-614 CFU/ml compared with 17,510+/-1,983 CFU/ml in patients with cicatrical stenosis of the larynx unrelated to malignant neoplastic growth and 19,375+/-2,103 CFU/ml in patients who had experienced surgical intervention for the treatment of malignancy. A total of 312 microbial strains were isolated and identified. Coccal bacteria were the predominant group (streptococci-74 strains, neisseria-72, staphylococci-62, micrococci-12). Collectively, they comprised 70.5% of all isolated strains representing autochthonous microflora. Corynebacteria, moraxellas, and enterobacteria (transitory forms) were rare. The occurrence of neisseria, staphylococci and fungi (genus Candida) in patients with cicatrical stenosis of the larynx was significantly higher than in the healthy subjects. Moreover, the patients developed dysbacteriosis with the predominance of N. flavescens, S. aureus, S. epidermidis, S. alpha-haemoliticus, and Candida sp. It is concluded that elucidation of the microbial landscape in patients with cicatrical stenosis of the larynx is of importance for planning prevention and management of pyoseptic complications in the course of surgical treatment.

Bacteriology of granulation tissue in laryngotracheal stenosis patients.

BACKGROUND: The formation of granulation tissue is an important factor promoting recurrence after surgical treatment of laryngotracheal stenosis. Bacterial infection was claimed to be the cause. OBJECTIVE: The present study aimed to identify the bacteriology of granulation tissue in laryngotracheal stenosis patients. MATERIAL AND METHOD: Data was collected prospectively. Granulation tissue found in the site of laryngotracheal stenosis was removed and sent to the microbiologic study to identify the organisms. RESULTS: Twenty-four specimens from 17 patients were included in the present study. Coagulase-positive Staphylococcus (45.8%) was the most common gram-positive organism and Pseudomonas aeruginosa as well as Enterobacter species (16.7%) were the most common gram-negative bacteria. Ciprofloxacin may be the oral antibiotic that should be recommended. CONCLUSION: Coagulase-positive Staphylococcus, Pseudomonas aeruginosa as well as Enterobacter species were the common organisms identified from the granulation tissue in recurrent laryngotracheal stenosis. Oral antibiotics, such as ciprofloxacin, may have benefit in reducing the formation of this granulation tissue.

Postmortem diagnostics using MSCT and MRI of a lethal streptococcus group A infection at infancy: a case report.

Postmortem cross-sectional imaging using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) was considered as a base for a minimal invasive postmortem investigation in forensic medicine such as within the Virtopsy approach. We present the case of a 3-year-old girl with a lethal streptococcus group A infection and the findings of postmortem imaging in this kind of natural death. Postmortem MSCT and MRI revealed an edematous occlusion of the larynx at the level of the vocal cords, severe pneumonia with atelectatic parts of both upper lobes and complete atelectasis of both lower lobes, purulent fluid-filled right main bronchus, enlargement of cervical lymph nodes and pharyngeal tonsils, and additionally, a remaining glossopharyngeal cyst as well as an ureter fissus of the right kidney. All relevant autopsy findings could be obtained and visualized by postmortem imaging and confirmed by histological and microbiological investigations supporting the idea of a minimal invasive autopsy technique.

Acquired subglottic stenosis caused by methicillin resistant Staphylococcus aureus that produce epidermal cell differentiation inhibitor.

Local infection of the trachea in intubated neonates is one of the main risk factors for development of acquired subglottic stenosis, although its role in the pathogenesis is unclear. Methicillin resistant Staphylococcus aureus (MRSA) is often the cause of critical illness in neonatal patients. Two cases are reported of acquired subglottic stenosis following bacterial infection of the trachea, suggesting an association with the staphylococcal exotoxin, epidermal cell differentiation inhibitor (EDIN). EDIN-producing MRSA were isolated from purulent tracheal secretions from both infants. Acquired subglottic stenosis in both cases was probably caused by delayed wound healing as the result of EDIN inhibition of epithelial cell migration.

Infectious pseudomonas subglottic stenosis occurring in a patient with acquired immunodeficiency syndrome.

Pseudomonas aeruginosa is emerging as an increasingly common opportunistic infective agent in the immunocompromised human immunodeficiency virus (HIV) positive patient (Kielhofner et al., 1992). Improvements in the prevention and treatment of opportunistic infections in HIV and acquired immunodeficiency syndrome (AIDS) has led to longer life expectancy (Graham et al., 1992), and this has changed the incidence of Pseudomonas aeruginosa infection in this population (Baron and Hollander, 1993). We present a case of a patient with AIDS who developed a fulminant Pseudomonas aeruginosa stenosing subglottic infection. We are unaware of any previous reports of this particular manifestation of Pseudomonas aeruginosa infection.

Microbial flora of the subglottis in intubated pediatric patients.

Infection of the intubated subglottis is felt to be one of the many factors involved in the pathogenesis of acquired cicatricial subglottic stenosis. The precise role of infection is unclear and the microbial flora has not been established. An analysis of subglottic culture material, from 22 intubated pediatric patients undergoing tracheotomy, has been performed to establish the nature of the subglottic microbial flora. Fifty-nine isolates were found, including 19 types of organisms. The number of isolates per patient ranged from one to eight, with an average of 2.7 isolates per patient. The most common isolates in the 22 patients were alpha-hemolytic Streptococcus viridans (17 isolates-77%), Neisseria sp. (6 isolates-27%), Pseudomonas sp. (5 isolates-22%), and coagulase negative Staphylococcus sp. (5 isolates-22%). This data indicates that colonization of the subglottis in intubated pediatric patients is polymicrobial in nature. alpha-Hemolytic Streptococcus viridans and Neisseria sp. were most common, with a shift in cultured flora towards Pseudomonas sp. in patients intubated for more than 10 days. In view of this, antimicrobial therapy may be of benefit in preventing acquired cicatricial subglottic stenosis.