Effects of Tham Nasal Alkalinization on Airway Microbial Communities: A Pilot Study in Non-CF and CF Adults

Objectives: In cystic fibrosis (CF), loss of CFTR-mediated bicarbonate secretion reduces the airway surface liquid (ASL) pH causing airway host defense defects. Aerosolized sodium bicarbonate can reverse these defects, but its effects are short-lived. Aerosolized tromethamine (THAM) also raises the ASL pH but its effects are much longer lasting. In this pilot study, we tested the hypothesis that nasally administered THAM would alter the nasal bacterial composition in adults with and without CF. Methods: Subjects (n = 32 total) received intranasally administered normal saline or THAM followed by a wash out period prior to receiving the other treatment. Nasal bacterial cultures were obtained prior to and after each treatment period. Results: At baseline, nasal swab bacterial counts were similar between non-CF and CF subjects, but CF subjects had reduced microbial diversity. Both nasal saline and THAM were well-tolerated. In non-CF subjects, nasal airway alkalinization decreased both the total bacterial density and the gram-positive bacterial species recovered. In both non-CF and CF subjects, THAM decreased the amount of Corynebacterium accolens detected, but increased the amount of Corynebacterium pseudodiphtheriticum recovered on nasal swabs. A reduction in Staphylococcus aureus nasal colonization was also found in subjects who grew C. pseudodiphtheriticum. Conclusions: This study shows that aerosolized THAM is safe and well-tolerated and that nasal airway alkalinization alters the composition of mucosal bacterial communities. Clinical Trial Registration: NCT00928135 ( https://clinicaltrials.gov/ct2/show/NCT00928135 ).

Upper Respiratory Microbiota in Relation to Ear and Nose Health Among Australian Aboriginal and Torres Strait Islander Children

Background We explored the nasal microbiota in Indigenous Australian children in relation to ear and nasal health. Methods In total, 103 Indigenous Australian children aged 2–7 years (mean 4.7 years) were recruited from 2 Queensland communities. Children’s ears, nose, and throats were examined and upper respiratory tract (URT) swabs collected. Clinical histories were obtained from parents/medical records. URT microbiota were characterized using culturomics with Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification. Real-time PCR was used to quantify otopathogen (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis) loads and detect respiratory viruses. Data were analyzed using beta diversity measures, regression modeling, and a correlation network analysis. Results Children with historical/current otitis media (OM) or URT infection (URTI) had higher nasal otopathogen detection and loads and rhinovirus detection compared with healthy children (all P < .04). Children with purulent rhinorrhea had higher nasal otopathogen detection and loads and rhinovirus detection (P < .04) compared with healthy children. High otopathogen loads were correlated in children with historical/current OM or URTI, whereas Corynebacterium pseudodiphtheriticum and Dolosigranulum pigrum were correlated in healthy children. Conclusions Corynebacterium pseudodiphtheriticum and D. pigrum are associated with URT and ear health. The importance of the main otopathogens in URT disease/OM was confirmed, and their role relates to co-colonization and high otopathogens loads.

Investigation of a Large Diphtheria Outbreak and Co-circulation of Corynebacterium pseudodiphtheriticum among Forcibly Displaced Myanmar Nationals, 2017–2019

Background Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic Corynebacteria, such as C. pseudodiphtheriticum rarely causes diphtheria-like illness. Recently several global diphtheria outbreaks have resulted from the breakdown of healthcare infrastructures particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among Forcibly Displaced Myanmar Nationals in Bangladesh. Methods Specimens and clinical information were collected from patients presenting at Diphtheria Treatment Centers. Swabs were tested for toxin-gene (tox) bearing C. diphtheriae by real-time (RT) PCR and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. Results Among 382 patients; 153 (40%) tested tox-positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture-confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. Conclusions We report the confirmation of a diphtheria outbreak and identification of a co-circulating Corynebacterium species. The high proportion of C. pseudodiphtheriticum co-detection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms.

The Ability of Respiratory Commensal Bacteria to Beneficially Modulate the Lung Innate Immune Response Is a Strain Dependent Characteristic

We investigated whether the ability of commensal respiratory bacteria to modulate the innate immune response against bacterial and viral pathogens was a shared or strain-specific characteristic. Bacterial strains belonging to the Corynebacterium pseudodiphtheriticum and Dolosigranulum pigrum species were compared by studying their influence in the Toll-like receptor (TLR)-2- and TLR3-triggered immune responses in the respiratory tract, as well as in the resistance to Respiratory Syncytial Virus (RSV) and Streptococcus pneumoniae infections. We demonstrated that nasally administered C. pseudodiphteriticum 090104 or D. pigrum 040417 were able to modulate respiratory immunity and increase the resistance against pathogens, while other strains of the same species did not influence the respiratory immune responses, demonstrating a clear strain-dependent immunomodulatory effect of respiratory commensal bacteria. We also reported here that bacterium-like particles (BLP) and cell walls derived from immunomodulatory respiratory commensal bacteria are an interesting alternative for the modulation of the respiratory immune system. Our study is a step forward in the positioning of certain strains of respiratory commensal bacteria as next-generation probiotics for the respiratory tract.

Antimicrobial Susceptibility Testing for Corynebacterium Species Isolated from Clinical Samples in Romania

Antimicrobial resistance is one of the most important public health issues. Besides classical multidrug resistance species associated with medical care involved in superficial or invasive infections, there are strains less commonly associated with hospital or outpatient setting’s infections. Non-diphtheria Corynebacterium spp. could produce infections in patients with or without immune-compromised status. The aim of our study was to determine the susceptibility to antimicrobial agents to Corynebacterium spp. from clinical samples collected from Romanian hospitalized individuals and outpatients. Twenty Corynebacterium strains were isolated and identified as Corynebacterium striatum (n = 7), Corynebacterium amycolatum (n = 7), C. urealyticum (n = 3), Corynebacterium afermentans (n = 2), and Corynebacterium pseudodiphtheriticum (n = 1). All isolates have been tested for antibiotic susceptibility by standardized disc diffusion method and minimal inhibitory concentration (MIC) tests. Seventeen isolates demonstrated multidrug resistance phenotypes. The molecular support responsible for high resistance to quinolones for ten of these strains was determined by the detection of point mutation in the gene sequence gyrA.