Bacterial Respiratory Infections Research Articles

Disposable Peptidoglycan-Specific Biosensor for Noninvasive Real-Time Detection of Broad-Spectrum Gram-Positive Bacteria in Exhaled Breath Condensates.

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.

Serum procalcitonin as a diagnostic biomarker in dogs with bacterial respiratory diseases.

Procalcitonin (PCT) is a useful biomarker in humans in the identification of bacterial respiratory infections. The aim of this study was to investigate the utility of serum PCT measurements as a diagnostic biomarker in canine bacterial lower respiratory tract diseases. PCT concentrations were measured in serum samples with an ELISA method previously validated for dogs. All dogs underwent thorough clinical examinations, and the diagnosis of respiratory disease was based on clinical and laboratory findings, diagnostic imaging, as well as cytology and bacterial culture of respiratory samples. PCT concentrations between different cohorts of dogs were compared with an ANOVA-model. Sixty-two privately owned dogs with respiratory diseases, 25 with bacterial pneumonia (BP), 17 with bacterial bronchitis caused by Bordetella bronchiseptica (BB), and 20 with chronic bronchitis (CB) as well as 44 healthy controls were included in the study. Serum PCT concentrations in dogs with bacterial respiratory diseases (BP mean 51.8 ng/L ± standard deviation [SD] 40.6 ng/L and BB mean 61.4 ng/L ± SD 35.3 ng/L) were not significantly different when compared with dogs with a non-bacterial respiratory disease (CB mean 89.7 ± SD 73.5 ng/L) or healthy dogs (mean 51.0 ng/L ± SD 37.5 ng/L, p > .05 in all comparisons). These results indicate that despite being a valuable diagnostic, prognostic, and follow-up marker in humans with pneumonia, serum PCT concentrations are not elevated in dogs with bacterial respiratory diseases and, therefore, cannot be used as a diagnostic biomarker in dogs.

Neuropeptide Y affects B-cell activation functions

Introduction: Sympathetic nerves secrete neurotransmitters in response to pathogenic organisms in various immunological contexts. Most studies have focused on norepinephrine (NE) which has shown numerous immunomodulatory effects involving pro- and anti-inflammatory responses. However, sympathetic neurons contain also varicosities where neuropeptides, mainly neuropeptide Y (NPY), are stored. NPY play roles in various physiological processes, including regulating metabolism, vascular function, and immune function but little is known on its action during bacterial respiratory infection. The regulation of its secretion and its impact on the immune system during infection remains unclear. We investigated the role of NPY in B-cell responses during bacterial infection. Methods: Naïve B-cells isolated from mice splenocytes (2M/2F) were stimulated with IL-4 and LPS, along with NE or NPY. After 96 hours, cells were stained and analyzed by flow cytometry and transcripts were isolated for quantitative real-time PCR. Media was collected until immunoglobulin analysis. To investigate NPY role during infection, we used a mice model of bacterial lung infection. Mice were intranasally exposed twice with streptococcus pneumoniae (serotype 19F on day 0: 104 CFU and on day 9: 108 CFU); experiments took place 16 hours later. Control animals were infused with vehicle only. Results: Apart from beta2-adrenergic receptor, isolated B-cells were found to express alpha2- and beta1-adrenergic receptor transcripts. In vitro stimulation of B-cell with IL-4 and LPS (T-cell independent activation) downregulated beta-adrenergic and upregulated alpha2-adrenergic, as well as NPY receptors (Npy1r, Npy2r, Npy4r, Npy5r). Unlike NE, NPY has shown to affect B-cell proliferation and drastically increases IgG positive-cells during stimulation. However, neither NE nor NPY seem to regulate IgG release in this condition. In vivo experiments indicate that NPY level increased in the lung in response to streptococcal challenge, contrasting with the unchanged levels of NE. Conclusion: Our findings contribute to our understanding of how sympathetic neurotransmitters regulates B-cell expansion, memory, and antibody production during infection. Furthermore, our research gives new insights into the function(s) and antimicrobial capacity of neuropeptide Y. These findings allow for the development of new and more effective therapeutic strategies for invasive bacterial infections. 1R21AI159221, UCOP TRDRP T32KT4708. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Automatic Microfluidic Harmonized RAA-CRISPR Diagnostic System for Rapid and Accurate Identification of Bacterial Respiratory Tract Infections.

Respiratory tract infections (RTIs) pose a grave threat to human health, with bacterial pathogens being the primary culprits behind severe illness and mortality. In response to the pressing issue, we developed a centrifugal microfluidic chip integrated with a recombinase-aided amplification (RAA)-clustered regularly interspaced short palindromic repeats (CRISPR) system to achieve rapid detection of respiratory pathogens. The limitations of conventional two-step CRISPR-mediated systems were effectively addressed by employing the all-in-one RAA-CRISPR detection method, thereby enhancing the accuracy and sensitivity of bacterial detection. Moreover, the integration of a centrifugal microfluidic chip led to reduced sample consumption and significantly improved the detection throughput, enabling the simultaneous detection of multiple respiratory pathogens. Furthermore, the incorporation of Chelex-100 in the sample pretreatment enabled a sample-to-answer capability. This pivotal addition facilitated the deployment of the system in real clinical sample testing, enabling the accurate detection of 12 common respiratory bacteria within a set of 60 clinical samples. The system offers rapid and reliable results that are crucial for clinical diagnosis, enabling healthcare professionals to administer timely and accurate treatment interventions to patients.

Vitamin E (Alpha-tocopherol) Central Nervous System (CNS) Effects [Increasing Ramified Microglia; Decreasing Astrocytosis; Decreasing Oxidative Stress Biomarkers; Slowing Amyotrophic Lateral Sclerosis (ALS) Progression from Early to Advanced Disease] and Respiratory System Effects [Decreasing Vital Capacity Loss with Age by Increasing Alpha-tocopherol and Decreasing Gamma-tocopherol; Improving Resistance to Respiratory Bacterial Infections] Require Proper Dose/Dose Exposure Time and Outcome Measures for Future

Vitamin E (Alpha-tocopherol) Central Nervous System (CNS) Effects [Increasing Ramified Microglia; Decreasing Astrocytosis; Decreasing Oxidative Stress Biomarkers; Slowing Amyotrophic Lateral Sclerosis (ALS) Progression from Early to Advanced Disease] and Respiratory System Effects [Decreasing Vital Capacity Loss with Age by Increasing Alpha-tocopherol and Decreasing Gamma-tocopherol; Improving Resistance to Respiratory Bacterial Infections] Require Proper Dose/Dose Exposure Time and Outcome Measures for Future

Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair.

Bacterial and viral respiratory tract infections are the most common infectious diseases, leading to worldwide morbidity and mortality. In the past 10 years, the importance of lung microbiota emerged in the context of pulmonary diseases, although the mechanisms by which it impacts the intestinal environment have not yet been fully identified. On the contrary, gut microbial dysbiosis is associated with disease etiology or/and development in the lung. In this review, we present an overview of the lung microbiome modifications occurring during respiratory infections, namely, reduced community diversity and increased microbial burden, and of the downstream consequences on host-pathogen interaction, inflammatory signals, and cytokines production, in turn affecting the disease progression and outcome. Particularly, we focus on the role of the gut-lung bidirectional communication in shaping inflammation and immunity in this context, resuming both animal and human studies. Moreover, we discuss the challenges and possibilities related to novel microbial-based (probiotics and dietary supplementation) and microbial-targeted therapies (antibacterial monoclonal antibodies and bacteriophages), aimed to remodel the composition of resident microbial communities and restore health. Finally, we propose an outlook of some relevant questions in the field to be answered with future research, which may have translational relevance for the prevention and control of respiratory infections.

Antimicrobial Sensitivity Profile in Psittacine Birds at an Avian Teaching Hospital: A Retrospective Study, 2015-2022.

Veterinary hospitals house patient populations with diverse infectious statuses, microbiota, and histories of prior antibiotic therapy. Choanal swabs are commonly used for assessing the upper respiratory tract of birds for bacterial disease, with the samples submitted for cytologic testing and/or culture and antimicrobial sensitivity testing. The aim of this retrospective study was to identify and quantify bacteria isolated from choanal swabs collected from psittacine patients at a veterinary teaching hospital in Mexico City, Mexico. Data regarding bacterial isolates from choanal swabs were obtained from the medical records of companion psittacines suspected of upper respiratory bacterial disease that presented between November 2015 and December 2022. A total of 47.8% (175 of 366) of the bacterial isolates were from specimens obtained from red-lored Amazons (Amazona autumnalis). Gram-negative bacteria predominated, with 27 different genera identified. Klebsiella, Staphylococcus, and Escherichia were the most frequently isolated genera. A total of 90.4% (331 of 366) of the isolates were resistant to at least 1 antibiotic tested in the sensitivity panel, and a single Klebsiella isolate was resistant to 13 different antibiotics. Gentamicin had a high percentage of efficacy (79.5%; 182 of 229) against the bacterial isolates, whereas isolates tested against sulfonamide-trimethoprim (46.7%, 98 of 210), streptomycin (43.8%; 88 of 201), and clindamycin (12.9%; 15 of 116) had susceptibilities <50%. This is the first study to report common bacterial isolates and their antimicrobial susceptibility patterns from choanal swab samples collected from companion psittacines suspected of upper respiratory disease in Mexico. Clinicians can use the information presented in this study as a guide for therapeutic decision-making when managing upper respiratory bacterial infections in companion psittacine patients.

Mucoadhesive Buccal Tablet Formulation of Azithromycin dihydrate for treatment of Upper Respiratory Tract Infection

The buccal drug delivery system is a versatile delivery system which can be designed for local or systemic effect. The objective of the study was to developed patient complacent tablet which can give sustain release of antibacterial agent for relief of upper respiratory tract infection. Azithromycin dihydrate is a semi-synthetic macrolide antibiotic widely used to prevent bacterial infections in the upper respiratory tract. The mucoadhesive buccal tablets of azithromycin dihydrate were formulated by varying concentrations of polymers (natural and synthetic), glidant and other excipients. The drug-excipient compatibility studies were carried out through DSC and FTIR studies. The selected excipients were found to be compatible. Further the dry blend of drug-excipients was evaluated for pre-compression properties. The prepared tablets were evaluated as per the general monograph for tablets of IP. The studies were also carried out to evaluate sustained release of the drug and mucoadhesivity of the tablets. A 23 level (2 level and 3 factors) factorial design was navigated to study the effect of natural, synthetic polymers and the glidant on mucoadhesive strength and percentage cumulative drug release at 8 hours. The responsive variables were analysed using ANOVA by Design-Expert version 12.0. It was concluded that these excipients significantly affected the response variables. The optimized tablet formulation was found to have an adequate mucoadhesion and a cumulative percentage release. The final product was performed for accelerated stability studies, optimized formulation was found to be stable at room temperature and accelerated temperature for three months.

Allergia agli antibiotici beta-lattamici: i miti da sfatare e le azioni pratiche da adottare

The penicillins (amoxicillin) are among the most effective and safe antibiotics for many common bacterial respiratory infections in paediatric age and should be avoided only when a true allergy is highly suspected. Severe true antibiotic allergies are rare and allergies are often overestimated. In high-income countries, 5-15% of patients report a penicillin allergy. However, in most cases (&gt; 95%), these patients do not have a true immunologically mediated allergy and they may very likely tolerate the antibiotic upon a new exposure. All patients defined as allergic should be carefully evaluated and their levels of antibiotic allergy risk determined. In cases of suspected penicillin allergy (e.g. those with cutaneous manifestations), skin tests are not necessary before prescribing a beta-lactam antibiotic (amoxicillin) and direct oral administration can be performed in low-risk phenotypes carefully selected according to simple protocols that do not always require a specialist evaluation. The article, based on the recommendations of the WHO Aware Manual, provides current evidence and practical guidance, and fosters a correct interpretation and management of an overestimated problem that does not promote an optimal and judicious antibiotic use.

Evaluation of a Clinical Decision Support System and an Automated Electronic Health Record Alert on Outpatient Prescribing of Cefdinir.

Acute bacterial upper respiratory infections are common indications for antibiotics in pediatrics, and many prescriptions may be inappropriate. Novel approaches to outpatient antimicrobial stewardship interventions are needed. This quasi-experimental study of an order set and best practice advisory alert targeting cefdinir prescriptions demonstrated an 8.4% decrease in cefdinir prescribing (P ≤ .001).

Bacterial respiratory infection epidemiology and antibiogram profile in patients attending in regional hospital, Meknes, Morocco

Bacterial respiratory infection epidemiology and antibiogram profile in patients attending in regional hospital, Meknes, Morocco

Laboratory tools for the direct detection of bacterial respiratory infections and antimicrobial resistance: a scoping review.

Rapid laboratory tests are urgently required to inform antimicrobial use in food animals. Our objective was to synthesize knowledge on the direct application of long-read metagenomic sequencing to respiratory samples to detect bacterial pathogens and antimicrobial resistance genes (ARGs) compared to PCR, loop-mediated isothermal amplification, and recombinase polymerase amplification. Our scoping review protocol followed the Joanna Briggs Institute and PRISMA Scoping Review reporting guidelines. Included studies reported on the direct application of these methods to respiratory samples from animals or humans to detect bacterial pathogens ±ARGs and included turnaround time (TAT) and analytical sensitivity. We excluded studies not reporting these or that were focused exclusively on bioinformatics. We identified 5,636 unique articles from 5 databases. Two-reviewer screening excluded 3,964, 788, and 784 articles at 3 levels, leaving 100 articles (19 animal and 81 human), of which only 7 studied long-read sequencing (only 1 in animals). Thirty-two studies investigated ARGs (only one in animals). Reported TATs ranged from minutes to 2 d; steps did not always include sample collection to results, and analytical sensitivity varied by study. Our review reveals a knowledge gap in research for the direct detection of bacterial respiratory pathogens and ARGs in animals using long-read metagenomic sequencing. There is an opportunity to harness the rapid development in this space to detect multiple pathogens and ARGs on a single sequencing run. Long-read metagenomic sequencing tools show potential to address the urgent need for research into rapid tests to support antimicrobial stewardship in food animal production.

Mucosal administration of an immunotherapy provides long-term protection against a bacterial respiratory infection

Mucosal administration of an immunotherapy provides long-term protection against a bacterial respiratory infection

Co-spray dried inhalable composite powders of ciprofloxacin and alginate oligosaccharide as anti-biofilm therapy

The treatment of chronic respiratory infections caused by biofilm formation are extremely challenging owing to poor drug penetration into the complex biofilm structure and high drug resistance. Local delivery of an antibiotic together with a non-antibiotic adjuvant to the lungs could often enhance the therapeutic responses by targeting different bacterial growth pathways and minimizing drug resistance. In this study, we designed new inhalable dry powders containing ciprofloxacin (CIP) and OligoG (Oli, a low-molecular-weight alginate oligosaccharide impairing the mucoid biofilms by interacting with their cationic ions) to combat respiratory bacterial biofilm infections. The resulting powders were characterized with respect to their morphology, solid-state property, surface chemistry, moisture sorption behavior, and dissolution rate. The aerosol performance and storage stability of the dry powders were also evaluated. The results showed that inhalable dry powders composed of CIP and Oli could be readily accomplished via the wet milling and spray drying process. Upon the storage under 20 ± 2 °C/20 ± 2 % relative humidity (RH) for one month, there was no significant change in the in vitro aerosol performances of the dry powders. In contrast, the dry powders became non-inhalable following the storage at 20 ± 2 °C/53 ± 2 % RH for one month due to the hygroscopic nature of Oli, which could be largely prevented by incorporation of leucine. Collectively, this study suggests that the newly developed co-spray-dried powders composed of CIP and Oli might represent a promising and alternative treatment strategy against respiratory bacterial biofilm infections.

A Polyclonal Antibody against a Burkholderia cenocepacia OmpA-like Protein Strongly Impairs Pseudomonas aeruginosa and B. multivorans Virulence.

Despite advances in therapies, bacterial chronic respiratory infections persist as life-threatening to patients suffering from cystic fibrosis (CF). Pseudomonas aeruginosa and bacteria of the Burkholderia cepacia complex are among the most difficult of these infections to treat, due to factors like their resistance to multiple antibiotics and ability to form biofilms. The lack of effective antimicrobial strategies prompted our search for alternative immunotherapies that can effectively control and reduce those infections among CF patients. Previous work from our group showed that the anti-BCAL2645 goat polyclonal antibody strongly inhibited Burkholderia cenocepacia to adhere and invade cultured epithelial cells. In this work, we showed that the polyclonal antibody anti-BCAL2645 also strongly inhibited the ability of P. aeruginosa to form biofilms, and to adhere and invade the human bronchial epithelial cell line CFBE41o-. The polyclonal antibody also inhibited, to a lesser extent, the ability of B. multivorans to adhere and invade the human bronchial epithelial cell line CFBE41o. We also show that the ability of B. cenocepacia, P. aeruginosa and B. multivorans to kill larvae of the Galleria mellonella model of infection was impaired when bacteria were incubated with the anti-BCAL2645 antibody prior to the infection. Our findings show that an antibody against BCAL2645 possesses a significant potential for the development of new immunotherapies against these three important bacterial species capable of causing devastating and often lethal infections among CF patients.

Disease-specific plasma protein profiles in patients with fever after traveling to tropical areas.

Fever is common among individuals seeking healthcare after traveling to tropical regions. Despite the association with potentially severe disease, the etiology is often not determined. Plasma protein patterns can be informative to understand the host response to infection and can potentially indicate the pathogen causing the disease. In this study, we measured 49 proteins in the plasma of 124 patients with fever after travel to tropical or subtropical regions. The patients had confirmed diagnoses of either malaria, dengue fever, influenza, bacterial respiratory tract infection, or bacterial gastroenteritis, representing the most common etiologies. We used multivariate and machine learning methods to identify combinations of proteins that contributed to distinguishing infected patients from healthy controls, and each other. Malaria displayed the most unique protein signature, indicating a strong immunoregulatory response with high levels of IL10, sTNFRI and II, and sCD25 but low levels of sCD40L. In contrast, bacterial gastroenteritis had high levels of sCD40L, APRIL, and IFN-γ, while dengue was the only infection with elevated IFN-α2. These results suggest that characterization of the inflammatory profile of individuals with fever can help to identify disease-specific host responses, which in turn can be used to guide future research on diagnostic strategies and therapeutic interventions.

Lipid-based nanomedicines for the treatment of bacterial respiratory infections: current state and new perspectives.

The global threat posed by antimicrobial resistance demands urgent action and the development of effective drugs. Lower respiratory tract infections remain the deadliest communicable disease worldwide, often challenging to treat due to the presence of bacteria that form recalcitrant biofilms. There is consensus that novel anti-infectives with reduced resistance compared with conventional antibiotics are needed, leading to extensive research on innovative antibacterial agents. This review explores the recent progress in lipid-based nanomedicines developed to counteract bacterial respiratory infections, especially those involving biofilm growth;focuses on improved drug bioavailability and targetingand highlights novel strategies to enhance treatment efficacy while emphasizing the importance of continued research in this dynamic field.

Bronchial Tree System Analysis of Live Beluga Whale (Delphinapterus leucas) Using Bronchoscopy.

Cetaceans, including beluga whales (Delphinapterus leucas), have high morbidity and mortality rates due to bacterial or fungal lower respiratory infections. Bronchoalveolar lavage fluid (BALF) collection by bronchoscopy is beneficial for detecting pathogenic microorganisms in the lower respiratory tract. Efficient and safe bronchoscopy requires characterizing the bronchial tree systems of beluga whales, as no reports exist on bronchial length and bifurcation. In this study, bronchoscopy was performed on five captive beluga whales (9-44 years old) to detect bronchial length and bifurcation. The lengths from the blowhole to the scope impassable points due to the minimized bronchi diameters of the left principal bronchus (LPB), right principal bronchus (RPB), and tracheal bronchus (TB) were 110-155, 110-150, and 80-110 cm, respectively, and were correlated with the body length. Bronchoscopy identified more than 10, 10, and 6 bifurcated bronchi from the LPB, RPB, and TB, respectively. This is the first report to clarify the differences in bronchial tree systems between beluga whales and other cetaceans, as well as the differences for each individual beluga whale. These results could be useful for obtaining BALF via bronchoscopy to detect pathogenic microorganisms causing infections in the lower respiratory tract of beluga whales.

Bacterial pathogens in Xpert MTB/RIF Ultra-negative sputum samples of patients with presumptive tuberculosis in a high TB burden setting: a 16S rRNA analysis.

In patients with presumptive tuberculosis (TB) in whom the diagnosis of TB was excluded, understanding the bacterial etiology of lower respiratory tract infections (LRTIs) is important for optimal patient management. A secondary analysis was performed on a cohort of 250 hospitalized patients with symptoms of TB. Bacterial DNA was extracted from sputum samples for Illumina 16S rRNA sequencing to identify bacterial species based on amplicon sequence variant level. The bacterial pathogen most likely to be responsible for the patients' LRTI could only be identified in a minority (6.0%, 13/215) of cases based on 16S rRNA amplicon sequencing: Mycoplasma pneumoniae (n = 7), Bordetella pertussis (n = 2), Acinetobacter baumanii (n = 2), and Pseudomonas aeruginosa (n = 2). Other putative pathogens were present in similar proportions of Xpert Ultra-positive and Xpert Ultra-negative sputum samples. The presence of Streptococcus (pseudo)pneumoniae appeared to increase the odds of radiological abnormalities (aOR 2.5, 95% CI 1.12-6.16) and the presence of S. (pseudo)pneumoniae (aOR 5.31, 95% CI 1.29-26.6) and Moraxella catarrhalis/nonliquefaciens (aOR 12.1, 95% CI 2.67-72.8) increased the odds of 6-month mortality, suggesting that these pathogens might have clinical relevance. M. pneumoniae, B. pertussis, and A. baumanii appeared to be the possible causes of TB-like symptoms. S. (pseudo)pneumoniae and M. catarrhalis/nonliquefaciens also appeared of clinical relevance based on 16S rRNA amplicon sequencing. Further research using tools with higher discriminatory power than 16S rRNA sequencing is required to develop optimal diagnostic and treatment strategies for this population.IMPORTANCEThe objective of this study was to identify possible bacterial lower respiratory tract infection (LRTI) pathogens in hospitalized patients who were initially suspected to have TB but later tested negative using the Xpert Ultra test. Although 16S rRNA was able to identify some less common or difficult-to-culture pathogens such as Mycoplasma pneumoniae and Bordetella pertussis, one of the main findings of the study is that, in contrast to what we had hypothesized, 16S rRNA is not a method that can be used to assist in the management of patients with presumptive TB having a negative Xpert Ultra test. Even though this could be considered a negative finding, we believe it is an important finding to report as it highlights the need for further research using different approaches.

Bacterial respiratory tract infection in dog

Bacterial respiratory tract infection in dog