Common Respiratory Tract Pathogens Research Articles

A review of clinical and preclinical data supporting a role for resveratrol in the treatment of common respiratory tract pathogens

Respiratory infections are a relevant issue during infancy and childhood, constituting a major source of morbidity and imposing a substantial burden on healthcare systems. Conditions such as bronchiolitis, pneumonia, and influenza exemplify the gravity of these infections among pediatric populations. In the context of this health challenge, resveratrol, a naturally occurring polyphenolic antioxidant has emerged as a focal point of extensive research, known for its antioxidant, anti-inflammatory, and antimicrobial properties. This comprehensive review delves into the compound's extensive antimicrobial activities against a diverse range of bacteria and viruses, both as a standalone agent and in combination with conventional antibiotics. This compound exhibits notable antiviral activity against viruses implicated in severe respiratory infections, offering a potential therapeutic avenue. By exploring the antiviral mechanisms and highlighting the anti-inflammatory potential of resveratrol, this comprehensive overview contributes to a deeper understanding of its applicability in mitigating the complexities associated with pediatric respiratory infections.

Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

Modeling airway persistent infection of Moraxella catarrhalis and nontypeable Haemophilus influenzae by using human in vitro models.

Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are two common respiratory tract pathogens often associated with acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) as well as with otitis media (OM) in children. Although there is evidence that these pathogens can adopt persistence mechanisms such as biofilm formation, the precise means through which they contribute to disease severity and chronicity remains incompletely understood, posing challenges for their effective eradication. The identification of potential vaccine candidates frequently entails the characterization of the host-pathogen interplay in vitro even though this approach is limited by the fact that conventional models do not permit long term bacterial infections. In the present work, by using air-liquid-interface (ALI) human airway in vitro models, we aimed to recreate COPD-related persistent bacterial infections. In particular, we explored an alternative use of the ALI system consisting in the assembly of an inverted epithelium grown on the basal part of a transwell membrane with the aim to enable the functionality of natural defense mechanisms such as mucociliary clearance and cellular extrusion that are usually hampered during conventional ALI infection experiments. The inversion of the epithelium did not affect tissue differentiation and considerably delayed NTHi or Mcat infection progression, allowing one to monitor host-pathogen interactions for up to three weeks. Notably, the use of these models, coupled with confocal and transmission electron microscopy, revealed unique features associated with NTHi and Mcat infection, highlighting persistence strategies including the formation of intracellular bacterial communities (IBCs) and surface-associated biofilm-like structures. Overall, this study demonstrates the possibility to perform long term host-pathogen investigations in vitro with the aim to define persistence mechanisms adopted by respiratory pathogens and individuate potential new vaccine targets.

881. Saliva-Based, Extraction-Free PCR Testing For The Detection Of Key Respiratory Pathogens

Abstract Background Efforts to control and monitor transmissible infectious diseases rely on large-scale screening often impaired by logistically difficult or invasive sample collection. The use of saliva as a non-invasive sample type could alleviate bottlenecks encountered in mass testing strategies. Having extensively demonstrated saliva as a sensitive sample type for SARS-CoV-2 detection, we sought to validate the approach for other common upper respiratory tract pathogens. Methods We modified our RNA-extraction-free SARS-CoV-2 PCR test for multiplexed detection of four additional respiratory viruses (“SalivaDirect+”): influenza A/B, RSV, and hMPV, and singleplex detection of pneumococcus. Stability of detection was tested after storage of saliva from pathogen-positive patients at +4°C, room temperature (∼19°C) and 30°C for 72 hours. De-identified saliva samples were collected from consenting adults ≥ 18 years of age with respiratory symptoms, requiring nasopharyngeal-swab based SARS-CoV-2 testing at Yale Health, New Haven, CT, USA. Saliva samples from individuals testing nasopharyngeal-swab negative for SARS-CoV-2 at the clinical laboratory were stored at -80°C until further processing in the research laboratory. Results We confirmed the limit of assay detection at 4 copies/µl for each target. We confirmed pathogen detection remained stable at +4°C, room temperature and 30°C for up to 72 hours. From the symptomatic testing site, 804 nasopharyngeal swabs tested negative for SARS-CoV-2; their paired saliva samples were tested with the SalivaDirect+ assay. Of those, 17 (2.1%) tested positive for one of the viruses targeted (influenza A, n=7; RSV, n=4; hMPV, n=6). No samples tested positive for influenza B. For influenza A and RSV, detection by SalivaDirect+ was comparable to testing following RNA extraction but detection of hMPV was less sensitive, even following assay modifications. In singleplex testing, 87 (10.8%) samples tested positive for pneumococcus. Conclusion We expanded a low-cost, open-source saliva-based PCR test for detection of other common respiratory pathogens. By testing saliva samples from symptomatic, SARS-CoV-2-negative adults, we detected common respiratory viruses which were otherwise missed in testing focused solely on SARS-CoV-2. Disclosures Anne L. Wyllie, PhD, Co-Diagnostics: Board Member|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support

Development of a rapid, sensitive detection method for SARS-CoV-2 and influenza virus based on recombinase polymerase amplification combined with CRISPR-Cas12a assay.

Respiratory tract infections are associated with the most common diseases transmitted among people and remain a huge threat to global public health. Rapid and sensitive diagnosis of causative agents is critical for timely treatment and disease control. Here, we developed a novel method based on recombinase polymerase amplification (RPA) combined with CRISPR-Cas12a to detect three viral pathogens, including SARS-CoV-2, influenza A, and influenza B, which cause similar symptom complexes of flu cold in the respiratory tract. The detection method can be completed within 1 h, which is faster than other standard detection methods, and the limit of detection is approximately 102 copies/μL. Additionally, this detection system is highly specific and there is no cross-reactivity with other common respiratory tract pathogens. Based on this assay, we further developed a more simplified RPA/CRISPR-Cas12a system combined with lateral flow assay on a manual microfluidic chip, which can simultaneously detect these three viruses. This low-cost detection system is rapid and sensitive, which could be applied in the field and resource-limited areas without bulky and expensive instruments, providing powerful tools for the point-of-care diagnostic.

Brief research report: OM-85 reduces SARS-COV-2 viral RNA expression in nasopharyngeal cells from COVID-19 patients

OM-85 is a bacterial lysate from common respiratory tract pathogens, with an excellent safety profile, widely used to prevent recurrent respiratory tract infections. Several studies have been reporting the immunomodulating properties and antiviral roles of OM-85. The COVID-19 pandemic, originating in 2019, has presented a significant global public health crisis. While effective vaccines have been developed, vaccination rates vary considerably, and numerous concerning viral variants continue to emerge. The challenge persists in creating early interventions to halt the progression of the disease to its severe stages. To examine the therapeutic effect of OM-85 after SARS-CoV-2 infection and compared to recombinant human (rhINF-β) we collected nasopharyngeal cells from COVID-19 patients. The cells were treated ex-vivo with OM-85 or hrINF-β and the response was analyzed after 24h for gene expression by real-time PCR. We found that OM-85 decreased the SARS-CoV-2 N1 gene expression and increased RIG-I (DDX58) in these cells. The expression of ACE2 was undetected in these samples. These data support the antiviral effect of OM-85 against SARS-CoV-2.

Metaproteomic Analysis of Nasopharyngeal Swab Samples to Identify Microbial Peptides in COVID-19 Patients.

During the COVID-19 pandemic, impaired immunity and medical interventions resulted in cases of secondary infections. The clinical difficulties and dangers associated with secondary infections in patients necessitate the exploration of their microbiome. Metaproteomics is a powerful approach to study the taxonomic composition and functional status of the microbiome under study. In this study, the mass spectrometry (MS)-based data of nasopharyngeal swab samples from COVID-19 patients was used to investigate the metaproteome. We have established a robust bioinformatics workflow within the Galaxy platform, which includes (a) generation of a tailored database of the common respiratory tract pathogens, (b) database search using multiple search algorithms, and (c) verification of the detected microbial peptides. The microbial peptides detected in this study, belong to several opportunistic pathogens such as Streptococcus pneumoniae, Klebsiella pneumoniae, Rhizopus microsporus, and Syncephalastrum racemosum. Microbial proteins with a role in stress response, gene expression, and DNA repair were found to be upregulated in severe patients compared to negative patients. Using parallel reaction monitoring (PRM), we confirmed some of the microbial peptides in fresh clinical samples. MS-based clinical metaproteomics can serve as a powerful tool for detection and characterization of potential pathogens, which can significantly impact the diagnosis and treatment of patients.

Longitudinal investigation of pathogenic bacterial colonization in early childhood: Emphasis on the determinants of Moraxella catarrhalis colonization.

Moraxella catarrhalis is a common, potential pathogen colonizing the respiratory tract in children. However, there is little information regarding the determinants of M. catarrhalis colonization and disease development. A population-based cohort study was conducted to collect nasopharyngeal swabs from children aged 1, 2, 4, 6, 12, 18, 24, 36, and 60 months for the detection of four common respiratory tract pathogens, including Staphylococcus aureus, M. catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae. Questionnaires on breastfeeding status were administered during each visit. A total of 921 children were enrolled between 2012 and 2018. S.aureus was the most common pathogen, although the rates declined during the initial 18 months of life; in contrast, the other three pathogens increased during the first 5 years of life. M. catarrhalis was the second most common colonizing pathogen in all age groups, with prevalence ranging from 0.8% (7/842) at one month to 20.4% (33/162) at 60 months of age. Breastfed children (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.35-0.92; P=0.02) had a lower potential for M. catarrhalis carriage; however, infants with a longer duration of exclusive breastfeeding (OR: 1.12; 95% CI: 1.01-1.25; P=0.04), especially >12 months of age, had a higher rate of M. catarrhalis carriage. Breastfeeding should be promoted because it may be correlated with a lower risk of M. catarrhalis carriage. However, an extended period of exclusive breastfeeding may be positively associated with M. catarrhalis colonization.

Formulation, evaluation and optimization of orally disintegrating films of Azithromycin using DOE approach for the pediatrics with acute otitis media

Acute otitis media (AOM) is a common infection of early childhood with an inflammation of the middle ear and tympanic membrane. Azithromycin is a macrolide antibiotic which is proficient to provide effective treatment for pediatric AOM due to its in-vitro activity against the most common upper respiratory tract pathogens. The objective of this study was to develop and optimize orally disintegrating films (ODF) of azithromycin as an alternative patient compliant dosage form. Using casting method of films, five formulations (F1-F5) were fabricated and evaluated for different physico-chemical and mechanical parameters along with drug release kinetics. Design of Experiment approach was applied to discover the optimized ratio of the two disintegrants used in the formulations. FT-IR spectra confirmed the identity of azithromycin and absence of any chemical interaction between the drug and excipients. Optimized formulation was selected as F2 which comprised of two disintegrants i.e. crospovidone and croscarmellose sodium in 1:1 ratio. F2 possessed excellent physico-chemical, mechanical properties along with rapid dissolution. F2 demonstrated concentration dependent erosional type release pattern from a planer surface of hydrophilic matrix system. Addition of the disintegrating agents resulted in rapid fragmentation of the films following the above process. Accelerated stability study assured the longer shelf life of optimized ODFs. Rapid disintegration and dissolution may accelerate the onset of action bypassing hepatic first-pass metabolism which confirmed the utility of azithromycin loaded ODFs as alternative dosage form in management of pediatric AOM.

Antimicrobial Resistance Trends of the Most Common Causative Pathogens Associated with Community-acquired Respiratory Infections in China: 2009-2018.

BackgroundEmergence of antimicrobial resistance poses new challenges in the management of community acquired respiratory tract infections (CARTIs). Therefore, surveillance on the antimicrobial susceptibilities of common respiratory pathogens is valuable and guides empirical therapeutic choices in management of CARTIs.ObjectiveThe objective of the current study is to summarize the antimicrobial resistance trends in common respiratory tract pathogens isolated from patients with CARTIs in China, over a 10-year period (2009–2018).MethodsStreptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis strains were collected from multicenter, and antimicrobial susceptibility testing was performed in the research central laboratory of each study period from 2009–2018. The pathogens that accounted for CARTIs in the adult population was considered and summarized.ResultsFrom 2009–2018 a total of 3750 isolates were collected from 22 cities located across different regions of China. Among these the most common bacterial isolates include S. pneumoniae (53.7%) followed by H. influenza (32.4%), M. catarrhalis (13.9%). S. pneumoniae exhibited reduction in susceptibility and increase in resistance to penicillin, cephalosporins (cefaclor, cefuroxime, ceftriaxone) during the surveillance period. Invasive and noninvasive S. pneumoniae showed similar resistance. In the case of H. influenzae susceptibility to β-lactam and β-lactamase inhibitors (ampicillin, amoxicillin and AMC), SXT, clarithromycin and cephalosporins (cefuroxime, cefaclor, ceftazidime) was reduced over the past 10 years with an exception of ceftriaxone. Overall, moxifloxacin and levofloxacin have the highest susceptibility rates against S. pneumoniae (>95%) and H. influenza (>90%). M. catarrhalis exhibited susceptibility to almost all the tested antimicrobials.ConclusionIn China the 10-year trends showed a substantial increase in resistance to β-lactam drugs and reduction in sensitivity. However, certain antimicrobial agents namely fluoroquinolones including moxifloxacin and levofloxacin maintained low resistance rates with better susceptibility. Further, with few exceptions decline in susceptibility rates to macrolides and cephalosporins was observed among the tested pathogens.

Mild encephalitis/encephalopathy with a reversible splenial lesion associated with systemic Mycoplasma pneumoniae infection in North America: a case report

BackgroundMild encephalitis/encephalopathy with reversible splenial lesion is a clinical-radiological entity found to occur in the setting of an acute systemic inflammatory state with isolated lesions of the splenium of the corpus callosum and mild encephalopathy. Mild encephalitis/encephalopathy with reversible splenial lesion is commonly found to occur in children in the setting of viral infections. It has rarely been associated with Mycoplasma pneumoniae in the United States, unlike in Eastern and Southern Asia where this is much more prominent.Case presentationsA 5-year-old African-American boy with autism spectrum disorder presented to our emergency department with acute onset intractable vomiting, diarrhea, and abnormal tensing movements for 2 days, following a 6-day period of fatigue, fever, and spastic abdominal pain. Emergent work-up in our department ruled out acute gastrointestinal pathologies. Given the high fevers and encephalopathy, there was concern for meningitis or encephalitis. His cerebrospinal fluid profile was concerning for viral meningitis, however extensive infectious workup was negative. Magnetic resonance imaging of his brain demonstrated a T2 fluid-attenuated inversion recovery sequence hyperintensity in the splenium of the corpus callosum, read as postictal changes by radiology. Continuous video electroencephalography demonstrated mild diffuse encephalopathy without electrographic correlate of his tensing episodes. He was determined to have mild encephalitis/encephalopathy with a reversible splenial lesion in the setting of a postinfectious etiology. He was treated with a single pulse-dose of intravenous methylprednisolone, following which he gradually returned to his baseline the next day. Repeat magnetic resonance imaging and cerebrospinal fluid evaluation demonstrated resolution of previous findings. He was ultimately diagnosed with an acute M. pneumoniae infection, which was determined to be the etiology of his mild encephalitis/encephalopathy with a reversible splenial lesion.ConclusionsThe presentation of mild encephalitis/encephalopathy with a reversible splenial lesion is often nonspecific, with behavioral symptoms ranging from irritability to disturbances in consciousness. Its prevalence is higher in the pediatric population, and is thought to be more of an infection-associated encephalopathy syndrome in this group. The infections are typically viral, more so than bacterial. M. pneumoniae, a small, atypical bacterium lacking a peptidoglycan cell wall, is a common respiratory tract pathogen found in children. Despite infection being so rampant in the pediatric community, very few cases of M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion in the United States have been reported. In Eastern and Southern Asian countries, however, M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion is much more commonly reported. This difference may potentially lie in the prevalence of macrolide-resistant M. pneumoniae, which is significantly higher in Asian countries given more liberal antibiotic use in M. pneumoniae infections. Infections with macrolide-resistant M. pneumoniae are reportedly greater in severity and duration. This amplified state may suggest a correlation between intensity of inflammatory response and the development of mild encephalitis/encephalopathy with a reversible splenial lesion. Given the rarity of M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion in the United States, much remains unknown regarding predilection and optimum treatment strategy. As rates of macrolide-resistant M. pneumoniae begin to rise in the United States, maintaining a high level of suspicion remains key in better understanding this unique phenomenon.

In Vitro Antibacterial and Antibiofilm Activity of Hungarian Honeys against Respiratory Tract Bacteria.

Honey is a rich source of carbohydrates, while minor compounds such as amino acids and polyphenols contribute to its health-promoting effects. Honey is one of the oldest traditional remedies applied for microbial infections, due to its antibacterial, anti-inflammatory, and antioxidant properties. The aim of this study was to investigate the antibacterial and antibiofilm effects of Hungarian black locust, linden, and sunflower honeys against the most common biofilm-forming respiratory tract pathogens Haemophilus spp., Pseudomonas aeruginosa, and Streptococcus pneumoniae. The unifloral character of all three honey types was confirmed by melissopalynological analysis. The antibacterial activity of each honey sample against each bacterium strain was proven with agar well diffusion assay and thin layer chromatography—direct bioautography. Kinetics and mechanisms of antibacterial action were clarified with time-kill assay and membrane degradation study. The anti-biofilm activity was evidenced using crystal violet assay. In each assay, linden honey was the most effective, followed by sunflower and black locust honey. In addition, each honey sample had greater potential to suppress respiratory tract bacteria, compared to major sugar components. In conclusion, honey in general and linden honey in particular, can have a role in the treatment of respiratory tract infections caused by biofilm-forming bacteria.

Early-onset neonatal sepsis due to Streptococcus Pneumoniae: A rare causative organism in neonates

Streptococcus pneumoniae (pneumococcus) is a common respiratory tract pathogen in children causing otitis media, sinusitis, bacteremia, and meningitis. Although comparatively rare, this pathogen can also cause early-onset neonatal sepsis (EONS) as well as late-onset neonatal sepsis and can mimic Group B streptococcal sepsis-like illness in neonates. S. pneumoniae can be transmitted vertically from maternal vaginal tract colonization or from the placenta through hematogenous spread. Two consecutive case reports of EONS are reported. Vaccination of the mother with pneumococcal polysaccharide vaccine during the third trimester may provide protection to infants by enhancing the transplacental transfer of active immunoglobulin (IgG) to the fetus, as well as improving the availability of secretory antibodies for the fetus through mother's milk. Immunization of the mother may also prevent genital colonization through resulting high levels of IgG plus mucosal CD17 lymphocytes.

Diversity of upper respiratory tract infections and prevalence of Streptococcus pneumoniae colonization among patients with fever and flu-like symptoms

BackgroundMany upper respiratory pathogens cause similar symptoms. In China, routine molecular tests for upper respiratory pathogens are not widely performed and antibiotics abuse in treating upper respiratory tract infections (URTIs) is a major public health concern.MethodsWe performed qualitative real-time PCR tests to detect common upper respiratory tract pathogens including 9 viruses and 3 bacteria in 1221 nasopharyngeal swabs from patients with fever and influenza-like symptoms in a Chinese city. A quantitative real-time PCR was also performed to measure the bacterial density of the colonizing Streptococcus pneumoniae in these samples.ResultsWe found very diverse pathogens including 81.7% viruses, 11.6% bacteria and 6.7% mixed viruses and bacteria. S. pneumoniae colonization was found in 8.0% of the cases but most of them had low bacterial density (Mean = 3.9 log cfu/ml). We also discovered an increase of S. pneumoniae colonization frequency (but not the density) in patients with detectable upper respiratory tract pathogens, in a pathogen variety-dependent manner.ConclusionsOur study provided strong evidence against empiric antibiotic use for treating URTIs, and highlighted a strong need for improving the diagnostic capacity for URTIs by using more molecular testing in China.

Rapid detection of Mycoplasma pneumoniae by loop-mediated isothermal amplification assay.

To improve the diagnosis and treatment of Mycoplasma pneumoniae (Mp) infection and reduce the misuse of antibiotics, we sought to establish a loop-mediated isothermal amplification (LAMP) assay for rapid detection of Mp.Six primers specific for the Mp P1 gene were designed, and the LAMP method was used to rapidly detect Mp. The sensitivity of the LAMP method was determined by serial dilution of the standard Mp strain FH (standard strains of Mycoplasma pneumoniae). Specificity was assessed with 17 common pathogenic microorganisms in the respiratory tract. Patient samples were collected from the Department of Respiratory and Critical Care Medicine at the 307th Hospital of Chinese People's Liberation Army from March 2016 to May 2017, examined prospectively, and compared with diagnosis by quantitative real-time polymerase chain reaction (qRT-PCR).The LAMP assay for Mp detection can be completed within 60 minutes. The minimum detection limit was 39 pg/μL, and no cross-reaction was observed with 17 common respiratory tract pathogens. Of the 125 clinical specimens tested, 43 cases were positive by LAMP assay, and 40 cases were positive by qRT-PCR (P = .162). All 43 samples determined as positive by LAMP test were confirmed to be Mp by Mp P1 protein sequencing.The LAMP assay is suitable for rapid detection of Mp. It has high sensitivity and specificity, and the detection results are not inferior to those of qRT-PCR.

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections.

Bacterial sexually transmitted infections are widespread and common, with Neisseria gonorrhoeae (gonorrhea) and Chlamydia trachomatis (chlamydia) being the two most frequent causes. If left untreated, both infections can cause pelvic inflammatory disease, infertility, ectopic pregnancy, and other sequelae. The recommended treatment for gonorrhea is ceftriaxone plus azithromycin (to empirically treat chlamydial coinfections). Antibiotic resistance to all existing therapies has developed in gonorrheal infections. The need for new antibiotics is great, but the pipeline for new drugs is alarmingly small. The aminomethyl spectinomycins, a new class of semisynthetic analogs of the antibiotic spectinomycin, were developed on the basis of a computational analysis of the spectinomycin binding site of the bacterial 30S ribosome and structure-guided synthesis. The compounds display particular potency against common respiratory tract pathogens as well as the sexually transmitted pathogens that cause gonorrhea and chlamydia. Here, we demonstrate the in vitro potencies of several compounds of this class against both bacterial species; the compounds displayed increased potencies against N. gonorrhoeae compared to that of spectinomycin and, significantly, demonstrated activity against C. trachomatis that is not observed with spectinomycin. Efficacies of the compounds were compared to those of spectinomycin and gentamicin in a murine model of infection caused by ceftriaxone/azithromycin-resistant N. gonorrhoeae; the aminomethyl spectinomycins significantly reduced the colonization load and were as potent as the comparator compounds. In summary, data produced by this study support aminomethyl spectinomycins as a promising replacement for spectinomycin and antibiotics such as ceftriaxone for treating drug-resistant gonorrhea, with the added benefit of treating chlamydial coinfections.

Virulence factors of Moraxella catarrhalis outer membrane vesicles are major targets for cross-reactive antibodies and have adapted during evolution

Moraxella catarrhalis is a common human respiratory tract pathogen. Its virulence factors associated with whole bacteria or outer membrane vesicles (OMVs) aid infection, colonization and may induce specific antibodies. To investigate pathogen-host interactions, we applied integrated bioinformatic and immunoproteomic (2D-electrophoresis, immunoblotting, LC-MS/MS) approaches. We showed that OMV proteins engaged exclusively in complement evasion and colonization strategies, but not those involved in iron transport and metabolism, are major targets for cross-reacting antibodies produced against phylogenetically divergent M. catarrhalis strains. The analysis of 31 complete genomes of M. catarrhalis and other Moraxella revealed that OMV protein-coding genes belong to 64 orthologous groups, five of which are restricted to M. catarrhalis. This species showed a two-fold increase in the number of OMV protein-coding genes relative to its ancestors and animal-pathogenic Moraxella. The appearance of specific OMV factors and the increase in OMV-associated virulence proteins during M. catarrhalis evolution is an interesting example of pathogen adaptation to optimize colonization. This precisely targeted cross-reactive immunity against M. catarrhalis may be an important strategy of host defences to counteract this phenomenon. We demonstrate that cross-reactivity is closely associated with the anti-virulent antibody repertoire which we have linked with adaptation of this pathogen to the host.

Children with respiratory tract infections in Swedish primary care; prevalence of antibiotic resistance in common respiratory tract pathogens and relation to antibiotic consumption

BackgroundThe majority of antibiotics consumed in developed countries are prescribed in primary care. However, little is known about resistance levels in the primary care population.MethodNasopharyngeal cultures were obtained from children, 0-10 years of age, seeking care at their Primary Health Care Centre with symptoms of respiratory tract infection. Parental questionnaires were used to retrieve information about the child’s previous antibiotic consumption.ResultCultures from 340 children were gathered. The level of resistant Haemophilus influenzae was low and the prevalence of penicillin non-susceptible pneumococci (PNSP MIC ≥ 0.125 mg/L) was 6% compared to 10% (p = 0.31) in corresponding cultures from children diagnosed at the local clinical microbiology laboratory. Antibiotic treatment within the previous 4 weeks predisposed for resistant bacteria in the nasopharynx, OR: 3.08, CI 95% (1.13-8.42).ConclusionLow prevalence of PNSP supports the use of phenoxymethylpenicillin as empirical treatment for childhood upper respiratory tract infections attending primary care in our setting. It is important that studies on resistance are performed in primary care populations to evaluate data from microbiological laboratories. Recent antibiotic treatment increases risk of bacterial resistance in children and continuous work to reduce unnecessary antibiotic prescribing should be prioritised.

CD71+ erythroid suppressor cells impair adaptive immunity against Bordetella pertussis

Infant’s immune system cannot control infection or respond to vaccination as efficiently as older individuals, a phenomenon that has been attributed to immunological immaturity. Recently, we challenged this notion and proposed the presence of actively immunosuppressive and physiologically enriched CD71+ erythroid cells in neonates. Here we utilized Bordetella pertussis, a common neonatal respiratory tract pathogen, as a proof of concept to investigate the role of these cells in adaptive immunity. We observed that CD71+ cells have distinctive immunosuppressive properties and prevent recruitment of immune cells to the mucosal site of infection. CD71+ cells ablation unleashed induction of B. pertussis-specific protective cytokines (IL-17 and IFN-γ) in the lungs and spleen upon re-infection or vaccination. We also found that CD71+ cells suppress systemic and mucosal B. pertussis-specific antibody responses. Enhanced antigen-specific adaptive immunity following CD71+ cells depletion increased resistance of mice to B. pertussis infection. Furthermore, we found that human cord blood CD71+ cells also suppress T and B cell functions in vitro. Collectively, these data provide important insight into the role of CD71+ erythroid cells in adaptive immunity. We anticipate our results will spark renewed investigation in modulating the function of these cells to enhance host defense to infections in newborns.

Prevalence of Moraxella catarrhalis in patients of lower respiratory tract infection with underlying risk factors

Background: Moraxella catarrhalis is a Gram-negative diplococcus, commonly found as a normal flora in the human upper respiratory tract. Recently, M. catarrhalis has emerged as an important and common human respiratory tract pathogen. This study was aimed to determine the rate of isolation of M. Catarrhalis in patients attending a tertiary care hospital with lower respiratory tract infection (LRTI), antibiotic susceptibility pattern and predisposing factors responsible for their infection.Methods: A prospective study was carried out in 1001 lower respiratory specimens from patients (above 20 years’ age) with suspected LRTI. The study investigated by microscopic examination, culture and antibiotic sensitivity test according to the standard guidelines. Assessment of clinical significance of M. Catarrhalis was ascertained on the basis of preformed criteria.Results: A total of 60 clinically significant M. Catarrhalis were isolated from the 930 culture positive samples. The isolates showed maximum sensitivity to second and third generation cephalosporins (95%), azithromycin (90%) followed by amoxicillin clavulanic acid (85%). Rate of isolation was more in males (70%) and elderly people above 60 years (63.33%) were found to be more affected. Patients (58.33%) with Chronic Obstructive Pulmonary Diseases (COPD) were found to be more prone to get infection by M. Catarrhalis.Conclusions: Moraxella catarrhalis should be considered as significant lower respiratory tract pathogen especially in elderly patients with underlying risk factors like COPD.