Moraxella Catarrhalis Research Articles

1673. In vitro Activities of Ceftaroline and Comparator Agents against Bacterial Pathogens Frequently Causing Community-Acquired Respiratory Tract Infections in Patients from a Global Population: ATLAS Surveillance Program 2017-2020

Abstract Background Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved for treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program. Methods Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2017-2020 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). In total, 2,284 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (579/25.4%); Europe (1281/56.1%); Latin America (298/13.0%); Middle East/Africa (55/2.4%); and North America (Canada only) (71/3.1%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2022 CLSI M100 MIC breakpoints. Results Ceftaroline and comparator agent in vitro activities are summarized in the table. Greater than 98% of S. pneumoniae and >99% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Fifty-eight (31.4%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) China (18), S. Korea (8), and Japan (8). Three isolates, all from China, were resistant to CPT (MIC of 8 µg/mL). 99.3% of H. influenzae were susceptible to ceftaroline. Conclusion Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection. Disclosures All Authors: No reported disclosures.

889. Another Respiratory Culture Nudge Improves Pneumonia Prescribing

Abstract Background Nudging with purposeful, directed comments to microbiology results appears to improve antibiotic prescribing. The study objective was to assess prescribing before and after a β-lactamase interpretative comment for Haemophilus influenzae and Moraxella catarrhalis lower respiratory tract infections (LRTI). Methods IRB approved, quasi-experiment. Included: hospitalized adults prescribed antibiotics for H. influenzae or M. catarrhalis LRTI from 8/20/17-3/19/19 (pre-group) and 3/20/19-8/20/21 (post-group). Excluded: non-LRTI, polymicrobial infections, antibiotic prophylaxis, IgE-mediated β-lactam allergy. Intervention- automated comment for β-lactamase negative: “this organism is predictably susceptible to ampicillin or amoxicillin”; β-lactamase positive: “this organism is predictably susceptible to ampicillin-sulbactam or amoxicillin-clavulanate”. Primary endpoint: optimal de-escalation, defined as ampicillin, amoxicillin or aminopenicillins for β-lactamase negative; amoxicillin/clavulanate or ampicillin/sulbactam for β-lactamase positive. Secondary endpoints: clinical success, antibiotic duration, time to de-escalation. Sample size: 200 calculated for 30% difference in de-escalation, α=0.05, β=0.2. Results Enrolled 100 pre- and 101 post. 61% vs. 64% male; 63% vs. 73% community-acquired pneumonia; 20% vs. 15% hospital acquired pneumonia; 17% vs. 12% ventilator associated pneumonia; 81% vs. 77% H. influenzae; 46% vs. 52% β-lactamase positive; 4% vs. 7% non-IgE β-lactam allergy, respectively. Optimal de-escalation: 19 (19%) pre-, 51 (51%) post- (p< 0.001). After adjustment, post-group associated with 5-fold increased odds of optimal de-escalation (Table 1). Secondary endpoints pre and post: median (IQR) duration 7 (6, 8) and 7 days (6, 10); median time to de-escalation: 1 (0, 2) and 0 (0, 1) days; clinical success: 79 (79%) and 81 (80%). Conclusion An automated, β-lactamase nudge was associated with a reduction in definitive broad-spectrum antibiotics. Stewardship programs should continue to evaluate persuasive comments as an effective and efficient intervention. Disclosures All Authors: No reported disclosures.

Screening and identification of candidate therapeutic drugs from plants for the management of patients infected bacterial infection associated with SARS COV-2

The emergence of COVID-19 (SARS-COV-2) has resulted in millions of deaths worldwide. Nigeria has recorded over 2000 deaths due to the disease. Development of alternative medicine from plants against SARS-COV-2 can be a potential therapy for treatment of secondary complications. To investigate plants with potential to manage respiratory tract infections. The plants were extracted and screened for phytochemical constituents; their acute and subacute toxicity profile was evaluated. The plant extracts were tested against clinical microbial isolates associated with respiratory tract infection. All the plants extract were found to have acute toxicity dose above 5000 mg per kg body weight. Among the four tested medicinal plants Guiera senegalensis was found to have significant zone of inhibition against Klebsiella pneumonia and Moraxella catarrhalis more than the standard drug (Gentamicin). Guiera senegalensis has been used in traditional medicine to treat bacterial infections without any report of toxicity. The preclinical study indicated that Guiera senegalensis can be used in the management of respiratory infections associated with symptoms of COVID 19. Guiera senegalensis can therefore be used as a potential medicinal plant for management of secondary bacterial infections in Covid19 patients.

Structural and functional insights into iron acquisition from lactoferrin and transferrin in Gram-negative bacterial pathogens

Iron is an essential element for various lifeforms but is largely insoluble due to the oxygenation of Earth’s atmosphere and oceans during the Proterozoic era. Metazoans evolved iron transport glycoproteins, like transferrin (Tf) and lactoferrin (Lf), to keep iron in a non-toxic, usable form, while maintaining a low free iron concentration in the body that is unable to sustain bacterial growth. To survive on the mucosal surfaces of the human respiratory tract where it exclusively resides, the Gram-negative bacterial pathogen Moraxella catarrhalis utilizes surface receptors for acquiring iron directly from human Tf and Lf. The receptors are comprised of a surface lipoprotein to capture iron-loaded Tf or Lf and deliver it to a TonB-dependent transporter (TBDT) for removal of iron and transport across the outer membrane. The subsequent transport of iron into the cell is normally mediated by a periplasmic iron-binding protein and inner membrane transport complex, which has yet to be determined for Moraxella catarrhalis. We identified two potential periplasm to cytoplasm transport systems and performed structural and functional studies with the periplasmic binding proteins (FbpA and AfeA) to evaluate their role. Growth studies with strains deleted in the fbpA or afeA gene demonstrated that FbpA, but not AfeA, was required for growth on human Tf or Lf. The crystal structure of FbpA with bound iron in the open conformation was obtained, identifying three tyrosine ligands that were required for growth on Tf or Lf. Computational modeling of the YfeA homologue, AfeA, revealed conserved residues involved in metal binding.

Respiratory and diarrhoeal pathogens in Malawian children hospitalised with diarrhoea and association with short-term growth: A prospective cohort study

Background: Pneumonia and diarrhoea are the leading causes of childhood mortality and morbidity worldwide. The gut-lung axis is associated with disease, and these common infections, especially the parasite Cryptosporidium, are associated with malnutrition. We sought to evaluate the association of respiratory and gastrointestinal (GI) pathogens with short-term growth among children hospitalised with diarrhoeal disease. Methods: In this sub-study, we followed 27 children (two-24 months) who tested positive for Cryptosporidium spp. for eight weeks with two weekly sampling of the respiratory and GI tract. Respiratory and stool pathogens were detected using quantitative molecular methods. Nutritional outcomes were assessed as length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z-scores. Changes over the study period were compared using repeated analysis of variance and mixed effects model analysis. Results: In this period,104 sputum and stool samples were collected. All stool samples had at least one pathogen detected, with an average of 5.1 (SD 2.1) stool pathogens, compared to 84% of the sputum samples with an average 3.5 (SD 1.8). Diarrhoeagenic E. coli were the most common stool pathogens (89%), followed by Cryptosporidium (57.6%) and Adenovirus pan (41%). In sputum, Streptococcus pneumoniae was the most prevalent pathogen (84%), followed by hinovirus (56%) and Moraxella catarrhalis (50%). There was a significant change in WAZ over the follow-up period. Children who had ≥3 GI pathogens had significantly a lower LAZ mean score at enrolment (-1.8 [SD 1.4]) and across the follow-up period. No relationship between respiratory pathogens and short-term growth was observed. Out of 49 sputum samples that had ≥3 pathogens, 42 (85%) concurrent stool samples had ≥3 GI pathogens. Conclusions: Among young children hospitalised with diarrhoea, multiple GI and respiratory pathogens were prevalent over an eight-week follow-up period. The presence of more GI, but not respiratory, pathogens was significantly associated with reduced short-term growth.

Value of sputum Gram stain, sputum culture, and bronchoalveolar lavage fluid Gram stain in predicting single bacterial pathogen among children with community-acquired pneumonia

BackgroundCurrently, the microbial etiology of community-acquired pneumonia in children remains challenging. While Gram stain and sputum culture are commonly used to detect bacterial pathogens, it is unclear whether these approaches can predict single pathogen from bronchoalveolar lavage fluid (BALF) culture.MethodsA retrospective study involving 287 children hospitalized for pneumonia was conducted. Sputum specimens were collected on admission; and BALF specimens were collected within 24 h after admission. Taking BALF culture as the reference standard, the sensitivity and specificity of Sputum Gram stain (SGS), sputum culture, and BALF Gram stain (BGS) were calculated. The agreement between these approaches and BALF culture was compared using kappa statistics.ResultsFor SGS, the specificity was 23%. The overall sensitivity was 70%, including 87% for Gram-positive (G+) cocci, 56% for Gram-negative (G-) cocci, and 50% for G-bacilli. For sputum culture, the specificity was 70%. The overall sensitivity was 64%, including 71% for Streptococcus pneumoniae, 71% for Moraxella catarrhalis, and 64% for Haemophilus influenzae. For BGS, the specificity was 71%. The overall sensitivity was 60%, including 77% for G+cocci, 38% for G-cocci, and 44% for G-bacilli. While SGS had poor agreement with BALF culture, both sputum culture and BGS had moderate agreement with BALF culture.ConclusionsBoth sputum culture and BGS are helpful in predicting single bacterial pathogen from BALF culture among children with community-acquired pneumonia. Sputum cultures and BGS can provide early clues for BALF pathogen when BALF culture results are pending or bronchoscopy is not performed.

Hyper N-Glycosylated SEL1L3 As B-Cell Receptor Autoantigen of Primary Vitreoretinal Lymphoma

Chronic antigenic stimulation of B lymphocytes through their B-cell receptor (BCR) is thought to play an important role in the genesis of B-cell lymphomas. SAMD14/neurabin-I has been described as auto-antigenic target of primary central nervous system lymphoma (PCNSL) BCRs. Primary vitreoretinal lymphoma (PVRL) is a rare subtype of DLBCL and can progress to PCNSL. Besides manifestation in an immunologically privileged site, PVRL and PCNSL share frequent recurrent genetic alterations like MYD88 and CD79B mutations. Both PVRL and PCNSL are considered being related to the MCD subtype of DLBCLs and may depend on chronic BCR signaling through antigenic stimulation. To investigate the role of chronic antigenic stimulation in PVRL, we cloned and expressed BCRs from PVRL patients as antibody fragments (Fabs) and tested for specific binding against common antigens. All cases with corresponding BCR sequences were previously reported by Belhouachi et al. (Blood Adv. 2020;4(7):1357-1366). For 20 of 55 PVRL BCR sequences both immunoglobulin heavy and light chain variable region (V) genes were available. DNA clones comprising an ApaLI restriction site, the complete light chain V gene, a κ- or λ-constant region gene, a ribosome binding site, a signal sequence, the heavy chain V gene and a BstEII restriction site were ordered from GeneCust® (GeneCust, 5690 Ellange, Luxembourg) in a pUC57 vector. DNA fragments were cloned in front of a γ-1 constant region gene and a Histidine-tag into a modified pCES-1 vector for expression as Fabs. PVRL-BCRs were screened on protein macroarrays representing clones of UniPEx human cDNA expression libraries expressed in E. coli (Bioscience, Dublin, Ireland). SEL1L3 was identified as the auto-antigenic target of the B-cell receptors in 3 out of 20 PVRL cases. None of the PVRL Fabs bound to LRPAP1 (common BCR antigen of mantle cell lymphomas), RpoC (Moraxella catarrhalis bacterial antigen and target of nodular lymphocyte-predominant Hodgkin lymphoma cells) or galectin-3 (member of the lectin family). SEL1L3 is a 1132 amino acid long protein with multiple glycosylation and phosphorylation sites (uniprot.org). This is especially important since previously identified BCR antigens from different lymphoma entities showed post-translational modifications such as hyper-N-glycosylation or hypo-phosphorylation. Furthermore, SEL1L3 is highly expressed in the pigmented layer of the retina. Western Blot analysis of the blood of a PVRL patient with serum antibodies against SEL1L3 showed an increased molecular weight of SEL1L3 as compared to SEL1L3 of controls. After treatment with N-acetyl-β-d-glucosaminidase or PNGase F, this difference in molecular weight disappeared, indicating a hyper N-glycosylation of SEL1L3 in PVRL patients with SEL1L3-reactive BCRs as trigger for its' immunogenicity. SEL1L3 induced proliferation of aggressive lymphoma cell lines transfected with SEL1L3-reactive BCRs. Moreover, the BCR binding epitope of SEL1L3 (aa 560 - 585) conjugated to a truncated form of Pseudomonasaeruginosa exotoxin A, killed exclusively lymphoma cells expressing BCRs with the respective reactivity. Additionally, BCRs of a locally treated PVRL patient with serum antibodies against SEL1L3 were cloned from biopsies of the vitreous body at initial diagnosis and of a lymphoma manifestation in the breast at relapse. Both BCRs showed binding to SEL1L3 suggesting a continued dependence of the BCR on antigen stimulation. These results suggest an important role of chronic antigenic stimulation by the post-translationally modified auto-antigen SEL1L3 in the genesis of a subgroup of patients with PVRL, might give an explanation for the selective tropism of PVRLs and provide the basis for a new treatment approach with high specificity.

Phytochemical Analysis, Antibacterial and Antibiofilm Activities of Aloe vera Aqueous Extract against Selected Resistant Gram-Negative Bacteria Involved in Urinary Tract Infections

In bacterial infections, including urinary tract infections (UTIs), the gap between the development of new antimicrobials and antimicrobial resistance is dramatically increasing, especially in Gram-negative (Gram–) bacteria. All healthy products that can be used per se or that may be sources of antibacterial compounds should be considered in the fight against this major public health threat. In the present study, the phytochemical composition of Aloe vera extract was investigated by HPLC–MS/MS, and we further evaluated its antibacterial and antibiofilm formation activity against selected resistant Gram– bacteria involved in UTIs, namely, Achromobacter xylosoxidans 4892, Citrobacter freundii 426, Escherichia coli 1449, Klebsiella oxytoca 3003, Moraxella catarrhalis 4222, Morganella morganii 1543, Pseudomonas aeruginosa 3057, and a reference strain E. coli ATCC 25922. Inhibition zones (IZs) of the extract were determined using the well diffusion method, minimum inhibitory (MIC), and bactericidal (MBC) concentration by the two-fold serial microdilution assay, and antibiofilm formation activity by the crystal violet attachment assay. Aloe-emodin and its derivatives were the major constituent (75.74%) of A. vera extract, the most important of them being aloesin (30.22%), aloe-emodin-diglucoside (12.58%), and 2′-p-methoxycoumaroylaloeresin B (9.64%). The minerals found in the extract were sulfur (S), silicon (Si), chlorine (Cl), potassium (K), and bromine (Br). Except for the clinical strain E. coli 1449, which was totally non-susceptible, A. vera demonstrated noteworthy antibacterial activity with MIC and MBC values ranging from 0.625 to 5 mg/mL and 5 to 10 mg/mL, respectively. A. vera also demonstrated dose-dependent antibacterial effects, and the reference strain E. coli ATCC 25922 was the most susceptible with MIC = 0.625 and IZ = 19 mm at 20 mg/mL. The antibiofilm formation potential of A. vera extract was strong at 2MIC and MIC (93–100% of biofilm formation inhibition), moderate at MIC/2 (32–41%), weak at MIC/4 (14–21%), and nil at MIC/8.

The Review on Azithromycin

Azithromycin is broad spectrum macrolide antibiotic with long half life and excellent tissue penetration. Azithromycin is an azalide antimicrobial agent active in vitro major pathogens responsible for infectious of the respiratory tract, skin and soft tissue in children. In children azithromycin is usually given as either a 3- day course of 10 mg/kg/day on the first day,followed by 5 mg/kg/day for a further 4 days. Azithromycin is a subclass of microlide antibiotics. It is derived from erythromycin with a methyl–substituted nitrogen atom incorporated in lactone ring, thus making the lacctone ring 15-membered. Pathogen that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chalmydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae Streptococcus pyogens and streptococcus agalactiae. Azithromycin is administerd once daily achieves clinically relevent concentration at sites of infection, is slowly eliminated from the body and has few drug interaction.A five day treatment administration (500 mg on day 1 followed by 250 mg on days 2-5 ) or a three day regimen (500 mg daily for three days).

Changes in Pre- and Post-adenoidectomy Bacterial Profile in Children With Chronic Rhinosinusitis.

We aimed to investigate the difference between the bacterial profiles of the nasal cavities and adenoid surfaces of children with chronic rhinosinusitis (CRS). We also intended to determine and analyze the potential correlation between the pre- and post-adenoidectomy differences in the nasal bacterial profile and clinical prognosis. The clinical information of pediatric patients was collected. All the children underwent adenoidectomy (with or without tonsillectomy), and swab samples were collected during the operation. Visual analog scales (VAS) were used at 3, 6, and 12months postoperatively. At the 12-month follow-up examination, swab samples were collected again. PCR amplification was performed of the v3-v4 variable regions of 16S rRNA of the collected specimens, as well as high-throughput sequencing using the Illumina platform. The species information was obtained by OTUs clustering, species annotation, and α-diversity analysis. Twenty-two male and eight female pediatric patients were included in the investigation The most abundant genus level bacterial representatives on the nasal surface before adenoidectomy were Moraxella catarrh, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus, whereas on the surface of adenoids, they were Streptococcus pneumonia, Haemophilus influenza, Nucleobacter, and Moraxella catarrhalis. One year postoperatively, the bacteria with the highest abundance on the nasal surface at the genus level were Moraxella catarrhalis, Streptococcus pneumonia, Staphylococcus aureus, and non-culturable Dolosigranulum. One year postoperatively, the bacterial richness in the nasal cavity was significantly higher than at baseline (P < .05). Furthermore, the subjective nasal score of all children significantly decreased at 3, 6, and 12months postoperatively (P < .01). The preoperative bacterial abundance of the nasal cavity and the adenoid surfaces was similar, showing a clear correlation. No single specific bacterium was established to be a dominant species associated with the development of CRS in children. The post-adenoidectomy bacterial richness in the nasal cavity was significantly increased, which may be closely related to the relief of postoperative sinusitis symptoms.

Changes in Respiratory Pathogens before and after the COVID-19 Pandemic (2018-2021).

Objective This study is aimed at investigating the pattern of change occurring in respiratory pathogens before and after the outbreak of COVID-19, a type of viral pneumonia for which a pandemic was declared (March 2020). The results were analyzed by gender and age to identify the association between personal hygiene and prevention of infection by respiratory pathogens. Methods A retrospective analysis was performed on 39,814 sputum, bronchial aspirate, and transtracheal aspirate samples obtained from 15,398 patients visiting a university hospital, located in Chungcheongnam-do, South Korea, between January 2018 and December 2021. From 4,454 patients whose samples were culture positive for bacteria, 6,389 strains were isolated and further cultured. Results The mean age of the outpatients with respiratory pathogens was 66.2 years, and the comparison of the culture test results by gender showed that 64.9% (2,892/4,454) were male and 35.1% (1,562/4,454) were female. Compared to the pre-COVID-19 pandemic period, the number of outpatients with a request for respiratory microbial cultures after the onset of the pandemic was reduced by 20.7% and the number of outpatients with a positive culture result was reduced by 23.0%. The number of respiratory samples received was reduced by 6.7% after the pandemic, while the sample positive rate was reduced by 18.3%. Among the isolated microbial strains, there was a significant decrease of 43.1% for the Acinetobacter baumannii complex, 60.5% for Streptococcus pneumoniae, 67.2% for Haemophilus influenzae, and 78.1% for Moraxella catarrhalis when compared with pre-COVID-19 levels. The distribution of respiratory microbial strains by age group showed that the highest percentage of isolated strains was in patients in their 70s. Conclusions The improvements in personal hygiene due to the COVID-19 pandemic exerted a substantial influence on the pattern of change in other common respiratory microorganisms, which highlights the importance of personal hygiene management in the prevention of respiratory infections.

Allergic Sensitization Is Crucial for the Suppressive Role of Streptococcus pneumoniae in the Acute Exacerbation of Asthma

Introduction: Allergic sensitization is an important factor in the development, severity, and exacerbation of asthma, which is attributed to type 2 (T2) inflammation. Evidence suggests that respiratory bacterial pathogens (e.g., Streptococcus pneumoniae) exert suppressive effects on airway T2 inflammation. To clarify the role of allergic inflammation in bacterial colonization in asthma based on allergic sensitization, we investigated pharyngeal bacterial colonization, biomarkers (e.g., serum eosinophil cationic protein (ECP) and cytokines/chemokines), and symptoms in the acute exacerbation of childhood asthma. Methods: Pharyngeal samples were collected from 53 children (mean/median age 2.7/2.5 years). Serum levels of total and allergen-specific IgE against aeroallergens, ECP, and 17 cytokines/chemokines were measured. Results: Allergic sensitization was recognized in 62.2% patients. S. pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and other bacteria were detected in 47.1%, 11.3%, 11.3%, and 30.1% of all patients, respectively. Patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.7 ± 3.6 vs. 7.1 ± 3.5 days, p = 0.024). In patients with allergic sensitization, patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.0 ± 3.6 vs. 7.7 ± 4.0 days, p = 0.003). Serum total IgE was significantly lower in patients with S. pneumoniae than in those without (81.9 [7.8–894] vs. 287 [4.4–1,840] IU/mL, p = 0.014). Serum ECP was significantly higher (33.1 [2–109] vs. 7.8 [3–35] ng/mL, p = 0.042), and IFN-γ was significantly lower (5.6 [4–10] vs. 16.4 [7–28] pg/mL, p = 0.032) in patients with allergic sensitization than those without. Discussion/Conclusion: Our results suggested that the suppressive effects of S. pneumoniae colonization were observed only in patients with allergic sensitization, wherein serum total IgE, ECP, and IFN-γ may have an important role on acute exacerbation of asthma.

FHUSPA2/10 is a bactericidal monoclonal antibody targeting multiple repeated sequences of Moraxella catarrhalis UspA2

Moraxella catarrhalis is an important and common respiratory pathogen that can cause Otitis Media, Community Acquired Pneumonia, and has been associated with an increased risk of exacerbations in chronic obstructive pulmonary disease in adults, leading to morbidity and mortality. Its ubiquitous surface protein A2 (UspA2) has been shown to interact with host structures and extracellular matrix proteins, suggesting a role at an early stage of infection and a contribution to bacterial serum resistance. The UspA proteins are homo-trimeric autotransporters that appear as a lollipop-shaped structure in electron micrographs. They are composed of an N-terminal head with adhesive properties, followed by a stalk, which ends by an amphipathic helix and a C-terminal membrane domain. The three family members UspA1, UspA2 and UspA2H, present different amino acid signatures both at the head and membrane-spanning regions. By combining electron microscopy, hydrogen deuterium exchange mass spectrometry and protein modeling, we identified a shared and repeated epitope recognized by FHUSPA2/10, a potent cross-bactericidal monoclonal antibody raised by UspA2 and deduced key amino acids involved in the binding. The finding strengthens the potential of UspA2 to be incorporated in a vaccine formulation against M. catarrhalis.

Study of Microbial Infections and Some Immunological Parameters among Covid-19 in ICU Patients in Najaf Governorate, Iraq.

The present study aimed to investigate some microbial infections and immunological parameters associated with Covid-19 patients admitted to the intensive care unit (ICU) of Al-Amal Specialized Hospital in AL-Najaf Governorate during February and March 2021. The study included 50 patients who were assigned to two groups: 20 patients aged ≤70 years and 30 patients aged ≥70 years. The method of microbial culture was adopted to isolate bacteria and yeasts by collecting sputum specimens and oral swabs from patients and cultivating them on diagnostic media and then confirming the diagnosis by Vitek. Moreover, serum samples were collected from patients' blood to diagnose fungal infections. Thereafter, some immunological criteria were assessed, including Covid-19 diagnosis by measuring Immunoglobulin M (IgM) and IgG, as well as examining the concentration of cytokines (Interleukin 6 (IL-6) and IF ) using the enzyme-linked immunosorbent assay (ELISA) method. The results demonstrated that bacterial species Streptococcus pneumonia (n=5; 25%), Haemophilus Influenzae (n=7; 35%), and Moraxella catarrhalis (n=3; 15%) were isolated from the first group of patients (≤70 years). The recorded data pointed out that Streptococcus pneumonia (n=10; 33.3%), Streptococcus pyogenes (n=5; 16.6%), Streptococcus viridans (n=1; 3.3%), Haemophilus Influenzae (n=6; 20%), Mycobacterium tuberculosis (n=2; 6.6%), and Pseudomonas aeruginosa (n=2; 6.6%) were the isolated and identified microorganisms in the second age group (≥ 70 years). The results revealed that the isolated yeast from the first age group was Candida albicans (n=5; 25%) and Candida glabrata (n=3; 10%), while in the second age group, 1 (3.3%) Candida albicans was isolated. The results of this study proved that 30% and 10% of patients in the first and second age groups had invasive pulmonary aspergillosis co-infection by detecting Galactomannan (GM) in the blood serum (1.05±0.59, 1.25±0.38), respectively. The results indicated that IgM and IgG levels in the serum of patients in the first age group were 11.42±6.82 and 0.47±6.82, respectively. Moreover, the levels of IgM and IgG in the second age group were 14.84±9.21 and 0.12±0.11, respectively. Furthermore, IFɤ and IL6 levels were 98.37±65.70, and 146.12±46.35 in the first group, while IFɤ and IL6 were obtained at 110.69±47.60 and 133.28±116.94 in the second group, respectively. Elderly patients with severe COVID-19 are more frequently admitted to ICUs since the proportion of severe cases and comorbidities caused by a weakened immune system is higher among this age group. Secondary bacterial infections can also occur, especially Gram-negative bacteria which are among the most significant public health problems worldwide. Moroever, aspergillosis may infect patients hospitalized with COVID-19 and lead to death.

The Microbial Etiology of Community-Acquired Pneumonia in Adults: from Classical Bacteriology to Host Transcriptional Signatures.

All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Enterobacteriaceae, Pseudomonas, and normal respiratory flora. Urine antigen detection is useful in identifying Legionella and pneumococcus. The low yield of bacteria in recent studies is due to the failure to obtain valid sputum samples before antibiotics are administered. The use of high-quality sputum specimens enables identification of recognized ("typical") bacterial pathogens as well as a role for commensal bacteria ("normal respiratory flora"). Nucleic acid amplification technology for viruses has revolutionized diagnosis, showing the importance of viral pneumonia leading to hospitalization with or without coinfecting bacterial organisms. Quantitative PCR study of sputum is in its early stages of application, but regular detection of high counts of bacterial DNA from organisms that are not seen on Gram stain or grown in quantitative culture presents a therapeutic dilemma. This finding may reflect the host microbiome of the respiratory tract, in which case treatment may not need to be given for them. Finally, host transcriptional signatures might enable clinicians to distinguish between viral and bacterial pneumonia, an important practical consideration.

Microbiologic and virulence characteristics of Moraxella catarrhalis isolates from Zambian children presenting with acute pneumonia.

Moraxella catarrhalis is one of the bacterial pathogens associated with childhood pneumonia, but its clinical importance is not clearly defined. This study aimed to investigate the microbiologic and virulence characteristics of M. catarrhalis isolates obtained from children with pneumonia in Lusaka, Zambia. This retrospective, cross-sectional study analyzed 91M. catarrhalis isolates from induced sputum samples of children less than 5 years of age with pneumonia enrolled in the Pneumonia Etiology Research for Child Health study in Lusaka, Zambia between 2011 and 2014. Bacteria identification and virulence genes detection were performed by PCR and DNA sequencing, while antimicrobial susceptibility testing was determined by the Kirby-Bauer method. All the M. catarrhalis isolates were obtained from good-quality sputum samples and were the predominant bacteria. These isolates harbored virulence genes copB (100%), ompE (69.2%), ompCD (71.4%), uspA1 (92.3%), and uspA2 (69.2%) and were all β-lactamase producers. They showed resistance to ampicillin (100%), amoxicillin (100%), trimethoprim-sulfamethoxazole (92.3%), ciprofloxacin (46.2%), chloramphenicol (45.1%), erythromycin (36.3%), tetracycline (25.3%), cefuroxime (11.0%), and amoxicillin-clavulanate (2.2%), with 71.4% displaying multi-drug resistant phenotype but all susceptible to imipenem (100%). This study showed that M. catarrhalis isolates were the predominant or only bacterial isolates from the sputum samples analyzed. The findings provide supportive evidence for the pathogenic potential role of this bacterium in pediatric pneumonia. High multidrug resistance was also observed amongst the isolates, which can result in affected patients not responding to standard treatment, leading to prolonged illness, increased healthcare costs, and risk of death.

Surfactant proteins and innate immunity of otitis media.

Otitis media (OM) is the most common disease among young children and one of the most frequent reasons to visit the pediatrician. Development of OM requires nasopharyngeal colonization by a pathogen which must gain access to the tympanic cavity through the eustachian tube (ET) along with being able to overcome the defense mechanisms of the immune system and middle ear mucosa. OM can be caused by viral or bacterial infection. The three main bacterial pathogens are Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis. Innate immunity is important in OM resolution as the disease occurs in very young children before the development of specific immunity. Elements of innate immunity include natural barriers and pattern recognition receptors such as Toll like receptors (TLRs), and Nod like receptors (NLRs). Surfactant proteins A (SP-A) and D (SP-D) act as pattern recognition receptors and are found in the lung and many other tissues including the ET and the middle ear where they probably function in host defense. Surfactant has a potential for use in the treatment of OM due to surface tension lowering function in the ET, and the possible immune functions of SP-D and SP-A in the middle ear and ET.

Systematic review and meta-analysis on the etiology of bacterial pneumonia in children in sub-Saharan Africa.

IntroductionBefore the introduction of vaccination to protect children from pneumonia, Streptococcus pneumoniae and Haemophilus influenzae type B (HiB) were the most frequent aetiological agents causing bacterial pneumonia in children under five years old. However, the etiology of childhood pneumonia appears to be changing and nonvaccine- type S. pneumoniae, non-typeable H. influenzae, and Staphylococcus aureus are becoming more relevant.ObjectiveWe conducted a systematic review aimed at identifying the common causes of bacterial pneumonia in children in sub-Saharan Africa.MethodsWe searched PubMed, Web of Science and African Index Medicus and included primary studies conducted since January 2010 that reported on the bacterial causes of pneumonia in children under five from sub-Saharan Africa. We extracted data items (about the study setting, pneumonia diagnosis, sampling, microbiological methods, and etiological agents) as well as study quality indicators.ResultsStreptococcus pneumoniae was the most common bacteria in blood cultures from children with pneumonia (8%, 95% CI: 4-14%), and H. influenzae was second (3%, 95% CI: 1-17%). Children’s nasopharynx commonly contained S. pneumoniae (66%), Moraxella catarrhalis (62%), and H. influenzae (44%).ConclusionS. pneumoniae and H. influenzae cause bacterial pneumonia in sub-Saharan African children. Our review also highlights the prevalence of potentially pathogenic bacteria in the nasopharynx of children under five and calls for more research into how nasopharyngeal colonization causes pneumonia.

Isolation, characterization, and bioactivity profiling of oxazoline containing madurastatin siderophores from Actinomadura sp.

Nine new hydroxyphenyloxazolines, madurastatin B4, C2, D3 and D4, E1 and E2, F1 as well as G1 and G2 (8-16), along with two new enantiomers of madurastatin D1 (ent-6) and D2 (ent-7) and two known congeners, madurastatin B1 (2) and C1 (5), were isolated from the liquid culture of Actinomadura sp. ST100801 based on the initial activity against Escherichia coli screened in bicarbonate-supplemented Mueller Hinton II medium and identification via molecular networking. Structure elucidation was achieved by comprehensive 1D and 2D NMR as well as MS/MS fragmentation analyses. Their absolute configuration was determined by Marfey's analysis. Complemented with functionalized hydroxyphenyloxazolines (2, 4,17-18) obtained by total synthesis, the isolated compounds were evaluated for antibacterial activities revealing MICs down to 4 µg ml-1 against Moraxella catarrhalis. Therefore, this study enlarges the family of madurastatin siderophores.

A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial

BackgroundAn investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation. MethodsPatients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2–4), 40–80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses. ResultsOf 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6–12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001). ConclusionResults suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial. Trial registrationClinicalTrials.gov, NCT03281876.