Agents Of Respiratory Infections Research Articles

4-(3-Phenylsulfonylindol-2-yl)-1-(pyridin-2-yl)piperazinyl-methanones as Potent Inhibitors of both SARS-CoV-2 and HCoV-OC43 Viruses.

SARS-CoV-2 and HCoV-OC43 belong to the same β genus of the Coronaviridae family. SARS-CoV-2 was responsible for the recent COVID-19 pandemic, and HCoV-OC43 is the etiological agent of mild upper respiratory tract infections. SARS-COV-2 and HCoV-OC43 co-infections were found in children with respiratory symptoms during the COVID-19 pandemic. The two β-coronaviruses share a high degree of homology between the 3CLpro active sites, so much so that the safer HCoV-OC43 has been suggested as a tool for the identification of new anti-SARS-COV-2 agents. Compounds 5 and 24 inhibited effectively both Wuhan and British SARS-CoV-2 patient isolates in Vero E6 cells and the HCoV-OC43 in MRC-5 cells at low micromolar concentrations. The inhibition was apparently exerted via targeting the 3CLpro active sites of both viruses. Compounds 5 and 24 at 100 μM inhibited the SARS-CoV-2 3CLpro activity of 61.78 and 67.30%, respectively. These findings highlight 5 and 24 as lead compounds of a novel class of antiviral agents with the potential to treat SARS-COV-2 and HCoV-OC43 infections.

An energy coupling factor transporter of Streptococcus sanguinis impacts antibiotic susceptibility as well as metal and membrane homeostasis.

Streptococcus sanguinis is a prevalent member of human microbiome capable of acting as a causative agent of oral and respiratory infections. S. sanguinis competitive success within the infection niche is dependent on acquisition of metal ions and vitamins. Among the systems that bacteria use for micronutrient uptake is the energy coupling factor (ECF) transporter system EcfAAT. Here we describe physiological changes arising from EcfAAT transporter disruption. We found that EcfAAT contributes to S. sanguinis antibiotic sensitivity as well as metal and membrane homeostasis. Specifically, our work found that disruption of EcfAAT results in increased polymyxin susceptibility. We performed assessment of cell-associated metal content and found depletion of iron, magnesium, and manganese. Furthermore, membrane composition analysis revealed significant enrichment in unsaturated fatty acid species resulting in increased membrane fluidity. Our results demonstrate how disruption of a single EcfAAT transporter can have broad consequences on bacterial cell homeostasis. ECF transporters are of interest within the context of infection biology in bacterial species other than streptococci, hence work described here will further the understanding of how micronutrient uptake systems contribute to bacterial pathogenesis.

Nanobody peptide conjugate: a novel CD163 based broad neutralizing strategy against porcine reproductive and respiratory syndrome virus

BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent swine pathogen, which has caused adverse impact on the global swine industry for almost 30 years. However, due to the immune suppression caused by the virus and the genetic diversity in PRRSV, no virus-targeting broad neutralizing strategy has been successfully developed yet. Antiviral peptide and nanobody have attracted extensive attention with the ease in production and the efficacy in practice. In this study, four new fusion proteins named nanobody peptide conjugates (NPCs) were developed by combining PRRSV specific non-neutralizing nanobodies with CD163-derived peptides targeting the receptor binding domain (RBD) of PRRSV proteins.ResultsFour NPCs were successfully constructed using two nanobodies against PRRSV N and nsp9 individually, recombining with two antiviral peptides 4H7 or 8H2 from porcine CD163 respectively. All four NPCs demonstrated specific capability of binding to PRRSV and broad inhibitory effect against various lineages of PRRSV in a dose-dependent manner. NPCs interfere with the binding of the RBD of PRRSV proteins to CD163 in the PRRSV pre-attachment stage by CD163 epitope peptides in the assistance of Nb components. NPCs also suppress viral replication during the stage of post-attachment, and the inhibitory effects depend on the antiviral functions of Nb parts in NPCs, including the interference in long viral RNA synthesis, NF-κB and IFN-β activation. Moreover, an interaction was predicted between aa K31 and T32 sites of neutralizing domain 4H7 of NPC-N/nsp9-4H7 and the motif 171NLRLTG176 of PRRSV GP2a. The motif 28SSS30 of neutralizing domain 8H2 of NPC-N/nsp9-8H2 could also form hydrogens to bind with the motif 152NAFLP156 of PRRSV GP3. The study provides valuable insights into the structural characteristics and potential functional implications of the RBD of PRRSV proteins. Finally, as indicated in a mouse model, NPC intranasally inoculated in vivo for 12–24 h sustains the significant neutralizing activity against PRRSV. These findings inspire the potential of NPC as a preventive measure to reduce the transmission risk in the host population against respiratory infectious agents like PRRSV.ConclusionThe aim of the current study was to develop a peptide based bioactive compound to neutralize various PRRSV strains. The new antiviral NPC (nanobody peptide conjugate) consists of a specific nanobody targeting the viral protein and a neutralizing CD163 epitope peptide for virus blocking and provides significant antiviral activity. The study will greatly promote the antiviral drug R&D against PRRSV and enlighten a new strategy against other viral diseases.Graphical abstract image

Epidemiological impact of human adenovirus as causative agent of respiratory infections: An Italian multicentre retrospective study, 2022-2023.

Human adenoviruses are the causative agents of 5-7% of viral respiratory infections, mainly caused by species B and C. They can infect all age groups, but children are usually at high risk of infections. Adenovirus epidemiology is well documented in East-Asian countries but little is known about adenovirus circulation in Europe in recent years. This multicentre retrospective study aimed to investigate the circulation and molecular epidemiology of hAdVs. This surveillance collected a total of 54463 respiratory specimens between January 1 2022 and June 20 2023 were tested for the presence of respiratory viruses. Our results showed that adenovirus was detected in 6.6% of all cases of acute respiratory infection included in the study and the median age of positive patients was 3 years, with male children in 1-2 years age group being the most affected. 43.5% of adenovirus cases were co-infected with at least one other respiratory virus, and rhinovirus was co-detected in 54% of cases. Genotyping of adenovirus allowed the identification of 6 different genotypes circulating in Italy, among which type B3 was the most frequently detected.

Clinical-epidemiological characterization and etiological agents of severe acute respiratory infections in adults in Paraguay

Clinical-epidemiological characterization and etiological agents of severe acute respiratory infections in adults in Paraguay

Diversity of Fungi and Bacteria Associated with Respiratory Infections among Commercial Bank Tellers in South-Eastern Nigeria

Introduction: Fungi - associated respiratory Infections are serious health challenges that have become inextricably linked with handling of paper currencies in some countries of the world Dermici et al., [1]. Given the quantity of Old-worn-out and mutilated Naira notes in circulation, and other prevailing circumstances in Nigerian banking halls, study was undertaken to evaluate the incidence and spread of fungi -associated respiratory infections among tellers from selected commercial Banks in South-Eastern Nigeria. Methods: A total of 504 Cash Bank Tellers; 196 Males and 308 females aged 25 – 48years (mean age 32.4 years) were evaluated for Fungi-associated infections using Sputum and Nasal secretions-smear Microscopy and Culture simultaneously. Twenty-Seven bacterial strains; Staphylococcus aureus (12), Streptococcus Pneumonia (7) and Klebsiella pneumoniae (8) were tested for their antibiogram Results: One hundred and fifty-nine (31.5%) of the 504 Bank Cash Tellers were diagnosed of respiratory infections due to Aspergillus Sp. (13.5%), Candida albicans (5.8%), Candida tropicalis 6(.4%), Staphylococcus aureus (2.4%), Streptococcus pneumoniae (1.4%), Klebsiella pneumoniae (1.6%), and Nocardia Sp. (0.6%). The yield of micro-pathogens appeared to rise from 18.8% to 55.6% as duration of currency note handling increased from ≤ 6months to 43 – 48 months respectively. Analysis of the differences of the Micro-Pathogens isolated among tellers from Bulk Rooms (42.9%) and those from open Halls (20.2%) was statistically significant (X2cal=68.3) P < 0.05. Forty-eight (88.9%), 26(123.8%), 41(44.6%) and 43(113.2%) Strains of micro-pathogens were isolated from Tellers who indicated with history of respiratory infections, smoking only, alcohol consumption only and smoking/alcohol consumption respectively. The proportions of the micro-pathogens isolated are shown in the Table 1, with Aspergillus sp. yield appearing highest. The antibiogram of the 27 strains of bacteria isolated in the study appeared relatively high; 92.6% for Ofloxacin and 66.7% for Gentamycin, while Streptomycin, Erythromycin, Cephalexin, Ampiclox, and Chloramphenicol responded poorly. Conclusion: The micro-pathogens isolated from this study are important agents of respiratory infections. The relatively high proportions (31.6%) of micro-pathogens isolated may serve as relevant indication that most Nigerian Currency notes in circulation are old, worn-out, mutilated, and are contaminated with micro-pathogens commonly linked with serious public health problems.

Adhesion of Klebsiella oxytoca to bladder or lung epithelial cells is promoted by the presence of other opportunistic pathogens

The intestinal and respiratory tracts of healthy individuals serve as habitats for a diverse array of microorganisms, among which Klebsiella oxytoca holds significance as a causative agent in numerous community- and hospital-acquired infections, often manifesting in polymicrobial contexts. In specific circumstances, K. oxytoca, alongside other constituents of the gut microbiota, undergoes translocation to distinct physiological niches. In these new environments, it engages in close interactions with other microbial community members. As this interaction may progress to co-infection where the virulence of involved pathogens may be promoted and enhance disease severity, we investigated how K. oxytoca affects the adhesion of commonly co-isolated bacteria and vice versa during co-incubation of different biotic and abiotic surfaces. Co-incubation was beneficial for the adhesion of at least one of the two co-cultured strains. K. oxytoca enhanced the adhesion of other enterobacteria strains to polystyrene and adhered more efficiently to bladder or lung epithelial cell lines in the presence of most enterobacteria strains and S. aureus. This effect was accompanied by bacterial coaggregation mediated by carbohydrate-protein interactions occurring between bacteria. These interactions occur only in sessile, but not planktonic populations, and depend on the features of the surface. The data are of particular importance for the risk assessment of the urinary and respiratory tract infections caused by K. oxytoca, including those device-associated. In this paper, we present the first report on K. oxytoca ability to acquire increased adhesive capacities on epithelial cells through interactions with common causal agents of urinary and respiratory tract infections.

Prevalence and antibiotic susceptibility pattern of Streptococcus pneumoniae amongst residents of Obong Ntak in Etim Ekpo Local Government of Akwa Ibom State, Nigeria

Streptococcus pneumonia is among the major causative agents of respiratory tract infections and colonizes the nasopharyngeal cells of asymptomatically healthy individuals. Prevalence and antibiotics sensitivity of Streptococcus pneumonia amongst residents in a rural setting was evaluated. A total of 250 nasal swab samples (125 males and 125 females) were collected using sterile swab sticks. Administration of open-ended questionnaires, culture of the samples, identification of isolates, antimicrobial sensitivity test and determination of prevalence rate were all done using standard protocols. Out of the 250 samples collected, 35 were positive for S. pneumonia giving an overall prevalence of 14%. Based on sex, the prevalence rates were 15% and 20% for males and females, respectively. Prevalence rates of 12.5%, 13.7%, 12.7% and 25% were recorded for age groups of 10-20, 21-40, 41-60 and >60 years, respectively. The presence of S. pneumoniae based on the health status of the participants showed that the prevalence rates were 20% and 11.70% for clinically ill and clinically healthy individuals, respectively. The resistance profile to the test antibiotics were 22.9%, 22.9%, 11.4%, 100%, 100%, 34.3%, 34.3%, 100%, 54.3% and 77.1% respectively to perfloxacin, septrin, ciprofloxacin, amoxacilin, zinacef, gentamicin, erythromycin, ampliclox, streptomycin and rocephin. Ciprofloxacin was the most effective antibiotic followed by perfloxacin and septrin. Our isolates showed 100% multi-drug resistance and is a cause for concern.

Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity.

The human orthopneumovirus, Respiratory Syncytial Virus (RSV), is the causative agent of severe lower respiratory tract infections (LRTI) and exacerbations of chronic lung diseases. In immune competent hosts, RSV productively infects highly differentiated epithelial cells, where it elicits robust anti-viral, cytokine and remodeling programs. By contrast, basal cells are relatively resistant to RSV infection, in part, because of constitutive expression of an intrinsic innate immune response (IIR) consisting of a subgroup of interferon (IFN) responsive genes. The mechanisms controlling the intrinsic IIR are not known. Here, we use human small airway epithelial cell hSAECs as a multipotent airway stem cell model to examine regulatory control of an intrinsic IIR pathway. We find hSAECs express patterns of intrinsic IIRs, highly conserved with pluri- and multi-potent stem cells. We demonstrate a core intrinsic IIR network consisting of Bone Marrow Stromal Cell Antigen 2 (Bst2), Interferon Induced Transmembrane Protein 1 (IFITM1) and Toll-like receptor (TLR3) expression are directly under IRF1 control. Moreover, expression of this intrinsic core is rate-limited by ambient IRF1• phospho-Ser 2 CTD RNA Polymerase II (pSer2 Pol II) complexes binding to their proximal promoters. In response to RSV infection, the abundance of IRF1 and pSer2 Pol II binding is dramatically increased, with IRF1 complexing to the BRD4 chromatin remodeling complex (CRC). Using chromatin immunoprecipitation in IRF1 KD cells, we find that the binding of BRD4 is IRF1 independent. Using a small molecule inhibitor of the BRD4 acetyl lysine binding bromodomain (BRD4i), we further find that BRD4 bromodomain interactions are required for stable BRD4 promoter binding to the intrinsic IIR core promoters, as well as for RSV-inducible pSer2 Pol II recruitment. Surprisingly, BRD4i does not disrupt IRF1-BRD4 interactions, but disrupts both RSV-induced BRD4 and IRF1 interactions with pSer2 Pol II. We conclude that the IRF1 functions in two modes- in absence of infection, ambient IRF1 mediates constitutive expression of the intrinsic IIR, whereas in response to RSV infection, the BRD4 CRC independently activates pSer2 Pol II to mediates robust expression of the intrinsic IIR. These data provide insight into molecular control of anti-viral defenses of airway basal cells.

Evaluation of Etiologic Agents of Lower Respiratory Tract Infections in Children Hospitalized Just Before Normalization of COVID-19

Lower respiratory tract infections (LRTIs) are one of the most common causes of hospitalization among children in the earlychildhood period. Knowing the pathogens that cause pneumonia, its management will be more exact and effective. In this study,we aimed to investigate the frequency of pathogens causing LRTIs in children at the end of the COVID-19 pandemic by performinga real-time multiplex polymerase chain reaction (RT-MPCR) test within our hospital. We included two hundred forty-seven children,aged between 1 month and 18 years, diagnosed with LRTIs, and hospitalized between May 2021 and April 2022. Demographiccharacteristics and clinical and laboratory findings were retrospectively collected from patients’ hospital records. Of the 247 childrendiagnosed with LRTIs, 153 (61.9%) were female. At least one pathogen was identified in the nasopharyngeal swap specimens of218 (88.3%) patients, and 74.9% (n=185) of them were viruses. The most common identified pathogens were respiratory syncytialvirus (24.7%), human bocavirus (21.1%), and severe acute respiratory syndrome coronavirus 2 (15.4%). 7.7% of identifiedpathogens were bacteria. Haemophilus influenzae was the most commonly detected bacteria. Despite a lengthy period of isolatingthe community causative agents of pneumonia, their frequency remains unchanged from before the isolation time. RT-MPCR isbeneficial for the early detection of pathogens and in the prevention of unnecessary antibiotic usage.

Pathogenic agents causing acute respiratory tract infections in pediatric patients in Spring, 2023, in Beijing

Objective: To explore the pathogenic agents of acute respiratory infection (ARI) in children in Beijing. Methods: In the cross-sectional study, 3 groups of children from different departments were enrolled from Feb 6th, 2023 (6th week) to May 28th (21th week), 2023, including influenza-like case group from emergency department for nucleic acid testing of influenza virus (Flu) and human metapneumovirus (HMPV), the outpatient ARI group under nucleic acid testing for Flu, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza virus (PIV), and the inpatient ARI group under nucleic acid testing for Flu, RSV, HMPV, ADV, human bocavirus (HBoV), Rhinovirus (Rh), PIV, coronavirus (HCoV), Mycoplasma pneumoniae (Mp) and Chlamydia pneumonia (Cp). Results: There were 320 influenza-like cases enrolled, including 192 males and 128 females, aged 4.7 (3.6, 6.9) years, and 117 cases (36.6%) positive for Flu A, which contained similar proportion of pandemic H1N1 (H1N1) 47.0% (55/117) and H3N2 53.0% (62/117), and 13 cases for HMPV 4.1% (13/320). The rate of Flu reached its peak at the 10th week, with H1N1 as the predominant one from the 6th to 9th week (10.0%-50.0%) and then H3N2 from the 10th to 16th week (15.0%-90.0%). HMPV was detected from the 15th week 5.0% (1/20), and then reached to 30.0% (6/20) at the 20th week. In the outpatient ARI group, 7 573 were enrolled, including 4 131 males and 3 442 females, aged 4.0 (2.1, 5.3) years, and the highest positive rate for RSV 32.9% (2 491/7 573), followed by Flu A 12.1% (915/7 573). The dominant one was Flu A in weeks 6-14 (23.2%-74.7%), then RSV in the 15th week 24.8% (36/145). In the inpatient ARI group, 1 391 patients were enrolled, including 804 males and 587 females, aged 3.3 (0.4, 5.8) years, and the highest positive rate for Rh 18.7% (260/1 391), followed by RSV 12.4% (173/1 391), Flu A 10.2% (142/1 391, of which 116 cases (81.7%) were H1N1, and 26 cases (18.3%) were H3N2) and HMPV 3.1% (43/1 391). H1N1 was detected from the 7th week 10% (6/60), to peak in the 11th week 31.8% (21/66). H3N2 was detected from the 8th week 1.5% (1/68), and then kept in low level. The proportion of H1N1 among Flu was 81.7% (116/142) in the inpatient ARI group. RSV was detected from 12th week 1.3% (1/80), reaching 30.4% (35/115) at 19th week. The positive rate of HMPV reached 12.1% (14/116) at 21th week. Conclusions: In the spring of 2023, the first one in Beijing is the Flu epidemic, with H1N1 being the predominant one in the early stage and H3N2 in the later stage. Then, there is a postponed RSV epidemic and an increased HMPV detection. In addition, nucleic acid testing for outpatient children should be strengthened to provide early warning of epidemics.

Change of epidemiological characteristics of four respiratory viral infections in children before and during COVID-19 pandemic

ObjectivesViruses are the main infectious agents of acute respiratory infections (ARIs) in children. We aim to describe the changes in epidemic characteristics of viral ARIs in outpatient children before and during the COVID-19 pandemic. Patients and methodsFrom 2017 to 2022, the results of viral detection in oral pharyngeal swabs in 479,236 children with ARIs in the outpatient department of Children’s Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. Viral antigens, including adenovirus (ADV), influenza A (FLUA), influenza B (FLUB) and respiratory syncytial virus (RSV) were detected by the colloidal gold method. ResultsThe median age was 3.4 (1.6–5.6) years. Among all the children, 159,895 cases (33.4 %) were positive for at least one virus. The total positive rate for ADV, FLUA and FLUB during the pandemic period was lower than during the pre-pandemic period in every season (pre-pandemic period vs. pandemic period11.7 % vs. 4.7 %, 13.9 % vs. 9.2 %, 7.0 % vs. 5.2 %, respectively, with overall p value < 0.001). However, the positive rate fir RSV was not significantly different between the pre-pandemic period and the pandemic period (5.6 % vs. 5.8 %, p = 0.117). Atypical timing of RSV (summer-autumn 2021) and FLUA (summer 2022) was noted. ConclusionsPublic health interventions for different pathogens are maximally effective. While positive rates for ADV, FLUA and FLUB decreased during the COVID-19 pandemic period, positive rates for RSV remained similar. In RSV and FLUA, off-season outbreaks were observed. Measures need to be taken to protect children from possible infection surges due to immunity debt having accrued over the last three years.

НОВЫЕ ВОЗМОЖНОСТИ ЛЕЧЕНИЯ И ПРОФИЛАКТИКИ ИНФЕКЦИОННО-ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ РЕСПИРАТОРНОГО ТРАКТА

Management of patients with infectious and inflammatory diseases of the upper respiratory tract is one of the most pressing problems of modern medicine, which is associated with the widespread prevalence of this pathology. The main causative agents of acute respiratory infections (ARI) are viruses, but the frequency of unjustified prescription of antibiotic therapy remains high. Despite significant advances in healthcare, questions of the effectiveness and safety of treatment of patients with ARI and the prevention of complications remain largely open to the present day. In this aspect, the possibility of using the original domestic antiviral drug of plant origin Panavir® in respiratory medicine is of particular interest to doctors and patients. The action of Panavir® is aimed at increasing the body’s resistance to the effects of pathogens and the production of interferons - protective proteins produced by the body in response to pathogen invasion. Panavir® is a biologically active polysaccharide obtained from the plant Solanum tuberosum (tuberous nightshade). This substance has a long-term protective effect, prevents the development of inflammation, and accelerates the restoration of the mucous membrane.

Evaluation of Etiological Causes and Factors Affect Length of Hospitalization in Neonates Hospitalized with Lower Respiratory Tract Infection.

This study aims to determine the risk factors by examining the sociodemographic characteristics of infants hospitalized in the neonatal intensive care unit (NICU) due to lower respiratory tract infection (LRTI), to determine the factors that affect the duration of hospitalization, and to determine the underlying microbial factors and evaluate them in the light of the literature. This study evaluated the data of newborns hospitalized with LTRI between 01 October 2022 and 31 March 2023. Demographic characteristics of the patients detected viral agents, duration of hospitalization and risk factors were recorded in the study form. Babies divided viral LRTI and non-viral LRTI, and then compared with each other. Additionally, the facts that might affect the duration of hospitalization were investigated. The study included 57 babies. Viral agent was detected in 50.9% of the babies, the most frequently viral agent was respiratory syncytial virus (RSV) (48.2%). Other viral factors, in order of frequency; Adenovirus, SARS-CoV-2, Influenza A and B. There is no demographic difference between the viral agent positive and negative groups. The patients were evaluated according to length of hospitalization, it was seen that the hospital stay was longer in babies who were found to be viral positive and needed oxygen therapy (p=0.02, p=0.03, respectively). The male gender ratio was higher in the group with longer hospital stays, but this difference was not statistically significant. Although the rate of exclusive breastfeeding was higher in the group with a short hospitalization period, this difference was not statistically significant (p>0.05). RSV is currently the most frequently detected viral agent in lower respiratory tract infections in newborns. The hospital stay of babies diagnosed with RSV is longer than those with non-RSV viral agents. So struggling with RSV is important in preventing lower respiratory tract infections in newborns. It is necessary to develop a vaccine or immunoglobulin application against RSV infection not only for preterm babies but also for all newborn babies.

Prevalence of Parainfluenza Viruses in Seoul, 2021 - 2022.

Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.

Mycoplasma Pneumoniae as a Causative Agent of Community-Acquired Lower Respiratory Tract Infections in Children

Mycoplasma pneumoniae (M. pneumoniae) causes respiratory tract infections in all age groups but older children and young adults are more affected than other age groups.

RSV Induces Activation of Intracellular EGFR on the Mitochondrial Membrane for Virus Propagation.

Respiratory syncytial virus (RSV) infects people of all ages and is one of the most common causative agents of lower respiratory tract infections, such as pneumonia, especially in infants under one year of age. However, no direct treatment has been developed for RSV infections. Maintenance of mitochondrial homeostasis and epidermal growth factor receptor (EGFR) activity is important for human cell growth. This study reported that RSV infection maintained the total cellular ATP levels and promoted the intracellular activity of EGFR to replicate RSV. RSV activates the intracellular EGFR-mediated cell survival signaling cascade and maintains mitochondrial EGFR expression for viral production during early events after infection. The approved EGFR inhibitor, vandetanib, markedly reduces RSV propagation, suggesting that EGFR is an attractive host target for RSV therapeutics. Our results suggest that RSV infection maintains cellular ATP levels and promotes the activation of intracellular EGFR in the mitochondrial membrane, significantly contributing to robust RSV propagation.

Changing Infection Dynamics with the Pandemic: Distribution of Viral Agents of Respiratory Tract Infections in the Last 5 Years

Changing Infection Dynamics with the Pandemic: Distribution of Viral Agents of Respiratory Tract Infections in the Last 5 Years

Evaluation of the BioFire® FilmArray® Pneumonia plus Panel for Detecting Bacterial Etiological Agents of Lower Respiratory Tract Infections in an Oncologic Hospital. Comparison with Conventional Culture Method.

Conventional methods used to determine pneumonia pathogens are characterized by low sensitivity and long turnaround times. Introducing new tests with better parameters in patients at higher risk of infections is highly anticipated. The results of the conventional quantitative culture method (CM) in determining the bacterial etiology of pneumonia were compared with the results of the Pneumonia plus Panel test (PNP; BioFire® Diagnostics, USA) in 79 samples of bronchoalveolar lavage (BAL). Materials were collected from 79 patients with suspected pneumonia treated in an oncologic hospital due to solid tumors. Only 16/79 BAL samples (20.3%) were true positive (TP) for bacterial etiology in CM vs. 27/79 samples (34.2%) true positive in the PNP test. The total agreement between methods of interpreting the result (positive or negative) was 84.8%. The most prevalent pathogens in both methods were Staphylococcus aureus, followed by Escherichia coli, Pseudomonas aeruginosa, and Haemophilus influenzae. The PNP test identified several respiratory pathogens that were not grown in culture. The semiquantitative value reported by the PNP test was higher than that reported by culture. The PNP test vs. combined test (PNP test and CM methods) demonstrated positive predictive value (PPV) and negative predictive value (NPV) values of 100.0% and 98.1%, and the sensitivity and specificity were 96.4% and 100.0%. The PNP test is a good tool for determining the etiology of bacterial pneumonia and may support the care of an oncologic patient. However, further large-sample studies are needed to research in strictly defined groups of oncologic patients.

2263. Amoxicillin Use for Common Acute Respiratory Infections During a National Shortage: Results from the SHARPS-OP Benchmarking Collaborative

Abstract Background Amoxicillin is a first-line agent for most pediatric acute respiratory infections (ARIs). In Fall 2022, a nationwide amoxicillin shortage occurred. This study sought to provide precise estimates in outpatient amoxicillin usage during the shortage, using a nationally representative sample of institutions providing pediatric care. Methods Twenty-two institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship Outpatient (SHARPS-OP) Collaborative provided aggregate quarterly data from Jan 2019 - Dec 2022. Data included total counts of encounters with an ARI ICD-10 code and proportions of ARIs treated with any oral antibiotic, amoxicillin, and azithromycin. Data were stratified by location type (Emergency Department [ED], Urgent Care [UC], and primary care clinics [PCC]). We compared ARI prescribing (ARI encounters resulting in any antibiotic prescription) and the amoxicillin and azithromycin indices (ARI encounters resulting in amoxicillin or azithromycin prescription out of ARI encounters resulting in any antibiotic prescription) between pre-shortage (Jan 2019 - Sep 2022) and shortage (Oct 2022 - Dec 2022) time periods by location type. Results A total 4.89 million ARI encounters (4.24 million during pre-shortage and 0.65 million during the shortage) were reported across 22 institutions. Overall antibiotic prescribing for ARI encounters changed slightly from pre-shortage to shortage period for ED (28.7% to 22.6%; delta: -6.1 [-6.4, -5.8]), UC (41.1% to 39.6%; delta: -1.6 [-1.8, -1.3]) and PCC (38.1% to 38.1%; delta: 0.03 [0.001, -0.003]). Substantial declines in the amoxicillin index were observed for ED (76.1% to 60.9%; delta: -15.1 [-15.8, -14.5]), UC (71.9% to 60.1%; delta: -11.7 [-12.1, -11.3]) and PCC (63.9% to 53.3%; delta: -10.6 [-14.2, -9.6] with considerable variation within and between SHARPS-OP institutions (Figure 1). Azithromycin use among ARI encounters decreased slightly during the amoxicillin shortage (-0.3% [-0.38%, -0.20%]).Figure 1:Amoxicillin indices for pre-shortage and amoxicillin shortage time periods for included SHARPS-OP institutions, stratified by location type.Location types: Emergency Department [ED]; Urgent Care [UC]; Primary Care Clinic [Primary] Conclusion Amoxicillin utilization disproportionately decreased compared to overall antibiotic prescribing for ARIs during the shortage. Providers may have prescribed alternative antibiotics rather than no therapy for ARIs. Disclosures Michael J. Smith, M.D., M.S.C.E, Merck: Grant/Research Support|Pfizer: Grant/Research Support Bethany A. Wattles, PharmD, MHA, Merck: Grant/Research Support