Community-acquired Respiratory Infections Research Articles

Improving antibiotic prescribing – Recommendations for funding and pricing policies to enhance use of point-of-care tests

IntroductionDiagnostics can contribute to the improved quality of antibiotic prescribing. However, there is potential to enhance the use of point-of-care tests (POCTs) in general practice. This paper presents fit-for-purpose policy recommendations related to funding and pricing for POCTs applied for community-acquired acute respiratory tract infections (CA-ARTIs). MethodsThe development of the recommendations was informed by an analysis of the current status of funding and pricing policy frameworks for CA-ARTI POCTs in European countries, and an identification of barriers and facilitators for their uptake. Draft recommendations were developed and subsequently revised based on written and verbal feedback from meetings with experts. ResultsThe proposal includes four recommendations for policy interventions related to funding and three recommendations regarding pricing policies. Two of the funding policy-related recommendations concern physicians’ remuneration, and two relate to product-specific reimbursement (public coverage) of the CA-ARTI POCTs. The pricing-related recommendations include a proposal to explore the introduction of price regulation, to pilot subscription-fee procurement models and to enhance more strategic approaches in public procurement of CA-ARTI POCTs. ConclusionsOptimised pricing and funding policies could make a difference in enhancing uptake of CA-ARTI POCTs. It is crucial for the successful implementation of policies to consider country settings. Additionally, supportive policy action is recommended, including the systematic use of health technology assessment, stakeholder communication, and monitoring and evaluation.

Pathogenic features and clinical characteristics of acute community-acquired lower respiratory tract infections.

To investigate the pathogen distribution and clinical characteristics of acute community-acquired lower respiratory tract infections (CALRTIs). This was a retrospective study. The clinical data of 218 patients with CALRTIs admitted to Baoding No.1 Central Hospital from December 2021 to December 2022 were retrospectively collected and were divided into two groups according to the results of polymerase chain reaction(PCR) testing using a nasopharyngeal swab: streptococcus pneumoniae positive group(observation group) and non-streptococcus pneumoniae positive group(control group). Clinical symptoms, blood gas analysis indicators were compared between the two groups. Haemophilus influenzae and Staphylococcus aureus, as well as virus and atypical pathogen infection, were the predominant pathogenic bacteria in both groups. No statistically significant differences were observed in the positive rates of sputum smear, sputum culture, respiratory virus detection and atypical pathogen detection between the two groups(P>0.05). However, the control group had a higher detection rate of gram-positive bacteria, gram-negative bacteria and Legionella pneumophila in sputum smears than the observation group, with a statistically significant difference(P<0.05). One death occurred in each group, with no significant difference in mortality and six in each group left the hospital or were transferred due to deterioration, with no significant difference in improved discharge rates. Acute community-acquired lower respiratory tract infections(CALRTIs) take bacteria, viruses and atypical pathogens as its leading pathogenic bacteria. In the treatment of patients with acute CALRTIs, early pathogenic examination should be performed to assist in guiding antibiotic therapy for rapid control, early recovery and ameliorated clinical outcomes.

Chlamydia pneumoniae Upsurge at Tertiary Hospital, Lausanne, Switzerland.

Chlamydia pneumoniae infection cases have usually accounted for <1.5% of community-acquired respiratory tract infections. Currently, Lausanne, Switzerland is experiencing a notable upsurge in cases, with 28 reported within a span of a few months. This upsurge in cases highlights the need for heightened awareness among clinicians.

Syndromic testing for respiratory pathogens but not National Early Warning Score can be used to identify viral cause in hospitalised adults with lower respiratory tract infections

Background Community-acquired lower respiratory tract infection (LRTI) is a common reason for hospitalisation. Antibiotics are frequently used while diagnostic microbiological methods are underutilised in the acute setting. Objectives We aimed to investigate the relative proportion of viral and bacterial infections in this patient group and explore methods for proper targeting of antimicrobial therapy. Methods We collected nasopharyngeal samples prospectively from adults hospitalised with LRTIs during three consecutive winter seasons (2016–2019). Syndromic nasopharyngeal testing was performed using a multiplex PCR panel including 16 viruses and four bacteria. Medical records were reviewed for clinical data. Results Out of 220 included patients, a viral pathogen was detected in 74 (34%), a bacterial pathogen in 63 (39%), both viral and bacterial pathogens in 49 (22%), while the aetiology remained unknown in 34 (15%) cases. The proportion of infections with an identified pathogen increased from 38% to 85% when syndromic testing was added to standard-of-care testing. Viral infections were associated with a low CRP level and absence of pulmonary infiltrates. A high National Early Warning Score did not predict bacterial infections. Conclusions Syndromic testing by a multiplex PCR panel identified a viral infection or viral/bacterial coinfection in a majority of hospitalised adult patients with community-acquired LRTIs.

Patterns and predictors of positive multiplex polymerase chain reaction respiratory panel among patients with acute respiratory infections in a single center in Lebanon.

Infectious agents associated with community-acquired acute respiratory infections (ARIs) remain understudied in Lebanon. We aim to assess the microbiological profiles of ARIs by employing polymerase chain reaction (PCR) and identifying predictors of positive PCR results among patients admitted for ARI. We conducted a retrospective single-center study at the American University of Beirut Medical Center, including all respiratory PCR panels performed on pediatric (< 18) and adult (≥ 18) patients presenting with an ARI from January 2015 to March 2018, prior to the onset of the COVID-19 pandemic. We aimed to identify the epidemiological patterns of ARIs and the factors associated with positive PCRs in both adult and pediatric patients. Among 281 respiratory PCRs, 168 (59.7%) were positive for at least one pathogen, with 54.1% positive PCR for viruses, 7.8% for bacteria species, and 3.9% with virus-bacteria codetection. Almost 60% of the patients received antibiotics prior to PCR testing. PCR panels yielded more positive results in pediatric patients than in adults (P = 0.005). Bacterial detection was more common in adults compared to pediatrics (P < 0.001). The most common organism recovered in the entire population was Human Rhinovirus (RhV) (18.5%). Patients with pleural effusion on chest CT were less likely to have a positive PCR (95% Cl: 0.22-0.99). On multivariate analysis, pediatric age group (P < 0.001), stem cell transplant (P = 0.006), fever (P = 0.03) and UTRI symptoms (P = 0.004) were all predictive of a positive viral PCR. Understanding the local epidemiology of ARI is crucial for proper antimicrobial stewardship. The identification of factors associated with positive respiratory PCR enhances our understanding of clinical characteristics and potential predictors of viral detection in our population.

Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO)

BackgroundCommunity-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region.MethodsRESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis.DiscussionThe RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Unraveling the complexity of Stenotrophomonas maltophilia – a comprehensive review of current knowledge

Abstract Stenotrophomonas maltophilia is a Gram-negative (G−) opportunistic pathogen, prevalent and concerning for susceptible patients. It primarily causes nosocomial and some community-acquired respiratory and bloodstream infections. Reservoirs include water, plant rhizospheres, food, and animals. Virulence factors include motility, biofilm formation, and quorum sensing, with ongoing research on these mechanisms. A major concern is its multidrug resistance to antimicrobial agents like trimethoprim-sulfamethoxazole (TMP-SMX), β-lactams, macrolides, fluoroquinolones, aminoglycosides, chloramphenicol, tetracyclines, and polymyxins. Effective treatments include TMP-SMX, quinolones, penicillins, and penicillins with β-lactamase inhibitors. Rapid diagnosis is crucial for successful treatment, leading to the development of new detection methods such as selective steno medium agar (SMA) and molecular techniques for nucleic acid detection. Patients with S. maltophilia are prone to co-infections with other G− bacteria. A study by Safdar et al. on cancer patients from 1986 to 2002 showed an increase in S. maltophilia infections from 2% to 7%, making it the 5th most commonly isolated G-bacterium in this group. It commonly infects ICU patients and individuals with SARS-CoV-2, with pneumonia being the most frequent clinical manifestation. The COVID-19 pandemic increased intensive care unit admissions and mechanical ventilation use, leading to higher infection rates of S. maltophilia.

7-Year (2015-21) longitudinal surveillance of lefamulin in vitro activity against bacterial pathogens collected worldwide from patients with respiratory tract infections including pneumonia and characterization of resistance mechanisms.

Lefamulin (Xenleta™), a pleuromutilin antibiotic, was approved for the oral and IV treatment of community-acquired bacterial pneumonia (CABP) in adults in 2019/2020. This study evaluated the in vitro activity of lefamulin and comparators against 19 584 unique bacterial isolates collected from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia within the global SENTRY Antimicrobial Surveillance Program during 2015-21. Isolates were susceptibility tested by the CLSI broth microdilution method, and resistance mechanisms were investigated in isolates with elevated lefamulin MICs. Lefamulin exhibited potent antibacterial activity against the most common and typical CABP pathogens tested, including Streptococcus pneumoniae [MIC50/90, 0.06/0.25 mg/L; 99.9% susceptible (S)], Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/L; 99.6% S), Haemophilus influenzae (MIC50/90, 0.5/2 mg/L; 99.1% S) and Moraxella catarrhalis (MIC50/90, 0.06/0.12 mg/L; 100.0% S). Potent activity was also observed against the less common pneumonia pathogens: β-haemolytic (MIC50/90 of 0.03/0.06 mg/L) and viridans group Streptococcus spp. (MIC50/90 of 0.06/0.25 mg/L) and Haemophilus parainfluenzae (MIC50/90 of 1/4 mg/L). Lefamulin's activity was not adversely affected by resistance to macrolides, penicillin, tetracyclines, fluoroquinolones and other resistance phenotypes. Non-susceptibility/resistance to lefamulin was rare and primarily determined by ribosomal protection through vga(A) variants in S. aureus, overexpression of AcrAB-TolC efflux pump in H. influenzae or modifications in L3, L4 and 23SrRNA in Streptococcus spp. Based on the coverage of the most important CABP pathogens and lacking cross-resistance, lefamulin may represent a valuable empirical treatment option for ambulatory and hospitalized patients with CABP, particularly in settings with high prevalence of resistance.

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.

Changes in the levels of WBC count, PCT, CRP and ESR in Patients with acute Community-acquired Lower Respiratory tract infections and their diagnostic value.

To investigate the levels of white blood cell count (WBC), procalcitonin (PCT), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in patients with acute community-acquired lower respiratory tract infections and the value of their combined detection in predicting the occurrence of complications. A retrospective analysis was conducted on the clinical data of 218 patients with acute community-acquired lower respiratory tract infections admitted to Baoding No.1 Central Hospital from January 2021 to December 2021. All patients were divided into two groups according to the presence of complications during treatment: the group with complications (observation group) and the group without complications (control group). The treatment situation of the two groups was compared, and their levels of WBC, PCT, CRP and ESR were quantitatively detected and compared. Patients in the observation group were hospitalized for significantly longer days than those in the control group (P<0.05), and their combined pleural effusion percentage and oxygen uptake rate were higher than those in the control group (P<0.05). The levels of WBC, PCT, CRP and ESR in the observation group were significantly higher than those in the control group at admission, with statistically significant differences (P<0.05). Moreover, the positive rates of WBC, PCT, CRP and ESR in the observation group were higher than those in the control group in the single detection and the combined detection (P<0.05). The combined detection of WBC, PCT, CRP and ESR has substantial predictive value in predicting the occurrence of complications in patients with community-acquired lower respiratory tract infections.

Predicting adverse outcomes in adults with a community-acquired lower respiratory tract infection: a protocol for the development and validation of two prediction models for (i) all-cause hospitalisation and mortality and (ii) cardiovascular outcomes

BackgroundCommunity-acquired lower respiratory tract infections (LRTI) are common in primary care and patients at particular risk of adverse outcomes, e.g., hospitalisation and mortality, are challenging to identify. LRTIs are also linked to an increased incidence of cardiovascular diseases (CVD) following the initial infection, whereas concurrent CVD might negatively impact overall prognosis in LRTI patients. Accurate risk prediction of adverse outcomes in LRTI patients, while considering the interplay with CVD, can aid general practitioners (GP) in the clinical decision-making process, and may allow for early detection of deterioration. This paper therefore presents the design of the development and external validation of two models for predicting individual risk of all-cause hospitalisation or mortality (model 1) and short-term incidence of CVD (model 2) in adults presenting to primary care with LRTI.MethodsBoth models will be developed using linked routine electronic health records (EHR) data from Dutch primary and secondary care, and the mortality registry. Adults aged ≥ 40 years with a GP-diagnosis of LRTI between 2016 and 2019 are eligible for inclusion. Relevant patient demographics, medical history, medication use, presenting signs and symptoms, and vital and laboratory measurements will be considered as candidate predictors. Outcomes of interest include 30-day all-cause hospitalisation or mortality (model 1) and 90-day CVD (model 2). Multivariable elastic net regression techniques will be used for model development. During the modelling process, the incremental predictive value of CVD for hospitalisation or all-cause mortality (model 1) will also be assessed. The models will be validated through internal-external cross-validation and external validation in an equivalent cohort of primary care LRTI patients.DiscussionImplementation of currently available prediction models for primary care LRTI patients is hampered by limited assessment of model performance. While considering the role of CVD in LRTI prognosis, we aim to develop and externally validate two models that predict clinically relevant outcomes to aid GPs in clinical decision-making. Challenges that we anticipate include the possibility of low event rates and common problems related to the use of EHR data, such as candidate predictor measurement and missingness, how best to retrieve information from free text fields, and potential misclassification of outcome events.

Barriers and Facilitators in Pricing and Funding Policies of European Countries That Impact the Use of Point-of-Care Diagnostics for Acute Respiratory Tract Infections in Outpatient Practices

Antimicrobial resistance is a major global health threat, which is increased by the irrational use of antibiotics, for example, in the treatment of respiratory tract infections in community care. By using rapid point-of-care diagnostics, overuse can be avoided. However, the diagnostic tests are rarely used in most European countries. We mapped potential barriers and facilitators in health technology assessment (HTA), pricing, and funding policies related to the use of rapid diagnostics in patients with community-acquired acute respiratory tract infections. Expert interviews were conducted with representatives of public authorities from five European case study countries: Austria, Estonia, France, Poland, and Sweden. Barriers to the HTA process include the lack of evidence and limited transferability of methods established for medicines to diagnostics. There was no price regulation for the studied diagnostics in the case study countries, but prices were usually indirectly determined via procurement. The lack of price regulation and weak purchasing power due to regional procurement processes were mentioned as pricing-related barriers. Regarding funding, coverage (reimbursement) of the diagnostic tests and the optimized remuneration of physicians in their use were mentioned as facilitators. There is potential to strengthen peri-launch policies, as optimized policies may promote the uptake of POCT.

2127. 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 2018-2021

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 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 2018-2021 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). Community-acquired infections were defined as those from patients &amp;lt; 48 hours in hospital. In total, 7,886 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 (1,893/24.0%); Europe (4,283/54.3%); Latin America (671/8.5%); Middle East/Africa (659/8.4%); and North America (Canada only) (380/4.8%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2023 CLSI M100 MIC breakpoints. Results The in vitro activity of ceftaroline and comparator agents is summarized in the table. Greater than 99% of S. pneumoniae and 100% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Sixty-two (9.6%) 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) Thailand (9), S. Korea (7), and China (6). Four isolates, from S. Korea (2), China (1), and Ukraine (1) were resistant to CPT (MIC of ≥8 µg/mL). 99.6% 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 Meredith Hackel, PhD, Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Gregory Stone, PhD, Pfizer: Stocks/Bonds Daniel F. Sahm, PhD, Merck &amp; Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation

Clinical characteristics of hospitalized children with community-acquired pneumonia and respiratory infections: Using machine learning approaches to support pathogen prediction at admission.

Acute respiratory infections (ARIs) are common in children. We developed machine learning models to predict pediatric ARI pathogens at admission. We included hospitalized children with respiratory infections between 2010 and 2018. Clinical features were collected within 24h of admission to construct models. The outcome of interest was the prediction of 6 common respiratory pathogens, including adenovirus, influenza virus types A and B, parainfluenza virus (PIV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP). Model performance was estimated using area under the receiver operating characteristic curve (AUROC). Feature importance was measured using Shapley Additive exPlanation (SHAP) values. A total of 12,694 admissions were included. Models trained with 9 features (age, event pattern, fever, C-reactive protein, white blood cell count, platelet count, lymphocyte ratio, peak temperature, peak heart rate) achieved the best performance (AUROC: MP 0.87, 95% CI 0.83-0.90; RSV 0.84, 95% CI 0.82-0.86; adenovirus 0.81, 95% CI 0.77-0.84; influenza A 0.77, 95% CI 0.73-0.80; influenza B 0.70, 95% CI 0.65-0.75; PIV 0.73, 95% CI 0.69-0.77). Age was the most important feature to predict MP, RSV and PIV infections. Event patterns were useful for influenza virus prediction, and C-reactive protein had the highest SHAP value for adenovirus infections. We demonstrate how artificial intelligence can assist clinicians identify potential pathogens associated with pediatric ARIs upon admission. Our models provide explainable results that could help optimize the use of diagnostic testing. Integrating our models into clinical workflows may lead to improved patient outcomes and reduce unnecessary medical costs.

Stakeholders' views and experiences on implementing new diagnostics in primary care to support management of community-acquired acute respiratory tract infections: a qualitative study.

The majority of antibiotics are prescribed in primary care for respiratory tract infections. Point-of-care tests (POCTs) for the management of community-acquired acute respiratory tract infections (CA-ARTI) have been developed to help optimize antibiotic prescribing. While some countries in Europe have adopted these tests in primary care settings, most have not. Stakeholders, such as policy-makers, regulators, the diagnostic industry, and scientific associations, have roles in the implementation of new diagnostics in primary care. The aim of this study is to explore these stakeholders' views and experiences, and identify areas of unmet need relating to POCT implementation. Stakeholders were recruited using purposive sampling and snowballing. Between March 2021 and May 2022, semi-structured interviews were conducted online with stakeholders in Belgium, the UK and from European Union (EU) -level organizations. Interviews were audio recorded and transcribed verbatim. Transcripts were analysed inductively and deductively using thematic analysis. Twenty-six stakeholders participated: eleven from EU-level organizations, seven from Belgium, and eight from the UK. Five themes were identified. Stakeholders felt a balance of top-down and bottom-up approaches were an optimal strategy to the implementation of POCTs. Stakeholders stressed the need to engage with clinicians to act as champions for tests to help raise awareness and generate new evidence on how tests are used. While acknowledging the potential of POCTs for improving patient outcomes and impacting antibiotic prescribing behavior, some raised concerns on how tests would be used in practice and wished to see national data on effectiveness. COVID-19 catalyzed the use of tests, but stakeholders were pessimistic that processes for approving diagnostics during the pandemic would be replicated in the future. Stakeholders provided recommendations for research and practice. Robust reimbursement policies could alleviate financial burden from clinicians and patients, encouraging practices to adopt POCTs. Industry is likely to benefit from engaging as early on as possible with other stakeholders. Due to uncertainty among stakeholders on the impact of POCTs on antibiotic prescribing, further evidence is needed to understand how practices adopt POCTs and the implications for stewardship. Monitoring how POCTs are used can inform future guidelines on successful diagnostic implementation.

Comparison of serodiagnosis methods for community-acquired Mycoplasma pneumoniae respiratory tract infections in children.

This study aimed to evaluate the diagnostic value of chemiluminescence immunoassay (CLIA), passive particle agglutination (PPA), and indirect immunofluorescence assay (IFA) in detecting Mycoplasma pneumoniae infection in children. Serum samples from 165 children with acute community-acquired respiratory tract infections were examined using CLIA, PPA, and IFA, and consistency coefficient, specificity, and sensitivity were analyzed. Compared with the PPA (titer ≥ 1:160), the consistency coefficients of the immunoglobulin(Ig)M-CLIA, immunoglobulin(Ig)G-CLIA and IgM-IFA methods were 93.94%, 75.76%, and 83.64%, respectively. The positive likelihood ratio (PLR) and specificity of IgM-CLIA was 19.40 and 95.49%, respectively. The consistency coefficient of (IgM+IgG)-CLIA and PPA (titer ≥ 1:160) was 89.1%, and the sensitivity and negative predictive value of (IgM+IgG)-CLIA were 96.88% and 98.94%, respectively. CLIA MP-IgM has high concordance with PPA, and its specificity and sensitivity are higher than those of CLIA MP-IgG and IFA MP-IgM, suggesting its better diagnosis of early MP infection. The sensitivity and negative predictive value of CLIA MP (IgM+IgG) were higher than those of PPA or IFA, indicating that it should be considered as a priority in the diagnosis of MP infection.

Streptococcus pneumoniae serotyping and antimicrobial susceptibility: assessment for vaccine efficacy in Canada after the introduction of PCV13.

Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia, meningitis) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally assist in determining trends over geographical areas and allow comparisons between countries. To characterize invasive isolates of S. pneumoniae in terms of their serotype, antimicrobial resistance, genotype and virulence and to use the serotype data to determine the level of coverage by different generations of pneumococcal vaccines. SAVE (Streptococcus pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada) is an ongoing, annual, national collaborative study between the Canadian Antimicrobial Resistance Alliance (CARE) and the National Microbiology Laboratory, focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. Clinical isolates from normally sterile sites were forwarded by participating hospital public health laboratories to the Public Health Agency of Canada-National Microbiology Laboratory and CARE for centralized phenotypic and genotypic investigation. The four articles in this Supplement provide a comprehensive examination of the changing patterns of antimicrobial resistance and MDR, serotype distribution, genotypic relatedness and virulence of invasive S. pneumoniae obtained across Canada over a 10 year period (2011-2020). The data highlight the evolution of S. pneumoniae under pressure by vaccination and antimicrobial usage, as well as vaccine coverage, allowing both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.

Antibacterial therapy: questions posed by COVID-19 and real clinical practice

The COVID-19 pandemic was accompanied at different times by the prescription of various drugs. The prescription of antibacterial drugs was regarded differently, and even the term “pneumonia” was the subject of discussion. The frequency of antibiotic use during the pandemic varied widely across countries, with a general trend towards overprescribing. According to most studies, in the early period of this viral infection, there were no indications for antibiotic therapy, while later, when a bacterial process is attached, a rational choice of the drug is important, taking into account the potential resistance of the pathogen, including the production of beta-lactamase. In the current version of the guidelines on COVID-19, the topic of bacterial infections has been carefully worked out. It is clearly stated that antibiotic therapy is prescribed only if there are convincing signs of a bacterial infection. On the one hand, it was noted that most patients with COVID-19 do not need antibiotic therapy, and on the other hand, for patients who do not need hospitalization with signs of a bacterial infection, amoxicillin and amoxicillin/clavulanate are the drugs of choice. The latter combination is also approved for hospitalized patients. Literature analysis has shown that amoxicillin/clavulanate remains a highly effective antibiotic for the initial treatment of community-acquired respiratory tract infections. In the conditions of import substitution, the creation of effective and safe, affordable domestic generics that have therapeutic equivalence with original drugs is a significant achievement of the Russian pharmaceutical science and industry. This review assesses the efficacy and safety of antibiotic use during a pandemic, as well as the place of amoxicillin/clavulanate in modern clinical practice.

Ensemble Image Explainable AI (XAI) Algorithm for Severe Community-Acquired Pneumonia and COVID-19 Respiratory Infections

Since the onset of the COVID-19 pandemic in 2019, many clinical prognostic scoring tools have been proposed or developed to aid clinicians in the disposition and severity assessment of pneumonia. However, there is limited work that focuses on explaining techniques that are best suited for clinicians in their decision making. In this article, we present a new image explainability method named ensemble AI explainability (XAI), which is based on the SHAP and Grad-CAM++ methods. It provides a visual explanation for a deep learning prognostic model that predicts the mortality risk of community-acquired pneumonia and COVID-19 respiratory infected patients. In addition, we surveyed the existing literature and compiled prevailing quantitative and qualitative metrics to systematically review the efficacy of ensemble XAI, and to make comparisons with several state-of-the-art explainability methods (LIME, SHAP, saliency map, Grad-CAM, Grad-CAM++). Our quantitative experimental results have shown that ensemble XAI has a comparable absence impact (decision impact: 0.72, confident impact: 0.24). Our qualitative experiment, in which a panel of three radiologists were involved to evaluate the degree of concordance and trust in the algorithms, has showed that ensemble XAI has localization effectiveness (mean set accordance precision: 0.52, mean set accordance recall: 0.57, mean set <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${{\bm{F}}_1}$</tex-math></inline-formula> : 0.50, mean set IOU: 0.36) and is the most trusted method by the panel of radiologists (mean vote: 70.2%). Finally, the deep learning interpretation dashboard used for the radiologist panel voting will be made available to the community. Our code is available at <uri xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">https://github.com/IHIS-HealthInsights/Interpretation-Methods-Voting-dashboard</uri> .

Detection of Macrolide Resistant Mycoplasma pneumoniae in Children with Lower Respiratory Tract Infection by Sanger Sequencing Targeting Domain V Region of 23S rRNA Gene

Mycoplasma pneumoniae is recognized as the leading cause of community-acquired lower respiratory tract infection in children, accounting for a significant proportion of pediatric mortality. Macrolides are the first-line treatment for M. pneumoniae infections. However, the extensive use of macrolides in clinical practice resulted in the emergence of macrolide-resistant M. pneumoniae (MRMP), which has a negative impact on treatment outcomes. Hence, in the present study, MRMP was determined in hospitalized children with community-acquired pneumonia (CAP). Real-time PCR detected M. pneumoniae in 41 of 348 clinical samples. Sanger sequencing revealed that none of the isolates were associated with the A2063G or A2064G base mutation, which confers macrolide resistance, in domain V of the 23S rRNA gene. Although MRMP was not observed in children with CAP in our study, healthcare practitioners should be vigilant about the potential risk of MRMP infections.