Abstract Background Corynebacterium striatum (C. striatum) is a gram-positive, anaerobic bacillus found both environmentally and in human skin and nasal mucosa flora. It is reportedly the etiologic agent of community-acquired and nosocomial diseases and is significantly associated with bacteremia and medical endovascular devices. This is the rare case of mitral valve native valve endocarditis (NVE) caused by C. striatum occurring in a young adult without underlying structural heart disease or indwelling cardiovascular medical devices successfully treated with multidisciplinary therapy. Case presentation The patient was a 28-year-old female with no medical history. She was transferred our hospital due to sudden onset of vertigo and vomit. A computed tomography on day 2 revealed the hydrocephalus due to the cerebellar infarction, and she underwent posterior fossa decompression for cerebellar infarction. An angiography on day 8 revealed a left vertebral artery dissection, which was suspected be the etiology. Afterwards, a sudden fever of 39 degrees developed on day 38. She was diagnosed with aspiration pneumonia and treated with ampicillin/sulbactam but was still febrile at the time of transfer for rehabilitation. Treatment continued with levofloxacin, the patient had no fever decline, and she was readmitted to our hospital. Readmission blood cultures (3/3 sets) revealed C. striatum, and an echocardiogram revealed an 11 mm long mitral valve vegetation, leading to NVE diagnosis. On the sixth illness day, cardiac failure symptoms manifested. Echocardiography revealed mitral valve rupture. She was transferred again on the 11th day of illness, during which time her mitral valve was replaced. C. striatum was detected in the vegetation. Following surgery, she returned to our hospital, and vancomycin administration continued. The patient was discharged after 31 total days of postoperative antimicrobial therapy. The patient experienced no exacerbations thereafter. Conclusions We report the rare case of C. striatum mitral valve NVE in a young adult without structural heart disease or indwelling cardiovascular devices. Clinical trial number Not applicable. …

Abstract Background Human adenovirus (HAdV) is an important pathogen causing acute respiratory infection (ARI) in children. Many countries, including China, have experienced sporadic or outbreaks related to HAdV-4, and death cases were reported. However, there is little research on HAdV-4 and the epidemic situation of HAdV-4 in China is little known. This study was designed to comprehend the prevalence and genetic characteristics of HAdV-4 in ARI children in China. Methods Respiratory tract samples from ARI children hospitalized in six hospitals of Northern and Southern China from 2017 to 2020 were collected for HAdV detection and typing. Clinical information was collected from HAdV-4 positive patients for clinical characteristics and epidemiological analysis. The main capsid proteins and the whole genome sequences were amplified and sequenced for bioinformatics analysis. Results There were 2847 ARI children enrolled, and 156 (5.48%) HAdV positive samples were detected. Eleven HAdV-4 positive samples were identified, accounting for 0.39% of the total samples and 7.05% of the HAdV positive samples. The main manifestations were fever and cough. Two children had conjunctivitis. Two children were diagnosed with severe pneumonia and developed respiratory failure. One of them developed hemophagocytic syndrome and checked in pediatric intensive care unit (PICU). This child had ventricular septal defect. All the children recovered. The isolated strains of HAdV-4 obtained in this study and the reference strains from China located in the same phylogenetic branch (HAdV-4a), while the prototype strain and vaccine strains formed another branch (HAdV-4p). Upon comparison with the prototype strain, there were a few amino acid mutations existing in three major capsid proteins. According to recombination analysis, no new recombination was found. Conclusions The detection rate of HAdV-4 in children hospitalized with ARI was 0.39% in the total samples and 7.05% of all HAdV positive samples. HAdV-4 isolates obtained in this study and other reference strains from China belonged to the HAdV-4a subtype. Our data provided reference for the monitoring, prevention and control of HAdV-4, as well as the research and development of vaccines and drugs. …

Science Advances, Volume 10, Issue 36, September 2024.

Abstract Background The clinical significance of the presence or absence of Mycoplasma pneumoniae (MP) in pleural effusion in Mycoplasma pneumoniae pneumonia (MPP) children has not yet been elucidated. Herein, we investigated the clinical implication of pleural fluid MP positive in children with MPP. Methods A total of 165 MPP children with pleural effusion requiring thoracocentesis were enrolled in this study. They were subsequently divided into two groups according to the presence or absence of MP in pleural effusion, namely positive group (n = 38) and negative group (n = 127). Information on their clinical manifestations, laboratory findings, radiological characteristics and treatment modalities was retrospectively collected from medical chart reviews. Results The length of hospitalization (15.00 (10.75–19.25) vs. 11.00 (9.00–14.00) days, p=0.001) and total course of illness (23.00 (18.00–28.00) vs. 20.00 (17.00–24.00) days, p=0.010) were significantly longer in the positive group than in the negative group. The occurrence of pericardial effusion (23.7% vs. 7.9%, p=0.017), atelectasis (73.7% vs. 53.5%, p=0.027) and necrotizing pneumonia (23.7% vs. 7.9%, p=0.017) were more frequent in the positive group compared to the negative group. The levels of neutrophil percentages (82.35% (75.40%-85.78%) vs. 72.70% (64.30%-79.90%), p

Abstract Background Sepsis remains a leading cause of mortality in intensive care units, and rapid and accurate pathogen detection is crucial for effective treatment. This study evaluated the clinical application of multi-site metagenomic next-generation sequencing (mNGS) for the diagnosis of sepsis, comparing its performance against conventional methods. Methods A retrospective analysis was conducted on 69 patients with sepsis consecutively admitted to the Department of Intensive Care Medicine, Meizhou People’s Hospital. Samples of peripheral blood and infection sites were collected for mNGS and conventional method tests to compare the positive rate of mNGS and traditional pathogen detection methods and the distribution of pathogens. The methods used in this study included a comprehensive analysis of pathogen consistency between peripheral blood and infection site samples. Additionally, the correlation between the pathogens detected and clinical outcomes was investigated. Results Of the patients with sepsis, 57.97% experienced dyspnea, and 65.2% had underlying diseases, with hypertension being the most common. mNGS demonstrated a significantly higher pathogen detection rate (88%) compared to the conventional method tests (26%). The pathogen consistency rate was 60% between plasma and bronchoalveolar lavage fluid samples, and that of plasma and local body fluid samples was 63%. The most frequently detected pathogens were gram-negative bacteria, and Klebsiella pneumonia. There were no significant differences in the clinical features between the pathogens. Conclusion mNGS is significantly superior to conventional methods in pathogen detection. There was a notable high pathogen consistency detection between blood and local body fluid samples, supporting the clinical relevance of mNGS. This study highlights the superiority of mNGS in detecting a broad spectrum of pathogens quickly and accurately. Trial registration Not applicable. …

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Abstract Background K. pneumoniae become multidrug-resistant (MDR) and commonly poses a serious health threat to patients due to limited therapeutic options. As a result, determining the prevalence and antimicrobial susceptibility patterns of K. pneumoniae isolates from clinical specimens is substantial to patient diagnosis and treatment. Methods and materials A retrospective cross-sectional study was conducted from July 2021 to July 2022 at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. Sociodemographic and laboratory data were collected from registered books using a data collection sheet. All types of samples were collected and processed using standard procedures. Identification of K. pneumoniae was done using Gram stain, colony characterization on culture media, anda series of biochemical tests. Antimicrobial susceptibility testing was done by the Kirby Bauer disc diffusion technique. The data were entered using Epi-info version 7 and exported to SPSS version 20 for analysis. Results Among 2600 clinical specimens, 735 (28.3%) were positive for bacteria, and K. pneumoniae isolates accounted for 147 (20%). Most of them were isolated from neonates and mainly obtained from blood specimens (81.6%). These isolates were 100% resistant to Nalidixic acid, Cefotaxime, and Cefazolin. About 84% and 83.3% of the isolates were also resistant to Ceftriaxone and Tetracycline, respectively. However, they are sensitive to Nitrofurantoin (86.6%), Imipenem (85.7%), Meropenem (79%), and Amikacin (78.3%). The overall proportion of MDR K. pneumoniae isolates accounted for 57.1%. Conclusion The magnitude of MDR K. pneumoniae was very alarming. Therefore, strengthening antimicrobial stewardship programs and antimicrobial surveillance practices is strongly recommended in the study area. …

Abstract Background On March 16th 2024, the first case of Human infection with avian influenza H10N3 since the end of the global COVID-19 Pandemic was reported in Kunming, China. To enhance comprehension of the source of infection and risk factors of the H10N3 virus infection, this case report summarizes the clinical features, epidemiological investigation, and laboratory test results. Provides recommendations for the prevention and control of Human infection with avian influenza H10N3. Case presentation A 51-year-old male with a history of COVID-19 infection and a smoking habit of 30 years, worked in livestock breeding and was exposed to sick and dead poultry before falling ill with fever and chills on 28th February 2024. A week later, he was diagnosed with severe pneumonia, influenza, and respiratory failure by the Third People\'s Hospital of Kunming(KM-TPH). He was discharged on 17th April and none of his 6 close contacts showed any symptoms of illness. Environmental samples taken from the epidemic spot revealed that peacock feces tested positive for avian influenza sub-type H9 and waterfowl specimens showed positive results for avian influenza sub-type H5. Gene sequencing conducted on positive specimens from the patient\'s respiratory tract by the Chinese Centre for Disease Control and Prevention (CCDC) showed a high degree of similarity (98.6–99.5%) with the strain responsible for the second global case of human infected with H10N3 (reported from Zhejiang, China 2022). Conclusions According to the available epidemiological information, there is limited evidence to suggest that H10N3 viruses are excessively lethal. However, adaptive site mutations have been observed in the H10N3 isoform of mammals. While it is unlikely that the H10N3 virus will spread among humans, the possibility of additional cases cannot be entirely ruled out. Symptoms of human infection with H10N3 avian influenza are similar to those of common respiratory infections, which may result in them being overlooked during initial clinical consultations. Therefore, it is essential to improve surveillance of the H10 sub-type of avian influenza and to increase the awareness of hospital-related workers of cases of pneumonia of unknown origin. …

Abstract Background The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. Methods A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. Results Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. Conclusions Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP. …

Abstract Background Risk scores facilitate the assessment of mortality risk in patients with community-acquired pneumonia (CAP). Despite their utilities, there is a scarcity of evidence comparing the various RS simultaneously. This study aims to evaluate and compare multiple risk scores reported in the literature for predicting 30-day mortality in adult patients with CAP. Methods A retrospective cohort study on patients diagnosed with CAP was conducted across two hospitals in Colombia. The areas under receiver operating characteristic curves (ROC-curves) were calculated for the outcome of survival or death at 30 days using the scores obtained for each of the analyzed questionnaires. Results A total of 7454 potentially eligible patients were included, with 4350 in the final analysis, of whom 15.2% (662/4350) died within 30 days. The average age was 65.4 years (SD: 21.31), and 59.5% (2563/4350) were male. Chronic kidney disease was 3.7% (9.2% vs. 5.5%; p 

Abstract Background Pneumonia stands as a significant global contributor to mortality, particularly in South Africa, where it ranks as the second leading cause of death. The country’s high prevalence of HIV infection compounds this issue, significantly increasing mortality rates associated with community-acquired pneumonia (CAP). Objective This study aimed to audit CAP patient management at a regional rural hospital in KwaZulu-Natal. Method A retrospective review of patient files from September to December 2016 was undertaken. Data extraction from clinical files, conducted according to inclusion criteria, was transferred to a data collection sheet and analyzed using SPSS version 21. Results The review encompassed 124 patient files over four months, revealing that 117 (94.4%) patients were not managed by the Standard Treatment Guidelines and Essential Medicines List for South Africa. Of the patients admitted with CAP, 54% were HIV positive, and 49 (39.5%) patients succumbed to the illness. Notably, none of the patients underwent assessment using a severity score. Conclusion The findings underscore a need for more adherence to South African guidelines for managing CAP among staff at the rural regional hospital. This leads to severe consequences, exemplified by the high mortality rate. Urgent intervention is required to incorporate severity assessment scores into pneumonia evaluations, thus enabling appropriate clinical management. Contribution This study sheds light on the significant impact of CAP within the South African hospital context, delineating critical gaps in clinical care and emphasizing the imperative to address clinical inertia. …

Abstract Background The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. Methods A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. Results Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. Conclusions Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP. …

Abstract Background Risk scores facilitate the assessment of mortality risk in patients with community-acquired pneumonia (CAP). Despite their utilities, there is a scarcity of evidence comparing the various RS simultaneously. This study aims to evaluate and compare multiple risk scores reported in the literature for predicting 30-day mortality in adult patients with CAP. Methods A retrospective cohort study on patients diagnosed with CAP was conducted across two hospitals in Colombia. The areas under receiver operating characteristic curves (ROC-curves) were calculated for the outcome of survival or death at 30 days using the scores obtained for each of the analyzed questionnaires. Results A total of 7454 potentially eligible patients were included, with 4350 in the final analysis, of whom 15.2% (662/4350) died within 30 days. The average age was 65.4 years (SD: 21.31), and 59.5% (2563/4350) were male. Chronic kidney disease was 3.7% (9.2% vs. 5.5%; p 

Abstract Background Pneumonia stands as a significant global contributor to mortality, particularly in South Africa, where it ranks as the second leading cause of death. The country’s high prevalence of HIV infection compounds this issue, significantly increasing mortality rates associated with community-acquired pneumonia (CAP). Objective This study aimed to audit CAP patient management at a regional rural hospital in KwaZulu-Natal. Method A retrospective review of patient files from September to December 2016 was undertaken. Data extraction from clinical files, conducted according to inclusion criteria, was transferred to a data collection sheet and analyzed using SPSS version 21. Results The review encompassed 124 patient files over four months, revealing that 117 (94.4%) patients were not managed by the Standard Treatment Guidelines and Essential Medicines List for South Africa. Of the patients admitted with CAP, 54% were HIV positive, and 49 (39.5%) patients succumbed to the illness. Notably, none of the patients underwent assessment using a severity score. Conclusion The findings underscore a need for more adherence to South African guidelines for managing CAP among staff at the rural regional hospital. This leads to severe consequences, exemplified by the high mortality rate. Urgent intervention is required to incorporate severity assessment scores into pneumonia evaluations, thus enabling appropriate clinical management. Contribution This study sheds light on the significant impact of CAP within the South African hospital context, delineating critical gaps in clinical care and emphasizing the imperative to address clinical inertia. …

Abstract In allogeneic hematopoietic cell transplant (HCT)-recipients, prophylactic management strategies are essential for preventing CMV-reactivation and associated disease. We report on a 63-year-old male patient with a D-/R+ CMV-serostatus, who showed ongoing low-level CMV-replication post-HCT despite receiving letermovir prophylaxis. Sanger-sequencing failed to detect drug resistance mutations (DRM) until CMV-pneumonitis developed, revealing a UL56-C325R-DRM linked to high-level letermovir resistance. Retrospective analysis with next-generation-sequencing (NGS) revealed the DRM at a low frequency of 6% two weeks prior to detection by Sanger-sequencing. This study highlights the importance of advanced NGS-methods for early detection of CMV-DRMs, allowing for faster adjustments in antiviral treatment strategies.

Abstract Background While Streptococcus pneumoniae (Spn) is the leading cause of pediatric complicated community acquired pneumonia (cCAP), it is infrequently recovered by culture-based methods. We studied the real-world clinical impact of an Spn PCR assay for pleural fluid.Methods This pre-post quasi-experimental cohort study compared pathogen detection, antibiotic usage, and outcomes in children hospitalized with cCAP requiring pleural effusion or empyema drainage at Children’s Hospital Colorado between 2016 and 2023. Patients were compared across two diagnostic periods: pre-Spn PCR and post-Spn PCR. Cox proportional hazard models compared time from admission to pathogen detection, optimal therapy (narrowest pathogen-directed or guideline-recommended empiric therapy), and MRSA therapy discontinuation between periods.Results Compared to the pre-Spn PCR cohort (N=149), the post-Spn PCR cohort (N=79) was more likely to have a pathogen detected (73.4% post-PCR vs. 38.9% pre-PCR, p < 0.001), driven by more Spn detections (45.6% vs. 14.1%, p < 0.001). Time to pathogen detection during hospitalization was shorter in the post-Spn PCR period (p < 0.001). The post-PCR cohort was more likely to receive optimal therapy (84.8% vs. 53.0%, p < 0.001), with shorter median times to optimal antibiotics (4.9 vs. 10.0 days, p < 0.001) and MRSA therapy discontinuation (1.5 vs. 2.5 days, p = 0.03). There were no differences in hospital length of stay or readmissions.Conclusions Spn molecular testing of pleural fluid in children with cCAP resulted in significantly more microbiologic diagnoses and was associated with the optimization of antibiotics and decreased exposure to MRSA therapy, suggesting its clinical impact for pediatric complicated pneumonia.

ObjectiveThis study evaluates the safety/efficacy of sabatolimab plus spartalizumab in patients with melanoma or non-small cell lung cancer (NSCLC). Design, setting and participantsThis is a phase 1–1b/2, open-label, multinational, multicentre study of patients with advanced/metastatic melanoma or NSCLC with ≥1 measurable lesion. InterventionsPatients were given sabatolimab 800 mg every 4 weeks plus spartalizumab 400 mg every 4 weeks until unacceptable toxicity, disease progression and/or treatment discontinuation. Outcome measuresThe phase 2 primary outcome measure was overall response rate and secondary objectives included evaluation of the safety, tolerability, efficacy and pharmacokinetics of sabatolimab in combination with spartalizumab. Results33 patients (melanoma n=16, NSCLC n=17) received sabatolimab plus spartalizumab. 31 (94%) experienced ≥1 adverse event (AE); 15 (46%) experienced grade 3/4 events. The most frequent grade ≥3 AEs for NSCLC were anaemia, dyspnoea and pneumonia (each n=2, 12%); for patients with melanoma, the most frequent grade ≥3 AEs were physical health deterioration, hypokalaemia, hypophosphataemia, pathological fracture and tumour invasion (each n=1; 6%). One (3%) patient discontinued treatment due to AE. Stable disease was seen in three patients with melanoma (19%) and six patients with NSCLC (35%). Median progression-free survival was 1.8 (90% CI 1.7 to 1.9) and 1.7 (90% CI 1.1 to 3.4) months for patients with melanoma and NSCLC, respectively. Patients with stable disease had higher expression levels of CD8, LAG3, programmed death-ligand 1 and anti-T-cell immunoglobulin and mucin-domain containing-3 at baseline. The pharmacokinetics profile of sabatolimab was consistent with the phase 1 study. ConclusionsSabatolimab plus spartalizumab was well tolerated in patients with advanced/metastatic melanoma or NSCLC who had progressed following antiprogrammed death-1/antiprogrammed death-ligand 1 treatment. Limited antitumour activity was observed. The tolerability of sabatolimab administration supports the potential to explore treatment with sabatolimab in various combination regimens and across a spectrum of tumour types. Trial registration numberNCT02608268. …

ObjectivesThis analysis aims to better reflect the value of new antibiotic treatment strategies, thereby informing clinical antibiotic use, antimicrobial reimbursement and/or hospital formulary decision-making in China. DesignWe adapted a published and validated dynamic disease transmission and cost-effectiveness model to evaluate the clinical and economic outcomes of introducing a new antibiotic, ceftazidime/avibactam (CAZ-AVI) for treating resistant infections in Zhejiang province, China. Outcomes were assessed over a 10-year infectious period and an annual discount rate of 5%. Costs were extracted from the hospital’s Health Information System (HIS) and obtained after data cleaning, aggregation and discounting. SettingThe Chinese healthcare system perspective. Participants10 905 patients in a Chinese tier-3 hospital from 2018 to 2021 with any of the three common infections (complicated intra-abdominal infection (cIAI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) and infections with limited treatment options (LTO)) caused by three common resistant pathogens (Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa). Interventions(1) Current treatment strategy (piperacillin-tazobactam (pip/taz) and meropenem); (2) CAZ-AVI at the third line; (3) CAZ-AVI at the second line; (4) CAZ-AVI at the first line; (5) CAZ/AVI first line, two lines diversified (i.e., equal pip/taz and CAZ-AVI at the first line; meropenem at the last line) and (6) CAZ/AVI first line, all-lines diversified. Primary outcome measuresQuality-adjusted life years (QALYs) lost, hospitalisation costs and incremental net monetary benefit (INMB) were used to assess cost-effectiveness. ResultsOver 10 years, the introduction of CAZ-AVI to the current treatment strategy led to lower hospitalisation costs and more QALYs across all five treatment strategies, with between 68 284 and 78 571 QALYs gained whilst saving up to US$236.37 for each additional QALY gained. The INMB of introducing CAZ-AVI is estimated up to US$3 550 811 878. ConclusionsIntroducing CAZ-AVI had a positive impact on clinical and economic outcomes for treating antimicrobial resistance, and diversifying the antibiotics use early in the treatment might yield the best benefits. …

Abstract Background SARS-CoV-2 pneumonia can cause significant long-term radiological changes, even resembling pulmonary fibrosis. However, the risk factors for these long-term effects are unknown. This study aims to assess radiological abnormalities and their possible risk factors six months after hospital discharge due to COVID-19 pneumonia. Material and methods This cross-sectional study in a tertiary hospital included adults admitted for COVID-19 pneumonia from March 2020 to February 2021, who underwent high-resolution computed tomography (HRCT) scans of the chest six months after hospital discharge. The primary outcome was radiological abnormalities on HRCT, while the main explanatory variables were drawn from the patient’s medical history along with the disease course, analytical indicators, and the treatment received during admission. Results The 189 included patients had a mean age of 61.5 years; 70.9% were male, and hypertension was the main comorbidity (45%). About two-thirds (67.2%) presented acute respiratory distress syndrome (ARDS). Most (97.9%) received systemic corticosteroid therapy, and 81% presented pathological findings on HRCT, most commonly ground glass (63.5%), followed by bronchial dilatation (36%) and subpleural bands (25.4%). The multivariable analysis showed that age was the main risk factor, associated with most radiological changes. Other factors were the duration of corticosteroid therapy for ground glass (adjusted odds ratio [aOR] 1.020) as well as a longer stay in the intensive care unit (ICU) (aOR 1.290) and high levels of IL-6 for bronchial dilation (aOR 1.002). Conclusion Radiological involvement of the lungs six months after COVID-19 pneumonia is frequent, especially ground glass. Elderly patients with prolonged ICU admission and a significant inflammatory response measured by IL-6 are more likely to present worse radiological evolution and are candidates for radiological follow-up after COVID-19 pneumonia. …

Abstract Influenza-like illness (ILI) patients co-detected with respiratory pathogens exhibit poorer health outcomes than those with single infections. To address the paucity of knowledge concerning the incidence of concurrent respiratory pathogens, their relationships, and the clinical differences between patients detected with single and multiple pathogens, we performed an in-depth characterization of the oropharyngeal samples of primary care patients collected in Genoa (Northwest Italy), during winter seasons 2018/19–2019/20. The apriori algorithm was employed to evaluate the incidence of viral, bacterial, and viral-bacterial pairs during the study period. The grade of correlation between pathogens was investigated using the Phi coefficient. Factors associated with viral, bacterial or viral-bacterial co-detection were assessed using logistic regression. The most frequently identified pathogens included influenza A, rhinovirus, Haemophilus influenzae and Streptococcus pneumoniae. The highest correlations were found between bacterial-bacterial and viral-bacterial pairs, such as Haemophilus influenzae-Streptococcus pneumoniae, adenovirus-Haemophilus influenzae, adenovirus-Streptococcus pneumoniae, RSV-A-Bordetella pertussis, and influenza B Victoria-Bordetella parapertussis. Viruses were detected together at significantly lower rates. Notably, rhinovirus, influenza, and RSV exhibited significant negative correlations with each other. Co-detection was more prevalent in children aged 

Abstract Background Long-term sequelae of SARS-CoV-2 infection, namely long COVID syndrome, affect about 10% of severe COVID-19 survivors. This condition includes several physical symptoms and objective measures of organ dysfunction resulting from a complex interaction between individual predisposing factors and the acute manifestation of disease. We aimed at describing the complexity of the relationship between long COVID symptoms and their predictors in a population of survivors of hospitalization for severe COVID-19-related pneumonia using a Graphical Chain Model (GCM). Methods 96 patients with severe COVID-19 hospitalized in a non-intensive ward at the “Santa Maria” University Hospital, Terni, Italy, were followed up at 3–6 months. Data regarding present and previous clinical status, drug treatment, findings recorded during the in-hospital phase, presence of symptoms and signs of organ damage at follow-up were collected. Static and dynamic cardiac and respiratory parameters were evaluated by resting pulmonary function test, echocardiography, high-resolution chest tomography (HRCT) and cardiopulmonary exercise testing (CPET). Results Twelve clinically most relevant factors were identified and partitioned into four ordered blocks in the GCM: block 1 - gender, smoking, age and body mass index (BMI); block 2 - admission to the intensive care unit (ICU) and length of follow-up in days; block 3 - peak oxygen consumption (VO2), forced expiratory volume at first second (FEV1), D-dimer levels, depression score and presence of fatigue; block 4 - HRCT pathological findings. Higher BMI and smoking had a significant impact on the probability of a patient’s admission to ICU. VO2 showed dependency on length of follow-up. FEV1 was related to the self-assessed indicator of fatigue, and, in turn, fatigue was significantly associated with the depression score. Notably, neither fatigue nor depression depended on variables in block 2, including length of follow-up. Conclusions The biological plausibility of the relationships between variables demonstrated by the GCM validates the efficacy of this approach as a valuable statistical tool for elucidating structural features, such as conditional dependencies and associations. This promising method holds potential for exploring the long-term health repercussions of COVID-19 by identifying predictive factors and establishing suitable therapeutic strategies. …

Abstract Objective To analyze the epidemic characteristics of common respiratory tract infection pathogens in children with respiratory tract infection, and provide scientific basis for the prevention and control of respiratory tract infection. Methods A retrospective collection of clinical data was conducted on 11,538 children with respiratory tract infections at Luoyang Maternal and Child Health Hospital from December 2022 to November 2023. The types of respiratory tract infections, including upper and lower respiratory tract infections, as well as five respiratory pathogens: influenza A virus (influenza A), influenza B virus (influenza B virus, adenovirus (ADV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP) infections, were analyzed and compared for different genders, ages, temperatures, and air quality in different months; And the changes of five pathogens in children with respiratory tract infections of different disease severity. Results From December 2022 to November 2023, a total of 11,538 children with respiratory infections were included in the analysis, including 6436 males and 5102 females, with an age of 4.92 ± 2.03 years. The proportion of upper respiratory tract infections is as high as 72.17%, and lower respiratory tract infections account for 27.83%. Among them, 2387 were positive for Flu A antigen, with a positive rate of 20.69%, 51 cases were positive for Flu B antigen, and the positive rate was 0.4%, 1296 cases were positive for adv antigen, with a positive rate of 11.23%, 868 cases were positive for RSV antigen, with a positive rate of 7.52%, 2481 cases were positive for MP IgM antibody or MP antigen, and the positive rate was 21.50%. Flu B in male children The infection rate of ADV and MP was higher than that of female children (p 

BackgroundThe Hospital Readmission Reduction Programme (HRRP) was created to decrease the number of hospital readmissions for acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD), heart failure (HF), pneumonia (PNA), coronary artery bypass graft (CABG), elective total hip arthroplasty (THA) and total knee arthroplasty. ObjectivesTo analyse the impact of the HRRP on readmission rates from 2010 to 2019 and how time to readmission impacted outcomes. DesignPopulation-based retrospective study. SettingAll patients included in the US National Readmission database from 2010 to 2019. PatientsWe recorded demographic and clinical variables. MeasurementsUsing linear regression models, we analysed the association between readmission status and timing with death and length of stay (LOS) outcomes. We transformed LOS and charges into log-LOS and log-charges to normalise the data. ResultsThere were 31 553 363 records included in the study. Of those, 4 593 228 (14.55%) were readmitted within 30 days. From 2010 to 2019, readmission rates for COPD (20.8%–19.8%), HF (24.9%–21.9%), PNA (16.4%–15.1%), AMI (15.6%–12.9%) and TKR (4.1%–3.4%) decreased whereas CABG (10.2%–10.6%) and THA (4.2%–5.8%) increased. Readmitted patients were at higher risk of mortality (6% vs 2.8%) and had higher LOS (3 (2–5) vs 4 (3–7)). Patients readmitted within 10 days had a mortality 6.4% higher than those readmitted in 11–20 days (5.4%) and 21–30 days (4.6%). Increased time from discharge to readmission was associated with a lower likelihood of mortality, like LOS. ConclusionOver the last 10 years, readmission rates decreased for most conditions included in the HRRP except CABG and THA. Patients readmitted shortly after discharge were at higher risk of death. …

Abstract Background Systemic lupus erythematosus (SLE) has been less deadly since the advent of corticosteroid-sparing medications. SLE patients still have a higher mortality rate than the general population. Infectious disease is reported as one of the major causes of death in patients with SLE. Although bacteria are the most often isolated pathogens from patients with SLE, Pneumocystis jirovecii pneumonia (PJP) is more deadly than bacterial infection. Methods We retrospectively enrolled consecutive patients with SLE concurrent with PJP (SLE-PJP) in our center between January 2014 and December 2022. The participants were classified into two groups: survivors and non-survivors. Cox regression models and Kaplan‒Meier survival analyses were conducted to explore prognostic factors for survival. Results There were 57 patients with SLE (42.0 ± 15.8 years old, 78.9% female) complicated with PJP, 22 (38.6%) of whom died. Compared with the survival group, the non-survival group had more patients with hyperglycemia or diabetes mellitus, invasive ventilation (p 

Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are increasingly recognised as important complications in patients requiring intensive care for severe viral pneumonia. The diagnosis can typically be made in 10–20% of patients with severe influenza or COVID-19, but only when appropriate diagnostic tools are used. Bronchoalveolar lavage sampling for culture, galactomannan testing, and PCR forms the cornerstone of diagnosis, whereas visual examination of the tracheobronchial tract during bronchoscopy is required to detect invasive Aspergillus tracheobronchitis.

by Eun Jeong Won, Yu Jeong Lee, Moon-Ju Kim, Tae-Jong Kim, Hong-Joon Shin, Tae-Ok Kim, Yong-Soo Kwon Although gastroesophageal reflux has been recognized as one of the risk factors of nontuberculous mycobacterial pulmonary disease (NTM-PD) progression, the effect of reflux on the lower respiratory tract microbiota has not been studied in detail. We investigated the composition of the lower respiratory tract microbiota in patients with clinically suspected NTM-PD, comparing them based on the presence of reflux. Forty-seven patients suspected of having NTM-PD were enrolled and assigned according to presence of reflux (n = 22) and non- reflux (n = 25). We performed a pepsin ELISA assay to identify the presence of reflux and 16S ribosomal RNA gene amplicon sequencing to evaluate the microbiota in bronchoalveolar lavage fluid. There were no significant differences in the diversity or composition of the lower respiratory microbiota between the NTM-PD and non-NTM-PD groups. Bacterial richness was observed in the non-reflux group than in the reflux group [P = 0.03] and a cluster in the reflux group was observed. The reflux group showed a predominance for Pseudomonas aeruginosa or Staphylococcus aureus among the NTM-PD group and for P. aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, or Eikenella species among the non-NTM-PD group. The non-reflux groups presented diverse patterns. A linear discriminant analysis and volcano plot demonstrated that P. aeruginosa, H. haemolyticus, Selenomonas artemidis, and Dolosigranulum pigrum were specifically associated with the NTM-PD reflux group, while P. aeruginosa was specifically associated with the non-NTM-PD reflux group. These observations confirm that the lower respiratory microbiota is consistently altered by reflux but not in NTM-PD.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Rapid respiratory syndrome multiplex polymerase chain reaction (mPCR) panels have improved pathogen detection in patients with acute respiratory infections [1]. Most of the current guidelines do not recommend their routine use in emergency departments. A recent meta-analysis on the use of rapid respiratory virus testing in Emergency Departments (ED) including more than 6000 patients (84% children) found no association with antibiotic use but higher use of influenza antivirals and less use of chest X-ray and blood tests [2].

Proceedings of the National Academy of Sciences, Volume 121, Issue 35, August 2024.

by David Kessler, Meihua Zhu, Cynthia R. Gregory, Courosh Mehanian, Jailyn Avila, Nick Avitable, Di Coneybeare, Devjani Das, Almaz Dessie, Thomas M. Kennedy, Joni Rabiner, Laurie Malia, Lorraine Ng, Megan Nye, Marc Vindas, Peter Weimersheimer, Sourabh Kulhare, Rachel Millin, Kenton Gregory, Xinliang Zheng, Matthew P. Horning, Mike Stone, Fen Wang, Christina Lancioni Background and objectives Severe pneumonia is the leading cause of death among young children worldwide, disproportionately impacting children who lack access to advanced diagnostic imaging. Here our objectives were to develop and test the accuracy of an artificial intelligence algorithm for detecting features of pulmonary consolidation on point-of-care lung ultrasounds among hospitalized children. Methods This was a prospective, multicenter center study conducted at academic Emergency Department and Pediatric inpatient or intensive care units between 2018–2020. Pediatric participants from 18 months to 17 years old with suspicion of lower respiratory tract infection were enrolled. Bedside lung ultrasounds were performed using a Philips handheld Lumify C5-2 transducer and standardized protocol to collect video loops from twelve lung zones, and lung features at both the video and frame levels annotated. Data from both affected and unaffected lung fields were split at the participant level into training, tuning, and holdout sets used to train, tune hyperparameters, and test an algorithm for detection of consolidation features. Data collected from adults with lower respiratory tract disease were added to enrich the training set. Algorithm performance at the video level to detect consolidation on lung ultrasound was determined using reference standard diagnosis of positive or negative pneumonia derived from clinical data. Results Data from 107 pediatric participants yielded 117 unique exams and contributed 604 positive and 589 negative videos for consolidation that were utilized for the algorithm development process. Overall accuracy for the model for identification and localization of consolidation was 88.5%, with sensitivity 88%, specificity 89%, positive predictive value 89%, and negative predictive value 87%. Conclusions Our algorithm demonstrated high accuracy for identification of consolidation features on pediatric chest ultrasound in children with pneumonia. Automated diagnostic support on an ultraportable point-of-care device has important implications for global health, particularly in austere settings. …

by Estelle Ifrid, Hajer Ouertatani-Sakouhi, Hiba Zein El Dine, Tania Jauslin, Gianpaolo Chiriano, Leonardo Scapozza, Otmane Lamrabet, Pierre Cosson Phagocytic cells of the mammalian innate immune system play a critical role in protecting the body from bacterial infections. The multiple facets of this encounter (chemotaxis, phagocytosis, destruction, evasion and pathogenicity) are largely recapitulated in the phagocytic amoeba Dictyostelium discoideum. Here we identified a new chemical compound (K14; ZINC19168591) which inhibited intracellular destruction of ingested K. pneumoniae in D. discoideum cells. Concomitantly, K14 reduced proteolytic activity in D. discoideum phagosomes. In kil1 KO cells, K14 lost its ability to inhibit phagosomal proteolysis and to inhibit intra-phagosomal bacterial destruction, suggesting that K14 inhibits a Kil1-dependent protease involved in bacterial destruction. These observations stress the key role that proteases play in bacterial destruction. They also reveal an unsuspected link between Kil1 and phagosomal proteases. K14 can be used in the future as a tool to probe the role of different proteases in phagosomal physiology and in the destruction of ingested bacteria.

BackgroundUnderstanding the epidemiological patterns of febrile infants can offer valuable insights for optimising management strategies and developing quality improvement initiatives, aiming to improve healthcare delivery in high-volume, low-resource emergency departments (EDs). ObjectivesTo characterise the epidemiology of febrile infants presenting to the paediatric ED of a tertiary care hospital. MethodsA retrospective chart review of medical records was performed for febrile infants ≤1 year old, at paediatric ED, Indus Hospital and Health Network (IHHN), Karachi, Pakistan (1 January 2020–31 December 2020). ResultsThere were a total of 2311 patients in the study, with a male-to-female ratio of 1.4:1. The mean age of presentation was 4.9±2.7 months. Cough (n=1002, 43.2%) was the most frequent presenting symptom. The most common provisional ED diagnosis in ≤1 month of age was sepsis (n=98, 51%), bronchopneumonia (n=138, 28.6%) in 1.1–3 and 3.1–6 months (n=176, 36.45%); and upper respiratory tract illness (n=206, 47.4%) in 6.1–12 months of age. Age was significantly associated with provisional ED diagnosis and outcomes (p

Abstract Background Prior antibiotic exposure has been identified as a risk factor for VAP occurrence, making it a growing concern among clinical practitioners. But there is a lack of systematic research on the types of antibiotics and the duration of exposure that influence VAP occurrence in children at current. Methods We retrospectively reviewed 278 children admitted to the Pediatric Intensive Care Unit (PICU) and underwent invasive mechanical ventilation (MV) between January 2020 and December 2022. Of these, 171 patients with MV duration ≥ 48 h were included in the study, with 61 of them developing VAP (VAP group) and the remaining 110 as the non-VAP group. We analyzed the relationship between early antibiotic exposure and VAP occurrence. Results The incidence of VAP was 21.94% (61/278). The VAP group had significantly longer length of hospital stay (32.00 vs. 20.00 days, p

OBJECTIVES: To evaluate the effectiveness of ICU rounding checklists on outcomes. DATA SOURCES: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane Library, and Google Scholar) were searched from inception to May 10, 2024. STUDY SELECTION: Cohort studies, case-control studies, and randomized controlled trials comparing the use of rounding checklists to no checklists were included. Other article types were excluded. DATA EXTRACTION: The primary outcome was in-hospital mortality. Secondary outcomes included ICU and 30-day mortality; hospital and ICU length of stay (LOS); duration of mechanical ventilation; and frequency of catheter-associated urinary tract infections, central line-associated bloodstream infections (CLABSI), and ventilator-associated pneumonia. Additional outcomes included healthcare provider perceptions of checklists. DATA SYNTHESIS: Pooled estimates were obtained using an inverse-variance random-effects meta-analysis model. Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. There were 30 included studies (including > 32,000 patients) in the review. Using an ICU rounding checklist was associated with reduced in-hospital mortality (risk ratio [RR] 0.80; 95% CI, 0.70–0.92; 12 observational studies; 17,269 patients; I2 = 48%; very low certainty of evidence). The use of an ICU rounding checklist was also associated with reduced ICU mortality (8 observational studies, p = 0.006), 30-day mortality (2 observational studies, p < 0.001), hospital LOS (11 observational studies, p = 0.02), catheter-associated urinary tract infections (CAUTI) (6 observational studies, p = 0.01), and CLABSI (6 observational studies, p = 0.02). Otherwise, there were no significant differences with using ICU rounding checklists on other patient-related outcomes. Healthcare providers’ perceptions of checklists were generally positive. CONCLUSIONS: The use of an ICU rounding checklist may improve in-hospital mortality, as well as other important patient-related outcomes. However, well-designed randomized studies are necessary to increase the certainty of evidence and determine which elements should be included in an ICU rounding checklist.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) of ST11 was a common hospital lineage in China. Acquisition of virulence plasmids augments virulence levels of these strains and causes devastating clinical outcomes [1]. Cefiderocol is a siderophore-cephalosporin with activity against multidrug resistant gram-negative bacteria. It enters into bacteria via iron transport channels through active transport, with some entry into bacteria through traditional porin channels.

Abstract Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, requiring the use of last-resort antibiotics such as colistin. However, there is concern regarding the emergence of isolates resistant to this agent. The report describes two patients with urinary tract infection (UTI) and ventilator-associated pneumonia (VAP) infection caused by CRKP strains. The first case was a 23-year-old male with UTI caused by a strain of ST16 co-harboring blaCTX-M, blaTEM, blaSHV, blaNDM, blaOXA-48-like genes. The second case was a 39-year-old woman with VAP due to hypervirulent ST337-K2 co-harboring blaSHV, blaNDM, blaOXA-48-like, iucA, rmpA2 and rmpA. The patients’ general condition improved after combination therapy with colistin (plus meropenem and rifampin, respectively) and both of them recovered and were discharged from the hospital. This study highlights the necessary prevention and control steps to prevent the further spread of CRKP strains should be a priority in our hospital. …

by John Otieno Odhiambo, Jasmit Shah, Nancy Kunyiha, Charles Makasa, Felix Riunga Background Among therapeutic options for severe and critical COVID- 19 infection, dexamethasone six milligrams once daily for ten days has demonstrated mortality benefit and is guideline recommended at this dose. In practice, variable doses of steroids have been used, especially in critical care settings. Our study aimed to determine the pattern of steroid dosing and outcomes in terms of critical care mortality, occurrence of dysglycaemias, and occurrence of superadded infections in patients with critical COVID-19. Methods A retrospective cohort study was carried out on all eligible patients admitted to the Aga Khan University Hospital, Nairobi, with critical COVID-19 between 1st March 2020 and 31st December 2021. The intervention of interest was corticosteroids quantified as the average daily dose in milligrams of dexamethasone. A steroid dose of six milligrams once a day was compared to high dose steroid dosing, which was defined as any dose greater than this. The primary outcome measure was ICU mortality and secondary outcomes included occurrence of dysglycaemias, superadded infections and duration of critical care admission. Results The study included 288 patients. The median age was 61.2 years (IQR: 49.7, 72.5), with 71.2% of patients being male. The most common comorbidities were diabetes mellitus (60.7%), hypertension (58%), and heart disease (12.2%). The average oxygen saturation and C-reactive protein at admission were 82% [IQR: 70.0–89.0]and 113.0 [IQR: 54.0–186.0], respectively. Fifty-eight percent of patients received a standard dose (6mg) of steroids. The mortality rate was higher in the high-dose group compared to the standard-dose group; however, the difference was not statistically significant (47.9% vs 43.7% p = 0.549). The two most common steroid associated adverse effects were uncomplicated hyperglycemia (62.2%) and superimposed bacterial pneumonia (20.1%). The high-dose group had a higher incidence of uncomplicated hyperglycemia compared to the standard-dose group (63.6% vs 61.1%). However, the incidence of diabetic ketoacidosis was lower in the high dose group (0.6% vs 6.6%). Oxygen saturation at admission was associated with survival where it was lower among non-survivor patients with critical COVID-19. Conclusion The study found that high-dose steroids in the treatment of critically ill patients with COVID-19 pneumonia did not confer any mortality benefit and were associated with an increased risk of dysglycemia and superimposed infections. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background Crude and adjusted mortality rates for patients with non-ventilator hospital-acquired pneumonia (NV-HAP) are amongst the highest of all healthcare-associated infections, leading to calls for greater prevention. Patients prone to NV-HAP, however, tend to be severely ill at baseline making it unclear whether their high mortality rates are due to NV-HAP, underlying conditions, or both.Methods Two infectious disease physicians conducted detailed medical record reviews on 150 randomly selected adults from 4 hospitals who died in-hospital following an NV-HAP event between April 2016 and May 2021. Reviewers abstracted risk factors, estimated the preventability of NV-HAP, identified causes of death, and adjudicated the preventability of death.Results Patients’ median age was 69.3 (IQR 60.7-77.4) and 43.3% were female. Comorbidities were common: 57% had cancer, 30% chronic kidney disease, 29% chronic lung disease, and 27% heart failure. At least one hospice-eligible condition was present before NV-HAP in 54% and “Do Not Resuscitate” orders in 24%. Most (99%) had difficult-to-modify NV-HAP risk factors: 76% altered mental status, 35% dysphagia, and 27% nasogastric/orogastric tubes. NV-HAP was deemed possibly or probably preventable in 21% and hospital death likely or very likely preventable in 8.6%.Conclusions Most patients who die following NV-HAP have multiple, severe underlying comorbidities and difficult-to-modify risk factors for NV-HAP. Only 1 in 5 NV-HAPs that culminated in death and 1 in 12 deaths following NV-HAP were judged potentially preventable. This does not diminish the importance of NV-HAP prevention programs but informs expectations about the potential magnitude of their impact on hospital deaths.

by Noa Zychlinski, Ronen Fluss, Yair Goldberg, Daniel Zubli, Galia Barkai, Eyal Zimlichman, Gad Segal Background Hospital-at-home (HAH) is increasingly becoming an alternative for in-hospital stay in selected clinical scenarios. Nevertheless, there is still a question whether HAH could be a viable option for acutely ill patients, otherwise hospitalized in departments of general-internal medicine. Methods This was a retrospective matched study, conducted at a telemedicine controlled HAH department, being part of a tertiary medical center. The objective was to compare clinical outcomes of acutely ill patients (both COVID-19 and non-COVID) admitted to either in-hospital or HAH. Non-COVID patients had one of three acute infectious diseases: urinary tract infections (UTI, either lower or upper), pneumonia, or cellulitis. Results The analysis involved 159 HAH patients (64 COVID-19 and 95 non-COVID) who were compared to a matched sample of in-hospital patients (192 COVID-19 and 285 non-COVID). The median length-of-hospital stay (LOS) was 2 days shorter in the HAH for both COVID-19 patients (95% CI: 1–3; p = 0.008) and non-COVID patients (95% CI; 1–3; p < 0.001). The readmission rates within 30 days were not significantly different for both COVID-19 patients (Odds Ratio (OR) = 1; 95% CI: 0.49–2.04; p = 1) and non-COVID patients (OR = 0.7; 95% CI; 0.39–1.28; p = 0.25). The differences remained insignificant within one year. The risk of death within 30 days was significantly lower in the HAH group for COVID-19 patients (OR = 0.34; 95% CI: 0.11–0.86; p = 0.018) and non-COVID patients (OR = 0.38; 95% CI: 0.14–0.9; p = 0.019). For one year survival period, the differences were significant for COVID-19 patients (OR = 0.5; 95% CI: 0.31–0.9; p = 0.044) and insignificant for non-COVID patients (OR = 0.63; 95% CI: 0.4–1; p = 0.052). Conclusions Care for acutely ill patients in the setting of telemedicine-based hospital at home has the potential to reduce hospitalization length without increasing readmission risk and to reduce both 30 days and one-year mortality rates. …

Abstract Background The emergence and rapid spread of gram-negative bacteria resistant to carbapenems among newborns is concerning on a global scale. Nonetheless, the pooled estimate of gram-negative bacteria resistant to carbapenem that cause neonatal sepsis in developing nations remains unknown. Thus, this study aimed to determine the combined prevalence of gram-negative bacteria resistant to carbapenem in African newborns who were suspected of having sepsis. Methods All studies published from January 1, 2010, up to December 30, 2023, from PubMed, Science Direct, Scopus electronic databases, and the Google Scholar search engine were researched. Isolates tested for carbapenem from neonates with sepsis, English language papers conducted in Africa, and cross-sectional and cohort studies papers were included. Using PRISMA guidelines, we systematically reviewed and meta-analyzed studies that assessed the prevalence of carbapenem-resistant gram-negative bacteria. The “Joanna Briggs Institute” was used critically to evaluate the quality of the included studies. The data analysis was carried out using STATA™ version 17. Heterogeneity across the studies was evaluated using Q and I 2 tests. The subgroup analysis was done and, funnel plot and Egger’s regression test were used to detect publication bias. A sensitivity analysis was conducted. Results All 36 studies were included in the meta-analysis and systematic review. The pooled prevalence of carbapenem resistance in Africa was 30.34% (95% CI 22.03–38.64%). The pooled estimate of gram-negative bacteria resistant to imipenem, and meropenem was 35.57% (95% CI 0.67–70.54%) and 34.35% (95% CI 20.04% – 48.67%), respectively. A. baumannii and Pseudomonas spp. had pooled prevalence of 45.9% (95% CI 33.1–58.7%) and 43.0% (95% CI 23.0–62.4%), respectively. Similarly, Pseudomonas spp. and A. baumannii also exhibited strong meropenem resistance, with a pooled prevalence of 29.2% (95% CI 4.8–53.5%) and 36.7% (95% CI 20.1–53.3%), respectively. E. coli and K. pneumoniae were the two most common isolates. Conclusion There should be urgent antimicrobial stewardship practices, strengthened surveillance systems and effective treatment for neonates with sepsis. There was remarkable variation in resistance across the continent. …

Abstract Purpose We aimed to explore the prevalence and within-host evolution of resistance in polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP) in critically ill patients. Methods We performed an epidemiological analysis of consecutive patients with PHR-CRKP from clinical cases. Our study investigated the within-host resistance evolution and its clinical significance during polymyxin exposure. Furthermore, we explored the mechanisms underlying the dynamic evolution of polymyxin resistance at both subpopulation and genetic levels, involved population analysis profile test, time-killing assays, competition experiments, and sanger sequencing. Additionally, comparative genomic analysis was performed on 713 carbapenemase-producing K. pneumoniae strains. Results We enrolled 109 consecutive patients, and PHR-CRKP was found in 69.7% of patients without previous polymyxin exposure. 38.1% of PHR-CRKP isolates exhibited polymyxin resistance and led to therapeutic failure in critically ill scenarios. An increased frequency of resistant subpopulations was detected during PHR-CRKP evolution, with rapid regrowth of resistant subpopulations under high polymyxin concentrations, and a fitness cost in an antibiotic-free environment. Mechanistic analysis revealed that diverse mgrB insertions and pmrB hypermutations contributed to the dynamic changes in polymyxin susceptibility in dominant resistant subpopulations during PHR evolution, which were validated by comparative genomic analysis. Several deleterious mutations (e.g. pmrBLeu82Arg, pmrBSer85Arg) were firstly detected during PHR-CRKP evolution. Indeed, specific sequence types of K. pneumoniae demonstrated unique deletions and deleterious mutations. Conclusions Our study emphasizes the high prevalence of pre-existing heteroresistance in CRKP, which can lead to polymyxin resistance and fatal outcomes. Hence, it is essential to continuously monitor and observe the treatment response to polymyxins in appropriate critically ill scenarios. Graphical Abstract …

Abstract Purpose We aimed to explore the prevalence and within-host evolution of resistance in polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP) in critically ill patients. Methods We performed an epidemiological analysis of consecutive patients with PHR-CRKP from clinical cases. Our study investigated the within-host resistance evolution and its clinical significance during polymyxin exposure. Furthermore, we explored the mechanisms underlying the dynamic evolution of polymyxin resistance at both subpopulation and genetic levels, involved population analysis profile test, time-killing assays, competition experiments, and sanger sequencing. Additionally, comparative genomic analysis was performed on 713 carbapenemase-producing K. pneumoniae strains. Results We enrolled 109 consecutive patients, and PHR-CRKP was found in 69.7% of patients without previous polymyxin exposure. 38.1% of PHR-CRKP isolates exhibited polymyxin resistance and led to therapeutic failure in critically ill scenarios. An increased frequency of resistant subpopulations was detected during PHR-CRKP evolution, with rapid regrowth of resistant subpopulations under high polymyxin concentrations, and a fitness cost in an antibiotic-free environment. Mechanistic analysis revealed that diverse mgrB insertions and pmrB hypermutations contributed to the dynamic changes in polymyxin susceptibility in dominant resistant subpopulations during PHR evolution, which were validated by comparative genomic analysis. Several deleterious mutations (e.g. pmrBLeu82Arg, pmrBSer85Arg) were firstly detected during PHR-CRKP evolution. Indeed, specific sequence types of K. pneumoniae demonstrated unique deletions and deleterious mutations. Conclusions Our study emphasizes the high prevalence of pre-existing heteroresistance in CRKP, which can lead to polymyxin resistance and fatal outcomes. Hence, it is essential to continuously monitor and observe the treatment response to polymyxins in appropriate critically ill scenarios. Graphical Abstract …

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 4, Page 390-391, August 15, 2024.

Abstract Purpose This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. Methods The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. Results The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7–8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. Conclusion The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany. …

Abstract Background Acute respiratory infections are a leading cause of morbidity and mortality in children. However, studies on the prevalence of respiratory viruses among children with acute respiratory infections in Kunming, China, are lacking. Therefore, we aimed to investigate the epidemiological characteristics of respiratory pathogens among children with acute respiratory infections in Kunming during the coronavirus disease 2019 pandemic. Methods Nasopharyngeal swab samples were collected from 4956 children with acute respiratory infections at Yunnan Provincial First People’s Hospital between January 2020 and December 2022, patients with COVID-19 were excluded from the study. Multiplex reverse transcription polymerase chain reaction was used to detect respiratory pathogens. Results The frequency of respiratory pathogens among children was significantly lower in 2020 than in 2021 and 2022. The following pathogens had the highest prevalence rates (in descending order) from 2020 to 2022: HRV > RSV > PIV > ADV > MP; HRV > RSV > HADV > PIV > MP and HRV > Mp > HADV > H3N2 > HMPV. The overall frequency of respiratory pathogens exhibited an inverted U-shape with increasing age among the children. Human bocavirus, human parainfluenza virus, and human respiratory syncytial virus were the dominant respiratory viruses in children aged ≤ 3 years, whereas Mycoplasma pneumoniae was the dominant respiratory pathogen in children aged > 3 years. HRV has the highest prevalence and is the main pathogen of mixed infection. The prevalence of the influenza A virus has decreased significantly, whereas HRSV and Mp are found to be seasonal. Conclusions Our findings offer an objective evaluation of transmission dynamics and epidemiological shifts in respiratory pathogens during the coronavirus disease 2019 pandemic in Kunming, serving as a basis for informed decision-making, prevention, and treatment strategies. …

Machine learning (ML) tools for acute respiratory distress syndrome (ARDS) detection and prediction are increasingly used. Therefore, understanding risks and benefits of such algorithms is relevant at the bedside. ARDS is a complex and severe lung condition that can be challenging to define precisely due to its multifactorial nature. It often arises as a response to various underlying medical conditions, such as pneumonia, sepsis, or trauma, leading to widespread inflammation in the lungs. ML has shown promising potential in supporting the recognition of ARDS in ICU patients. By analyzing a variety of clinical data, including vital signs, laboratory results, and imaging findings, ML models can identify patterns and risk factors associated with the development of ARDS. This detection and prediction could be crucial for timely interventions, diagnosis and treatment. In summary, leveraging ML for the early prediction and detection of ARDS in ICU patients holds great potential to enhance patient care, improve outcomes, and contribute to the evolving landscape of precision medicine in critical care settings. This article is a concise definitive review on artificial intelligence and ML tools for the prediction and detection of ARDS in critically ill patients.

Abstract Background In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data.Methods Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged 12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%–4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28–.84] and 1.12 [0.71–1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, −60.9 to −40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (−9.6 to 39.7).Interpretations The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Abstract Background In the hospital environment, carbapenemase-producing Pseudomonas aeruginosa (CPPA) may lead to fatal patient infections. However, the transmission routes of CPPA often remain unknown. Therefore, this case study aimed to trace the origin of CPPA ST357, which caused a hospital-acquired pneumonia in a repatriated critically ill patient suffering from Guillain-Barré Syndrome in 2023. Methods Antimicrobial susceptibility of the CPPA isolate for 30 single and combination therapies was determined by disk-diffusion, Etest or broth microdilution. Whole-genome sequencing was performed for three case CPPA isolates (one patient and two sinks) and four distinct CPPA ST357 patient isolates received in the Dutch CPPA surveillance program. Furthermore, 193 international P. aeruginosa ST357 assemblies were collected via three genome repositories and analyzed using whole-genome multi-locus sequence typing in combination with antimicrobial resistance gene (ARG) characterization. Results A Dutch patient who carried NDM-1-producing CPPA was transferred from Kenya to the Netherlands, with subsequent dissemination of CPPA isolates to the local sinks within a month after admission. The CPPA case isolates presented an extensively drug-resistant phenotype, with susceptibility only for colistin and cefiderocol-fosfomycin. Phylogenetic analysis showed considerable variation in allelic distances (mean = 150, max = 527 alleles) among the ST357 isolates from Asia (n = 92), Europe (n = 58), Africa (n = 21), America (n = 16), Oceania (n = 2) and unregistered regions (n = 4). However, the case isolates (n = 3) and additional Dutch patient surveillance program isolates (n = 2) were located in a sub-clade of isolates from Kenya (n = 17; varying 15–49 alleles), the United States (n = 7; 21–115 alleles) and other countries (n = 6; 14–121 alleles). This was consistent with previous hospitalization in Kenya of 2/3 Dutch patients. Additionally, over half of the isolates (20/35) in this sub-clade presented an identical resistome with 9/17 Kenyan, 5/5 Dutch, 4/7 United States and 2/6 other countries, which were characterized by the blaNDM-1, aph(3’)-VI, ARR-3 and cmlA1 ARGs. Conclusion This study presents an extensively-drug resistant subclone of NDM-producing P. aeruginosa ST357 with a unique resistome which was introduced to the Netherlands via repatriation of critically ill patients from Kenya. Therefore, the monitoring of repatriated patients for CPPA in conjunction with vigilance for the risk of environmental contamination is advisable to detect and prevent further dissemination. …