Infectious Diseases and Therapy最新文献

{"title":"Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation.","authors":"Na Hu, Fengjiao Xiao, Yechao Chen, Qiaoling Gu, Pei Liang, Yin Xu, Jinchun Liu, Yunxing Liu, Yi-Chen Li, Yinqiu Xu, Mengyin Liu, Dayu Chen, Haixia Zhang","doi":"10.1007/s40121-025-01164-9","DOIUrl":"https://doi.org/10.1007/s40121-025-01164-9","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited, with polymyxin B (PMB) and ceftazidime-avibactam (CZA) being among the available choices. However, research on these options is scarce and significantly heterogeneous. This study aims to analyze the efficacy, safety, and cost-effectiveness of PMB and CZA within a standardized target trial emulation (TTE) framework.</p><p><strong>Methods: </strong>This retrospective study emulated a target trial to evaluate the efficacy, safety, and cost-effectiveness of CZA versus PMB for treating CRE infections. Conducted at Nanjing Drum Tower Hospital, this study included adult patients treated with CZA or PMB from July 2020 to December 2022. Data on demographics, treatment outcomes, and costs were collected. The primary outcomes included clinical cure, incidence of adverse drug reactions (ADRs), and cost-effectiveness. Secondary outcomes assessed 28-day all-cause mortality, microbiological eradication rates, incidence of acute kidney injury (AKI), and gastrointestinal events. The outcomes were assessed using the modified intention-to-treat (mITT) effects, per-protocol effects, and propensity score overlap weighting (PSOW) methods.</p><p><strong>Results: </strong>Between July 1, 2020, and December 31, 2022, 492 hospitalized patients treated with CZA or PMB were screened at Nanjing Drum Tower Hospital. Following inclusion and exclusion criteria, 176 patients were included in the mITT analysis, and 153 in the per-protocol analysis. The clinical cure rate was significantly higher in the CZA group compared to the PMB group across all analyses. The 28-day mortality was similar between groups, while the microbial eradication rate was significantly higher in the CZA group compared to the PMB group across all analyses. The incidence of ADRs was consistent between groups, but AKI occurred more frequently in PMB patients, while gastrointestinal events were more common in the CZA group. The CZA strategy demonstrated a 28.1% increase in efficacy, with an incremental cost-effectiveness ratio of 71,651.76 yuan. Sensitivity analyses confirmed the robustness of these findings.</p><p><strong>Conclusions: </strong>This study demonstrates that CZA has a higher clinical cure rate compared to PMB within a standard TTE framework. However, the overall incidence of ADRs was similar between the two treatments. Pharmacoeconomic analysis also indicated that CZA is cost-effective.</p><p><strong>Trial registration: </strong>https://www.chictr.org.cn ; identifier, ChiCTR2300067946.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding \"Risk of Invasive Escherichia coli (E. coli) Disease After Elective Urologic Procedures Among Older Adults in the United States\".","authors":"Ariel Chen","doi":"10.1007/s40121-025-01158-7","DOIUrl":"https://doi.org/10.1007/s40121-025-01158-7","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to: Letter to the Editor Regarding \"Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination\".","authors":"Timothy E Albertson, Caitlin Hansen, Juleen Gayed, Xia Xu, Ye Feng, Hua Ma","doi":"10.1007/s40121-025-01138-x","DOIUrl":"10.1007/s40121-025-01138-x","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1137-1141"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Timing of Vaccination: A Narrative Review of Integrating Strategies for COVID-19, Influenza, and Respiratory Syncytial Virus.","authors":"Paolo Bonanni, Jung Yeon Heo, Hitoshi Honda, Ping-Ing Lee, Aminatou Mouliom, Hoe Nam Leong, Maria Del Pilar Martin Matos, Rachel Dawson","doi":"10.1007/s40121-025-01135-0","DOIUrl":"10.1007/s40121-025-01135-0","url":null,"abstract":"<p><p>Lower respiratory tract infections caused by SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) cause a significant disease burden globally, despite the availability of effective vaccines. Certain populations, such as older adults (≥ 60 years) and individuals of all ages with particular comorbidities, are at increased risk for severe outcomes, including hospitalization and death. National administration schedules for available vaccines against respiratory viruses are not unified, and not all current guidelines are clear and directive, concerning the optimal timing of vaccination. Herein, we formulate an evidence-based position regarding the optimal timing of COVID-19, influenza, and RSV vaccination for older adults and individuals with chronic comorbidities, based on a synthesis of the literature and current guidelines. Vaccination impact and timing were found to be influenced by vaccinee risk factors, including age and comorbidities, and waning vaccine effectiveness and seasonal pathogen burden. Because COVID-19, influenza, and RSV display unique seasonal patterns within and between regions, local epidemiological surveillance of each virus is crucial for determining optimal vaccination timing and guidelines. To maximize the benefits of these respiratory virus vaccines, the timing of peak vaccine effectiveness and period of greatest risk for severe outcomes should be aligned. Thus, COVID-19, influenza, and other recommended vaccines given ahead of the start of the respiratory virus season (or other regionally appropriate time) and co-administered at a single, routine visit represent the optimal approach to protecting at-risk populations. More data will be required to establish the clinical benefit of additional RSV vaccine doses and whether these may be integrated within a seasonal schedule. Coordinated policy decisions that align with strain selection for new and annually reformulated vaccines would enable the timely raising of public health awareness, ultimately leading to enhanced vaccine uptake. Implementation strategies will require engagement of healthcare providers and strong, evidence-based public health recommendations for integrated vaccine schedules.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"911-932"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics and Outcomes of Patients Treated with Carbapenem Versus Non-carbapenem Therapy for AmpC-Producing Enterobacterales Bacteremia: A Retrospective Study.","authors":"Shuroug A Alowais, Atheer Aldairem, Sumaya N Almohareb, Yara Alsaeed, Rema Aldugiem, Tariq Alqahtani, Rawnd Alamri, Raghad Aied, Hisham A Badreldin, Khalid Bin Saleh","doi":"10.1007/s40121-025-01133-2","DOIUrl":"10.1007/s40121-025-01133-2","url":null,"abstract":"<p><strong>Introduction: </strong>Inducible AmpC β-lactamases in Gram-negative Enterobacterales pose therapeutic challenges. Although carbapenems are the preferred treatment, other antibiotics can serve as a viable alternative. Studies comparing treatment options report varied outcomes. This study evaluates 30-day mortality, treatment failure, and length of hospitalization in patients with AmpC-producing Enterobacterales bacteremia.</p><p><strong>Methods: </strong>This retrospective cohort study included adult patients with bacteremia caused by AmpC-producing Enterobacterales. Exclusion criteria included: therapy duration < 72 h, coinfection, resistant isolates, and death within 72 h of diagnosis. Patients were divided into definitive carbapenem and noncarbapenem therapy. The primary outcome was 30-day mortality, while secondary outcomes evaluated treatment failure and length of hospitalization. Statistical analysis used descriptive statistics, group comparisons, and logistic regression.</p><p><strong>Results: </strong>Of 214 screened patients, 80 met the inclusion criteria. Enterobacter cloacae (60%) was the predominant pathogen, primarily originating from line-related infections (55%). Carbapenems were the primary empirical (45%) and definitive (75%) therapies; 30-day mortality was higher in the non-carbapenem group (20% versus 3.3%, p = 0.08). Treatment failure was significantly higher in the non-carbapenem group (20% versus 1.6%, p < 0.01). The mean hospital stay was longer in the carbapenem group (26 ± 38.40 days) than the non-carbapenem group (11.15 ± 7.15 days, p = 0.87). Older age was significantly associated with higher mortality (odds ratio (OR) 1.07, 95% confidence intervals (CI): 0.98-12.20, p = 0.015).</p><p><strong>Conclusions: </strong>Carbapenem use was significantly associated with improved survival, highlighting its importance in treatment strategies. Age significantly affects survival, stressing the need for personalized treatments. Further research and strategies are needed to address clinical failures and enhance antimicrobial stewardship.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1061-1074"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Hepatic and Extrahepatic Outcomes of Chronic Hepatitis C Patients After Sofosbuvir-Based Treatment (LONGHEAD Study).","authors":"Chung-Feng Huang, Jeong Heo, Rong-Nan Chien, Yang-Hyun Baek, Jia-Horng Kao, Ju-Hyun Kim, Ting-Tsung Chang, Kwan-Soo Byun, Jyh-Jou Chen, Sook-Hyang Jeong, Tsung-Hui Hu, Young-Seok Kim, Cheng-Yuan Peng, Won-Young Tak, Horng-Yuan Wang, Seung-Kew Yoon, I-Shyan Sheen, Youn-Jae Lee, Yu-Chun Hsu, Hyung-Joon Yim, Pei-Chien Tsai, Ming-Lun Yeh, Sang-Hoon Ahn, Chia-Yen Dai, Seung-Woon Paik, Jee-Fu Huang, Yoon-Jun Kim, Wan-Long Chuang, Young-Suk Lim, Ming-Lung Yu","doi":"10.1007/s40121-025-01145-y","DOIUrl":"10.1007/s40121-025-01145-y","url":null,"abstract":"<p><strong>Background/aims: </strong>Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C virus (HCV) infection. The long-term hepatic and extrahepatic outcomes of DAAs in chronic hepatitis C (CHC) patients receiving curative antivirals are elusive.</p><p><strong>Methods: </strong>CHC patients were retrieved from two phase III sofosbuvir-based clinical trials conducted from 2013-2014. Patients who achieved a sustained virological response have been followed prospectively for 5 years since 2016. A propensity score-matched interferon-based historical control with a 1:3 ratio was used for comparison. Quality of life (QoL) was measured by the SF-36, liver fibrosis was measured by electrography, and fibrosis-related markers were followed annually in the prospective cohort.</p><p><strong>Results: </strong>A total of 160 DAA- and 480 interferon-treated patients were enrolled. Twenty-eight patients developed hepatocellular carcinoma (HCC) over a follow-up period of 4424 person-years (annual incidence: 0.6%). The incidence of HCC did not differ significantly between the DAA cohort and interferon-treated patients (P = 0.07). Cox regression analysis revealed that FIB-4 was the only factor independently associated with HCC development (hazard ratio [HR]: 95% confidence interval [CI] 3.59/1.68-7.66, P = 0.001). The incidence of newly developed cardio-cerebrovascular disease was 13.8 per 1000 person-years and 0.9 per 1000 person-years in interferon-treated patients and the DAA cohort, respectively (P < 0.001). Interferon-based patients had a significantly greater incidence of cardio-cerebrovascular disease (HR/CI 3.39/1.28-8.96, P = 0.014). There was a substantial decrease in liver stiffness (P_trend = 0.08) and M2BPGi (P_trend = 0.05) and a significant reduction in LOXL2 (P_trend = 0.02) over 5 years. A significant decrease in QoL was observed in role limitations due to physical health and emotional problems, whereas the other parameters were maintained consistently throughout the 5 years of follow-up.</p><p><strong>Conclusions: </strong>HCV eradication by DAAs improved liver- and non-liver-related outcomes, constantly promoted liver fibrosis regression, and maintained quality of life after HCV cure.</p><p><strong>Clinical trial number: </strong>NCT03042520.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1089-1101"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics of Patients Who Acquired Gram-Negative Bacteria During Ceftazidime-Avibactam Therapy.","authors":"Chien Chuang, Tzu-Chi Kao, Chih-Han Juan, Sheng-Hua Chou, Yu-Chien Ho, Szu-Yu Liu, Yi-Ru Huang, Hsiang-Ling Ho, Yi-Tsung Lin","doi":"10.1007/s40121-025-01126-1","DOIUrl":"10.1007/s40121-025-01126-1","url":null,"abstract":"<p><strong>Introduction: </strong>Ceftazidime-avibactam (CZA) is recommended to treat infections caused by carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa with difficult-to-treat resistance. The selective pressure of CZA results in the isolation of multidrug-resistant Gram-negative bacteria (MDR-GNB), causing superinfection or hospital-wide spread. We aimed to study the clinical characteristics of patients who acquired GNB during CZA treatment.</p><p><strong>Methods: </strong>Adult patients treated with CZA for ≥ 5 days for proven or suspected MDR-GNB were retrospectively enrolled at Taipei Veterans General Hospital between December 2019 and June 2021. GNB acquisition was defined as new GNB species resulting in infection or colonization isolated during the period from 5 days after the initiation of CZA until the end of treatment. Clinical features were compared between patients who acquired GNB from clinical specimen and those who did not. Multivariable analysis was used to explore risk factors for acquisition of GNB and 28-day mortality in patients who acquired GNB.</p><p><strong>Results: </strong>Among 321 patients treated with CZA, 68 GNB were identified in 55 patients (17.1%). Elizabethkingia species (n = 15) was the most common GNB, followed by Acinetobacter species (n = 13) and Burkholderia cenocepacia (n = 11). The presence of diabetes mellitus, and mechanical ventilation were independent risk factors for GNB acquisition. There was a statistically nonsignificant trend toward increased 28-day mortality in patients with GNB acquisition compared to those without (38.2% vs. 27.8%, P = 0.105). Cerebrovascular disease and acquired GNB resulting in infection were associated with 28-day mortality in patients who acquired GNB.</p><p><strong>Conclusions: </strong>Elizabethkingia species, Acinetobacter species, and B. cenocepacia were the major GNB acquired during CZA treatment. A trend toward increased mortality was observed in patients with GNB acquisition during CZA treatment. Further studies on optimal treatments for these patients were warranted.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1027-1042"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Broad-Spectrum Antimicrobials on Patients with Community-Acquired Pneumonia with Low Risk for Drug-Resistant Pathogens: Historical Cohort Study in Japan.","authors":"Takahiro Takazono, Naoki Hosogaya, Yoshiyuki Saito, Masahiko Takemura, Naoki Iwanaga, Noriho Sakamoto, Junichi Hirayama, Rie Ueno, Hiroshi Mukae","doi":"10.1007/s40121-025-01142-1","DOIUrl":"10.1007/s40121-025-01142-1","url":null,"abstract":"<p><strong>Introduction: </strong>Broad-spectrum antimicrobials are commonly administered for community-acquired pneumonia (CAP); however, unnecessary administration may cause adverse events and poor outcomes. This study aimed to understand the impact of broad-spectrum anti-pseudomonal β-lactam use on clinical outcomes and healthcare resource utilization (HCRU) in inpatients with CAP and a low risk of drug-resistant pathogens (DRPs).</p><p><strong>Methods: </strong>This historical cohort study reviewed Japan's hospital claims database (January to December of 2018) and included inpatients aged ≥ 20 years who received intravenous antimicrobial therapy for CAP. Those with high DRP risk were excluded. According to the initial antimicrobial regimen, patients were divided into broad-spectrum (anti-pseudomonal β-lactam therapy) and narrow-spectrum (non-anti-pseudomonal β-lactam therapy) groups. This study evaluated 30-day hospital mortality as a primary outcome using inverse probability of treatment weighting (IPTW) to adjust for differences between both groups and HCRU as an exploratory analysis.</p><p><strong>Results: </strong>A total of 15,617 patients were analyzed (2627 in the broad-spectrum group and 12,990 in the narrow-spectrum group). In the broad-spectrum group, the 30-day mortality rate was 10.6%, which was higher than that in the narrow-spectrum group (5.3%). Furthermore, it was associated with an increased 30-day mortality compared with the narrow-spectrum group after IPTW (adjusted odds ratio, 1.77; 95% confidence interval, 1.52-2.06; p < 0.001). The mean inpatient cost was USD 6139 and USD 5184 for the broad- and narrow-spectrum groups, respectively.</p><p><strong>Conclusions: </strong>The initial use of anti-pseudomonal β-lactams for CAP with low DRP risk is associated with poor outcomes, including death and high HCRU. Thus, initial antimicrobials should be judiciously selected for CAP management.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1043-1059"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding \"Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination\" by Albertson et al. 2024.","authors":"Ivan Pourmir, Adrian Alanis, Niccolò Clemente","doi":"10.1007/s40121-025-01136-z","DOIUrl":"10.1007/s40121-025-01136-z","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1133-1136"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016-2024).","authors":"Giovanni Scaglione, Marta Canuti, Martina Offer, Valentina Breschi, Antonio Piralla, Fausto Baldanti, Gabriele Del Castillo, Francesco Scovenna, Sabrina Buoro, Federica Morani, Danilo Cereda, Alessandra Bandera, Andrea Gori, Marta Colaneri","doi":"10.1007/s40121-025-01148-9","DOIUrl":"10.1007/s40121-025-01148-9","url":null,"abstract":"<p><strong>Introduction: </strong>Severe lower respiratory tract infections often require hospitalization, but a significant proportion lack microbiological diagnosis, leading to challenges in management. This study aimed to compare clinical outcomes of S-LRTIs with unknown versus known bacteria or viral etiology in Lombardy, Italy.</p><p><strong>Methods: </strong>A retrospective study analyzed respiratory infection-related hospitalizations in Lombardy over 8 years (2016-2024) using patient discharge charts. Patients were categorized into four groups: bacterial, viral (non-COVID-19), COVID-19-related, and unknown etiology. Outcomes included length of stay, intensive care unit admissions, and intra-hospital mortality. Temporal, seasonal, and age-specific trends were evaluated.</p><p><strong>Results: </strong>Among 683,741 hospitalizations, 338,211 (49.5%) were of unknown etiology, showing a 12.3% intra-hospital mortality rate (41,627 deaths) and 4.0% intensive care unit admission rate (13,625 admissions). COVID-19-related hospitalizations had the highest intra-hospital mortality rate (22.0%, 36,446 deaths in 165,605 COVID-19-related hospitalizations) and number of intensive care unit admissions (14,725 admissions, 8.9% of COVID-19-related hospitalizations), while viral non-COVID-19 hospitalizations showed the lowest intra-hospital mortality rate (3.2%, 1114 deaths in 34,769 viral-non-COVID-19 hospitalizations) and shortest length of stay (11.9 days). Hospitalizations with unknown etiology were more common in minors (42,190 episodes, 57.6% of total in < 18 years) and elderly (358,534 episodes, 56.2% of total in > 75 years), especially during warm seasons. Post-pandemic years saw increased bacterial and viral hospitalizations alongside a reduced proportion of those without an unknown etiology.</p><p><strong>Conclusions: </strong>Respiratory infection-related hospitalizations with unknown etiology are associated with distinct seasonal and demographic patterns, and poorer outcomes compared to viral non-COVID-19 hospitalizations. COVID-19 reshaped S-LRTI epidemiology and diagnostic approaches, highlighting the need for comprehensive pathogen panels and tailored management strategies, while promoting their expanded use. Future research should integrate detailed clinical data to improve understanding and outcomes of severe respiratory infections, especially in vulnerable populations.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1075-1087"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}