Infectious Diseases and Therapy最新文献

Introduction: Influenza is a highly transmissible respiratory viral infection, with a risk of severe complications and excess respiratory mortality. Clinical trial data showed that baloxavir was more effective than oseltamivir for reducing duration of virus shedding, which is a key predictor of transmission. Consideration of the effect of treatments on transmission rates is important to ensure that the value of treatments is captured. This study assessed the cost-effectiveness of different treatment strategies with baloxavir and oseltamivir, considering their impact on influenza transmission.

Methods: The analysis used two models: a dynamic transmission model to estimate influenza incidence, with outputs incorporated in a static population-level decision tree model, in order to evaluate the clinical outcomes and cost-effectiveness of treatment strategies with different shares of baloxavir and oseltamivir from the healthcare payer's perspective in Japan. Clinical data were sourced from phase 3 trials, and cost inputs were informed by the Ministry of Health, Labour and Welfare, as well as JammNet. Sensitivity and scenario analyses were also conducted.

Results: Increasing the use of baloxavir in adults from 40% to 50% reduces the number of influenza cases by 17%, hospitalizations by 18%, and deaths by 23%, with cost savings of JPY (Japanese yen) 16,280 million and 10,486 quality-adjusted life years (QALYs) gained, in the total population in Japan. Across all risk and age subgroups, increasing the share of baloxavir was cost-saving and more effective, and, therefore, was considered dominant, which was also confirmed by the sensitivity analysis.

Conclusion: Treatment of influenza with baloxavir is anticipated to offer value for money within Japan's healthcare system, delivering significant clinical benefits both for the general population and for all age and risk groups. Accounting for the treatment's impact on influenza transmission adds another dimension of value and further reinforces the evidence supporting the growing use of baloxavir in Japan.

Introduction: Early antibacterial treatment is critical for patients with hematologic malignancies (HMs) and sepsis. Droplet digital polymerase chain reaction (ddPCR) can rapidly detect pathogens and antimicrobial resistance (AMR) genes, but its clinical value in HMs is unknown. This study aimed to systematically evaluate the role of ddPCR in diagnosis, clinical outcomes, and antimicrobial stewardship.

Methods: From January 2023 to March 2025, 400 patients with hematologic malignancies (HMs) and sepsis were enrolled in the study. Of these, 150 received both ddPCR and blood culture (BC), while 250 underwent BC alone. Using propensity score matching (PSM), as well as subgroup and sensitivity analyses, we evaluated ten indicators, including 28-day mortality, treatment efficacy, and antibiotic use density (AUD).

Results: ddPCR showed a 49.33% positive rate (vs. BC's 17.50%, P < 0.01) with a 4.06-h diagnostic turnaround (vs. 72.47 h for BC, P < 0.01), achieving 70.37% sensitivity and 55.28% specificity. The ddPCR group had lower 28-day mortality (HR = 0.55, P = 0.01), higher clinical response rates, and greater inflammatory marker decline. Antimicrobial optimization via ddPCR improved efficacy to 85.11%, with reduced AUD (OR = - 28.93, P < 0.01), the quantity and proportion of combined antimicrobial usage. However, a non-significant difference was observed in the proportion of antibacterial treatment costs (P = 0.14). PSM and sensitivity analysis results were consistent, indicating data robustness.

Conclusions: ddPCR outperforms BC in diagnostic efficiency for patients with HMs and sepsis, accelerating pathogen and AMR genes identification, optimizing antibacterial therapy and management, improving clinical effectiveness, and reducing 28-day all-cause mortality. The findings support the application of ddPCR in immunosuppressed populations.

Tuberculosis (TB) remains a significant global public health challenge, despite recent advances in drug development. However, a comprehensive and systematic overview of the current clinical trial landscape in TB prevention and treatment is still lacking. This study aims to systematically review recent breakthroughs in TB drug development, assess their scientific value and global impact, and provide valuable insights for clinicians and policymakers involved in TB control efforts. We systematically searched the INFORMA pharmaceutical database to identify 1041 clinical trial projects related to TB. Two independent researchers screened and extracted the data, and discrepancies were resolved through consultation with a third researcher. Inclusion criteria were: (1) trials explicitly focused on TB drug development, (2) studies containing detailed descriptions of drug mechanisms or therapeutic targets, and (3) interventional studies. Exclusion criteria were the absence of key information, incomplete datasets, or non-interventional study designs. Descriptive statistical analyses were employed to systematically summarize trial characteristics, and data distribution features were visualized accordingly. Between 1990 and 2025, the number of TB-related clinical trials increased significantly, with a notable peak observed between 2018 and 2023. China and South Africa emerged as leading contributors to research activity, while the United States and the United Kingdom accounted for the majority of "Completed" trials. Despite the emergence of novel agents, traditional cornerstone drugs continued to dominate the development pipeline. Bedaquiline, in particular, demonstrated rapid, largely driven by supportive health policies. Academic institutions were the primary funding of TB trials, and regional analysis revealed heightened research activity in Asia and Africa. However, the global distribution of research resources remained uneven, highlighting the need for improved collaboration mechanisms to promote both health equity and innovation. This study systematically offers a comprehensive review of recent breakthroughs in TB drug development, revealing the current status and persistent challenges facing global clinical trials. Realizing the goal of ending TB will require sustained investment in scientific innovation, equitable resource allocation, and steadfast political commitment. Through coordinated global efforts, a new era in TB prevention and treatment is within reach.

Introduction: Oral nucleos(t)ide analogues (NAs) are widely used in managing hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Among first-line therapies, entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are commonly prescribed. However, their comparative efficacy and safety remain unclear in HBV-ACLF.

Methods: We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to January 2025 for studies evaluating ETV, TDF, and TAF in HBV-ACLF. The data were analyzed using standardized mean differences (SMD), 95% confidence intervals (95% CI), and surface under the cumulative ranking curve (SUCRA).

Results: Nine studies (five prospective, four retrospective) were included. TDF significantly improved 12-week survival compared to ETV (SMD = - 0.21; 95% CI - 0.36 to - 0.06), with no significant difference between TDF and TAF. For 12-week HBV-DNA clearance, TAF outperformed ETV (SMD = - 0.40; 95% CI - 0.77 to - 0.02), ranking highest in SUCRA (83.5%). TAF also showed superior virological suppression at 4 weeks (SUCRA: TAF 72.2% > ETV 49.1% > TDF 28.8%). TDF improved 12-week model for end-stage liver disease (MELD) scores more than ETV (SMD = 1.05; 95% CI 0.15-1.94). The drugs did not differ significantly in improving liver function at 4 weeks, as measured by alanine aminotransferase (ALT) and total bilirubin (TBIL) levels. Regarding renal function, ETV had a greater impact on the 4-week estimated glomerular filtration rate (eGFR) than TAF (SMD = - 0.35; 95% CI - 0.52 to 0.18), and both TDF and ETV showed a more significant effect on the 4-week creatinine (cr) levels than TAF (TDF: SMD = 0.29; 95% CI 0.00-0.57; ETV: SMD = 0.30; 95% CI 0.09-0.51).

Conclusions: Overall, TDF and TAF provide superior survival and antiviral benefits over ETV in HBV-ACLF, with three drugs showing similar effects in improving liver function. Moreover, TAF demonstrated the most favorable profile in viral suppression and renal safety.

Introduction: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea, with recurrence rates of 15-20% after standard treatment and ≥ 30% after a second relapse. In Germany, reliable epidemiological data remain limited.

Methods: A retrospective claims data analysis of the period 2017-2022 was performed using the German Analysis Database for Evaluation and Health Services Research (DADB), which covers 4.1 million insured individuals. Incident CDI cases, recurrent cases, and mortality were assessed and stratified by diagnosis setting. A propensity-score-matched control group without CDI adjusted for age, sex, and comorbidities was created. Cox proportional hazards models were used to determine mortality risk factors.

Results: CDI incidence decreased from 119 to 66 per 100,000 (2017-2022). First-recurrence rate declined from 15% to 11% and second-recurrence rate from 20% to 15%. Of all recurrences, 43% were managed in the outpatient setting. In 2022, severe CDI accounted for 38% of extrapolated statutory health insurance (SHI) cases. Metronidazole use in outpatients decreased from 79% to 53% for incident cases, while vancomycin prescriptions increased from 18% to 39%. In 2022, 72% of first CDI recurrences were treated with vancomycin, 20% with metronidazole, and 2% with fidaxomicin. Despite guideline recommendations, only 8% of patients with a second recurrence received fidaxomicin. In 2021, the 30-day mortality rate for secondary inpatient CDI cases was 20%, compared with 8% for primary inpatient cases and 4% for outpatient cases. Corresponding 1-year mortality rates were 44%, 32%, and 16%. In patients with CDI, 1-year mortality was 1.9 to 2.1 times higher than in controls (p < 0.001), with advanced age (≥ 65 years) being the strongest predictor (hazard ratio [HR] 12.21; 95% confidence interval [CI] 10.91-13.67).

Conclusions: Despite declining incidence and recurrence rates, CDI remains a major health burden in Germany, especially for older adults. High severity, limited adherence to treatment guidelines, and excess mortality underscore the need for targeted prevention, individualized therapy, and improved guideline implementation.

Introduction: Respiratory syncytial virus (RSV) is a common respiratory virus that can cause severe disease, particularly in older adults and adults with underlying medical conditions. However, RSV infections often go underdiagnosed due to infrequent testing and assay sensitivity limitations. To better understand RSV epidemiology and disease burden, we investigated respiratory virus testing patterns and characteristics associated with RSV testing among United States (US) adults aged ≥ 50 years with acute respiratory illnesses (ARIs).

Methods: This was a retrospective study using Optum^® electronic health records data from 2015 to 2023. Medically-attended ARIs were identified among adults aged ≥ 50 years; percentages of ARIs tested for RSV and other respiratory viruses were calculated and stratified by epidemiological year (EY) and most intensive care setting during the ARI episode. Patient, provider, and ARI characteristics associated with the likelihood of RSV testing were assessed using multivariable logistic regression models.

Results: Among 22,475,891 included ARIs, RSV testing occurred in 2.4% (n = 530,452) of episodes. RSV testing increased over time (1.3-5.9% from 2016-2017 to 2022-2023 EYs), though it remained markedly lower than influenza (5.8-15.1%; 2016-2017 to 2022-2023 EYs) and SARS-CoV-2 (5.8-22.6%; 2019-2020 to 2022-2023 EYs) testing. By most intensive level of care received, RSV testing from 2016-2023 was more frequent in inpatient (9.5-27.5%) and emergency department (ED; 1.4-17.9%) settings than the outpatient setting (0.3-1.4%). Among included covariates in adjusted analyses, most intensive care setting [ED: 9.3-fold, inpatient: 31.2-fold (versus outpatient)] and healthcare organization (0.02-13.8-fold) were most significantly associated with likelihood of RSV testing.

Conclusion: The likelihood of RSV testing varied significantly by most intensive care setting and healthcare organization. Despite increasing RSV testing over time, RSV remains infrequently tested among US adults. Under-detection of medically-attended RSV cases should be accounted for when estimating RSV disease burden and the potential impact of RSV prevention strategies. A Graphical Abstract is available for this article.

Introduction: Comprehensive data on ethambutol (EMB)-related optic neuropathy (EON) are lacking, creating a knowledge gap. Accordingly, this prospective programmatic study established a collaborative multidisciplinary team to explore EON.

Methods: This study enrolled patients who received EMB as part of their treatment regimen for mycobacterial infections. Programmatic assessments of visual abnormalities were performed for each patient by the team. EON was diagnosed by ophthalmologists. Patients diagnosed as having EON completed short-term (6-month) and long-term (5-year) follow-up.

Results: Of 476 patients, 31 (6.5%) were diagnosed as having EON. Older age (≥ 65 years, odds ratio [OR] = 2.5, P = 0.043) and diabetes mellitus (OR = 2.2, P = 0.045) were independent predictors of EON, and coexisting subjective and objective ocular abnormalities (OR = 4.8, P = 0.009) and concomitant visual acuity and color discrimination impairment (OR = 5.9, P = 0.009) were independently associated with EON in patients with ocular abnormalities at EMB discontinuation. Among patients with EON, 56.7% and 50.0% had favorable 6-month visual acuity and color discrimination outcomes, respectively. Among patients with unfavorable 6-month visual acuity outcomes, 45.5% had favorable outcomes at the 5-year follow-up. Moreover, 88.2% and 100% of patients with favorable and unfavorable 6-month visual acuity outcomes, respectively, already had these outcomes at the third month of follow-up. Additionally, 50.0% and 100% of patients with favorable and unfavorable 6-month color discrimination outcomes, respectively, already had these outcomes at the fourth month of follow-up.

Conclusions: The incidence of EON exceeded 6%. This study provides a feasible model for the comprehensive management of EON in clinical practice.

Introduction: The high mortality of Coronavirus Disease 2019 (COVID-19) highlights the need for safe and effective antiviral treatment. Small molecular antivirals (remdesivir, molnupiravir, nirmatrelvir/ritonavir) and immunomodulators (baricitinib, tocilizumab) have been developed or repurposed to suppress viral replication and ameliorate cytokine storms, respectively. Despite U.S. Food and Drug Administration (FDA) approval, serious cardiovascular adverse events (CVAEs) may not be apparent in initial trials.

Methods: A retrospective analysis of CVAEs linked to five World Health Organization (WHO) recommended COVID-19 therapies was conducted using the WHO VigiBase database from March 2020 to July 2023. Adjusted reporting odds ratios (aROR) with 95% confidence intervals (CI) were calculated to assess CVAE risks.

Results: A total of 276,631 AEs were reported to be associated with COVID-19, of which 13,091 were classified as cardiovascular events. Remdesivir was associated with significantly increased odds of CVAEs, particularly bradycardia (aROR 2.4, 95% CI 2.28-2.52). In contrast, nirmatrelvir/ritonavir and molnupiravir showed reduced CVAEs odds. Among immunomodulators, baricitinib was associated with increased CVAEs risk (aROR 2.31, 95% CI 2.07-2.59), with deep vein thrombosis being the most prominent (aROR 45.34, 95% CI 34.89-58.9), accounting for 38.8% of reported study cases in the database. Also, CVAEs odds were higher during the Omicron period compared to pre-Omicron period.

Conclusions: These findings highlight the importance of continued pharmacovigilance and suggest potential CV safety differences among COVID-19 immunomodulators. Since tocilizumab and baricitinib are similarly indicated for severe patients with COVID-19, further clinical trials are warranted to explore whether tocilizumab represents a safer alternative to baricitinib for these patients. Insights from this study may guide future antiviral repurposing and pandemic preparedness strategies.

Introduction: Oxacillinase-48 (OXA-48)-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) infections have been increasingly reported in Taiwan. Real-world studies regarding effective treatments for these infections are limited, and recommendations from international guidelines are controversial. The aim of this study was to compare clinical outcomes of OXA-48-producing CRKP bacteremia between patients treated with ceftazidime/avibactam (CZA) and those receiving other active therapies.

Methods: Unique adult patients with OXA-48-producing CRKP bacteremia who received CZA or other therapies in vitro for at least 3 days between June 2017 and December 2024 at Taipei Veterans General Hospital were enrolled. Clinical characteristics and outcomes were compared among the treatment groups. OXA-48 strains were detected using polymerase chain reaction (PCR) followed by Sanger sequencing.

Results: Of 45 patients included in this study, 18 were treated with CZA, and 27 were treated with other active therapies. Four patients received combination therapy. Most strains were OXA-48 producers (n = 42), and the rest were OXA-181 producers. No significant difference in 30-day mortality rate was observed between the treatment groups (22.2% versus 33.3%, p = 0.420), and even in critically ill patients (28.6% versus 43.8%, p = 0.389). Acute Physiology and Chronic Health Evaluation II (APACHE II) score (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01-1.15, p = 0.028) was an independent risk factor for 30-day mortality, and colistin-based therapy (HR 3.02, 95% CI 1.00-9.13, p = 0.050) showed marginal significance with 30-day mortality. CZA use was not associated with 30-day mortality.

Conclusions: Our findings revealed that CZA and other active therapies showed similar outcomes, but colistin-based regimens should be used cautiously.