Infectious Diseases and Therapy最新文献

Introduction: Clofazimine (CFZ) is an antimycobacterial agent used primarily for leprosy and multidrug-resistant tuberculosis. Despite its long clinical history, comprehensive pharmacovigilance data remain limited. This study aimed to analyze CFZ-associated adverse events (AEs) reported in the FDA Adverse Event Reporting System (FAERS), identifying and pharmacovigilance signals.

Methods: We conducted a retrospective pharmacovigilance analysis of the FAERS database from 2004 to 2025 Q1. ASCII-format data were imported into R 4.4.2 and deduplicated using FDA guidelines. Reports Listing CFZ as the primary suspect drug were identified using generic and brand names. AEs were coded using MedDRA 27.1. Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM), identified signals of disproportionate reporting. Subgroup analyses examined sex differences, while time-to-onset (TTO) analyses characterized latency patterns.

Results: A total of 1287 CFZ-related AE reports were identified, with 995 (77.3%) classified as serious. Death (11.6%) and hospitalization (18.1%) were the most frequent serious outcomes. The majority of reports originated from the United States (59.4%). Demographic analysis showed higher reporting among females (49.6%) and patients aged 18-64 years (46.5%). Disproportionality analyses identified 135 preferred terms with positive safety signals. The most prominent signals included QT prolongation (ROR ~ 37.61), drug resistance (ROR ~ 17.31), skin hyperpigmentation (ROR ~ 13.07), and respiratory failure (ROR ~ 7.46), ranging from moderate to strong signal intensity. Subgroup analyses revealed significant sex differences in specific AE signals. TTO analysis indicated varied latency distributions across System Organ Class (SOC) and preferred term levels.

Conclusion: Our pharmacovigilance assessment of FAERS data from 2004 to 2025 not only identified multiple serious and consistent safety signals associated with clofazimine such as prolonged QT intervals but also revealed a life-threatening AE respiratory failure. Although the analysis of these AEs cannot directly reflect causal relationships due to the nature of the FAERS data from spontaneous reporting, our findings highlight the critical importance of continuous pharmacovigilance, targeted clinical monitoring, and consideration of sex-based risk differences to ensure the safe use of clofazimine in clinical practice.

An advisory board meeting was held with five participants living with chronic respiratory conditions or having experienced a severe episode of respiratory syncytial virus (RSV) infection, to understand the challenges faced by such individuals and their experiences with lung health. In this podcast, we relate the points discussed during that meeting, providing further reflections from a patient and a physician on awareness, the lived experience of RSV, the risks it poses to adults living with chronic respiratory conditions and healthcare system support in managing lung health. Experiences shared by participants illustrate how RSV and chronic respiratory conditions can impact many aspects of a person's life, beyond the acute illness, such as feelings of isolation. While many individuals are at risk of severe outcomes from RSV infection, the general population and healthcare practitioners (HCPs) are often unaware of the disease and its potential consequences in adults. Knowing the risk factors for severe RSV and exacerbation of underlying conditions, such as chronic obstructive pulmonary disease, asthma and cardiovascular diseases, could support physicians in discussing risks and preventive measures with their patients. This could help align patients' expectations of HCPs and the healthcare system with the care they receive by providing more guidance on the multifactorial management of their respiratory health. Discussions about the preferred sources of information identified patient groups as the most trustworthy source, followed by HCPs, who can play a key role in helping patients to identify reliable sources of information. Despite involving only a small group of people, the discussion provided valuable insights from participants which can raise awareness about the risks and impact of RSV on people's lives and empower healthcare professionals to better support their patients in managing their patients' lung health.

The clinical landscape of Gram-positive infections has been reshaped with the introduction of long-acting lipoglycopeptides, particularly dalbavancin and oritavancin. Both agents share broad-spectrum activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant strains, yet differ markedly in pharmacokinetics, pharmacodynamics, resistance profiles, and clinical adoption. This review presents a comprehensive comparative analysis of their structural innovations, distinct pharmacokinetic and pharmacodynamic characteristics, and dual mechanisms of action, supported by minimum inhibitory concentration data across key pathogens. Despite belonging to the same antimicrobial class, these agents exhibit important differences in real-world applications and clinical integration. We highlight real-world evidence supporting off-label use in osteomyelitis, endocarditis, and bloodstream infections, where traditional therapies fall short. Furthermore, we explore resistance development, drug-drug interaction profiles, and outpatient utility, providing actionable insights for optimizing treatment strategies. These findings underscore the need for tailored clinical integration of dalbavancin and oritavancin and spotlight their potential roles in future antimicrobial stewardship frameworks.

Introduction: While pneumococcal conjugate vaccines (PCVs) are typically administered to infants using a three- or four-dose regimen, children may receive less immunogenic regimens due to missed doses or alternative schedules. The level of direct protection in children vaccinated with a single dose of PCV remains unclear.

Methods: We performed a systematic review of observational studies published during 2000-2024 on vaccine effectiveness (VE) of a single dose of PCV7, PCV10, or PCV13 against vaccine-type invasive pneumococcal disease (IPD) in children. Results were stratified by vaccine and age at administration, and meta-analysis performed to generate pooled VE estimates.

Results: Twenty-seven studies met the inclusion criteria: nine reported VE for PCV7, four for PCV10, seven for PCV13, and seven reported VE separately for more than one PCV. For PCV7, pooled VE was 64.6% (95% CI 47.3, 76.2) when administered < 12 months or age unspecified and 81.6% (95% CI 72.5, 87.7) when given ≥ 12 months. For PCV10, pooled VE was 73.0% (95% CI - 29.4, 94.4) when age at vaccination was unspecified, and one study reported 68.0% (95% CI 17.6, 87.6) VE when administered ≥ 12 months. For PCV13, pooled VE was 56.8% (95% CI 44.1, 66.6) when administered < 12 months or age unspecified, and 79.2% (95% CI 65.5, 87.5) when given ≥ 12 months.

Conclusions: Available evidence demonstrates that a single dose of PCV provides protection against vaccine-type IPD, especially when administered after age 12 months. While complete vaccination according to licensed schedules provides optimal protection, our findings support single-dose catch-up programs for toddlers. Potential single-dose strategies for infants in humanitarian emergencies warrant further exploration.

Introduction: Limited data are available on the epidemiology and clinical burden of respiratory syncytial virus (RSV) among adults with underlying medical or immunocompromising conditions ("high-risk adults") and ≥ 50-year-old adults in developing countries.

Methods: To better understand the impact of RSV in these populations, a systematic literature review of articles published from the year 2000 onward reporting RSV data among high-risk 18-59-year-old adults and ≥ 50-year-old adults in low, lower-middle, upper-middle, and selected high-income countries was undertaken. Searches were run on Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica DataBASE (EMBASE), and were supplemented by additional searches (e.g., congress abstracts, gray literature). A combination of artificial intelligence models was used for title/abstract screening. After this, full-text screening of inclusions was conducted, followed by prioritization.

Results: Overall, 77 citations were selected for final inclusion. Of these, 69 reported outcomes related to RSV epidemiology and clinical burden, and are reported in this article. There were limited data on RSV incidence, prevalence, disease severity, and subtype distribution. Adequate evidence was available for RSV positivity among patients with respiratory illnesses, seasonality, complications, and mortality. Incidence in ≥ 65-year-olds was in the range of ~10-178 episodes per 1000 person-years across studies. Ranges for RSV positivity among patients with different underlying respiratory conditions were 1.5-31.9% and 0-9.1%, in high-risk and ≥ 50-year-old adults, respectively. Case fatality rates of up to 15.2% and 27.0% were reported across studies for high-risk and > 60-year-old adults, respectively.

Conclusions: Overall, there were considerable evidence gaps for RSV epidemiology among high-risk and ≥ 50-year-old adults in developing countries. However, available data indicate a substantial negative health impact of RSV on these populations, highlighting the need for further data generation.

Introduction: Cognitive frailty (CF), which typically precedes dementia and functional decline, serves as a more robust predictor of adverse health outcomes compared to physical frailty alone, representing a critical challenge in promoting healthy aging among older people living with HIV (PLWH) aged ≥ 50 years. This study aimed to investigate the prevalence of cognitive frailty and identify its associated factors among PLWH aged ≥ 50 years.

Methods: A convenience sample of 344 PLWH ≥ 50 years was recruited from a tertiary Grade A hospital in Zunyi, China. Physical frailty: evaluated via the Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) Scale; Cognitive function: assessed via the Chinese version of the Montreal Cognitive Assessment (MoCA). Participants were divided into the cognitive frailty group (FRAIL score ≥ 3 and MoCA score < 26), the non-cognitive frailty group. Binary logistic regression analysis was conducted with SPSS 29.0 to identify factors associated with CF.

Results: The prevalence of CF among the 344 PLWH aged ≥ 50 years was 37.5%. Regression analysis revealed that the following associated factors (p < 0.05) were independent risk factors for CF in PLWH aged ≥ 50 years: age, education level, weekly frequency of physical activity ≤ 2 sessions, depression, sleep disorders, and EFV-containing regimens.

Conclusions: Cognitive frailty is highly prevalent among PLWH aged ≥ 50 years. Early screening and comprehensive healthcare interventions targeting modifiable risk factors are crucial for delaying or reversing CF progression in this population.

This study reports three patients with hematologic malignancy patients and Carbapenem-resistant Enterobacterales (CRE) bloodstream infections and organ dissemination during neutropenia. After failed conventional therapy, a novel "through Combination therapies including eravacycline" regimen achieved fever control within 10 days and lesion resolution by 20 days approximately, demonstrating breakthrough efficacy for CRE bacteremia management.

Introduction: Multi-drug-resistant organisms (MDROs) that mostly contribute to nosocomial infections include carbapenem-resistant Enterobacterales that produce Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM), carbapenem-resistant Acinetobacter baumannii (CRAB) and vancomycin-resistant Enterococcus faecium (VRE). Patients colonised by these MDROs are at high risk for developing bloodstream infections (BSIs) by the same pathogen, emphasising the need for surveillance and intervention.

Methods: This retrospective study included patients admitted to medical, surgical, and intensive care unit (ICU) wards in the IRCCS Policlinico San Matteo (Pavia, Italy) between January 2019 and October 2024 with rectal colonisation by KPC, NDM, VRE and CRAB. Demographic, clinical and microbiological data were extracted from electronic records. Logistic regression with stepwise model-building identified risk factors for BSI development.

Results: A total of 1969 patients colonised with MDRO were identified: 79% of them were colonised by KPC, VRE, CRAB or NDM. Among the 1960 hospitalisations involving these specific rectal colonisations, the overall rate of BSIs was 9.4%, with CRAB and KPC showing the highest rates (20.0% and 12.6%, respectively). ICU hospitalisation was significantly associated with an increased risk of BSI in patients colonised with KPC, NDM and VRE. Haematological malignancies and bone marrow transplantation were independent risk factors for BSI in patients colonised with KPC (odds ratio [OR] = 3.22, p = 0.037) and VRE (OR = 4.07, p = 0.004) whereas solid organ transplantation increased BSI risk among patients colonised with CRAB (OR = 11.83, p = 0.034).

Conclusions: Our findings show heterogeneous BSI risk among MDROs, with CRAB and KPC being the most dangerous, especially in patients in the ICU, followed by VRE in onco-haematological cases. These results support developing prevention strategies for critically ill and immunocompromised patients.

Introduction: Reports of direct-acting antivirals (DAA) use for chronic hepatitis C virus (HCV) infection after successful treatment of hepatocellular carcinoma (HCC) have suggested higher rates of HCC recurrence. However, other studies have indicated no increased risk of HCC recurrence.

Methods: To estimate the comparative risk of early HCC recurrence in adults successfully treated for HCC and subsequently treated with interferon (IFN)-free DAAs versus not treated with DAAs for chronic HCV, we conducted a systematic literature review and meta-analysis following established guidelines.

Results: Forty-one cohort studies (10,563 total participants) were identified. The following mutually exclusive comparisons to DAA therapy were determined: IFN-based therapy; no DAA; and no antiviral therapy. Random effects meta-analysis results indicated no increased risk of HCC recurrence with IFN-free DAA therapy when compared with IFN (combined risk ratio (RR) 1.29 [95% CI 0.69, 2.40] at 12 months, 0.88 [95% CI 0.56, 1.39] at 24 months, and 0.67 [95% CI 0.51, 0.88] at longest follow-up), no DAA (combined RR 0.55 [95% CI 0.25, 1.23] at 12 months, 0.67 [95% CI 0.51, 0.86] at 24 months and 0.72 [95% CI 0.61, 0.85] at longest follow-up), or no antiviral therapy (combined RR 0.95 [95% CI 0.76, 1.20] at 12 months, 0.48 [95% CI 0.11, 2.12] at 24 months, and 0.42 [95% CI 0.24, 0.73] at longest follow-up). Results were confirmed in sensitivity analyses.

Conclusions: There is no evidence to suggest that DAA therapy has a higher risk of early HCC recurrence when compared with IFN, no DAA, or no antiviral therapy at any timepoint analyzed. Hence the benefit-risk profile of DAAs in HCV remains positive in relation to the risk of early HCC recurrence.

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.