Infectious Diseases and Therapy最新文献

Introduction: Infections caused by nonfermenting gram-negative bacilli (NF-GNB), particularly Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, are associated with high morbidity and mortality, especially among critically ill or immunocompromised patients. The rise of multidrug resistance has rendered many first-line antibiotics ineffective, highlighting the need for novel agents such as cefiderocol, a siderophore cephalosporin with unique pharmacokinetics and broad in vitro activity against resistant gram-negative pathogens.

Methods: A multidisciplinary panel of French experts in infectious diseases, microbiology, pharmacology, and intensive care reviewed the available evidence and clinical experience of cefiderocol. Using a structured consensus process, the group developed pragmatic, expert-based recommendations for its use against A. baumannii, S. maltophilia, and P. aeruginosa, considering clinical scenarios, resistance mechanisms, pharmacokinetic/pharmacodynamic (PK/PD) optimization, and practical implementation.

Results: Cefiderocol demonstrates potent in vitro activity against NF-GNB, including colistin- and imipenem-resistant isolates. Clinical success, however, depends on optimized PK/PD exposure, particularly in high-inoculum infections or patients with augmented renal clearance. Cohort studies and meta-analyses suggest lower mortality and markedly reduced nephrotoxicity compared with colistin-based regimens in A. baumannii infections. For S. maltophilia, cefiderocol shows consistently low minimum inhibitory concentration (MIC) and serves as a reliable alternative to trimethoprim-sulfamethoxazole or fluoroquinolones. Against P. aeruginosa, it retains high in vitro activity and should be considered after failure of newer β-lactams, with caution in New Delhi metallo-β-lactamase (NDM)-producing isolates. Continuous infusion and early therapeutic drug monitoring are encouraged to maximize efficacy.

Conclusions: Cefiderocol is a valuable therapeutic option for severe NF-GNB infections when conventional agents fail. Its use should be guided by pathogen-specific MICs and PK/PD-based dosing. The expert panel underscores the importance of early microbiological diagnosis, susceptibility testing, and optimized administration to achieve maximal clinical benefit while preserving cefiderocol's role within antimicrobial stewardship.

Introduction: Respiratory syncytial virus (RSV) infection in adults causes lower respiratory tract disease (LRTD) encompassing lower respiratory tract infection (LRTI), and exacerbations of chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF), yet RSV testing rates among these patients, especially among outpatients, are not well documented. This study evaluated RSV and influenza testing practices among United States (U.S.) adults seen in outpatient settings with LRTI, COPD exacerbation, or CHF exacerbation.

Methods: We quantified RSV and influenza testing rates in a retrospective cohort of adults ≥ 18 years old seen in outpatient settings for LRTI, COPD exacerbations, or CHF exacerbations from August 2017 to March 2024 using Optum^® Electronic Health Records (EHR). The primary outcome was the occurrence of a standard-of-care RSV or influenza test.

Results: A total of 2,208,009 LRTI outpatient encounters, 396,891 COPD and 422,648 CHF exacerbation events from the Optum^® EHR database were included in the analysis. The proportion of LRTI encounters with RSV testing increased from 0.6% in 2017 to 9.4% in 2024, but remained lower than influenza (7.1-31.7%). Viral testing among COPD and CHF exacerbation events followed similar trends. Of all eligible outpatient LRTI encounters, less than 3% (60,265/2,208,009) were tested for RSV whereas 15% (333,232/2,208,009) were tested for influenza. Exacerbation events for COPD (1.9% RSV, 6.0% influenza) were tested more frequently than CHF exacerbations (0.5% RSV, 1.1% influenza).

Conclusion: Despite increases over time, RSV testing remains infrequent among U.S. adult outpatients. This is particularly true among adults with COPD or CHF exacerbations, where RSV should be part of the differential diagnosis. Infrequent testing may reflect lack of specific RSV treatment options.

Introduction: This study aimed to investigate whether droplet digital polymerase chain reaction (ddPCR) assay can be integrated with antimicrobial stewardship for rapid diagnosis to improve clinical outcomes in patients with suspected bloodstream infections (BSIs). We also explored whether combining ddPCR assay with procalcitonin (PCT) could better guide antibiotic discontinuation in patients with suspected BSIs.

Methods: This prospective observational study was conducted in Zhejiang Provincial People's Hospital from April 2019 to October 2023. Antimicrobial drug combinations were categorized as appropriate or inappropriate based on the findings of the ddPCR assay. Propensity score matching (PSM) was conducted to address possible confounding variables. The primary outcome was 28-day all-cause mortality.

Results: A total of 703 patients were evaluated for the consistency of pathogens detected by ddPCR with those covered by the initial antibiotic regimen (IAR). Among these patients, 355 received appropriate IAR, 256 were adjusted for inappropriate IAR, and 92 were unadjusted for inappropriate IAR. A significant difference in 28-day mortality among the three cohorts was observed before and after PSM (P ≤ 0.002). Multivariate Cox regression analysis showed that IAR adjustment [inappropriate IAR unadjusted as reference, appropriate IAR: hazard ratio (HR) = 0.47; P < 0.001; inappropriate IAR adjusted: HR = 0.54; P < 0.001] remained independent predictors for 28-day mortality. In addition, in a subgroup analysis of 257 patients receiving > 7 days of antibiotic therapy and antibiotic discontinuation, the 28-day mortality using the ddPCR assay combined with PCT-guided antibiotic discontinuation was significantly lower (12.0 vs. 37.3 vs. 39.6%; P < 0.001) than that of those guided by ddPCR assay or PCT alone.

Conclusions: Integrating a ddPCR assay for rapid diagnosis with antibiotic stewardship could improve the prognosis in patients with BSIs, not only by guiding antibiotic regimen adjustment but also by making decisions on antibiotic discontinuation in conjunction with PCT.

Trial registration: ChiCTR, ChiCTR2600116655.

Introduction: Invasive meningococcal disease poses a substantial disease burden worldwide, including older adults (aged ≥ 56 years) along with higher case fatality rates. MenACYW-TT, a quadrivalent meningococcal tetanus toxoid-conjugate vaccine, is indicated worldwide in individuals ≥ 56 years of age and is the only licensed vaccine in the USA for this age group. The annual Hajj pilgrimage is considered an epidemiologic event with approximately two million pilgrims per year; hence, immunization with a quadrivalent meningococcal vaccine is mandatory for visitors traveling to Saudi Arabia for Umrah and Hajj. We evaluated the immunogenicity and safety of a single dose of MenACYW-TT in prospective Hajj/Umrah pilgrims aged ≥ 56 years in Turkiye and Lebanon.

Methods: In this open-label phase III study (NCT03869866), conducted in Turkiye and Lebanon, healthy adults aged ≥ 56 years received a single dose of the MenACYW-TT vaccine. Serum bactericidal assays were performed using human (hSBA) and rabbit (rSBA) complements to measure antibody titers against all four serogroups at baseline (D0) and 30 days post vaccination (D30). Safety data were collected up to 30 days (+ 14 days) post vaccination.

Results: A total of 290 individuals were enrolled in the study. On D30, vaccine seroprotection rates (hSBA titers ≥ 1:8) for serogroups A, C, Y, and W were 82.8%, 92.5%, 92.1%, and 83.5%, respectively, and rSBA titers (≥ 1:128) were 83.4%, 90.0%, 94.3%, and 88.9%, respectively. hSBA geometric mean titers (GMTs) were 32 [95% confidence interval (CI) 26.3-39.1], 132 (102-169), 126 (99.3-161), and 56.4 (43.8-72.6) for serogroups A, C, Y, and W, respectively. On D30, seroresponse rates in the per-protocol analysis set (PPAS) were 48-71.0%. Safety concerns and any serious adverse events related to the study vaccine were not observed.

Conclusions: MenACYW-TT vaccine induced a robust immune response against all serogroups (per seroprotection rates and GMTs). A single dose of the vaccine demonstrated acceptable safety profile in potential pilgrims aged ≥ 56 years.

Trial registration: ClinicalTrials.gov, NCT03869866. A Graphical Abstract is available for this article.

Introduction: Implementing pre-exposure prophylaxis (PrEP) is hindered by a significant "PrEP Cliff", a sharp decline from willingness to uptake and adherence. This study aimed to integrate status quo bias theory with a dual-process model, seeking to understand how this bias influences the PrEP cascade among men who have sex with men (MSM) in China.

Methods: A cross-sectional survey was conducted among 1022 MSM across six provinces in China from November 2024 to February 2025. Through regression models, we tested a moderated mediation framework to examine how status quo bias influenced PrEP willingness, uptake, and adherence, focusing on the mediating role of PrEP resistance intention and the moderating role of condom-use inertia.

Results: Participants were generally young (≤ 30 years; 63.1%), mostly unmarried (88.5%), and well-educated (89% with a bachelor's degree or higher). The "PrEP Cliff" was evident, characterized by high awareness (91.3%) and willingness among non-users (58.9%), but low uptake (46.2%) and poor adherence, with 53.4% of users self-reporting lower adherence. In the initiation phase (willingness and uptake), PrEP resistance intention significantly mediated the associations of transition costs and social norms on PrEP cascade outcomes. Condom-use inertia significantly moderated this mediation pathway by strengthening the associations of transition costs (β = 0.06, 95% CI 0.01 to 0.11) and social norms (β = - 0.05, 95% CI - 0.10 to 0.00) on PrEP resistance intention. However, the mechanism shifted during the adherence phase. Adherence was instead predominantly predicted by the direct associations of transition costs (β = - 0.44, 95% CI - 0.64 to - 0.23) and social norms (β = 0.56, 95% CI 0.38 to 0.74).

Conclusion: This study provides an evidence-based framework for clinicians and public health programs to design stage-specific interventions tailored to the distinct psychological barriers that dominate each phase.

Introduction: Aging in people with HIV (PWH) is accompanied by an increased burden of multimorbidity and persistent inflammation. Identifying biomarkers that reflect comorbidity risk can help improve long-term care. This study evaluated the association of multimorbidity with GDF-15, sICAM-1, sVCAM-1, and sP-selectin in PWH.

Methods: A cross-sectional study was performed in two cohorts of adults receiving antiretroviral therapy: a discovery cohort (n = 74) and a validation cohort (Spanish CoRIS network) (n = 150). Median age was 53 years in both cohorts (IQR 44-60 and 45-58), and women represented 19 (25.7%) and 75 (50.0%), respectively. Multimorbidity was defined as ≥ 2 comorbidities, including but not limited to cardiovascular, metabolic, renal, and non-AIDS-defining cancers. Plasma GDF-15, sICAM-1, sVCAM-1, and sP-selectin were quantified by multiplex immunoassay. Associations with log-transformed GDF-15 were assessed using multivariable linear regression including age-multimorbidity ordinal categories, tobacco smoking, and CD4+ nadir.

Results: Multimorbidity prevalence was 48.6% (36) in the hospital cohort and 54.7% (82) in CoRIS. In both cohorts, participants with multimorbidity had significantly higher GDF-15 levels (hospital: 771.5 vs. 390.0 pg/ml; CoRIS: 485.2 vs. 360.1 pg/ml; both p < 0.001). In the hospital cohort, smoking and age-multimorbidity were independently associated with elevated GDF-15, with 26.1% and 16.0% increases per category, respectively (p < 0.05). These associations were confirmed in CoRIS, with 5.44% and 19.0% increases (p < 0.01). CD4+ nadir showed no significant association with GDF-15. No significant associations were observed between multimorbidity and sICAM-1, sVCAM-1, or sP-selectin (all p > 0.05).

Conclusions: Elevated GDF-15 was consistently associated with multimorbidity in PWH, primarily driven by aging and tobacco smoking. GDF-15 appears to reflect a broader state of multisystem physiological stress than traditional endothelial activation markers, supporting its utility as a biomarker to identify PWH at higher risk of age-related comorbidities and to monitor the impact of modifiable risk factors in clinical care.

Introduction: Malaria continues as a public health threat through symptomatic/febrile cases, asymptomatic and low-density infections of Plasmodium falciparum, P. vivax, and their mixed infections. Mixed infections have not been studied much regarding their burden, clinical manifestations, and implications, and therefore, this study was conducted.

Methods: Febrile patients were recruited from four patient-care settings from June to November 2020 through the collection of dried blood spots (DBS) and their paired microscopy and/or rapid diagnostic test (RDT) data. Polymerase chain reaction (PCR)-based molecular diagnosis of both parasite species was performed from genomic DNA isolated from the DBS. Clinico-demographic details were recorded from patients from one of the sites, wherein patients with mixed infections were telephonically followed for subsequent clinical development.

Results: Out of the 1030 samples collected and analyzed, 27% (280) were infected with P. falciparum and/or P. vivax: 188 (18%) mono-P. falciparum, 6 (0.5%) mono-P. vivax and 86 (8%) mixed. None of the infections were detected by microscopy and/or RDT, meaning that all 27% were febrile sub-microscopic infections with 8% burden of mixed infections. The quality of microscopic slides was found to be unsatisfactory when a sub-sample of slides was cross-examined by level 1-competent microscopists. None of the nine mixed-infection patients from Gandhi Medical College and Hospital (GMCH) reported recurrences or any clinical development during the 12-month follow-up. No clinically/statistically significant difference was observed between mono- and mixed infections.

Conclusions: A high 27% febrile sub-microscopic Plasmodium infections with 8% mixed infections represent a significant challenge for malaria elimination, considering the quality of microscopy and the fact that Madhya Pradesh is classified under category 1 in the National Strategic Plan for malaria elimination 2023-2027.

We provide a taxonomy of the full health and societal value of maternal vaccination (MV) to prevent infant respiratory syncytial virus (RSV) disease. RSV is the leading cause of acute lower respiratory tract infections in infants and young children. Most children are infected by RSV before age one, and by age two, infection is nearly universal. Most cases are mild, but some are severe and can result in hospitalization, death, or long-term complications. RSV disease burdens have global scope but are typically higher in low- and middle-income countries. Globally, most severe cases occur among term and previously healthy infants, making RSV prevention in all infants a public health priority. Preventing infant RSV requires reliance on passive rather than active immunity. One recently developed passive immunization is RSVpreF, which has been found to be efficacious and to have an overall favorable safety profile, and which national immunization authorities will soon consider for inclusion in immunization schedules. Essential to realizing MV's potential contribution to this global public health priority are optimal coverage decisions by vaccine payers, informed by accurate value-for-money (VfM) assessments. To support VfM assessments and optimal coverage decisions, we formulate a taxonomy of the values promoted by MV. This taxonomy distinguishes between narrow health benefits and broader socioeconomic benefits. It distinguishes among benefits to infants; the mother, parents, caregivers, and household members; the health system; and the broader population, society, and government. Value elements include infant health (including from reduced mortality, severe disease, and long-term complications), reduced health system costs, reduced caregiver burdens, financial risk protection, parental peace of mind, averted parental bereavement, process utility from transference of injection burdens and risks from infant to mother, health and socioeconomic equity, antimicrobial resistance reduction from averted inappropriate antibiotic use, potential enhanced education from reduced long-term sequelae, and potential herd effects.