Antibiotic Resistance in the Elderly: Mechanisms, Risk Factors, and Solutions

Microorganisms, Год журнала: 2024, Номер 12(10), С. 1978 - 1978

Опубликована: Сен. 30, 2024

Antibiotic resistance presents a critical challenge in healthcare, particularly among the elderly, where multidrug-resistant organisms (MDROs) contribute to increased morbidity, mortality, and healthcare costs. This review focuses on mechanisms underlying key bacterial pathogens highlights how aging-related factors like immunosenescence, frailty, multimorbidity increase burden of infections from MDROs this population. Novel strategies mitigate include development next-generation antibiotics teixobactin cefiderocol, innovative therapies such as bacteriophage therapy antivirulence treatments, implementation antimicrobial stewardship programs optimize antibiotic use. Furthermore, advanced molecular diagnostic techniques, including nucleic acid amplification tests sequencing, allow for faster more precise identification resistant pathogens. Vaccine development, through approaches multi-epitope vaccines nanoparticle-based platforms, holds promise preventing MDRO elderly. The role machine learning (ML) predicting patterns aiding vaccine is also explored, offering promising solutions personalized treatment prevention By integrating cutting-edge diagnostics, therapeutic innovations, ML-based approaches, underscores importance multidisciplinary efforts address global aging populations.

Язык: Английский

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Key Insights into Respiratory Virus Testing: Sensitivity and Clinical Implications

Microorganisms, Год журнала: 2025, Номер 13(1), С. 63 - 63

Опубликована: Янв. 2, 2025

Acute respiratory infections are a significant challenge in primary care and hospital settings. Viruses the most common etiology overlapping symptomatology among major viruses, such as influenza, severe acute syndrome coronavirus 2, syncytial virus, requires use of diagnostic tests that deliver early accurate results. With increasing availability rapid antigen (RATS), it is tempting to prefer them over polymerase chain reaction (PCR) tests. However, compelling arguments support existing recommendations some European countries maintain PCR testing for patient management throughout year. RATs show sensitivities below 30% with lower viral loads, which can have clinical implications. perform well at cycle threshold (Ct) values, sensitivity reaching 97.9% Ct values 20, drops significantly above 25. Factors affecting load include disease stage, vaccination status, variants, all compromise accuracy Multi-target effectively overcome these issues, ensuring reliable diagnosis. Additionally, detection paucisymptomatic cases essential settings facilitate isolation prevent secondary infections. Economic analyses comprehensive tests, triplex-type detecting SARS-CoV-2, influenza RSV, first-line approach, they reduce case numbers healthcare resource utilization. Maintaining year-round therefore crucial effective

Язык: Английский

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Lifelong partners: Gut microbiota-immune cell interactions from infancy to old age

Mucosal Immunology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase 1b clinical trial

Science Translational Medicine, Год журнала: 2025, Номер 17(788)

Опубликована: Март 5, 2025

Norovirus is a leading cause of acute gastroenteritis globally, with infections in older adults associated heightened severity and increased risk mortality. Currently, no licensed vaccines are available to prevent norovirus infection. We developed an orally administered vaccine tablet (VXA-G1.1-NN) that delivers nonreplicating adenoviral vector expressing GI.1 major capsid protein VP1 the small intestine. Here, we report safety immunogenicity results randomized, double-blind, placebo-controlled clinical trial (NCT04854746) investigated oral administration VXA-G1.1-NN two groups healthy aged 55 65 66 80 years. was at three dose levels by prime boost, 28 days apart. Immunization well tolerated regardless dose, mild moderate reported solicited symptoms related serious or grade 3 adverse events. Oral delivery elicited VP1-specific serum immunoglobulin G (IgG) IgA functional antibodies dose-dependent manner postvaccination remained above baseline for 210 days. Moreover, robust circulating antibody-secreting cells were detected 1 week along IgA+ plasmablasts mucosal-homing marker α4β7. saliva nasal lining fluid both age concentrations through days, demonstrating durable mucosal responses. This established safe, tolerated, induces systemic immune responses up years old.

Язык: Английский

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The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience

Frontiers in Aging, Год журнала: 2024, Номер 5

Опубликована: Окт. 16, 2024

As we age, our immune system’s ability to effectively respond pathogens declines, a phenomenon known as immunosenescence. This age-related deterioration affects both innate and adaptive immunity, compromising function leading chronic inflammation that accelerates aging. Immunosenescence is characterized by alterations in cell populations impaired functionality, resulting increased susceptibility infections, diminished vaccine efficacy, higher prevalence of diseases. Chronic low-grade further exacerbates these issues, contributing decline overall health resilience. review delves into the characteristics immunosenescence examines various intrinsic extrinsic factors aging how hallmarks fates can play crucial role this process. Additionally, it discusses impact sex, social determinants, gut microbiota on aging, illustrating complex interplay altering function. Furthermore, concept resilience explored, focusing metrics for assessing identifying strategies enhance These include lifestyle interventions such diet, regular physical activity, stress management, use gerotherapeutics other approaches. Understanding mitigating effects are developing support robust responses aged individuals.

Язык: Английский

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Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Язык: Английский

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Immunogenicity and safety of a monovalent Omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine in previously unvaccinated, SARS-CoV-2 seropositive participants: primary day-28 analysis of a phase 2/3 open-label study

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Summary Background Most of the population has been infected with SARS-CoV-2 and, thus, is primed by natural exposure. As such, it was assessed whether a single dose monovalent XBB.1.5 vaccine, NVX-CoV2601, elicited comparable immune response to in seropositive unvaccinated participants that previously vaccinated participants, thereby allowing former forego two-dose primary series. Methods In this phase 2/3, open-label, single-arm study (2019nCoV-313/ NCT05975060 [part 2]), vaccine-naive ≥18 years previous infection received one NVX-CoV2601. This analysis compared 28-day immunogenicity and safety NVX-CoV2601 (≥3 prior mRNA-based vaccines, from 2019nCoV-313 part 1) participants. Noninferiority neutralizing antibody (nAb) versus objective. The day-28 geometric mean titer (GMT) ratio (GMTR) seroresponse rate (SRR; percentage ≥4-fold rise baseline) were measured, assessed. Results Of enrolled September 11–November 15, 2023, per-protocol sets included 306/338 (90.5%) 309/332 (93.1%) At day 28, adjusted GMTs (95% CI) against groups 1491.5 (1277.5–1741.4) 841.4 (723.9–978.0), respectively. vaccine-naïve—vaccinated nAb GMTR 1.8 CI 1.43–2.20) SRRs 74.3% 64.3% for respectively (SRR difference: 10.0 [95% 2.6–17.4]). No new signals or events special interest reported. Conclusions A history robust noninferior observed vaccine well-tolerated. These data support use as dose, regardless vaccination history. Trial registration:

Язык: Английский

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Sex, Age, and Previous Herpes Zoster Infection Role on Adverse Events Following Immunization with Adjuvanted Recombinant Vaccine

Pathogens, Год журнала: 2025, Номер 14(2), С. 195 - 195

Опубликована: Фев. 15, 2025

Adverse events following immunizations (AEFIs) with recombinant zoster vaccine (RZV) are underexplored in fragile populations. This study aims to assess incidence, duration, and characteristics of AEFIs, focusing on the impact sex, age, prior Herpes Zoster (HZ) infection a frail population, including solid organ transplant recipients. We conducted an observational patients receiving RZV, AEFIs were classified as local or systemic analyzed for patterns across groups. showed that females had higher incidence (p = 0.02), both symptoms, such swelling +/- redness at site injection fatigue, after first second doses. Younger adults experienced more reactions, while older reported (e.g., swelling, p 0.01). Moreover, previous HZ exhibited dose (68% vs. 38%, 0.001). In conclusion, clinical history significantly influenced AEFI manifestations. Therefore, it is important personalize vaccination strategies populations, by tailored administration monitoring plans, especially individuals infection, improve safety patient outcomes.

Язык: Английский

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Perceived benefits, information, vaccination history, and conspiracy beliefs as significant determinants of RSV vaccine acceptance among Arab seniors

Therapeutic Advances in Vaccines and Immunotherapy, Год журнала: 2025, Номер 13

Опубликована: Янв. 1, 2025

Background: Respiratory syncytial virus (RSV) poses a significant respiratory health risk to senior citizens, contributing substantially hospitalizations and mortality. With the recent approval of three RSV vaccines for elderly, it is critical understand factors that can shape vaccination attitudes inform public strategies enhance uptake among this vulnerable population. Objectives: This study aimed investigate potential could influence toward citizens in Arab countries. Design: A multinational cross-sectional study, adhering STROBE guidelines, was conducted using survey instrument previously validated through exploratory factor analysis assess newly approved vaccine. Methods: self-administered online distributed conveniently mainly across five The collected data on demographics, history, key constructs related vaccine attitude, including “Fear,” “Information,” “Accessibility,” “Benefits,” “Conspiracy.” Results: total 483 participants were included with majority from countries: Jordan ( n = 239, 49.5%), Kuwait 74, 15.3%), Egypt 68, 14.1%), Saudi Arabia 51, 10.6%), UAE 23, 4.8%), alongside other nations 28, 5.8%). Among respondents, 51.1% 247) expressed acceptance vaccine, 22.4% 108) hesitant, 26.5% 128) exhibited refusal. Multivariate identified perceived benefits (β 0.484, p < 0.001), information needs 0.229, previous history 0.087, 0.016) as positive predictors acceptance. Conversely, stronger conspiracy beliefs −0.083, 0.035) associated resistance. Fear accessibility not attitudes. Conclusion: findings showed benefits, access reliable information, are essential promote seniors. These recommended improve

Язык: Английский

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The Reduced Immunogenicity of Zoster Vaccines in CMV-Seropositive Older Adults Correlates with T Cell Imprinting

Vaccines, Год журнала: 2025, Номер 13(4), С. 340 - 340

Опубликована: Март 22, 2025

Background: Cytomegalovirus (CMV) infection and age impact immune responses to vaccines. The effect of sex remains controversial. We investigated the relationship between cytomegalovirus-seropositivity, age, immunogenicity recombinant (RZV) live (ZVL) zoster vaccines in adults ≥50 years age. Methods: Varicella virus (VZV) glycoprotein E (gE)-specific antibody, antibody avidity, cell-mediated immunity (CMI) were measured pre-vaccination at regular intervals over 5 post-vaccination 80 RZV 79 ZVL recipients, including 91 cytomegalovirus-seropositive 90 female participants. Results: Differences associated with CMV-seropositivity: lower VZV-gE-CMI recipients after first dose vaccine, but no differences 2nd dose; VZV-gE-specific avidity recipients; more abundant Th1 senescent T cells (Tsen) less regulatory (Treg) tissue-resident memory (Trm). older age: cells. sex: none for either vaccine. cell subset abundance: higher Tsens Tregs or Trms post-dose 1 CMI Th1s concentrations. Conclusions: correlation CMV- age-associated subsets ZVLs RZVs suggests that imprinting contributes CMV on vaccine responses.

Язык: Английский

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