Infectious Diseases and Therapy最新文献

Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials. Here we review the key differences in criteria for case definitions, highlight strategies to best approximate compatibility between definitions, and review vaccine efficacy results among currently US Food and Drug Administration (FDA)-approved vaccines using these strategies. We hope this overview will support the need to develop a consensus definition for LRTI/LRTD to improve future research related to viral respiratory disease.

Introduction: Health claims data are a valuable resource for health services research, enabling analysis of the costs of hospitalizations, outpatient visits, procedures, and medications, and providing an improved understanding of the economic burden and underlying cost drivers for a given health condition. Since no recent data were available from Germany on the medical costs and clinical outcomes of Clostridioides difficile infections (CDI), this study assessed the economic burden of CDI and all-cause mortality in adults in Germany.

Methods: A retrospective cohort study was conducted using a large, anonymized administrative health claims research database from Germany from which an age- and sex-representative sample of 4 million insured persons covered by approximately 60 statutory health insurances was extracted. Propensity score matching was conducted on age, sex, comorbidities, and antibiotic use to identify four matched controls (i.e., patients without CDI) for every eligible adult patient with CDI (i.e., case) in the study cohort. Costs, healthcare resource utilization, and CDI-attributable all-cause mortality were assessed.

Results: Overall, there were 15,342 CDI cases in the study cohort. One-year mortality in CDI cases (45.7%) was more than fourfold that of matched non-CDI controls (11.0%). In the year following the index date, average mortality-adjusted medical costs per person-time for CDI cases were almost fivefold that of matched non-CDI controls, representing a cost difference of €31,459, mainly driven by inpatient treatment. Overall excess costs for CDI cases were estimated at approximately €1.6 billion within 1 year after diagnosis.

Conclusions: CDI in Germany is associated with a high clinical and economic burden, including significantly higher mortality, costs, and healthcare resource utilization, in patients with CDI versus their matched patients without CDI. This has important implications for patients, healthcare providers, and the healthcare system.

Antimicrobial resistance is a significant global public health issue, and the dissemination of antibiotic resistance in Gram-positive bacterial pathogens has significantly increased morbidity, mortality rates, and healthcare costs. Among them, Staphylococcus, especially methicillin-resistant Staphylococcus aureus (MRSA), causes a wide range of diseases due to its diverse pathogenic factors and infection strategies. These bacteria also present significant issues in veterinary medicine and food safety. Effectively managing staphylococci-related problems necessitates a concerted effort to implement preventive measures, rapidly detect the pathogen, and develop new and safe antimicrobial therapies. In recent years, there has been growing interest in using endolysins to combat bacterial infections. These enzymes, which are also referred to as lysins, are a unique class of hydrolytic enzymes synthesized by double-stranded DNA bacteriophages. They possess glycosidase, lytic transglycosylase, amidase, and endopeptidase activities, effectively destroying the peptidoglycan layer and resulting in bacterial lysis. This unique property makes endolysins powerful antimicrobial agents, particularly against Gram-positive organisms with more accessible peptidoglycan layers. Therefore, considering the potential benefits of endolysins compared to conventional antibiotics, we have endeavored to gather and review the characteristics and uses of endolysins derived from staphylococcal bacteriophages, as well as their antibacterial effectiveness against Staphylococcus spp. based on conducted experiments and trials.

Vaccination represents a core preventive strategy for public health, with interrelated and multifaceted effects across health and socioeconomic domains. Beyond immediate disease prevention, immunization positively influences downstream health outcomes by mitigating complications of preexisting comorbidities and promoting healthy aging. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus, and respiratory syncytial virus (RSV) are common respiratory viruses responsible for broad societal cost and substantial morbidity and mortality, particularly among at-risk individuals, including older adults and people with frailty or certain comorbid conditions. In this narrative review, we summarize the overall impact of vaccination for these 3 viruses, focusing on mRNA vaccines, each of which exhibits unique patterns of infection, risk, and transmission dynamics, but collectively represent a target for preventive strategies. Vaccines for COVID-19 (caused by SARS-CoV-2) and influenza are effective against the most severe outcomes, such as hospitalization and death; these vaccines represent the most potent and cost-effective interventions for the protection of population and individual health against COVID-19 and influenza, particularly for older adults and those with comorbid conditions. Based on promising results of efficacy for the prevention of RSV-associated lower respiratory tract disease, the first RSV vaccines were approved in 2023. Immunization strategies should account for various factors leading to poor uptake, including vaccine hesitancy, socioeconomic barriers to access, cultural beliefs, and lack of knowledge of vaccines and disease states. Coadministration of vaccines and combination vaccines, such as multicomponent mRNA vaccines, offer potential advantages in logistics and delivery, thus improving uptake and reducing barriers to adoption of new vaccines. The success of the mRNA vaccine platform was powerfully demonstrated during the COVID-19 pandemic; these and other new approaches show promise as a means to overcome existing challenges in vaccine development and to sustain protection against viral changes over time.A graphical abstract and video abstract is available with this article.

Introduction: The use of antibody titers against SARS-CoV-2, as a method of estimating subsequent infection following infection or vaccination, is unclear. Here, we investigate whether specific levels of antibodies, as markers of adaptive immunity, can serve to estimate the risk of symptomatic SARS-CoV-2 (re-) infection.

Methods: In this real-world study, laboratory data from individuals tested for SARS-CoV-2 antibodies under routine clinical conditions were linked through tokenization to a United States medical insurance claims database to determine the risk of symptomatic/severe SARS-CoV-2 infection outcomes. Antibody titer levels were determined using the Elecsys^® Anti-SARS-CoV-2 S assay. Study outcomes included the first symptomatic SARS-CoV-2 infection (per ICD-10 diagnostic codes, occurring ≥ 7 days post-antibody titer test), and severe SARS-CoV-2 infection, characterized by adverse outcomes including hospitalization, intensive care unit admission, intubation, mechanical ventilation, or death within 30 days of infection. All outcomes were assessed for 12 months following antibody measurement. Hazard ratios of subsequent symptomatic and severe infections were estimated using Cox regression with inverse probability weighting.

Results: Of 268,844 individuals with antibody data (April 2021-June 2022), those with levels ≥ 0.8 to < 1,000 U/mL had a 42% reduced risk of symptomatic infection within 12 months, compared with < 0.8 U/mL (HR = 0.58, 95% CI [0.55, 0.61]). The risk decreased by 53% (HR = 0.47, 95% CI [0.45, 0.49]) with ≥ 1000 to < 2500 U/mL and by 62% (HR = 0.38 [0.36, 0.39]) for ≥ 2500 U/mL. Risk of severe SARS-CoV-2 outcomes was also reduced. Subgroup analyses showed a consistent association between antibody levels and infection risk, by immune status and age. Clinically meaningful thresholds of antibody titers varied between Delta and Omicron infections.

Conclusion: Higher antibody titer levels indicated reduced risk of developing symptomatic or severe COVID-19. Titers of ≥ 2500 U/mL indicated a 62-87% reduced infection risk. The quantitative determination of antibody titers allowed scaling of the correlate of risk to new variants.

Introduction: In 2023, recombinant zoster vaccine (RZV) replaced zoster vaccine live (ZVL) vaccine in the UK National Immunisation Programme (NIP) for prevention of herpes zoster (HZ). The vaccination age was reduced from 70 to 65 years, with a subsequent planned reduction to 60 years. This modelling study aimed to evaluate the public health impact (PHI) of RZV vaccination in the 70 years of age (YOA) population and in younger individuals 65 and 60 YOA.

Methods: PHI was evaluated from a National Health Service perspective, as cases of HZ, post-herpetic neuralgia (PHN), non-PHN complications and deaths, hospitalisations, and general practitioner (GP) visits avoided using a multicohort Markov model. Three scenarios (RZV vs. no vaccination, ZVL vs. no vaccination, and RZV vs. ZVL) were explored for each age group using population estimates from the UK Office for National Statistics, i.e. 70 YOA (n = 649,822), 65 YOA (n = 760,578) and 60 YOA (n = 849,501).

Results: Modelled outcomes in 70 YOA individuals estimated that RZV vaccination would avoid 32,894 cases of HZ and 5915 cases of PHN compared with no vaccination and 26,954 HZ and 3218 PHN cases compared with ZVL. Compared with no vaccination, 2264 fewer hospitalisations and 158,549 fewer GP visits were predicted with RZV vaccination. Hospitalisations were predicted to be reduced by 1996 and GP visits by 130,821 for RZV versus ZVL vaccination. In individuals 65 YOA, it was estimated that RZV vaccination would avoid 50,128 HZ cases, 8623 PHN cases, 222,646 GP visits, and 2671 hospitalisations versus no vaccination. In the 60 YOA group, RZV vaccination was predicted to avoid 57,182 HZ cases, 9327 PHN cases, 234,330 GP visits, and 2547 hospitalisations versus no vaccination.

Conclusion: The recent introduction of RZV into the NIP could substantially reduce HZ disease burden and healthcare resource use in the UK. A graphical abstract is available with this article.

Introduction: The World Health Organization (WHO) has established objectives for eradicating the hepatitis C virus (HCV). People who inject drugs (PWID), a major driver of HCV transmission, are an essential part of China's hepatitis C elimination program. This study aimed to estimate the requisite screening and antiviral treatment levels to achieve these goals among people who inject drugs in China and identify the most cost-effective strategy.

Methods: This study utilized models based on dynamic social networks to simulate HCV transmission and disease progression among people who inject drugs in China, incorporating a cost-effectiveness analysis from a healthcare perspective.

Results: To achieve the WHO targets, a minimum screening and treatment rate of 10% is required to meet the mortality goal, while a 25% rate is necessary for the incidence goal. The most cost-effective strategy includes a 25% screening rate and a 95% treatment rate. Compared to no intervention, this approach significantly reduces costs by - $85,873.38 (95% CI  - $94,311.16 to  - $77,435.59) and adds 24.66 (95% CI 23.68 to - 25.64) quality-adjusted life years. The intervention is dominant, with a cost-effectiveness ratio of - $3482.29 (95% CI  - $3982.73 to  - $3020.11) per quality-adjusted life year.

Conclusion: Achieving the WHO's hepatitis C virus elimination targets among people who inject drugs in China is feasible and cost-saving.

Introduction: Difficult-to-treat-resistant (DTR) infections caused by Pseudomonas aeruginosa represent a global public health threat, prioritizing the search and development of new antibiotics for this microorganism.

Methods: We present the real-life experience of the compassionate use of imipenem/cilastatin/relebactam in a descriptive study involving 14 patients with DTR-P. aeruginosa infection and limited treatment options.

Results: The primary source of infection was skin and soft tissue infection, 57.1% (8/14), followed by respiratory infection-pneumonia, 28.6% (4/14). At the onset of infection, 71.4% (10/14) of patients were in the intensive care unit (ICU). All our patients had a Charlson Score of ≥ 3. Septic shock was observed in 64.3% (9/14) of patients. The median treatment duration was 15 days, and no patient experienced an adverse event that required treatment interruption. All-cause 30-day mortality was observed in 42.9% of cases (6/14), while clinical efficacy and microbiological success were observed in 64.3% (9/14).

Conclusions: Imipenem/cilastatin/relebactam may represent a treatment option for patients with DTR-P. aeruginosa infections, which should be validated in prospective clinical trials.

Introduction: Central nervous system adverse events (AE) have been a cause of discontinuation of dolutegravir-containing therapy, especially in combination with abacavir. The main aim of the study was to evaluate whether the switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was associated with a reduction in severity and incidence of neuropsychiatric symptoms compared to continued dolutegravir/abacavir/lamivudine (DTG/ABC/3TC).

Methods: DOBINeuro is a randomized trial enrolling people living with HIV (PLWH) treated with DTG/ABC/3TC for > 6 months and with HIV-RNA < 50 cps/ml for > 12 months. At baseline, PLWH are randomized to continue DTG/ABC/3TC or switch to BIC/FTC/TAF. The original sample size was 50 PLWH per arm, but the enrollment was prematurely stopped due to a delayed recruitment process. Neuropsychiatric symptoms were evaluated by the self-report Symptom Checklist (SCL)-90-R and the Mini-International Neuropsychiatric Interview Plus.

Results: A total of 41 PLWH were enrolled and underwent randomization: 20 were randomized to continue DTG/ABC/3TC and 21 to switch to BIC/FTC/TAF. At baseline, clinical and laboratory characteristics were homogeneous in the two arms. Switching from DTG/ABC/3TC to BIC/FTC/TAF in virologically suppressed PLWH was associated with an improvement in sleep disorders but not in any other neuropsychiatric symptom.

Conclusions: Although limited by a low sample size, this study suggests neuropsychiatric tolerability may improve when switching virologically suppressed PLWH from DTG to BIC-based strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are highly infectious respiratory viruses that affect people of all ages and are typically associated with mild symptoms and few complications in immunocompetent individuals. However, the risk of severe outcomes (e.g., hospitalization and death) following infection with these respiratory viruses is higher in certain populations, including older adults and individuals of certain race/ethnic and sociodemographic groups. Additionally, immunocompromising conditions and pre-existing comorbidities, including underlying cardiovascular (e.g., congestive heart failure) and respiratory diseases (e.g., chronic obstructive pulmonary disease), diabetes, chronic kidney disease, and obesity, are key factors that predispose individuals to SARS-CoV-2-, influenza-, and RSV-related severe outcomes. Increased risk for severe outcomes associated with advancing age and comorbidities is compounded by residence in long-term care facilities due to the enhanced spread of respiratory infections in congregate living environments. In this narrative review, risk factors associated with severe outcomes following infection with SARS-CoV-2, influenza, and RSV in adult populations are explored. Additionally, distinct clinical outcomes based on underlying comorbidities following infection are discussed in the context of high-risk populations. Factors unique to each virus that underpin distinct risk profiles are described and suggest the potential for tailored surveillance and healthcare approaches to target and ultimately mitigate SARS-CoV-2-, influenza-, and RSV-associated disease burden in vulnerable populations. Mutual risk factors for severe outcomes are also highlighted; these similarities indicate that cohesive risk reduction strategies may also be feasible, particularly since vaccines are available for each of these respiratory viruses. Ultimately, a more thorough understanding of the risk factors that predispose individuals to develop SARS-CoV-2-, influenza-, and RSV-related severe outcomes may improve risk reduction strategies, inform healthcare policy, and contribute to the expansion and refinement of existing surveillance approaches to ultimately mitigate disease burden in vulnerable populations.