Infectious Diseases and Therapy最新文献

Introduction: Respiratory syncytial virus (RSV) and influenza pose major disease burdens in older adults due to an aging immune system and comorbidities; seasonal overlap exists between these infections. In 2023, the RSV prefusion protein F3 older adult (RSVPreF3 OA) vaccine was first approved in the USA as a single dose for prevention of lower respiratory tract disease due to RSV in adults aged ≥ 60 years. The vaccine has since been approved in the European Union and elsewhere. RSVPreF3 OA and FLU-QIV-HD could be coadministered if immunogenicity, safety, and reactogenicity are not affected.

Methods: This open-label, randomized (1:1), controlled, phase 3 study in 1029 adults aged ≥ 65 years in the USA evaluated the immunogenicity (up to 1 month after last vaccine dose) and safety (up to 6 months after last vaccine dose) of RSVPreF3 OA coadministered with FLU-QIV-HD (co-ad group) versus FLU-QIV-HD alone followed by RSVPreF3 OA at a separate visit 1 month later (control group). Non-inferiority criterion was defined as an upper limit of the two-sided 95% confidence interval of the geometric mean titer (GMT) group ratio (control/co-ad) ≤ 1.5. Secondary endpoints included safety and reactogenicity.

Results: Proportions of participants across age categories between groups and proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Group GMT ratios for RSV-A neutralizing titers, hemagglutination inhibition titers for four influenza vaccine strains, and RSV-B neutralizing titers were non-inferior in the co-ad group versus the control group. No clinically meaningful differences in local or systemic solicited and unsolicited adverse events (AEs), serious AEs, and potential immune-mediated diseases were identified. The most common solicited AEs in both groups were injection-site pain and myalgia.

Conclusion: In adults aged ≥ 65 years, coadministration of RSVPreF3 OA and FLU-QIV-HD was immunogenically non-inferior to the sequential administration of both vaccines 1 month apart, and had clinically acceptable safety and reactogenicity profile.

Trial registration: ClinicalTrials.gov identifier, NCT05559476.

Introduction: In Germany, the estimation of the disease burden of respiratory syncytial virus (RSV) in older adults is limited. This makes it challenging for public health decision-makers to develop evidence-based recommendations for newly available vaccines against RSV for individuals aged 60 years and older (60+). This study investigates publicly available data sources in Germany to address the current gaps in evidence regarding the burden of RSV.

Methods: Hospitalisation databases from the German Federal Statistical Office and national mortality statistic between 2000 and 2023, as well as regular surveillance reports from the national public health institute since 2014, were utilised to extract, combine and analyse data on RSV-related morbidity and mortality. These data were used to triangulate the age-specific burden of RSV.

Results: The data indicate that the number of RSV-related outpatient consultations ranges between 1,313,100 and 3,911,800 cases per season from 2014/2015 to 2022/2023 for all age groups, with approximately 13.0% of outpatient consultations occurring in adults 60+. The significant increase in hospitalisations over time suggests that heightened testing due to the coronavirus disease 2019 (COVID-19) pandemic revealed the underdetection of inpatient RSV cases in pre-pandemic seasons. In the most recent season recorded, 2022/2023, the data show 12,800 RSV-related hospitalisations in adults 60+ (24% of all RSV-related hospitalisations) and 1340 in-hospital deaths in adults 60+ (93% of all RSV-related deaths).

Conclusion: The comparison of pre- to post-pandemic seasons strongly suggest up to a sevenfold underdetection of RSV in individuals 60+, and the analysis of in-hospital mortality reveals higher mortality rates compared with the general German mortality statistics. These findings highlight the urgent need to improve surveillance and implement targeted prevention strategies to mitigate the impact of RSV in older adults.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20-35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC_0-24). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC_0-24 following a VAN LD of 20 mg/kg.

Methods: This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC_0-24. Therapeutic AUC_0-24 was defined as 400-600 mg/l*h.

Results: Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m² and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC_0-24, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC_0-24, patients with subtherapeutic AUC_0-24 were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m² (67 vs. 52%). In contrast, patients with supratherapeutic AUC_0-24 were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC_0-24. CONCLUSIONS: Only 50% of patients achieve the target AUC_0-24 following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.

Introduction: Oral antiviral medications are important tools for preventing severe COVID-19 outcomes. However, their uptake remains low for reasons that are not entirely understood. Our study aimed to assess the association between perceived risk for severe COVID-19 outcomes and oral antiviral use among those who were eligible for treatment based on Centers for Disease Control and Prevention (CDC) guidelines.

Methods: We surveyed 4034 non-institutionalized US adults in April 2023, and report findings from 934 antiviral-eligible participants with at least one confirmed SARS-CoV-2 infection since December 1, 2021 and no current long COVID symptoms. Survey weights were used to yield nationally representative estimates. The primary exposure of interest was whether participants perceived themselves to be "at high risk for severe COVID-19." The primary outcome was use of a COVID-19 oral antiviral within 5 days of suspected SARS-CoV-2 infection.

Results: Only 18.5% of antiviral-eligible adults considered themselves to be at high risk for severe COVID-19 and 16.8% and 15.9% took oral antivirals at any time or within 5 days of SARS-CoV-2 infection, respectively. In contrast, 79.8% were aware of antiviral treatments for COVID-19. Perceived high-risk status was associated with being more likely to be aware (adjusted prevalence ratio [aPR]: 1.11 [95% confidence interval (CI) 1.03-1.20]), to be prescribed (aPR 1.47 [95% CI 1.08-2.01]), and to take oral antivirals at any time (aPR 1.61 [95% CI 1.16-2.24]) or within 5 days of infection (aPR 1.72 [95% CI 1.23-2.40]).

Conclusions: Despite widespread awareness of the availability of COVID-19 oral antivirals, more than 80% of eligible US adults did not receive them. Our findings suggest that differences between perceived and actual risk for severe COVID-19 (based on current CDC guidelines) may partially explain this low uptake.

Introduction: This study aimed to evaluate the effectiveness of ensitrelvir, an oral antiviral, in reducing hospitalization risk in outpatients at high-risk for severe COVID-19 during the Omicron era.

Methods: This was a retrospective study using a large Japanese health insurance claims database. It included high-risk outpatients for severe symptoms who received their first COVID-19 diagnosis between November 2022 and July 2023. The study included outpatients aged ≥ 18 years. The primary endpoint was all-cause hospitalization during the 4-week period from the date of outpatient diagnosis and medication, comparing the ensitrelvir group (n = 5177) and the no antiviral treatment group (n = 162,133). The risk ratio and risk difference were evaluated after adjusting patient background distribution by the inverse probability of treatment weight (IPTW) method. Secondary endpoints were incidence of respiratory and heart rate monitoring, oxygen therapy, ventilator use, intensive care admission, and all-cause death.

Results: The risk ratio for all-cause hospitalization between the ensitrelvir group (n = 167,385) and the no antiviral treatment group (n = 167,310) after IPTW adjustment was 0.629 [95% confidence interval (CI) 0.420, 0.943]. The risk difference was - 0.291 [95% CI - 0.494, - 0.088]. The incidence of both respiratory and heart rate monitoring and oxygen therapy was lower in the ensitrelvir group. Ventilator use, intensive care admission, and all-cause death were difficult to assess because of the limited events.

Conclusions: The incidence of all-cause hospitalization was significantly lower in the ensitrelvir group than in the no antiviral treatment group, suggesting ensitrelvir is an effective treatment in patients at risk of severe COVID-19.

Introduction: The incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) are increasing globally. Approximately 80% of NTM-PD cases in Japan and five countries within Europe (Eur5; France, Germany, Italy, Spain, and the UK) are caused by Mycobacterium avium complex (MAC). This study describes the clinical decision-making process associated with the management of patients with NTM-PD in Japan and the Eur5.

Methods: We analyzed data from a survey conducted between July 2013 and October 2013 among physicians treating patients with NTM-PD in clinical practice to compare the healthcare settings, clinical presentation, and patient management in Japan and the Eur5.

Results: Overall, 619 physicians (Japan, 173; Eur5, 446) participated in the survey. Most patients in Japan (85%) and the Eur5 (79%) were diagnosed with MAC-PD. Patients were managed generally in hospital-based outpatient clinics (117/173, 68%) in Japan and research/teaching hospitals affiliated with medical schools (140/446, 31%) in the Eur5. The most common reason for delaying treatment was the patient's symptoms not being considered serious enough for treatment (55/128, 43%) in Japan and awaiting results of antimicrobial susceptibility testing (44/151, 29%) in the Eur5. Culture negativity was less commonly achieved after treatment in patients in Japan versus those in the Eur5 (31% [73/238] vs. 70% [300/426], p < 0.0001). In treatment phases that were either completed or discontinued, the primary goal was symptomatic improvement, followed by achieving culture conversion, in both Japan and the Eur5. Overall, 19% (16/85) of physicians in Japan and 43% (220/511) in the Eur5 were "entirely satisfied" with their patients' treatment outcomes.

Conclusions: Similarities and differences exist in the healthcare settings, clinical presentation, and management of patients with NTM-PD in Japan and the Eur5. Insufficient consideration of culture status by physicians, delayed treatment initiation, and symptom-based cessation emphasize the need for educational efforts on the guideline-based strategies.

Introduction: There is no reliable microbiological marker to guide responses to antiviral treatment in kidney transplant recipients (KTR) with COVID-19. We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) RT-PCR before and after receiving treatment with remdesivir compared with genomic RNA (gRNA) RT-PCR and its use as a surrogate marker of viral replication.

Methods: We analyzed gRNA and sgRNA at baseline and after remdesivir treatment in KTR who received remdesivir for SARS-CoV-2 infection from November 2021 to February 2022.

Results: Thirty-four KTR received remdesivir for SARS-CoV-2 infection. The median time since transplantation was 80 months (IQR 3-321) and 75% of patients had previously received 3 doses of a mRNA SARS-CoV-2 vaccine. Three patients (8%) were classified with mild, 25 (73%) with moderate, and 6 (17%) with severe SARS-CoV-2 infection. Thirty-two (94%) patients received 5 doses of remdesivir and two patients received 2 doses. The median time between symptom onset to remdesivir treatment was 5 days (IQR 3-8.5). The median days of hospitalization were 6 (IQR 2-112). gRNA was positive in all patients at baseline and after remdesivir. Five (15%) patients had negative sgRNA at baseline and 20 (59%) after receiving remdesivir. Patients presenting with negative sgRNA at baseline were discharged from hospital in ≤ 6 days without complications. Moreover, those with negative sgRNA after remdesivir therapy did not require ICU admission and had favorable outcomes. Nevertheless, patients with positive sgRNA after antiviral treatment presented worse outcomes, with 47% requiring ICU admission and the three (9%) recorded deaths in the study were in this group.

Conclusions: Based on these data, we hypothesize that sgRNA may have clinical utility to help monitor virologic response more accurately than gRNA in KTR who receive remdesivir. Moreover, patients with negative sgRNA at baseline may not require antiviral treatment and others presenting positive sgRNA at day 5 could benefit from prolonged or combined therapies.

Introduction: The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary.

Methods: A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 ("high-risk" individuals) was conducted from August 18-September 5, 2023. Objectives included characterizing demographics and attitudes associated with COVID-19 testing. Inverse propensity weighting was used to weight the data to accurately reflect the high-risk adult US population as reflected in IQVIA medical claims data. We describe here the weighted results modeled to characterize demographic factors driving hesitancy.

Results: In the weighted sample of 5019 respondents at high risk for severe COVID-19, 58.2% were female, 37.8% were ≥ 65 years old, 77.1% were White, and 13.9% had a postgraduate degree. Overall, 67% were Non-testers (who indicated that they were unlikely or unsure of their likelihood of being tested within the next 6 months); these respondents were significantly more likely than Testers (who indicated a higher probability of testing within 6 months) to be female (60.2 vs. 54.1%; odds ratio [OR] [95% confidence interval (CI)], 1.3 [1.1‒1.4]), aged ≥ 65 years old (41.5 vs. 30.3%; OR [95% CI] compared with ages 18‒34 years, 0.6 [0.5‒0.7]), White (82.1 vs. 66.8%; OR [95% CI], 1.4 [1.1‒1.8]), and to identify as politically conservative (40.9 vs. 18.1%; OR [95% CI], 2.6 [2.3‒2.9]). In contrast, Testers were significantly more likely than Non-testers to have previous experience with COVID-19 testing, infection, or vaccination; greater knowledge regarding COVID-19 and testing; greater healthcare engagement; and concerns about COVID-19.

Conclusions: Older, female, White, rural-dwelling, and politically conservative high-risk adults are the most likely individuals to experience COVID-19 testing hesitancy. Understanding these demographic factors will help guide strategies to improve US testing rates.

Introduction: Understanding antibiotic prescribing for uncomplicated urinary tract infection (uUTI) could help to optimize management. However, data on uUTI treatment patterns in the European Union are scarce. We used real-world data to evaluate adherence to antibiotic prescribing guidelines for femalepatients with uUTI in Germany.

Methods: This retrospective cohort study used anonymized German statutory health insurance claims data from the Wissenschaftliches Institut für Gesundheitsökonomie und Gesundheitssystemforschung from January 2013 to December 2019. Patients were female, aged ≥ 12 years, with an index uUTI diagnosis. Patient characteristics and treating physician specialties were examined overall and in sub-cohorts for recommended/non-recommended treatment (based on initial therapy adherence to German uUTI treatment guidelines) and optimal/sub-optimal outcome (based on a prescription of different antibiotics or a urinary tract infection-related episode).

Results: Overall, 144,645 uUTI cases in 124,971 patients were analyzed; 51,230 (35.4%) and 93,415 (64.6%) cases were assigned to the recommended/non-recommended treatment sub-cohorts, respectively. Clinically meaningful differences in age and comorbidities were observed between these sub-cohorts. Most cases had an optimal outcome (n = 122,823; 84.9%); of these, a higher proportion received antibiotics that were recommended but not as first-choice versus first-choice therapies as their initial treatment (58.6% vs. 35.3%). In the sub-optimal outcome cohort, 49.1% received antibiotics that were recommended but not as first-choice and 41.1% received first-choice therapies as their initial treatment. Most uUTIs were treated by general practitioners (GPs; 82.3%), followed by gynecologists (13.3%), and urologists (6.8%). Notably, 64.5% of initial therapy prescriptions filled by gynecologists and 32.1% by GPs were first-choice antibiotics.

Conclusion: A high proportion of prescribed treatments for the initial uUTI episode were not recommended by German uUTI guidelines as first-choice antibiotics. Prescribing adherence varied by physician specialty; specialists showed greater adherence to treatment guidelines versus GPs. This study provides a novel and multi-dimensional picture of uUTI treatment in Germany.

Introduction: Antimicrobial resistance (AMR) is a global public health challenge. Global efforts to decrease AMR through antimicrobial stewardship (AMS) initiatives include education and optimising the use of diagnostic technologies and antibiotics. Despite this, economic and societal challenges hinder AMS efforts. The objective of this study was to obtain insights from healthcare professionals (HCPs) on current challenges and identify opportunities for optimising diagnostic test utilisation and AMS efforts.

Methods: Three hundred HCPs from six countries (representing varied gross national incomes per capita, healthcare system structure, and AMR rates) were surveyed between November 2022 through January 2023. A targeted literature review and expert interviews were conducted to inform survey development. Descriptive statistics were used to summarise survey responses.

Results: These findings suggest that the greatest challenges to diagnostic test utilisation were economic in nature; many HCPs reported that AMS initiatives were lacking investment (32.3%) and resourcing (40.3%). High resistance rates were considered the greatest barriers to appropriate antimicrobial use (52.0%). Most HCPs found local and national guidelines to be very useful (≥ 51.0%), but areas for improvement were noted. The importance of AMS initiatives was confirmed; diagnostic practices were acknowledged to have a positive impact on decreasing AMR (70.3%) and improving patient outcomes (81.0%).

Conclusion: AMS initiatives, including diagnostic technology utilisation, are pivotal to decreasing AMR rates. Interpretation of these survey results suggests that while HCPs consider diagnostic practices to be important in AMS efforts, several barriers to successful implementation still exist including patient/institutional costs, turnaround time of test results, resourcing, AMR burden, and education. While some barriers differ by country, these survey results highlight areas of opportunities in all countries for improved use of diagnostic technologies and broader AMS efforts, as perceived by HCPs. Greater investment, resourcing, education, and updated guidelines offer opportunities to further strengthen global AMS efforts.