Infectious diseases (London, England)最新文献

Background: Randomised controlled trials (RCTs) are essential for evaluating new vaccines but often exclude high-risk populations, creating uncertainties about vaccine performance across diverse populations.

Objectives: We aimed to characterise recipients of the recombinant zoster vaccine (RZV) in Denmark during its early availability, assess differences from populations included in vaccine registration trials, and identify predictors of vaccination.

Methods: Using Danish national healthcare registries, we identified individuals who received at least one dose of RZV between 2019 and 2022 and extracted sociodemographic and clinical data. We compared the characteristics of RZV vaccinees with trial populations by applying the eligibility criteria from the RCTs supporting regulatory decisions, considering individuals eligible if they met the criteria for at least one trial. Additionally, vaccinees were matched 1:10 to unvaccinated controls by age, sex, and calendar time to identify predictors of RZV vaccination.

Results: We identified 8,326 RZV vaccinees, predominantly female, aged 60-79, highly educated, and often in the top income quartile. Over one-third (36%) would have been ineligible for the pivotal RCTs, primarily due to the use of chronic immune-modifying treatments. The strongest predictors of vaccination were prior herpes zoster vaccination or diagnosis. Individuals with HIV, haematologic malignancies, lupus, and other immunosuppressive conditions, along with those of higher socioeconomic position, were more likely to be vaccinated.

Conclusion: Early RZV uptake in Denmark reached some high-risk individuals but also reflected socioeconomic disparities. Targeted outreach and continued monitoring of vaccine effectiveness in populations excluded from trials are needed to ensure equitable vaccine coverage.

Background: The management of Acinetobacter baumannii infections has become increasingly challenging due to extensive antimicrobial resistance.

Objectives: This study evaluated the in vitro activity of cefiderocol and sulbactam-durlobactam and characterised OXA-type enzyme diversity in carbapenem-resistant A. baumannii isolates collected between March 2019 and December 2024.

Methods: A total of 159 unique carbapenem-resistant isolates were tested for susceptibility to cefiderocol and sulbactam-durlobactam using two Food and Drug Administration-cleared minimum inhibitory concentration (MIC) determination methods: the ComASP Cefiderocol panel (Liofilchem, Italy) for cefiderocol and Etest strips (bioMérieux, USA) for sulbactam-durlobactam. Carbapenemase genes, including bla_NDM, bla_KPC, bla_IMP, bla_VIM, bla_OXA-23, bla_OXA-24/40, bla_OXA-48, and bla_OXA-58, were detected using real-time PCR.

Results: Cefiderocol susceptibility was observed in 91.8% of isolates, with MIC₅₀ and MIC₉₀ values of 0.5 mg/L and 2 mg/L. Among bla_OXA-23-positive isolates, MIC₅₀ and MIC₉₀ values were also 0.5 mg/L and 2 mg/L, while bla_OXA-24/40-positive isolates showed MIC₅₀ and MIC₉₀ values of 0.25 mg/L and 1 mg/L, respectively. The sulbactam-durlobactam combination demonstrated potent in vitro activity against 97.5% of carbapenem-resistant Acinetobacter baumannii clinical isolates, with MIC₅₀ and MIC₉₀ values of 2 mg/L and 4 mg/L, respectively. Among the 159 carbapenem-resistant Acinetobacter baumannii isolates, 72.9% (n = 116) carried the bla_OXA-23 gene, 10.7% (n = 17) harboured bla_OXA-24/40, and 16.4% (n = 26) did not possess any of the carbapenemase genes included in the testing panel.

Conclusion: Cefiderocol and sulbactam-durlobactam exhibited strong in vitro activity against carbapenem-resistant A. baumannii isolates from a single University Hospital and may represent valuable treatment options for patients with limited therapeutic alternatives.

Background: Invasive pneumococcal disease (IPD) remains a significant public health concern, particularly in vulnerable populations such as the elderly. This study focuses on the Faroe Islands, a unique setting for monitoring pneumococcal disease trends due to its high vaccination coverage and geographic isolation.

Objective: To examine the prevalence, trends and serotype distribution of IPD in the Faroe Islands from 2000 to 2023, focusing on the impact of pneumococcal conjugate vaccines (PCVs) on disease incidence and serotype replacement.

Methods: Eighty-six pneumococcal isolates, representing all registered cases of IPD in the Faroe Islands, were analysed during the study period. Data on patient demographics, serotype identification and vaccination history were collected from national health records. Temporal trends in vaccine-type (VT) and non-vaccine-type (nVT) serotypes were analysed, particularly following the introduction of PCV13 in 2010.

Results: Following the introduction of PCV13, a shift from VT to nVT serotypes was observed, while the overall IPD rate remained stable. Notably, there was an increase in IPD cases among the elderly population. The analysis indicated that serotype replacement contributed to a rise in nVT cases despite reducing VT-related IPD.

Conclusions: The findings emphasise the need for ongoing evaluation of pneumococcal vaccine formulations and alternative strategies to address the increasing prevalence of nVT IPD. Higher-valency vaccines and sustained vaccination coverage are critical to mitigating the impact of serotype replacement and improving public health outcomes in the Faroe Islands.

Background: Antibiotics are frequently prescribed to children, often for respiratory infections that do not require treatment. Inappropriate use contributes to antimicrobial resistance and adverse health outcomes.

Objectives: The aim of this study was to examines systemic antibiotic prescribing trends in Danish children (2010-2023), focusing on prevalence, quantity, and temporal changes.

Methods: A nationwide drug utilisation study based on redeemed prescriptions from the Danish National Prescription Registry for children under 18 years from 1 January 2010, to 31 December 2023. Annual prevalence and incidence rates (IR) of antibiotic use were calculated, stratified by age, sex, region, and antibiotic type, classified by drug class and WHO AWaRe classification.

Results: A total of 5,518,308 antibiotic prescriptions were issued to 1,426,043 children. The highest IR was observed in 1-year-olds. Antibiotic prescriptions declined from 440 per 1,000 children in 2010 to 235 in 2019, followed by a sharp drop in 2020 (165 per 1,000) coinciding with the Covid-19 pandemic lockdown. However, IRs rose steeply post-pandemic, surpassing 2019 levels and reaching 287 per 1,000 children in 2023. Beta-lactamase-sensitive penicillins and extended-spectrum penicillins were the most prescribed antibiotics. A shift towards antibiotics associated with lower risk as per WHO AWaRe classification was noted, with variations by age, sex, and region.

Conclusion: Overall, a trend towards a more rational pattern in antibiotic prescriptions was observed among Danish children between 2010 and 2020. However, a steep increase in the prescription rate of antibiotics from 2021 and onwards warrants closer monitoring.

The COVID pandemic significantly impacted intensive care unit (ICU) antibiotic con sumption (AMC) and resistance (AMR). This study examines these effects over a 6-year period in 6 French ICUs.

Objectives: To evaluate the impact of the COVID pandemic on AMC and AMR in ICUs, focusing on changes in consumption patterns and bacterial resistance profiles.

Methods: Data were prospectively collected from 3 university hospitals, covering 6ICUs. The study compared two periods: before (2017-2019: befPAND period) and during (2020-2022: perPAND period) the pandemic. Antibiotic consumption was measured using Defined Daily Doses (DDD) globally per unit and per 1,000 patient-days in each unit. Antibiotic resistance was assessed from bacterial cultures from selected clinical cultures taken from ICU patients. Statistical analysis compared trends between the two periods.

Results: Total antibiotic consumption of all units increased by 28% during the pandemic period, but DDD/1000 patient-days of all units remained stable. There was an increase in the use of broad-spectrum antibiotics, particularly those classified as 'Reserve' by the WHO (5.6% to 9.6%, p < 0.0001).The number of positive cultures increased in the perPAND period for Staphylococcus epidermidis, Enterobacter sp., and Pseudomonas aeruginosa. Resistance levels showed an increase in Enterococcus species, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, while methicillin-resistant Staphylococcus aureus and 3rd generation cephalosporins enterobacterales resistance remained stable.

Conclusions: The COVID pandemic increased the overall antibiotic consumption, but not the 1000-patients-day consumption in ICUs. However, one of the main effects was to shift usage towards more broad-spectrum antibiotics, which may contribute to growing resistance.

Background: Influenza ranges from a mild and self-limiting infection to a life-threatening disease with high mortality despite intensive care. Conclusive data on the association between influenza type/subtype and mortality among adults treated at intensive care units (ICU) is lacking.

Objectives: To investigate the mortality in adults admitted to ICU with laboratory-confirmed influenza during three consecutive influenza seasons.

Methods: This observational multicenter study included adults with PCR-confirmed influenza requiring intensive care at four hospitals in southern Sweden between 2015-2018. The primary outcome was all-cause one-year mortality. Patient characteristics and the impact of influenza type/subtype were studied using Kaplan-Meier and logistic regression analyses.

Results: A total of 146 individuals were included: median age 67 years (interquartile range 56-74), 54% were male. Influenza type/subtype was available for 144/146 (99%); A(H1N1)pdm09 in 50 (35%), A(H3N2) in 37 (26%), and B in 57 (40%) patients. Mortality was 19% in the ICU and 32% before hospital discharge. At one year, 43% were deceased, ranging from 36% to 49%, depending on type/subtype (log-rank test p = 0.32). Mortality rates remained similar for all three influenza types/subtypes after adjusting for age, sex, and a modified comorbidity index. Antibiotics were prescribed for 125/145 (86%) within 48 h of ICU admission, with microbiological confirmation of coinfection in 53/125 (42%).

Conclusions: Among adults admitted to intensive care with PCR-confirmed influenza, mortality rates were similar independently of influenza type/subtype. Mortality increased from 19% in the ICU to 43% one year after admission, highlighting the importance of monitoring ICU-survivors and reporting long-term outcomes in critically ill influenza patients.

Background: Many countries reported declines in acute respiratory infections (ARIs) following public health and social measures to mitigate COVID-19.

Objectives: We describe the potential association with pandemic restrictions on the occurrence of non-COVID ARIs in Greenland, which experienced a late but sudden introduction of COVID-19.

Methods: We included national electronic medical records on ARIs in Greenland across three periods: pre-pandemic (January 2018-February 2020), pandemic (March 2020-June 2022), and endemic (July 2022-December 2023). Severe ARIs were defined using a case definition based on ICD-10/ICPC-2-R codes. Oral penicillin prescriptions served as a proxy for mild ARIs due to limited primary care data. We calculated ARI incidence and used Poisson regression to compare periods. Data on Influenza A/B and RSV PCR testing activity and results were included.

Results: During the pandemic, all ARIs decreased by 14% (IRR 0.86 [95% CI 0.84-0.88]) compared to pre-pandemic levels. In the endemic period, mild ARIs increased by 3% (IRR 1.03 [95% CI 1.02-1.06]), while severe ARIs increased by 40% (IRR 1.40 [95% CI 1.22-1.60]). The Influenza A/B positive rate declined during the pandemic (20.7% to 8.3%) but increased in the endemic period (14.2%), whereas RSV positive rate increased during the pandemic (19.8% to 57.2%).

Conclusions: We observed declines in mild and severe ARIs during the pandemic in Greenland. Unlike many other countries, mild ARIs did not rise during the endemic period, likely due to preventive travel measures limiting the spread of SARS-CoV-2 while allowing ongoing exposure to other respiratory viruses in society, preventing an infection rebound.

Background: Many Greenlanders move from Greenland, a tuberculosis (TB) high-incidence country, to Denmark, a TB low-incidence country. Surprisingly, according to official statistics, the TB incidence among Greenlanders in Denmark is much higher than in Greenland.

Objectives: This study investigates factors contributing to the extraordinarily high TB incidence among Greenlanders residing in Denmark.

Methods: Retrospective, register-based cohort study including all Greenlanders ≥18 years notified with TB in Denmark and Greenland, and Danes ≥18 years with TB in Denmark, 2006-2022. Demographic and microbiological characteristics were compared across groups using parametric and non-parametric statistical tests.

Results: The TB incidence was extraordinarily high among Greenlanders in Denmark (341/100,000; n = 813), compared to Danes in Denmark (2/100,000; n = 1799) and Greenlanders in Greenland (149/100,000; n = 1088). Additionally, they were more often part of a TB cluster (75.6%) compared to Danes in Denmark (53.3%) and Greenlanders in Greenland (64.0%) and demonstrated very high rates of recurrent TB (23.9%), with 75.6% of cases being reinfections involving new Mycobacterium tuberculosis strains.

Conclusion: TB poses a significant public health challenge for Greenlanders in Denmark. Their high incidence combined with elevated clustering and reinfection rates suggest substantial active TB transmission, and their cluster distribution indicates that many infections are locally acquired rather than reactivations of infection acquired in Greenland. Greenlanders with TB in Denmark are likely part of a socially marginalised minority with TB high-risk behaviours similar to Danes developing TB. These findings highlight the need for targeted TB prevention and control strategies for Greenlanders residing in Denmark.

Background: The impact of COVID-19-related nonpharmaceutical interventions (NPI) on the bacterial composition of upper airway infections remains largely unexplored.

Objectives: We aimed to investigate the incidence and microbiology of peritonsillar abscess (PTA) following the cessation of NPI and to compare these findings with the periods before and during NPI implementation.

Methods: We performed a cross-sectional analysis of all PTA cases and their microbiological findings from 12 March, 2018 to 11 March, 2024, among patients admitted to the Ear-Nose-Throat Department, Aarhus University Hospital. Patients were categorised into three two-year periods in relation to NPI. Age-stratified population data for the catchment area were sourced from Statistics Denmark.

Results: A total of 1,030 patients were included. The annual incidence rate of PTA was significantly higher post-NPI (26.9 cases/100,000) compared to both the NPI period (14.9 cases/100,000, p < 0.001) and the pre-NPI period (21.8 cases/100,000, p = 0.003). Increased post-NPI rates were observed across all age groups. The number of cases positive for Streptococcuspyogenes and Fusobacterium necrophorum increased post-NPI (n = 102 and n = 89, respectively) compared to during the NPI period (n = 28 and n = 64, p < 0.001 and p = 0.052, respectively) and pre-NPI (n = 67 and n = 60, p = 0.009 and p = 0.021, respectively). Statistically non-significant increasing trends were found for less prevalent bacteria.

Conclusion: Following NPI cessation, PTA incidence rates surpassed both the NPI and pre-NPI levels. The rising PTA incidence rates post-NPI were primarily driven by an increasing number of cases positive for S. pyogenes and F. necrophorum, suggesting an immunity debt to these prevalent pathogens.

Background: Early diagnosis of chronic hepatitis B virus (CHB) prevents onward transmission and liver disease progression. In Norway, CHB infections are concentrated among migrants from countries with a high CHB prevalence.

Objectives: To calculate time from migration to diagnosis and proportion presenting late (a hospital consultation for end-stage liver disease within 24 months after CHB diagnosis) among diagnosed cases of CHB in Norway from 2008-2022.

Method: We analysed linked national registry data and described each outcome by year, age, sex, region of residence and country of birth. We explored factors associated with time from migration to diagnosis in accelerated failure time models and presented adjusted time ratios (aTR) with 95% confidence intervals (CI).

Results: Among 10,542 cases of CHB, 273 (2.6%) presented late, with a higher proportion in older age groups (≥60 years: 11%). The median time from migration to diagnosis among 3,665 cases who migrated from 2008 onwards was 1.1 years (interquartile range: 0.3-3.1). Compared to cases from high-prevalence countries with a high proportion of refugees or asylum seekers to Norway, cases born in other high-prevalence countries (aTR: 1.37, 95% CI: 1.26-1.50) or low-prevalence countries (aTR: 1.66, 95% CI: 1.49-1.89) had a longer time from migration to diagnosis.

Conclusion: Among persons diagnosed with CHB in Norway, 2-3% present with severe liver disease within 2 years of CHB diagnosis. Initiatives to improve testing strategies could focus on migrants from high-prevalence countries arriving for reasons other than refuge or who arrived several years ago but have not yet been tested.