Infectious diseases (London, England)最新文献

Background: Piperacillin/tazobactam is frequently used empirically in patients subsequently diagnosed with bloodstream infections (BSIs) due to extended-spectrum β-lactamase (ESBL) Enterobacterales, yet its effectiveness remains uncertain.

Objective: This study aimed to compare piperacillin/tazobactam with carbapenems as empirical therapy for BSIs caused by ESBL-Enterobacterales.

Methods: A single-centre retrospective study was conducted at Niguarda Hospital in Milan,Italy, enrolling consecutive patients with BSIs caused by ESBL-Enterobacterales treated empirically with either piperacillin/tazobactam or carbapenems from January 2015 to December 2023. The primary outcome was in-hospital all-cause mortality. Propensity Score Matching(PSM) was employed to mitigate potential confounding factors when assessing the association between empirical therapy and mortality. A sensitivity analysis was performed to determine the role of definitive piperacillin/tazobactam or carbapenems on patient outcomes.

Results: A total of 264 patients were included in the study, median age was 72[64-81], 64% were males, 66% had sepsis and 17% septic shock. Among them, 200(76%) received empirical piperacillin/tazobactam and 64(24%) received carbapenems. After PSM adjustment, baseline characteristics were well balanced between the groups. Patients who received empirical piperacillin/tazobactam had a higher in-hospital mortality compared to those receiving empirical carbapenems (14.3% vs 3.5%, adjusted Risk Difference: 10%;95%CI: 2-19%). No difference in in-hospital mortality was observed when comparing definitive piperacillin/tazobactam to definitive carbapenems (6% vs 9%, Risk Difference: -2.5%; 95%CI: -9.2 - 4.2).

Conclusion: Empirical piperacillin/tazobactam may be associated with higher mortality compared tocarbapenemswhen treating patients with BSI due to ESBL-Enterobacterales. Further larger studies are needed to confirm the results andto identify specific scenarios in which piperacillin/tazobactam may be safely used.

Introduction: Infections, particularly sepsis, require rapid initiation of empirical antibiotic therapy. Delays or inadequacies in therapy can significantly increase patient morbidity, mortality and length of stay (LOS). This systematic review and meta-analysis aimed to evaluate the impact of adequate versus inadequate empirical antibiotic therapy on LOS.

Methods: A comprehensive search was conducted in EMBASE, Cochrane Library, Web of Science and MEDLINE for studies published between 2012 and 2024. Studies involving adult hospitalised patients with infections, assessment of antimicrobial adequacy based on microbiological cultures and LOS data were included. Statistical analysis was performed using Review Manager 5.3, with LOS treated as a continuous variable and outcomes assessed through mean difference and 95% confidence intervals (CIs).

Results: Thirteen studies with a total of 4158 participants met the inclusion criteria. The mean LOS for patients receiving adequate therapy was significantly lower than for those receiving inadequate therapy (mean difference -1.17 days; 95% CI: -1.40, -0.94). When pooling data from all included studies and weighting by sample size, the overall mean LOS for patients receiving adequate empirical antimicrobial therapy was 12.5 days, compared to 28.5 days among those receiving inadequate therapy. Additionally, adequate therapy resulted in a reduced ICU LOS by -0.89 days (95% CI: -1.22, -0.57).

Conclusion: Adequate antimicrobial therapy significantly reduces LOS in hospitalised patients with infections.

Background: Avian influenza A viruses (AIVs) remain a global public health concern. Sporadic human infections continue to be reported, particularly in areas with frequent human-poultry contact. We report four cases of human infection with AIVs in Zhejiang Province that occurred between December 2021 and January 2024.

Method: Epidemiological investigations were carried out to collect detailed demographic information, underlying diseases, symptoms, hospital admission details, recent exposures to domestic poultry or wild birds, recent visit to wet markets. Samples from patients and their related environments as well as contacts were collected and detected. Epidemiological sources were also traced based on patient's exposure history 10 days before symptom onset.

Results: The reported cases included two women aged 51 and 55 diagnosed with H5N6 infection in December 2021, a 33-year-old man identified in June 2022 as the first H10N3 case in Zhejiang Province and the second globally, and a 63-year-old woman from Anhui Province who became the world's first documented case of coinfection with H10N5 and H3N2.All patients had a history of unprotected exposure to infected or contaminated poultry, primarily during cleaning and handling processes. Three of the patients responded well to antiviral treatment and recovered, whereas the patient with H10N5 coinfection died due to disease progression. Genomic analyses confirmed that all infections were AIVs, with no evidence of sustained human-to-human transmission.

Conclusion: These cases highlight the continued risk of AIVs spill-over into humans and emphasise the need for strengthened surveillance, improved poultry-handling protocols, and early detection to prevent future outbreaks.

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.