Infectious diseases (London, England)最新文献

Introduction: Dalbavancin is a lipoglycopeptide with an exceptionally long half-life that allows simplified administration, which may be of value in long-term treatment of bone and joint infections, such as prosthetic joint infections (PJIs). The objective was to determine trough (C_min) values of dalbavancin during long-term PJI treatment according to the recommendation of the Swedish National Guidelines for Bone and Joint Infections: a loading dose of 1,500 mg on day 1 and another 1,500 mg on days 8-14, followed by day 28 administration of 1,000 mg every two weeks or 500 mg per week.

Patients/methods: Twelve patients with PJI treated with at least six doses of dalbavancin were prospectively followed up, serum samples were collected, and renal function was investigated. Dalbavancin concentrations were measured using ultra-high pressure liquid chromatography coupled with unispray tandem mass spectrometry (UHPLC-MS/MS).

Results: The median serum concentration (C_min) 14 days after the first 1,500 mg dose was 36.3 mg/L (range: 6.6-62.4 mg/L). The median trough value at the date of the last given dose (1,000 mg) after a total of 6-7 doses was 53.6 mg/L (range: 32.0-97.5 mg/L). Three patients showed a tendency towards successive accumulation of dalbavancin during treatment. None of the patients showed any significant impairment in renal function.

Conclusions: Therapeutic drug monitoring during long-term dalbavancin treatment is recommended to avoid the risk of accumulation and unnecessarily high trough levels. In many cases, such monitoring can allow the dosing interval to be extended.

Background: Monoclonal antibodies (mAbs) are an important option against SARS-CoV-2, especially as pre-exposure prophylaxis (PrEP) for patients with immune system impairment. PrEP mAbs like sipavibart and pemivibart have been approved for limited use in several countries. Certain SARS-CoV-2 variants carry mutations in the spike (S) protein, conferring resistance to these mAbs.

Objectives: We aimed to examine the relative abundance of different circulating SARS-CoV-2 variants/mutations in central Sweden between 2023 and 2024, and to predict the effectiveness of sipavibart and pemivibart.

Methods: An amplicon-based Nanopore sequencing method was used for sequencing SARS-CoV-2 samples. Coronapp was used to identify mutations in these sequences. Using the published in vitro resistance data for sipavibart and pemivibart, the effectiveness of these mAbs was inferred.

Results: We have observed that the relative abundance of the KP.3.1.1 variant and the Q493E mutation started to increase in the later part of 2024 in the region. Also, since April 2024, the relative abundance of the F456L mutation reached 100% during many weeks until the end of the study period. The KP.3.1.1 variant is significantly resistant to pemivibart. Further, the presence of the F456L mutation in the Omicron subvariants confers high fold resistance towards sipavibart.

Conclusion: The use of sipavibart or pemivibart as PrEP for COVID-19 in the region may currently not be effective unless new SARS-CoV-2 variants appear not containing these resistance mutations. Further, new mAbs under development as PrEP for COVID-19 can be effectively used by routinely sequencing SARS-CoV-2 in patients to identify variants and resistance mutations.

Background: In paediatric emergency departments the use of empirical antimicrobials is very common, even though most infections are caused by viruses, resulting in misuse of antimicrobials. We aimed to assess the impact of a comprehensive antimicrobial stewardship program (ASP) on the optimisation of antimicrobial prescribing and clinical outcomes in a paediatric Emergency Department Observation Unit (EDOU).

Methods: A quasi-experimental before-and-after longitudinal study was conducted at the EDOU of a paediatric hospital, over 24 quarters from January 2017 to December 2023, excluding 2020 due to the pandemic and the phase-in period. The ASP intervention included the development and implementation of clinical guidelines, rapid diagnostic tests (RDTs), and staff stabilisation. Data on antimicrobial use and clinical outcomes, such as revisits within 72 h and hospital admissions, were collected and analysed using Bayesian structural time series models.

Results: The study included 33,799 patients transferred to the EDOU. Mean antimicrobial consumption significantly decreased from 46.5 ± 12.9 pre-intervention defined daily doses (DDDs) per 100 patients transferred to the Observation Unit (TOs) to 20.1 ± 3.0 DDDs per 100 TOs in the intervention period (p < 0.0001). Significant reductions were observed for amoxicillin-clavulanic acid, amoxicillin, and azithromycin. The percentage of revisits and hospital admissions remained stable for the whole period.

Conclusion: The implementation of ASP measures improved antimicrobial prescribing in the paediatric EDOU. These findings support the need for continued efforts in ASP, emphasising the development and implementation of guidelines, RDTs, and staff stabilisation.

Background: Wild poliovirus type 1 (WPV1) transmission persists in Pakistan, with cases increasing from 6 in 2023 to 56 by November 2024, highlighting critical challenges in polio eradication efforts. The aim of this study is to assess the relationship between bivalent oral polio vaccine (bOPV) doses and the severity of paralysis in the confirmed WPV1 cases in Pakistan.

Methods: We analysed all confirmed WPV1 cases reported in Pakistan from January 1, 2024, to November 15, 2024. Bivariate analyses were first conducted to explore initial associations. Firth, logistic regression models were then employed to evaluate the strength of these associations while adjusting for potential confounders.

Results: Higher bOPV doses were significantly associated with a lower risk of severe paralysis in both univariate analysis (OR = 0.75, 95% CI: 0.60-0.93, p = 0.009) and after adjustment for age and sex (OR = 0.76, 95% CI: 0.59-0.97, p = 0.026). For residual paralysis after 60 days of onset, univariate analysis showed a significant association (OR = 0.77, 95% CI: 0.61-0.97, p = 0.026); however, this association was no longer statistically significant after adjustment (OR = 0.82, 95% CI: 0.64-1.05, p = 0.115).

Conclusion: The study found a significant association between higher bOPV dose count and reduced paralysis severity in confirmed WPV1 cases. These findings suggest that bOPV may help to moderate the severity of paralysis, in addition to preventing WPV1 infection.

Introduction: For public health purposes, it is essential to understand which population groups and their areas of residence are affected by a disease as COVID-19 and to what extent these groups are reached by preventive measures.

Aim: We investigated how individual-level and area-level characteristics are associated with COVID-19 morbidity and vaccine uptake.

Methods: A population-based observational study including the total adult population age 18 and older in Sweden from 1 January 2020 to 1 April 2022, except individuals living in nursing homes. Associations between both individual and area-level characteristics and COVID-19 morbidity (hospitalisation, admission to intensive care unit and death) and vaccine uptake were analysed using Cox proportional hazards regression and adjusted for age, sex, comorbidity and socioeconomic and demographic factors.

Results: In the fully adjusted model, the hazard ratio (HR) for COVID-19 hospitalisation was 34% lower for individuals living in the most affluent neighbourhoods (HR 0.66, 95%CI 0.63-0.68) compared to individuals in the most deprived neighbourhoods. For intensive care unit (ICU)-admission and COVID-19 death, the risks were 53% (HR 0.47, 95%CI 0.42-0.53) and 47% (HR 0.53, 95%CI 0.48-0.59) lower, respectively. When stratified by cross-classified sociodemographics, this pattern was consistent within all strata. A composite area-level measurement had a better predictive value compared to single measures.

Conclusions: Living in deprived neighbourhoods is associated with substantially higher risk of COVID-19 hospitalisation, ICU-admission, mortality and lower vaccine uptake. This risk factor remained strong even when taking individual level characteristics into account and within strata of individual-level factors.