Αρχειοθήκη ιστολογίου

Τετάρτη 4 Ιανουαρίου 2023

Effectiveness and pharmacokinetic exposures of first-line drugs used to treat drug-susceptible tuberculosis in children: a systematic review and meta-analysis

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Optimal doses of first line drugs for drug-susceptible tuberculosis (DS-TB) treatment in children and young adolescents remain uncertain. We aimed to determine if children treated using WHO-recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic exposures.
Methods
Titles, abstracts, and full-text articles were screened. We searched Pubmed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children <18 years, being treated for DS-TB with rifampicin, pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO, CRD42021274222.
Results
Of 304 studies identified, 46 studies were eligible for full-text review and 12 and 18 articles were included for the efficacy and pharmacokinetic analysis, respectively. Of 1,830 children in cluded in the efficacy analysis, 82% had favourable outcomes (range 25%-95%). At WHO-recommended doses, exposures to rifampicin, pyrazinamide, and ethambutol were lower in children as compared to adults. Children ≤6 years have 35% lower AUC than older children (14.4 (9.9-18.8) vs 22.0 (13.8-30.1) μg.h/mL) and children with HIV (CWHIV) had 35% lower rifampicin AUC than HIV negative children (17.3 (11.4-23.2) vs 26.5 (21.3-31.7) μg.h/mL). Heterogeneity and small sample sizes were major limitations.
Conclusion
There is large variability in outcomes with an average 82% favourable outcomes. Drug exposures are lower in children than in adults. Younger children and CWHIV are underexposed to rifampicin. Standardization of pharmacokinetic paediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.
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Severe bacterial non-AIDS infections in persons with HIV: the epidemiology and evolution of antibiotic resistance over an 18-year period (2000–2017) in the ANRS CO3 AquiVih-Nouvelle-Aquitaine cohort

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Severe non-AIDS bacterial infections (SBIs) are one of the leading causes of hospital admissions among persons with HIV (PWH) in regions with high ART coverage.
Methods
This large prospective cohort study of PWH examined the types of infections, bacterial documentation, and evolution of antibiotic resistance among PWH hospitalized with SBIs over an 18-year period.
Results
Between 2000 and 2017, 459 PWH had at least one SBI with bacterial documentation. Among the 847 SBIs, there were 280 cases of bacteremia, 269 cases of pneumonia, and 240 urinary tract infections. The 1025 isolated bacteria included Enterobacteriaceae (n = 394; mainly Escherichia coli), Staphylococcus aureus (n = 153) and Streptococcus pneumoniae (n = 82). The proportion of S. pn eumoniae as the causative agent in pneumonia and bacteremia decreased sharply over time, from 34% to 8% and from 21 to 3%, respectively.The overall antibiotic resistance of S. aureus and S. pneumoniae decreased progressively but it increased for Enterobacteriaceae (from 24% to 48% for amoxicillin-clavulanate, from 4 to 18% for cefotaxime, and from 5% to 27% for ciprofloxacin). Cotrimoxazole prophylaxis was associated with higher nonsusceptibility of S. pneumoniae to amoxicillin and erythromycin, higher nonsusceptibility of Enterobacteriaceae to beta-lactams and fluoroquinolones, and a higher risk of extended-spectrum β-lactamase producing Enterobacteriaceae.
Conclusions
The bacterial resistance pattern among PWH between 2014 and 2017 was broadly similar to that in the general population, with the exception of a higher resistance profile of Enteroba cteriaceae to fluoroquinolones. The use of cotrimoxazole as prophylaxis was associated with an increased risk of antibiotic resistance.
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Birth weight, gestational age and risk of cardiovascular disease in early adulthood: Influence of familial factors

alexandrossfakianakis shared this article with you from Inoreader
Abstract
The association between intrauterine growth restriction (IUGR) and cardiovascular disease (CVD) later in life might be confounded by familial factors. We conducted a bi-national register-based cohort study to assess associations of birthweight for gestational age (GA), a proxy for IUGR, and GA with CVD risk in early adulthood, before and after addressing familial factors via sibling comparison. We included 3,410,334 live non-malformed singleton births in Sweden (1973-1996) and Denmark (1978-1998). During a median follow-up of 10 years from age 18 onwards, 29,742 individuals developed incident CVD (hypertensive, ischemic heart, and cerebrovascular diseases). Compared with individuals born with appropriate birthweight for GA (AGA, 10th-90th percentiles) or full term (39-40 gestational weeks), individuals born severely small for GA (SGA, <3rd percentile) or preterm (22-36 weeks) were at increased risk of CVD [HRs (95% CIs): 1.38 (1.32-1.45) and 1 .31 (1.25-1.38), respectively]. The association was attenuated when comparing individuals born SGA with their AGA siblings (1.11, 0.99-1.25), but remained robust when comparing individuals born preterm with their term siblings (1.21, 1.07-1.37). Our findings suggest that both SGA and preterm birth are associated with CVD risk in early adulthood, with greater familial confounding noted for SGA.
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! # Ola via Alexandros G.Sfakianakis on Inoreader