PubMed Açık Erişimli Yayınlar

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    Low-Dose Antibiotic Prophylaxis Induces Rapid Modifications of the Gut Microbiota in Infants With Vesicoureteral Reflux
    (2021) Morello, William; D'Amico, Federica; Serafinelli, Jessica; Turroni, Silvia; Abati, Isabella; Fiori, Jessica; Baskin, Esra; Yalcinkaya, Fatos; Jankauskiene, Augustina; Pennesi, Marco; Zurowska, Aleksandra; Becherucci, Francesca; Drozdz, Dorota; Mekahli, Djalila; Krzemien, Grazyna; La Scola, Claudio; Taranta Janusz, Katarzyna; Mehls, Otto; Schaefer, Franz; Candela, Marco; Montini, Giovanni; 34222145
    Background and Objectives: Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants. Methods: We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naive to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed. Results: 36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by Bifidobacteriaceae and Enterobacteriaceae. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of Enterobacteriaceae and Bacteroidetes, especially in the genera Bacteroides and Parabacteroides, and showed a trend toward increased Klebsiella, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in Bifidobacterium. No differences were found in fatty acid levels. Conclusions: In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks.
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    Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients
    (2021) Arslan, Hande; 0000-0002-5708-7915; 34370578; ABG-7034-2021
    There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.