Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children: A French multicenter study.

OBJECTIVES: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL-producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. MATERIALS AND METHODS: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. RESULTS: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. CONCLUSIONS: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.

Clinical Prediction of Iron Deficiency at Age 2 Years: A National Cross-sectional Study in France.

OBJECTIVE: To assess the diagnostic accuracy of existing clinical criteria and to develop prediction tools for iron deficiency in 2-year-old children. STUDY DESIGN: In a national cross-sectional study conducted in primary care pediatricians' practices throughout France, 2-year-old children were consecutively included (2016-2017). Multivariable logistic regression modeling and bootstrapping were used to develop several clinical models to predict iron deficiency (serum ferritin <12 µg/L). These models used the best criteria and combinations among the American Academy of Pediatrics' (AAP) criteria adapted to the European context (n = 10), then all potential predictors (n = 19). One model was then simplified into a simple prediction tool. RESULTS: Among 568 included infants, 38 had iron deficiency (6.7%). In univariable analyses, no significant association with iron deficiency was observed for 8 of the 10 adapted AAP criteria. Three criteria (both parents born outside the European Union, low weight at 1 year old, and weaning to cow's milk without supplemental iron) were retained in the AAP model, which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.62 (95% CI, 0.58-0.67), 30% (95% CI, 22%-39%), and 95% (95% CI, 92%-97%), respectively. Four criteria were retained in a newly derived simple prediction tool (≥1 criterion among the 3 previous plus duration of iron-rich formula consumption <12 months), which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.72 (95% CI, 0.65-0.79), 63% (95% CI, 47%-80%), and 81% (95% CI, 70%-91%), respectively. CONCLUSIONS: All prediction tools achieved acceptable diagnostic accuracy. The newly derived simple prediction tool offered potential ease of use. TRIAL REGISTRATION: ClinicalTrials.gov NCT02484274.

Young children formula consumption and iron deficiency at 24 months in the general population: A national-level study.

BACKGROUND & AIMS: Iron deficiency (ID) is considered the most frequent micronutrient deficiency in industrialized countries where strategies for its primary prevention vary widely and are insufficiently evaluated. We aimed to study the effectiveness for iron status of a national iron deficiency prevention strategy based on recommendations for young-child formula (YCF) use after age 12 months, taking into consideration other sources of iron and the family's socio-economic status. METHODS: In a cross-sectional observational study conducted in primary care pediatrician offices throughout France from 2016 to 2017, infants aged 24 months were consecutively included for a food survey and blood sampling. Associations between YCF consumption and serum ferritin (SF) level were studied by multivariable regression after adjustment on sociodemographic, perinatal and dietary characteristics, notably other intakes of iron. RESULTS: Among the 561 infants analyzed, the ID prevalence was 6.6% (37/561; 95% confidence interval [CI] 4.7-9.0). Daily iron intake excluding YCF and total daily iron intake including YCF were below the 5-mg/day recommended average requirements for 63% and 18% of children, respectively. ID frequency was significantly decreased (or SF level was independently higher) with any YCF consumption after age 10 months (odds ratio 0.15, 95% CI 0.07-0.31), current YCF consumption at age 24 months (median SF level 29 vs 21 µg/L if none), prolonged YCF consumption (28 µg/L if >12 months vs 17 µg/L if none), and increasing daily volume of YCF consumed at age 24 months from a small volume (e.g., 29 µg/L if <100 mL/day vs 21 µg/L if none). CONCLUSIONS: Current or past YCF use was independently associated with a better iron status at age 24 months than non-use. The strategy recommending YCF use at weaning after age 12 months seems effective in the general population. CLINICALTRIALS. GOV IDENTIFIER: NCT02484274.

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption. OBJECTIVES: To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations. METHODS: We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression. RESULTS: We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (-0.5% per month; 95% CI -0.9 to -0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (-22.2%; 95% CI -33.0 to -11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence. CONCLUSIONS: In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.

Very low prevalence of iron deficiency among young French children: A national cross-sectional hospital-based survey.

Although iron deficiency (ID) is considered the most frequent micronutrient deficiency in industrialized countries and is associated with impaired neurodevelopment when occurring in early years, accurate recent estimations of its prevalence are lacking. Our objective was to estimate ID prevalence and associated sociodemographic markers in young children in France. The Saturn-Inf national cross-sectional hospital-based survey recruited 3,831 French children <6 years old between 2008 and 2009 to assess lead poisoning prevalence and to establish a biobank. This secondary analysis measured serum ferritinemia (SF) in sera kept frozen at -80 °C for children with sufficient serum aliquots and C-reactive protein <10 mg/L. For the 657 participating children (17% of the Saturn-Inf study), the median age was 3.9 years (interquartile range: 2.2-5.1); 52% were boys. The median SF was 44 µg/L (interquartile range: 28-71). ID prevalence was 2.8% (95% confidence interval [1.7, 4.7]) and 3.2% (95% confidence interval [2.0, 5.1]) with an SF threshold of 10 and 12 µg/L, respectively. Low SF was significantly associated (p < .05) with mother being a migrant (32 vs. 45 µg/L for a mother born in France) or unemployed (37 vs. 50 µg/L for a mother employed). In this first national cross-sectional hospital-based study in France, ID prevalence was much lower than that in other French and European studies performed in underprivileged populations but close to the lowest values observed in other population-based studies in Europe.