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1. Febrile urinary-tract infection due to extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: A French prospective multicenter study.

Author

Fouad Madhi, Camille Jung, Sandra Timsit, Corinne Levy, Sandra Biscardi, Mathie Lorrot, Emmanuel Grimprel, Laure Hees, Irina Craiu, Aurelien Galerne, François Dubos, Emmanuel Cixous, Véronique Hentgen, Stéphane Béchet, Urinary-tract Infection due to Extended-Spectrum Beta-lactamase–producing Enterobacteriaceae in Children Group, Stéphane Bonacorsi, and Robert Cohen

Subjects
Medicine, Science
Abstract

To assess the management of febrile urinary-tract infection (FUTIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) in children, the Pediatric Infectious Diseases Group of the French Pediatric Society set up an active surveillance network in pediatric centers across France in 2014.We prospectively analysed data from 2014 to 2016 for all children < 18 years old who received antibiotic treatment for FUTI due to ESBL-E in 24 pediatric centers. Baseline demographic, clinical features, microbiological data and antimicrobials prescribed were collected.301 children were enrolled in this study. The median age was 1 year (IQR 0.02-17.9) and 44.5% were male. These infections occurred in children with history of UTIs (27.3%) and urinary malformations (32.6%). Recent antibiotic use was the main associated factor for FUTIs due to ESBL-E, followed by a previous hospitalization and travel history. Before drug susceptibility testing (DST), third-generation cephalosporins (3GC) PO/IV were the most-prescribed antibiotics (75.5%). Only 13% and 24% of children received amikacine alone for empirical or definitive therapy, respectively, whereas 88.7% of children had isolates susceptible to amikacin. In all, 23.2% of children received carbapenems in empirical and/or definitive therapy. Cotrimoxazole (24.5%), ciprofloxacin (15.6%) and non-orthodox clavulanate-cefixime combination (31.3%) were the most frequently prescribed oral options after obtaining the DST. The time to apyrexia and length of hospital stay did not differ with or without effective empirical therapy.We believe that amikacin should increasingly take on a key role in the choice of definitive therapy of FUTI due to ESBL-E in children by avoiding the use of carbapenems.

Published
2018
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2. Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections

Author

Philippe Bidet, Anne Vachee, Aurélie Cointe, André Birgy, Emmanuel Cixous, Camille Jung, Philippe Traore, Sarah Ducrocq, Catherine Branger, Marion Decobert, Jocelyne Caillon, Benoit Starck, Said Aberrane, Sandra Timsit, Franck Labbee, Agnès Ferroni, Isabelle Andriantahina, M.-A. Dommergues, Isabelle Breant, Valérie Soussan-Banini, Marleèe Amara, François Dubos, Corinne Levy, Abdelmalek Belgaid, Hélène Garrec, Elsa Sobral, Rodrigue Dessein, Florence Doucet-Populaire, Vincent Gajdos, Irina Craiu, Valérie Sivadon-Tardy, Robert M. Cohen, Jack Breuil, Fouad Madhi, Olivier Vignaud, Stéphane Béchet, Hoang Vu-Thien, Marie Desmarest, H. Haas, Elise Launay, Sandra Biscardi, Emmanuel Grimprel, Didier Pinquier, Claire Amaris Hobson, Emilie Georget, Stéphane Bonacorsi, Anne Farges-Berth, Alain Fiacre, Aurélia Pitsch, Sophie Boyer, Bogdan Cojocaru, Laure Hees, Isabelle Poilane, Gaelle Cuzon, Laetitia Beraud, Marie-Noëlle Adam, Cécile Farrugia, and Aurélien Galerne

Subjects
Microbiology (medical), medicine.medical_specialty, Urinary system, Urine, Cefpodoxime, Gastroenterology, Pharmacokinetics, Cefixime, Internal medicine, medicine, Humans, Pharmacology (medical), Mecillinam, Child, Clavulanic Acid, Pharmacology, business.industry, Ceftizoxime, Amdinocillin, Amoxicillin, Anti-Bacterial Agents, Infectious Diseases, Urinary Tract Infections, Amoxicillin-Potassium Clavulanate Combination, business, medicine.drug
Abstract

Objectives Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales’ genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. Materials and methods In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates’ ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. Results All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). Conclusions Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

Published
2021

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