Clinical trial NCT02832258: Urinary Tract Infection Due to Beta-lactamase-producing Enterobacteriaceae in Children
Official title: Urinary Tract Infection Due to Extended-spectrum Beta-lactamase-producing Enterobacteriaceae in Children: an Observational French Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Urinary Tract Infections
Keywords: Enterobacteria
Children
Febrile urinary tract infection
Cystitis
Extended-spectrum beta-lactamase-producing Enterobacteriaceae
Lead sponsor: Centre Hospitalier Intercommunal Creteil
Sponsor class: OTHER
First posted: 2016-07-14
Enrollment: 590
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study was created by the GPIP/ACTIV network with 24 pediatric centers (pediatric and emergency department) working with their microbiology departments throughout France. Between March 2014 and March 2017, they enrolled all children treated for UTI by E-ESBL in this prospective observational study. These hospitals were located in 7 regions (Ile de France, Nord-Pas-de-Calais-Picardie, Provence-Alpes-Côte d'Azur, Seine-Maritime, Rhône and Loire-Atlantique). For this hospital-based active surveillance, a clinical investigator in each participating ward completed a standardized data form sent by electronic or postal mail to the investigating center. All data were validated by a scientific committee.

Brief summary: Urinary tract infection due to Extended-spectrum beta-lactamase producing enterobacteriaceae (E-ESBL UTI) become a frequent problem. A too large variety in the prescription of antibiotics for E-ESBL UTI in children and absolute recommendations regarding the optimal treatment of E-ESBL is nearly impossible at this time.

Our aim was to describe the characteristics and treatments of urinary tract infections caused by Extended spectrum betalactamase-producing Enterobacteriaceae in children.

Detailed description: In this prospective observational study between March 2013 and March 2017, children (0 to 18 years) with ESBL-E UTI were enrolled in 24 pediatric departments in France. Clinical and biological characteristics, risk factors of infection of E-ESBL, first and second lines of antibiotic therapies were analyzed. The investigators used the Kaplan-Meier method to estimate the time to fever defervescence and hospitalization duration, and Log-rank test to assess equality of survivor functions. The investigators also analyzed the resistance patterns and molecular characterization of ESBL types in the isolates.

Eligibility criteria: Inclusion Criteria:

* All inpatient or outpatient under 18 years with UTI (cystitis or febrile UTI)
* Clinical signs associated with a positive E-ESBL in urine culture dependent urine collection method as previously described (Stein R, EAU/ESPU guidelines) and an antibiotic treatment targeting this strain.

Exclusion Criteria:

* Refusal to participate in the study
* Children with mixed microbial strains and repeated infections were excluded

Primary outcomes:
measure: First and second lines used antibiotic therapies
timeFrame: at inclusion, at 3 days
Secondary outcomes:
measure: Resistance patterns of ESBL types in the isolates
timeFrame: at inclusion
measure: Clinical characteristics (fewer, clinical sepsis) of E-ESBL UTI in children
timeFrame: at inclusion
measure: Time to apyrexia (Kaplan-Meier method)
timeFrame: at inclusion
measure: Length of hospital stay (Kaplan-Meier method)
timeFrame: at inclusion
measure: Molecular characterization of ESBL types in the isolates
timeFrame: at inclusion
measure: Clinical history of patient with E-ESBL UTI in children
timeFrame: at inclusion
measure: C reactive protein level of patient with E-ESBL UTI in children
timeFrame: at inclusion
measure: procalcitonin level of patient with E-ESBL UTI in children
timeFrame: at inclusion
measure: Positive blood culture
timeFrame: at inclusion
measure: cytobacteriological examination of the urine results
timeFrame: at inclusion, at 3 days
measure: urine analysis by regent strip method
timeFrame: at inclusion
Other outcomes:
Locations:
city: Clamart
country: France
facility: Antoine Beclère Hospital
state: Ile-de France
city: Bondy
country: France
facility: Jean Verdier Hospital
state: Ile-de-France
city: Le Chesnay
country: France
facility: André Mignot Hospital
state: Ile-de-France
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Paré
city: Bry-sur-Marne
country: France
facility: Saint Camille Hospital
city: Colombes
country: France
facility: Louis Mourier Hospital
city: Créteil
country: France
facility: CHI Créteil
city: Dourdan
country: France
facility: Centre Hospitalier de Dourdan
city: Le Havre
country: France
facility: CHU Le Havre
city: Le Kremlin-Bicêtre
country: France
facility: CHU Le Kremlin-Bicêtre
city: Lille
country: France
facility: Roger Salengro Hospital
city: Longjumeau
country: France
facility: Centre Hospitalier Général de Longjumeau
city: Lyon
country: France
facility: CHU Lyon
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Melun
country: France
facility: Centre Hospitalier Marc Jacquet
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: CHU Lenval
city: Orsay
country: France
facility: Centre Hospitalier d'Orsay
city: Paris
country: France
facility: Hospital Trousseau
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Robert Debré
city: Roubaix
country: France
facility: Centre Hospitalier Roubaix
city: Rouen
country: France
facility: CHU Rouen
city: Villeneuve Saint-Georges
country: France
facility: Hôpital Intercommunal de Villeneuve Saint-Georges
Study officials:
References:
citation: Cheng CH, Tsai MH, Huang YC, Su LH, Tsau YK, Lin CJ, Chiu CH, Lin TY. Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy. Pediatrics. 2008 Dec;122(6):1212-7. doi: 10.1542/peds.2007-2926.
citation: Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, Bonomo RA, Rice LB, Wagener MM, McCormack JG, Yu VL. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. Clin Infect Dis. 2004 Jul 1;39(1):31-7. doi: 10.1086/420816. Epub 2004 Jun 8.
citation: Boyer-Mariotte S, Duboc P, Bonacorsi S, Lemeland JF, Bingen E, Pinquier D. CTX-M-15-producing Escherichia coli in fatal neonatal meningitis: failure of empirical chemotherapy. J Antimicrob Chemother. 2008 Dec;62(6):1472-4. doi: 10.1093/jac/dkn362. Epub 2008 Sep 4. No abstract available.
citation: Fournier S, Brun-Buisson C, Jarlier V. Twenty years of antimicrobial resistance control programme in a regional multi hospital institution, with focus on emerging bacteria (VRE and CPE). Antimicrob Resist Infect Control. 2012 Feb 13;1(1):9. doi: 10.1186/2047-2994-1-9.
citation: Birgy A, Cohen R, Levy C, Bidet P, Courroux C, Benani M, Thollot F, Bingen E. Community faecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in French children. BMC Infect Dis. 2012 Nov 21;12:315. doi: 10.1186/1471-2334-12-315.
citation: Madec JY, Lazizzera C, Chatre P, Meunier D, Martin S, Lepage G, Menard MF, Lebreton P, Rambaud T. Prevalence of fecal carriage of acquired expanded-spectrum cephalosporin resistance in Enterobacteriaceae strains from cattle in France. J Clin Microbiol. 2008 Apr;46(4):1566-7. doi: 10.1128/JCM.02299-07. Epub 2008 Feb 13. No abstract available.
citation: Andriatahina T, Randrianirina F, Hariniana ER, Talarmin A, Raobijaona H, Buisson Y, Richard V. High prevalence of fecal carriage of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a pediatric unit in Madagascar. BMC Infect Dis. 2010 Jul 12;10:204. doi: 10.1186/1471-2334-10-204.