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Evaluation of Risk Factors and Treatment of Extended Spectrum Beta Lactamase (ESBL) Urinary Tract Infections in Children Less than 1 Year of Age
Rima Bhakta, PharmD Candidate1, Stephen Canon, MD, FAAP2, Holly Maples, PharmD1.
1UAMS College of Pharmacy, Little Rock, AR, USA, 2Arkansas Children's, Little Rock, AR, USA.

INTRODUCTION: Urinary tract infections (UTIs) caused by extended-spectrum B-lactamases (ESBLs) are a public health concern due to therapeutic limitations, treatment failures, and increased healthcare costs. Therapeutic options are limited since ESBLs render bacteria resistant to 3rd generation cephalosporins, penicillins, and monobactams. Common risk factors for ESBL UTI's include previous antibiotic exposure like 3rd generation cephalosporins and urological disorders. A recent evaluation discovered that 28% of ESBL UTI's in a children's hospital over a 3-year period were in children < 1 year of age. The objective was to search for risk factors for UTIs caused by ESBL-producing bacteria in children aged < 1 year to improve empiric therapy selection.
METHODS: A retrospective chart review was performed on 80 pediatric patients, < 18 years of age who had an ESBL positive urine culture between June 1, 2015 and May 31, 2018. Twenty-two patients were < 1 year and were included in this sub-analysis. ESBL-producing isolates were phenotypically identified. Contaminated cultures were excluded and defined as > 2 pathogens. Demographics, birth history, nutrition, co-morbidities, antibiotic history, surgical history, urinalysis, microbiological data, and treatment regimens were recorded in RedCap. Therapeutic appropriateness was determined when the pathogen was susceptible to the selected antibiotic. Descriptive statistics were used to examine demographics and identify potential risk factors.
RESULTS: Of the 22 patients, 18 (82%) patients were female. Only 1/4 (25%) males was circumcised. The mean age was 5.6 months. Method of delivery: 13 (59%) vaginal, 6 (27%) C section, 3 (14%) unknown. 5/19 (26%) were breastfed, 7/19 (37%) were formula fed, and 7/19 (37%) were both. 9/22 (41%) had no significant past medical history. 9/22 (41%) had at least 1 urological disorder, and 5/22 (23%) had an urological structural abnormality. Of patients with urological disorders, 6 had hydronephrosis, and 3 had vesicoureteral reflux. 5/22 (23%) had a history of UTIs. 10/22 (45%) of children had previous antibiotic exposure, ranging from 1 to 3 courses. 20 children were treated empirically, and 75% were prescribed a 3rd generation cephalosporin. No empiric treatment was microbiologically appropriate. The primary uropathogen was Escherichia coli (n=19) followed by Klebsiella. All isolates were 100% susceptible to meropenem. For E. coli, nitrofurantoin, TMP-SMX, gentamicin, and ciprofloxacin were susceptible to 94%, 74%, 68% and 56%, respectively. All isolates were resistant to amoxicillin/clavulanate, ceftriaxone, and piperacillin/tazobactam. The mean time from culture date to initiation of appropriate antibiotics was 2.7 days (1 5 days). After therapy change, 16/20 (80%) were changed to appropriate therapy. The mean antimicrobial treatment duration was 12.75 days (9 18 days). 6/22 (27%) had a subsequent UTI within 5 to 86 days from previous UTI treatment completion. 4/6 (67%) were ESBL (+). These 4 patients were all < 1 year, and 75% had a urological disorder.
CONCLUSION: Identifying risk factors for ESBL UTI infections in children < 1 year of age is essential to improve empiric antimicrobial treatment and duration. Future work should include developing an antibiogram describing the susceptibility of the most common ESBL organisms.


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