Urinary Tract Infections With Extended-spectrum-β-lactamase-producing Bacteria

Abstract

Background: Urinary tract infections (UTI) are the most common bacterial infections among infants and young children with fever without a source. Extended-spectrum β-lactamases (ESBLs) have emerged as emerging cause of UTI globally; however, data about risk factors and clinical features of children with ESBL-UTI have been scarce. Objective: To describe the predisposing risk factors, clinical and microbiologic features associated with pediatric UTIs caused by ESBL-producing bacteria (ESBL-PB). Methods: Our nested case-control study ran from January 1, 2012 to December 31, 2016. Pediatric patients with ESBL-PB UTI were compared with patients with non-ESBL-PB UTI matched for age and year of diagnosis. Results: A total of 720 children were enrolled (240 cases and 480 controls). Patients with ESBL-PB UTI were more likely to have a history of prior intensive care unit (ICU) admission (22.5% vs. 12.3%, P < 0.001), at least one underlying comorbidity (19.2% vs. 5.8%, P < 0.001), prior hospitalization (47.1% vs. 32.9%, P < 0.001), exposure to a cephalosporin antibiotic within 30 days before culture (7.5% vs. 4.2%, P = 0.035), and to have cystostomy (7.9% vs. 1.5%, P < 0.001) compared with those with non-ESBL-PB UTI. Patients with ESBL-PB UTI were more likely to present with hypothermia (48.8% vs. 38.5%, P = 0.009); had significantly longer average hospital stays {8.7 days [95% confidence interval (CI): 3.2–14.3] vs. 4.0 days (95% CI: 2.5–5.5)} and were more likely to be admitted to the ICU [odds ratio (OR) 1.8; 95% CI: 1.1-2.9). Multivariate analysis determined that only having cystostomy (OR 3.7; 95% CI: 1.4–9.4] and at least one underlying comorbidity (OR 2.4; 95% CI: 1.3–4.3) were the independent risk factors for ESBL-PB UTI. All ESBL-PB isolates tested against meropenem were susceptible, majority were resistant to multiple non-beta-lactam antibiotics. Conclusions: Children with underlying comorbidities and cystostomy are at higher risk for ESBL-PB UTI, but majority of ESBL cases were patients without any known risk factors. Clinical signs/symptoms and commonly used biochemical markers were unreliable to differentiate cases caused by ESBL-PB from those caused by non-ESBL-PB. Further research is needed to elucidate the conditions most associated with ESBL-PB UTIs among children to properly guide empirical therapy in patients at-risk for these infections, to improve the outcomes, and finally, to determine strategies for rational antimicrobial use.

Predictive utility of prior positive urine culture of extended- spectrum β -lactamase producing strains

“…It is assumed that vulnerability of patients with urological condition to acquire resistant bacterial strains is enhanced, as the host's immune system is weakened [24][25][26][27][28]. Many previous studies showed that urinary instrumentation and/or a history of frequent UTIs were both linked to a higher hazard of ESBL-UTIs [25][26][27][28]. This finding is in line with current practice at the site of study conduction.…”

“…It is known that patients with comorbid conditions have frequent encounters at healthcare settings; lathering the way for ESBL colonization and recurrent infection [23]. It is assumed that vulnerability of patients with urological condition to acquire resistant bacterial strains is enhanced, as the host's immune system is weakened [24][25][26][27][28]. Many previous studies showed that urinary instrumentation and/or a history of frequent UTIs were both linked to a higher hazard of ESBL-UTIs [25][26][27][28].…”

Molecular characterization of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae among the pediatric population in Qatar

“…Particularly noteworthy was high proportion of isolates susceptible to amikacin despite the presence aac(6')-Ib-cr genes in 17% of strains. Although monotherapy with amikacin has been proposed to treat febrile UTI in children in regions with low resistance rates among ESBL producers [23,[28][29], it should be kept in mind that it is not uncommon to nd susceptible isolates according to the CLSI breakpoints (MIC ≤ 16 mg/L) harbouring aac(6')-Ib-cr with MICs between 4 and 8 mg/L [2430]. Therefore, it might be speculated that the ratio C max /MIC, the main pharmacodynamic parameter that predicts bacterial killing and prevent selection of resistance in aminoglycosides [31][32], could be often compromised when aac(6')-Ib-cr is carried.…”

Renal abscess with bacteremia caused by extended-spectrum β-lactamase-producing Escherichia coli: a case report

“…Although the preferred antibiotic for ESBL-positive microorganisms is carbapenem, the selection of other antibiotics is under discussion due to antimicrobial resistance. Carbapenem treatment needs to be given intravenously and requires a longer duration of hospital stay [15,16]. Two previous retrospective studies showed that the initial empiric antibiotic therapy for pediatric UTIs caused by ESBL did not worsen the outcome, and the authors concluded that switching to appropriate antibiotics after detection of ESBL-producing microorganisms was sufficient [17,18].…”