Susceptibility to Fosfomycin and Nitrofurantoin of ESBL-Positive Escherichia coli and Klebsiella pneumoniae Isolated From Urine of Pediatric Patients

Abstract

Background: Pediatric urinary tract infection (UTI) caused by extended-spectrum β-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBL-positive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin).

Methods: From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC₅₀ and MIC₉₀ were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae.

Results: There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0-18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC₅₀ and MIC₉₀ for fosfomycin were 0.5 μg/mL and 2 μg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 μg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027). For nitrofurantoin, both the MIC₅₀ and MIC₉₀ were 16 μg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 μg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC₅₀ and MIC₉₀ for fosfomycin was 2 μg/mL and 32 μg/mL, respectively. MIC₅₀ and MIC₉₀ for nitrofurantoin were 64 μg/mL and 128 μg/mL, respectively.

Conclusion: For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.

Keywords: Fosfomycin; Nitrofurantoin; Pediatric; Urinary Tract Infection.