J Korean Med Sci.  2023 Dec;38(48):e361. 10.3346/jkms.2023.38.e361.

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

• Park KS
• Kim DR
• Baek JY
• Shin A
• Kim KR
• Park H
• Son S
• Cho H
• Kim YJ

• KMID: 2549164
• DOI: http://doi.org/10.3346/jkms.2023.38.e361

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 ESBLpositive 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. MIC 50 and MIC 90 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, MIC ₅₀ and MIC ₉₀ 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 MIC ₅₀ and MIC ₉₀ 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 MIC ₅₀ and MIC ₉₀ for fosfomycin was 2 μg/mL and 32 μg/mL, respectively. MIC ₅₀ and MIC ₉₀ 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.

Keyword

Pediatric; Urinary Tract Infection; Fosfomycin; Nitrofurantoin

Figure

• 

  Fig. 1 Distribution of MICs and susceptibility of ESBL-positive E. coli isolates. (A) ESBL-positive E. coli fosfomycin MIC. (B) ESBL-positive E. coli nitrofurantoin MIC.MIC = minimum inhibitory concentration, ESBL = extended-spectrum β-lactamase, S = sensitive, I = intermediate, R = resistant.

• 

  Fig. 2 Distribution of MICs and susceptibility of ESBL-positive K. pneumoniae isolates. (A) ESBL-positive K. pneumoniae fosfomycin MIC. (B) ESBL-positive K. pneumoniae nitrofurantoin MIC.MIC = minimum inhibitory concentration, ESBL = extended-spectrum β-lactamase, S = sensitive, I = intermediate, R = resistant.

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