The purpose of this study was to investigate the clinical outcomes of non-carbapenem treatment for urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing
We retrospectively reviewed the medical records of children under 2 years of age who were diagnosed and treated for UTIs caused by ESBL-producing
Forty-three children under 2 years of age were treated with non-carbapenem antimicrobials for UTIs caused by ESBL-producing
In this study, the overall relapse rate of patients treated with non-carbapenem antimicrobials was 7.0%. The patients showed high success rates in the clinical and microbiological responses to the non-carbapenems regardless of the results of the
Urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing organisms are increasingly becoming prevalent [
Most clinicians experience improvement in clinical symptoms and the achievement of microbiological responses without the use of carbapenem in children with UTIs caused by ESBL-producing organisms. This phenomenon is difficult to explain clearly; however, the clinical and microbiological responses to antimicrobials used for UTIs and bloodstream infections are presumably different, since the urine drug concentration is generally higher than that achieved systemically [
We reviewed the electronic medical records of individuals diagnosed with UTIs caused by ESBL-producing
The antimicrobial susceptibility test was performed with a disc diffusion test recommended by the Clinical and Laboratory Standards Institute guidelines [
We used the median and interquartile range (IQR) to express continuous variables and percentages to express categorical variables. The Mann-Whitney test was used to evaluate differences in continuous variables, and chisquared test or Fisher’s exact test was used to evaluate differences in categorical variables between groups.
During the study period, 43 children treated with noncarbapenem for UTIs caused by ESBL-producing
The overall median age of patients was 6 months (IQR 4.0–9.0) and 24 patients were male (55.8%). With regards previous medical history, 6 patients (14.0%) had an underlying urologic disorder such as congenital hydronephrosis and mild pelviectasia, 4 patients (9.3%) had previously experienced UTIs, and 11 patients (25.6%) had been previously hospitalized. All patients underwent kidney ultrasonography (USG) and 16 patients (37.2%) showed abnormalities. Of the 20 patients who underwent the Tc-99m dimercaptosuccinic acid renal scan (DMSA) during the acute phase, 3 patients (15.0%) were found with cortical defects. Vesicoureteral reflux was found in 1 out of 11 patients (9.1%) who underwent voiding cystourethrography (VCUG). Since the number of patients who underwent DMSA and VCUG was small, statistical analysis could not be performed. In all patients, the strains isolated were sensitive to carbapenem and resistant to cefotaxime, a thirdgeneration cephalosporin. Of the strains isolated, amoxicillin- clavulanic acid were sensitive to 28 (65.1%) and piperacillin-tazobactam were sensitive to 41 (95.3%). The median total duration of fever before admission was 24 hours and the median total duration of treatment was 13 days (IQR 10.0–14.0) (
As shown in
The clinical outcomes of patients stratified by
Patients who experienced relapse after the completion of treatment with non-carbapenem treatment are presented in
Carbapenems are considered a gold standard treatment for infections due to ESBL-producing strains, even if the patient's infection is already clinically responsive to other β-lactams [
Few studies have been conducted on the efficacy of noncarbapenem treatment for UTIs caused by ESBL-producing organisms in children (
In this study, the overall relapse rate was 7.0% (3 of 43). We found no significant differences in the clinical characteristics and treatment outcomes according to the results of
Although the data from our study will add value to efforts to spare carbapenem as few studies have studied the efficacy of non-carbapenem treatments with UTIs caused by ESBL-producers in pediatric population, this study has several limitations. First, this is a retrospective observational study from a single center with a small sample size. Second, due to very small number of relapsed patients, risk factors for relapse after non-carbapenem treatment could not be evaluated. Although most patients were followed up for a month after discharge, there is a possibility that some patient visited another hospital when there were symptoms of relapse. Third, because identification for the type of β- lactamase enzymes in
In conclusion, we found that non-carbapenem treatment for UTIs caused by ESBL producing
This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors.
No potential conflict of interest relevant to this article was reported.
Flow chart of patients included in the study. 3rd Cephalosporin, third-generation cephalosporin; BLBLI, β-lactam/β-lactamase inhibitor.
Demographics and clinical characteristics of patients treated with non-carbapenem antimicrobials
Variables | Overall (N=43) | Susceptible (N=13) | Non-susceptible (N=30) | |
---|---|---|---|---|
Patients | ||||
Onset months | 6.0 (4.0–9.0) | 7.0 (4.5–9.5) | 6.0 (4.0–9.5) | 0.784 |
Sex (Male) | 24 (55.8%) | 8 (61.5%) | 16 (53.3%) | 0.619 |
History | ||||
Underlying urologic disorder | 6 (14.0%) | 3 (23.1%) | 3 (10.0%) | 0.345 |
Urinary tract infection | 4 (9.3%) | 2 (15.4%) | 2 (6.7%) | 0.572 |
Hospitalization | 11 (25.6%) | 5 (38.5%) | 6 (20.0%) | 0.262 |
Laboratory findings | ||||
WBC (/µL) | 13280 (10,440–17,010) | 14,390 (12,690–18,010) | 12,050 (9,458–17,025) | 0.130 |
ESR (mm/hr) | 17.0 (10.0–34.0) | 25.0 (15.0–68.5) | 16.0 (6.75–28.75) | 0.062 |
CRP (mg/L) | 21.8 (9.1–40.2) | 35.2 (12.9–72.3) | 15.1 (8.5–31.7) | 0.044 |
Pyuria (/HPF) | ||||
<20 | 7 (16.3%) | 2 (15.4%) | 5 (16.7%) | 0.987 |
20–49 | 7 (16.3%) | 2 (15.4%) | 5 (16.7%) | |
>50 | 29 (67.4%) | 9 (69.2%) | 20 (66.7%) | |
Abnormal image findings | ||||
Kidney USG | 16 (37.2%) | 7 (53.8%) | 9 (30.0%) | 0.178 |
DMSA | 3/20 (15.0%) | 2/5 (40.0%) | 1/15 (6.7%) | - |
VCUG | 1/11 (9.1%) | 1/5 (20.0%) | 0/6 (0%) | - |
Total duration of fever before admission (hours) | 24.0 (12.0–48.0) | 24.0 (11.0–48.0) | 24.0 (12.0–48.0) | 0.957 |
Total duration of treatment (days) | 13.0 (10.0–14.0) | 13.0 (10.0–14.0) | 13.5 (10.8–14.3) | 0.505 |
WBC, white blood cell; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; USG, ultrasonography; DMSA, Tc-99m dimercaptosuccinic acid renal scan; VCUG, voiding cystourethrography.
Statistical analysis was performed by using the chi-squared test or Fisher’s exact test and the Mann-Whitney test, as appropriate.
Clinical outcomes of patients treated with non-carbapenem antimicrobials
Variables | Overall (N=43) | Susceptible (N=13) | Non-susceptible (N=30) | |
---|---|---|---|---|
Time to defervescence (hours) | 6.0 (1.0–22.0) | 6.0 (2.0–24.0) | 5.5 (1.0–20.5) | 0.667 |
Clinical success | 39 (90.7%) | 12 (92.3%) | 27 (90.0%) | 1.000 |
Microbiological success | 42 (97.7%) | 13 (100.0%) | 29 (96.7%) | 1.000 |
Relapse | 3 (7.0%) | 2 (15.4%) | 1 (3.3%) | 0.213 |
Statistical analysis was performed by using the Fisher’s exact test and the Mann-Whitney test, as appropriate.
Description of patients with relapse of urinary tract infection
Patient ID | Onset months/Sex | Image findings | In vitro antimicrobial susceptibility to definitive antibiotics (MICs, μg/mL) | Relapse (weeks) |
---|---|---|---|---|
ID32 | 1/M | Renal pelvis wall thickening on USG | Cefotaxime R 8 | 3 |
No cortical defect on DMSA | ||||
No VUR on VCUG | ||||
ID40 | 5/F | Hydronephrosis, left kidney on USG | Piperacillin/tazobactam S ≤4 | 2 |
No cortical defect on DMSA | ||||
ID43 | 9/M | Renal pelvis wall thickening on USG No VUR on VCUG | Piperacillin/tazobactam S ≤4 | 4 |
USG, ultrasonography; DMSA, Tc-99m dimercaptosuccinic acid renal scan; VUR, vesicoureteral reflux; VCUG, voiding cystourethrography; R, resistant; S, sensitive.
Previous studies evaluating the efficacy of non-carbapenem treatment for urinary tract infections caused by extended-spectrum β-lactamase producing
Study | N | Organisms | Sources of infection | Non-carbapenems | Clinical outcomes |
---|---|---|---|---|---|
Tratselas et al. [ |
28 | Urinary (100%) | Cephalosporin (2nd & 3rd), Amoxicillin/clavulanate, Amikacin | Clinical success 94.4% | |
Microbiological success 95.0% | |||||
Peco-Antić et al. [ |
94 | Urinary (100%) | Ceftriaxone | Clinical success 81.6% | |
Microbiological success 87.5% | |||||
Lee et al. [ |
28 | Urinary (100%) | Cefotaxime, Amikacin, Piperacillin-tazobactam | Relapse 4.0%, Treatment success 100% | |
Blood stream (5%) | |||||
Han et al. [ |
22 | Urinary (100%) | Cephalosporin (2nd & 3rd), Amoxicillin/clavulanate, Amikacin | Clinical success 90.9% | |
Microbiological success 100% | |||||
Hyun et al. [ |
146 | Urinary (100%) | Cefotaxime, Aminoglycoside, Piperacillin-tazobactam | Relapse: susceptible 2.3% | |
Non-susceptible 3.3% |