Introduction
Urinary tract infection (UTI) is the most common bacterial infection in children under 2 years of age and also one of the most common bacterial infections in children (1). Although the numbers vary in studies conducted in different populations, UTI is common in males under one year of age, whereas it is common in girls above one year of age during their childhood (2,3). Empirical treatment is commenced according to the patient’s age, antimicrobial susceptibility patterns in the region, the clinical condition of the patient and the presence of any underlying diseases (2,4). Therefore, the determination of antimicrobial resistance patterns by regional centre studies is of great importance in terms of effective treatment and the prevention of complications. The aim of this study was to determine the pathogens which cause UTIs in patients admitted to a university hospital in Izmir and to determine their antimicrobial susceptibility patterns.
Materials and Methods
Patients and Urine Samples
The outpatient clinic files of 729 patients aged between 0-18 years, followed up with a diagnosis of UTI, vesicoureteral reflux and neurogenic bladder in Ege University Faculty of Medicine Paediatric Nephrology Unit between February, 2013 and November, 2018 were retrospectively reviewed. The urine culture results of the patients treated with a diagnosis of UTI were evaluated. The urine cultures of those patients who were not considered to be clinically diagnosed with UTI and were not treated, were excluded from this study. The diagnosis of UTI was made with positive urine cultures accompanied by the presence of leukocytes and/or nitrite and/or leukocyte esterase in the urinalysis. The significance of the positive urine culture was also evaluated with the clinical findings in the patient’s file. In those patients with no urinary control or those who were not toilet trained, urine samples were collected according to a standard hygiene protocol via urine bags. Catheterization or a clean catch method were used in cases of urine cultures which were thought to be contaminated. The urine samples were collected mid-stream in those who were toilet trained. Positive urine culture was accepted as ≥103 CFU/mL samples taken with the catheterization method, >104 CFU/mL with the mid-stream or clean catch in patients with symptoms, or >105 in those without symptoms (1). All the information regarding the culture results and antimicrobial susceptibility for the isolated pathogens was recorded. Those with intermediate susceptibility to antimicrobials were included in the resistant group (5). Second urine cultures from the same patient within one month were not included in this study. The urine culture results which were studied in laboratories other than Ege University Faculty of Medicine Bacteriology Laboratory were not included in this study.
Ethical Consideration
Ethical approval for this study was obtained from the Medical Research Ethics Committee of Ege University Faculty of Medicine (approval no: 22-12.1T/16, date: 16.12.2022).
Antimicrobial Susceptibility Tests
The cultures of the urine samples were studied in Ege University Faculty of Medicine Bacteriology Laboratory of the Medical Microbiology Department. MALDI-TOF MS (Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry) was used to identify the bacteria. The antimicrobial susceptibilities of these isolates were determined by VITEK 2 (bioMerieux, France) and EUCAST clinical breakpoints were used.
Statistical Analysis
For the evaluation of the study data, the SPSS (Statistical Package for the Social Sciences, version 22.0 for Windows, SPSS® Inc., Chicago, IL, USA) statistical analysis program was used. Frequencies, and means ± standard deviations of the data are provided.
Results
A total of 1,126 positive urine cultures were included in this study. Two hundred and seventy-four (24.3%) of the urine samples were taken via urine bag, 762 (67.7%) of them were obtained via mid-stream with the clean catch method and 90 (8%) with a catheter. Among the 729 cases, 64.7% of the samples were obtained from female and 35.3% from male patients. The mean infection time was 56±53 months. Most of the cultures were gram negative with a percentage of 88.2% (n=993). Escherichia coli (E. coli) was the most commonly isolated bacteria with a prevalence of 59.1% (n=666) followed by Klebsiella pneumonia with 17.9% (n=202), Enterococcus faecalis with 8.3% (n=93), Proteus mirabilis with 3.2% (n=37), Enterococcus faecium with 2.9% (n=33) and Pseudomonas aeruginosa with 2.5 % (n=28). The isolated bacteria and their frequencies are shown in Table I.
Enterobacteriaceae such as Escherichia spp., Klebsiella spp., Proteus spp., Enterobacter spp., Morganella spp., Citrobacter spp., and Serratia spp., were the causative pathogens in 962 cultures (85.4%) and they constitute most of the bacteria in this study, followed by Enterococcus spp. in 129 (11.5%), Pseudomonas spp. in 28 (2.5%), Staphylococcus spp. in 4 (0.4%) and Acinetobacter spp. in 3 cultures (0.3%).
There were 333 cases (29.5%) younger than one year old, among whom male gender was more prominent with a ratio of 61.6%. However, the male ratio declined to 24.2% in cases older than one year old. Enterobacteriaceae are the most common bacteria, followed by Enterococcus spp. and Pseudomonas spp. in both sexes.
Ampicillin, cefuroxime and trimethoprim-sulfamethoxazole with susceptibility rates of 18.6%, 39.6%, and 49.0% respectively, saw the highest resistance with Enterobacteriaceae. The antimicrobials with the highest susceptibility in this group were meropenem, imipenem and ertapenem with rates of 99.2%, 97.1% and 96.1% respectively. The antimicrobial susceptibility rates of microorganisms according to extended-spectrum beta-lactamase positivity are shown in Table II.
Enterococcus spp. showed the highest resistance to gentamycin with 50% resistance in tested cases. None of the tested cases showed resistance to vancomycin or linezolid. Pseudomonas spp. with 64.3% susceptibility, showed the highest resistance to piperacillin-tazobactam. With a rate of 96.4%, Pseudomonas spp. showed the highest susceptibility to imipenem and meropenem. The in vitro antimicrobial susceptibility rates of Pseudomonas spp. to common antimicrobials are shown in Table III.
Discussion
Bacterial resistance is an important challenging problem in UTI. Antimicrobial-resistant infections have been predicted to reach 10 million lives per year by 2050 (6). Especially in the paediatric population, antimicrobial prescriptions are higher, mostly in cases of over-diagnosed viral upper respiratory infections. If paediatricians have a symptomatic child with a positive urinalysis, it is inevitable to start the initial treatment of acute UTI without obtaining culture results (6-8). Certainly, early diagnosis and proper treatment is important, not only to prevent complications such as renal abscess or septicaemia, but also it is crucial to avoid renal scarring, and even renal failure (9). Additionally, the loss of schooltime as well as the loss of parental worktime are the indirect costs which cannot be underestimated (10,11).
The increment in the resistance to common antimicrobials, especially in paediatric uropathogens, has led to challenges due to the more difficult treatment of UTI over time (9). Antimicrobial resistance has variabilities such as geographic differences in bacterial patterns and local antimicrobial prescription practices (7,12-14).
The frequency of E. coli has been reported as having a wide range in the literature. Rai et al. (15) reported E. coli at a very high level of 93.3%. We also found that E. coli was the most common organism isolated with 59.1%, which was quite low compared to their paper. Other studies such as Akram et al. (16) reported a lower prevalence (21.4%) of E. coli. E. coli is reported as the most common pathogen in those studies conducted in the adult population. While the prevalence of E. coli in UTI was reported as 50% in a multicentre study conducted in China, in a meta-analysis conducted in Iran, the most common pathogen causing UTI was reported to be E. coli with a frequency of 62% (17,18). Catal et al. (12) demonstrated an increasing rate of Klebsiella spp. in urine cultures between 2000 and 2006, with rates of 7.2% and 18%, respectively. Gunduz and Uludağ Altun (19) reported the Klebsiella spp. rate to be 14.9%. In this study, we have a higher rate (18.6%) of Klebsiella spp. Unfortunately, non-E. coli pathogens are more resistant to most antimicrobial agents. Therefore, those patients with Klebsiella spp. needed hospitalization and parenteral antibiotic therapy also increases the treatment costs (20).
The current American Academy of Pediatrics guideline suggests giving oral or parenteral antimicrobials for 7-14 days for the management of UTIs in febrile infants and young children. Ceftriaxone, cefotaxime, ceftazidime, gentamicin, tobramycin, and piperacillin are the drugs of choice for parenteral therapy; amoxicillin-clavulanate, sulfonamide (trimethoprim-sulfamethoxazole or sulfisoxazole), or cephalosporin (cefixime, cefpodoxime, cefprozil, cefuroxime axetil, or cephalexin) are recommended as oral agents for treating UTI (7,8). For an antimicrobial to be considered as a first-line empirical treatment for UTI, resistance should not exceed 20% (13). In a meta-analysis conducted by Bryce et al. (14), this threshold was reached for many first-line antimicrobials used for paediatric E. coli UTIs. In most countries, half of all isolates were resistant to ampicillin, 1/3 to co-trimoxazole, and 1/4 to trimethoprim. This supports the increased risk of E. coli resistance to that particular antimicrobial due to previous antimicrobial usage (14). In our study, we also had similar resistance results with the exception of increased rates to cefuroxime. Our results showed the first resistance rates to ampicillin, cefuroxime, and trimethoprim-sulfamethoxazole, which have the highest resistance for Enterobacteriaceae, with resistance rates of 81.4%, 58.8% and 51.0% respectively.
Gunduz and Uludağ Altun (19) reported lower resistance rates of E. coli to ampicillin, co-trimoxazole, ceftriaxone, amikacin, amoxicillin-clavulanate and the same resistance rates for gentamicin, nitrofurantoin, and ciprofloxacin in comparison to Bryce’s meta-analysis. Al Benwan and Jamal (21) also showed that approximately 62% of E. coli and 77% of non-Coliform bacteria were resistant to ampicillin, similar to our study. Dejonckheere et al. (22) also reported that resistance to amoxicillin-clavulanic acid for E. coli strains had increased from 16% to 36% (2015-2019) over the last 20 years. They pointed out that the problem of increasing antimicrobial resistance to antimicrobials commonly used in UTIs is a growing health problem (22). Although it is known that in vivo antibiotic responses are important in the treatment of UTI, it is thought that the development of in vitro antimicrobial resistance may pose a risk for in vivo responses in the coming years.
Study Limitations
The retrospective nature of this study is its limitation.
Conclusion
This study, in line with the literature, shows that resistance to commonly used antimicrobials is still very important. This highlights the necessity of planning in this regard.
Ethics
Ethics Committee Approval: Ethical approval for this study was obtained from the Medical Research Ethics Committee of Ege University Faculty of Medicine (approval no: 22-12.1T/16, date: 16.12.2022).
Informed Consent: Written informed consent was obtained from all the patients or their parents/guardians.
Peer-review: Internally and externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: İ.K.B., A.K., A.T., C.K., Concept: İ.K.B., C.K., A.K., Design: S.T., Data Collection or Processing: S.T., E.A., Analysis or Interpretation: S.T., İ.K.B., S.Ö., Literature Search: S.T., S.Ş.A., Writing: S.T.
Conflict of Interest: None of the authors had any conflict of interest.
Financial Disclosure: The authors declared that this study received no financial support.
