Abstract
Background:
Childhood urinary tract infections (UTIs) are among the most prevalent diseases. In recent years, the overuse of common antibiotics has increased antibiotic resistance among urinary tract pathogens worldwide, with changes in the pattern of microbial resistance varying by geographical area and time.Objectives:
This study aims to investigate the pattern of microbial resistance of UTI pathogens in pediatric patients.Methods:
In this cross-sectional study, children aged < 13 years with UTI and positive urine cultures, who were admitted to Bahrami Hospital in Tehran, Iran, between 2015 and 2019, were evaluated. The pathogens' frequency, their antimicrobial resistance, and clinical and demographic information were extracted from the patients' files. Statistical relationships between clinical and demographic data and antibiotic resistance were analyzed using appropriate statistical tests.Results:
The files of 202 patients were evaluated. The majority of patients were female (79.2%). UTI was more common among the 12 - 60 months age group (36.3%) in females and the 1 - 12 months age group (50%) in males. The most common UTI pathogen was Escherichia coli (85.1%). The lowest rates of microbial resistance were related to Meropenem (0% resistance), Gentamicin (9.2%), and Amikacin (10.8%). Conversely, the highest resistance rates were observed for Cotrimoxazole (74.6%), Ampicillin (74.5%), and Cephalothin (64.9%).Conclusions:
UTI is more common in females aged 1 to 60 months. E. coli is the most common cause of UTI. Microbial resistance to antibiotics used for empirical treatment, such as ceftriaxone, is high and changes over time. It is recommended to use alternative antibiotics and avoid the inappropriate administration of antibiotics.Keywords
1. Background
Infectious diseases such as urinary tract infections (UTIs), meningitis, and otitis are very common in children (1-3). Childhood urinary tract infections can lead to severe complications, including chronic kidney failure, high blood pressure, scarring in the kidney tissue, and voiding dysfunctions (2, 4, 5). The exact prevalence of UTI depends on age, sex, and circumcision status (6). Generally, UTI is more common in females (about 3 - 5% in girls and about 1% in boys), but its prevalence changes with age. In the first year of life, these infections occur more frequently in boys; however, after one year, they are more common in girls (7, 8). Other factors that increase the risk of UTI include urinary reflux, overactive bladder, adhesions and tightness in the foreskin region, structural abnormalities in the lower urinary tract, and constipation (2). Therefore, timely diagnosis and appropriate management of these infections are imperative.
Childhood urinary tract infections can occur in children due to a variety of microorganisms. Gram-negative bacteria are the most common microorganisms affecting the urinary system across all age groups (9). These bacteria mostly reach the urethra through feces and ascend through the urethra (9, 10). Meanwhile, E. coli alone is the cause of 90 - 95% of pediatric UTIs acquired from the community and 50% of these infections acquired in medical centers and hospitals (11, 12). Other causes of these infections include Pseudomonas species, members of the Enterobacteriaceae family, including Klebsiella, Enterobacter, and Citrobacter, and Gram-positive bacteria such as Staphylococcus and Enterococcus (5, 13).
In recent years, the inappropriate use of common antibiotics has increased antibiotic resistance among urinary pathogens worldwide (14, 15). Timely diagnosis, correct treatment, and proper patient follow-up can significantly reduce complications (14, 15). In general practice, the therapeutic approach is often conducted empirically (7, 8, 16). Empirical treatment is implemented to relieve symptoms, suppress infection, prevent urosepsis, and reduce the possibility of kidney damage (7, 8, 16). However, these empirical treatments sometimes involve the inappropriate use of antibiotics, which contributes to the prevalence of antibiotic resistance (5, 17, 18).
One of the most critical threats to public health is the problem of antibiotic-resistant bacteria, which cause a high percentage of hospital deaths every year (5, 18). Genetic changes in the causative strains and differences in the access and consumption of antibiotics are major factors influencing drug resistance worldwide (8). Identifying antibiotic resistance patterns in UTIs is crucial for selecting appropriate antibiotics and their proper use in treating these diseases (19). Therefore, periodic research in this area is necessary.
2. Objectives
The present study aimed to investigate the frequency of bacteria causing UTIs and their antibiotic susceptibility in children admitted to the Bahrami Children’s Hospital, Tehran, Iran.
3. Methods
3.1. Patients and Sample Collection
This study was approved by the local ethical committee (IR.SHAHED.REC.1400.097). The archive of Bahrami Hospital in Tehran, Iran, was reviewed for pediatric inpatients aged < 13 years, diagnosed with UTI based on confirmed positive urine culture (colony count > 100,000) from 2015 to 2019. Cases were excluded if the patient's record was incomplete or the urine culture result was reported as a mixed growth culture.
Clinical information, including demographic data (age, sex, history of UTI, and history of oral antibiotic use in the previous six weeks), clinical symptoms, complications related to urinary infection (presence or absence of urinary reflux history), and laboratory information (type of microbe isolated from urine culture, microbial sensitivity and resistance to antibiotics, urine gravity, and pyuria), were extracted from patients' medical files. Only the results of urine samples taken at admission and before antibiotic therapy were included in the analysis.
3.2. Statistical Analysis
Finally, the collected information was entered into SPSS version 16 statistical software (IBM SPSS Statistics, New York, United States). Descriptive data were expressed as frequency percentages and mean ± standard deviation (SD). Analytical tests, including the chi-square test, were used to analyze the data and check the statistical relationship between the variables and the antibiotic resistance profile. A P-value of < 0.05 was considered statistically significant.
4. Results
A total of 202 inpatient children's urinary samples were analyzed in this study. Histories of urinary reflux, previous UTIs, and antibiotic use were present in 7.4%, 17.8%, and 30.35% of cases, respectively. The most common clinical symptoms were fever (75.2%) and vomiting (37.6%), while the most common laboratory findings were urine with low gravity (75.2%) and pyuria (72.3%).
Table 1 shows the distribution of age and isolated bacteria from urine cultures according to sex. The majority of patients were female (79.2%). The highest percentage of female patients were children aged 12 - 60 months (36.3%). Conversely, most male patients were children aged 1 - 12 months (50%). The most common pathogen isolated from the urine culture, in both females and males, was E. coli (85.1%), followed by Klebsiella pneumoniae (10.9%). Other pathogens (4%) included Enterococcus and Pseudomonas.
The Age Distribution and Isolated Bacteria from Urine Culture According to Sex
| Variables | Male (42, 20.8%) | Female (160, 79.2%) | Total (202, 100%) |
|---|---|---|---|
| Age groups | |||
| < 1 mo | 12 (28.6) | 18 (11.3) | 30 (14.9) |
| 1 - 12 mo | 21 (50) | 42 (26.3) | 63 (31.2) |
| 12 - 60 mo | 4 (9.5) | 58 (36.3) | 62 (30.7) |
| 60 mo < | 5 (11.9) | 42 (26.3) | 47 (23.3) |
| Pathogen | |||
| E. coli | 34 (81.0) | 138 (86.3) | 172 (85.1) |
| Klebsiella Pneumoniae | 4 (9.5) | 18 (11.3) | 22 (10.9) |
| Other | 4 (9.5) | 4 (2.4) | 8 (4.0) |
Figure 1 shows the resistance rates to different types of antibiotics. The lowest antibiotic resistance in pathogens obtained from urine cultures was to meropenem, gentamicin, and amikacin (no resistance, 9.2%, and 10.8%, respectively), while the highest resistance rates were to cotrimoxazole, ampicillin, and cefoxitin (74.6%, 74.5%, and 64.9%, respectively).
Relative frequency of antibiotic resistance in different types of antibiotics
The antibiotic resistance of E. coli is shown in Table 2. The resistance rates of cephalosporins were not related to demographic variables (P-Value > 0.05). However, resistance to ampicillin significantly increased with age (P-Value = 0.038).
Distribution of Escherichia coli Antibiotic Resistance According to Demographic Variables
| Antibiotic | Cephalosporins | Ampicillin | ||
|---|---|---|---|---|
| Resistant | P-Value | Resistant | P-Value | |
| Age (mo) | 0.947 | 0.038 | ||
| < 1 | 25.0 | 50 | ||
| 1 - 12 | 30.4 | 84.6 | ||
| 12 - 60 | 28.6 | 72.7 | ||
| 60 < | 32.5 | 100 | ||
| Gender | 0.526 | 0.484 | ||
| Male | 34.4 | 72.7 | ||
| Female | 28.7 | 73.3 | ||
| History of taking oral antibiotics | 0.300 | 0.826 | ||
| No | 27.4 | 81.5 | ||
| Yes | 35.3 | 78.6 | ||
| History of UTIs | 0.299 | 0.484 | ||
| No | 27.7 | 83.3 | ||
| Yes | 36.8 | 72.7 | ||
| History of urinary reflux | 0.506 | 0.169 | ||
| No | 29.0 | 79.5 | ||
| Yes | 38.9 | 100 | ||
5. Discussion
In this study, we retrospectively investigated the demographic characteristics of UTIs, the frequency of causative pathogens, and their antibiotic sensitivity in admitted pre-pubertal children. The findings showed that most cases of UTIs occurred in females (79.2%). The most common age range for UTIs was 1 to 60 months (61.9%). E. coli and Klebsiella were responsible for 96% of UTIs. Many other studies also show that UTIs are more common in females (15, 20-23) and at younger ages (15, 24). In this study, the most common clinical symptoms were fever and vomiting, and the most common laboratory findings were low urine gravity and pyuria. Previous studies have also identified fever and vomiting as common symptoms (4, 25).
Our study confirmed that E. coli and Klebsiella are the most common causes of UTIs, consistent with other research findings (22-24). Similarly, Kalantar et al. (26) found that E. coli and Klebsiella are the most common UTI pathogens in a study that examined data from 55 hospitals across 12 different cities in Iran. In our study, the highest microbial resistance was to cotrimoxazole, ampicillin, cephalothin, nalidixic acid, and co-amoxiclav, with resistance observed in more than 50% of UTIs. In contrast, resistance to carbapenems and aminoglycosides was very low, which is consistent with findings from other studies (8, 15, 20, 27).
Kalantar et al. (26) reported a resistance rate of 85.9% to cotrimoxazole, with high resistance rates also noted for cephalothin, cephalexin, cefixime, and ampicillin. However, resistance to aminoglycosides and carbapenems was low (8, 15, 20, 21, 26, 28). In a meta-analysis by Hadifar et al. (29), the overall prevalence of multidrug-resistant E. coli (MDR-UPEC) in Iran was reported to be 49.4%, ranging from 27.7% to 77%. In contrast, studies from other countries reported much lower microbial resistance to cotrimoxazole (24, 30).
In a meta-analysis by Bryce et al. (31), the pattern of antimicrobial resistance differed between member countries of the Organization for Economic Co-operation and Development (OECD) and non-member countries. In OECD member countries, resistance rates were 53.4% for ampicillin, 23.6% for trimethoprim, 8.2% for co-amoxiclav, and 2.1% for ciprofloxacin. In non-member countries, resistance rates were 79.8% for ampicillin, 60.3% for co-amoxiclav, and 26.8% for ciprofloxacin, with the results of non-member countries being much closer to those observed in our study.
One of the most important factors influencing the pattern of microbial resistance in different regions is the pattern of antibiotic prescription, as repeated exposure to an antibiotic can lead to resistance mutations in pathogens (32). In the study by Datta et al. (33), it was observed that frequent exposure of E. coli to cotrimoxazole is associated with multiple resistance mechanisms, whereas this was less common for imipenem and amikacin. Similar results have been observed in other studies (34). Therefore, it is recommended to avoid the inappropriate prescription of antibiotics.
In the present study, there was no correlation between demographic characteristics or patient histories and E. coli antibiotic resistance. Limited studies have investigated such a relationship. Unlike previous research, our study did not find an association between a history of antibiotic use and increased E. coli resistance. In the study by Long et al. (35), frequent and high doses of antibiotic prescriptions were linked to increased resistance. However, in our research, the quality and quantity of antibiotic consumption were not investigated.
Additionally, the prophylactic antibiotic prescribed for individuals with urinary reflux varies according to its grade and clinical course. Our study did not examine the duration of reflux or the length of antibiotic use, which could explain the lack of significance in the history of antibiotic use concerning E. coli resistance. Overall, in our study, E. coli resistance to cephalosporins was unrelated to age, sex, history of urinary reflux, history of UTI, and antibiotic use.
In the study by Mantadakis et al. (24), the resistance of E. coli to co-amoxiclav and ampicillin was higher in males than in females. In contrast, our study found no such difference, although we observed that resistance to ampicillin increased with age. In the study by Mostafavi et al. (28), the sensitivity of E. coli to cephalosporins and carbapenems was higher in females under 20 years of age. For instance, sensitivity to cefazolin was 28.1% in males and 40.6% in females, but we did not observe similar results in our study.
Finally, considering the high microbial resistance and the significant differences between OECD member and non-member countries, future studies should focus on identifying the causes of this high resistance, exploring the reasons for differences between OECD member and non-member countries, and providing solutions to reduce it.
5.1. Limitations
Some limitations need to be noted. This study was retrospective and confined to the geographical area of Tehran, with samples obtained from only one center. Therefore, the results should be cautiously generalized to other areas. Future studies should conduct prospective multi-center research in different geographical regions and include a larger sample size.
5.2. Conclusions
In this study, fever, vomiting, low urine gravity, and pyuria were the most common clinical manifestations of UTIs. Most cases of UTIs were female, with ages 1 to 60 months being the most common age group. E. coli and Klebsiella were the most common causes of UTIs. Microbial resistance to antibiotics used to treat UTIs was relatively high. In our study, the highest antibiotic resistance was to cotrimoxazole and ampicillin, while the lowest antibiotic resistance was to meropenem and gentamicin. Considering the dynamic course of microbial resistance, it is recommended to prescribe antibiotics based on the resistance pattern in any region and avoid the inappropriate administration of antibiotics.
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