European Journal of Cardiovascular Medicine

encountered bacterial infections in childhood and represents an important cause of acute morbidity in both community and hospital settings. The clinical importance of paediatric UTI extends beyond the immediate infectious episode because involvement of the upper urinary tract, particularly during early childhood, may be associated with renal parenchymal injury and subsequent renal scarring. Young infants are especially challenging because the manifestations of UTI are often nonspecific and may include fever, poor feeding, vomiting, irritability, lethargy, or failure to thrive rather than characteristic urinary symptoms. A meta-analysis by Shaikh et al. reported an overall UTI prevalence of approximately 7% among febrile infants, with prevalence varying according to age, sex, and circumcision status [1]. Consequently, an appropriate index of suspicion and timely microbiological evaluation are essential to avoid both missed infections and unnecessary antimicrobial exposure.

Accurate diagnosis of paediatric UTI is particularly important because clinical signs alone cannot reliably distinguish infection from other causes of fever. Urinalysis can support the diagnosis, but urine culture remains fundamental for establishing the causative organism and determining its antimicrobial susceptibility [2]. The American Academy of Pediatrics guideline emphasized that a reliable diagnosis in young febrile children requires evidence of inflammation on urinalysis together with significant growth of a uropathogenic organism from an appropriately collected urine specimen [3]. Obtaining the urine specimen before initiating antimicrobial therapy is therefore important, particularly when antimicrobial resistance is increasingly influencing the success of empirical treatment.

The microbiological spectrum of childhood UTI is dominated by Gram-negative enteric organisms. Escherichia coli is consistently identified as the principal uropathogen, particularly in uncomplicated and community-acquired infections. Its predominance is attributed to several virulence characteristics that facilitate colonisation of the periurethral region, adherence to uroepithelial cells, and ascent through the urinary tract. Nevertheless, the relative contribution of other organisms becomes greater among infants, boys, children with recurrent UTI, urinary tract abnormalities, previous antimicrobial exposure, catheterisation, or prolonged hospitalisation. Other clinically significant pathogens include Klebsiella spp., Proteus spp., Enterobacter spp., Pseudomonas aeruginosa, Enterococcus spp., and, less commonly, staphylococci and other organisms [2]. This variation in bacterial spectrum has important therapeutic implications because non-E. coli uropathogens frequently demonstrate susceptibility profiles different from those of uncomplicated E. coli infection.

Evidence from India demonstrates substantial diversity in organisms responsible for paediatric UTI. Taneja et al., in a tertiary-care study from North India, reported E. coli as the most frequently isolated pathogen, accounting for 47.1% of isolates, followed by Klebsiella spp. (15.6%), Enterococcus faecalis (8.7%), Proteae (5.9%), and Pseudomonas aeruginosa (5.9%) [4]. Importantly, the authors noted that a large proportion of infections in their cohort were nosocomial, highlighting the influence of the clinical setting on pathogen distribution. Among lactose-fermenting Enterobacteriaceae, comparatively lower resistance was observed to imipenem, nitrofurantoin, and amikacin than to several commonly used antimicrobials. These findings emphasized that susceptibility results obtained from hospital populations should not automatically be extrapolated to community-acquired infections.

A further study of infants from a tertiary-care hospital in northern India by Kaur et al. demonstrated a similar predominance of E. coli, which constituted 45.4% of bacterial isolates, followed by Klebsiella spp. (16.7%) and Enterococcus spp. (13.2%) [5]. Of particular concern was the high frequency of antimicrobial resistance among Gram-negative organisms and the presence of extended-spectrum β-lactamase (ESBL)-producing isolates. The investigators reported relatively favourable activity of nitrofurantoin and piperacillin-tazobactam in comparison with several other agents tested. Such observations illustrate the progressive challenge posed by multidrug-resistant Gram-negative organisms in paediatric practice and reinforce the importance of local antibiograms when choosing empirical treatment.

Antimicrobial resistance is not restricted to developing-country hospital settings. In a large United States study of more than 25,000 outpatient paediatric urinary isolates, Edlin et al. found that E. coli accounted for the majority of isolates, particularly among girls, whereas organisms such as Enterococcus, Proteus, and Klebsiella constituted a larger proportion among boys [6]. Resistance of E. coli to ampicillin and trimethoprim-sulfamethoxazole exceeded 20%, while resistance to several other agents was substantially lower. The authors emphasized that increasing resistance to traditional first-line antibiotics may compromise empirical treatment if local susceptibility patterns are not considered [6].

The selection of an appropriate antimicrobial agent in childhood UTI must therefore balance several considerations, including the likely pathogen, age of the child, severity and anatomical level of infection, previous antibiotic exposure, underlying urinary tract abnormalities, local antimicrobial resistance rates, and the results of culture and susceptibility testing. Indian paediatric nephrology recommendations similarly stress the importance of confirming UTI by culture and selecting therapy according to clinical severity and prevailing resistance patterns [7]. Earlier Indian recommendations also recognised that prompt and appropriate antimicrobial treatment is particularly important in younger children because of their increased susceptibility to renal parenchymal damage [8].

The continuing emergence of resistant uropathogens, including ESBL-producing Enterobacteriaceae, makes periodic surveillance of pathogen distribution and antibiotic susceptibility increasingly important. Empirical treatment based on outdated susceptibility data may result in treatment failure, prolonged symptoms, unnecessary hospitalisation, and increased use of broad-spectrum antibiotics, further accelerating antimicrobial resistance. Conversely, indiscriminate use of reserve antibiotics in infections caused by susceptible organisms can contribute to selection pressure and undermine antimicrobial stewardship. Therefore, determining the common bacterial pathogens and their antibiotic sensitivity patterns in paediatric UTI within a defined clinical population is essential for developing rational empirical treatment protocols, improving therapeutic outcomes, limiting unnecessary exposure to broad-spectrum agents, and supporting effective antimicrobial stewardship.

Study Design and Setting

This hospital-based, prospective observational study was conducted in the Department of Paediatrics, Andhra Medical College, King George Hospital, Visakhapatnam, Andhra Pradesh, India. in collaboration with the Department of Microbiology, over a period of six months from February 2016 to August 2016. The study was designed to determine the spectrum of bacterial pathogens responsible for urinary tract infection (UTI) in children and to evaluate their antimicrobial susceptibility patterns.

Study Population and Sample Size

A total of 110 paediatric patients with culture-confirmed urinary tract infection were included in the study. Children presenting to the outpatient department, emergency unit, or admitted to the paediatric wards with clinical features suggestive of UTI were screened. Consecutive eligible patients were recruited until the required sample size was achieved. For children with recurrent presentations during the study period, only the first microbiologically confirmed episode was included in the primary analysis to avoid duplication of isolates from the same patient.

Inclusion Criteria

Children were included if they:

1. were aged from 1 month to 18 years;
2. presented with clinical features suggestive of urinary tract infection, including fever without an obvious focus, dysuria, urinary frequency, urgency, suprapubic pain, abdominal or flank pain, vomiting, poor feeding, irritability, or unexplained failure to thrive;
3. had an appropriately collected urine specimen showing significant bacterial growth on culture; and
4. had complete microbiological and antimicrobial susceptibility data available.

Exclusion Criteria

Children were excluded if they:

1. had received systemic antibiotics for more than 48 hours before urine collection;
2. had an inadequately collected or improperly transported urine specimen;
3. demonstrated mixed growth suggestive of specimen contamination;
4. had fungal growth without concomitant bacterial UTI;
5. had an indwelling urinary catheter at the time of sampling, unless catheter-associated UTI was specifically suspected; or
6. had incomplete clinical or microbiological records.

Clinical Assessment

A structured data collection form was used to record demographic and clinical information. Variables included age, sex, presenting symptoms, duration of illness, previous episodes of UTI, recent antibiotic exposure, previous hospitalisation, known congenital abnormalities of the kidney or urinary tract, and other relevant comorbid conditions.

Patients were categorised into clinically appropriate age groups for subsequent analysis. Where available, information regarding previous urine cultures, antimicrobial exposure, and recurrent UTI was also recorded because these factors could influence the distribution of uropathogens and antimicrobial resistance.

Urine Specimen Collection

Urine specimens were collected before initiation of antimicrobial therapy whenever clinically feasible. The method of urine collection was selected according to the age, toilet-training status, and clinical condition of the child. In toilet-trained children, a freshly voided clean-catch midstream urine specimen was collected in a sterile, wide-mouthed container after appropriate cleansing of the periurethral area. In infants and non-toilet-trained children in whom a reliable clean-catch specimen could not be obtained, urine was collected by urethral catheterisation under aseptic precautions. Suprapubic aspiration was considered when clinically indicated.

Urine collected in adhesive perineal bags was not considered suitable for establishing a definitive microbiological diagnosis because of the high risk of contamination. All specimens were transported to the microbiology laboratory as soon as possible, preferably within 2 hours of collection. When immediate processing was not feasible, samples were refrigerated at approximately 2–8°C until microbiological examination.

Urinalysis

Fresh urine specimens were examined for evidence of pyuria and other abnormalities. Routine urinalysis included dipstick testing for leukocyte esterase and nitrite, where available, together with microscopic examination of centrifuged or uncentrifuged urine for white blood cells, red blood cells, epithelial cells, casts, and bacteria.

Pyuria was considered supportive of UTI but was not used as the sole diagnostic criterion. The definitive diagnosis was based on clinical findings in conjunction with significant growth of a recognised urinary pathogen on quantitative urine culture.

Quantitative Urine Culture

Urine specimens were cultured using a calibrated inoculating loop by the standard semiquantitative culture technique. A measured quantity of urine was inoculated onto appropriate bacteriological media, including cysteine-lactose-electrolyte-deficient agar and/or blood agar and MacConkey agar, according to routine laboratory protocol. Culture plates were incubated aerobically at 35–37°C for approximately 18–24 hours and examined for bacterial growth. Colony counts were calculated and expressed as colony-forming units per millilitre (CFU/mL). Significant bacteriuria was interpreted according to the method of specimen collection and the clinical context. For a properly collected clean-catch midstream specimen, growth of a single uropathogen at approximately ≥10⁵ CFU/mL was considered significant. Lower colony counts were interpreted cautiously when accompanied by compatible symptoms, pyuria, or specimens obtained by catheterisation. Any bacterial growth obtained from a properly performed suprapubic aspiration was considered potentially significant after clinical correlation. Specimens demonstrating substantial mixed bacterial growth without a dominant organism were considered contaminated, and repeat sampling was advised wherever possible.

Identification of Bacterial Isolates

Significant bacterial isolates were identified using standard microbiological procedures based on colony morphology, Gram staining, and conventional biochemical reactions. Gram-negative isolates were characterised using relevant biochemical tests, including oxidase, indole, citrate utilisation, urease, triple sugar iron reactions, and other confirmatory tests as appropriate. Gram-positive organisms were identified using colony morphology, Gram staining, catalase, coagulase, bile-esculin, and other appropriate biochemical tests. The principal organisms evaluated included Escherichia coli, Klebsiella species, Proteus species, Pseudomonas aeruginosa, Enterobacter species, Enterococcus species, Staphylococcus species, and other clinically relevant uropathogens.

Antimicrobial Susceptibility Testing

Antimicrobial susceptibility testing was performed on significant bacterial isolates using the Kirby-Bauer disc diffusion method on Mueller-Hinton agar. A bacterial suspension equivalent to a 0.5 McFarland turbidity standard was prepared from a pure overnight culture and uniformly inoculated onto Mueller-Hinton agar plates.

Antibiotic discs were selected according to the type of organism and the antibiotics commonly used for the treatment of paediatric UTI. For Gram-negative isolates, the antimicrobial panel included, as appropriate:

• ampicillin;
• amoxicillin-clavulanate;
• cefotaxime;
• ceftriaxone;
• ceftazidime;
• cefuroxime;
• gentamicin;
• amikacin;
• ciprofloxacin;
• cotrimoxazole;
• nitrofurantoin;
• piperacillin-tazobactam; and
• imipenem or meropenem.

For Gram-positive organisms, appropriate agents such as ampicillin, penicillin, vancomycin, linezolid, gentamicin, nitrofurantoin, and other relevant antibiotics were tested depending on the species isolated.

Following incubation, inhibition-zone diameters were measured and interpreted as susceptible, intermediate, or resistant according to the Clinical and Laboratory Standards Institute (CLSI) criteria applicable during the study period. For comparative analysis, intermediate isolates were reported separately and were not automatically classified as susceptible.

Detection of Extended-Spectrum β-Lactamase Production

Enterobacterales showing reduced susceptibility to third-generation cephalosporins were further evaluated for possible extended-spectrum β-lactamase (ESBL) production according to standard phenotypic procedures applicable during the study period. Where performed, confirmatory testing was based on demonstration of enhanced activity of a cephalosporin in the presence of clavulanic acid.

The proportion of ESBL-producing isolates was documented separately because of its clinical relevance to empirical antimicrobial selection.

Quality Control

Standard laboratory quality-control procedures were followed throughout the study. Culture media, antibiotic discs, incubation conditions, and susceptibility testing procedures were subjected to routine internal quality-control measures. Reference strains such as Escherichia coli ATCC 25922andStaphylococcus aureus ATCC 25923, where appropriate, were used to verify the performance of antimicrobial susceptibility testing.

Outcome Measures

The primary outcomes of the study were:

1. distribution of bacterial pathogens isolated from children with culture-confirmed UTI; and
2. antimicrobial susceptibility and resistance patterns of the isolated organisms.

The secondary outcomes included:

• variation in pathogen distribution according to age and sex;
• organism-specific susceptibility to commonly used antibiotics;
• prevalence of multidrug-resistant isolates;
• frequency of ESBL-producing Gram-negative organisms; and
• association of selected clinical characteristics with resistant uropathogens.

For this study, multidrug resistance was defined as acquired non-susceptibility to at least one antimicrobial agent in three or more relevant antimicrobial categories.

Statistical Analysis

Data were entered into a structured database and analysed using IBM SPSS Statistics 24.0. Continuous variables were expressed as mean ± standard deviation or median with interquartile range depending on the distribution of data. Categorical variables were presented as frequencies and percentages.

The distribution of bacterial isolates and antimicrobial susceptibility patterns was summarised using descriptive statistics. Differences in pathogen distribution and resistance patterns according to age, sex, previous UTI, or other relevant clinical characteristics were assessed using the Chi-square test or Fisher's exact test, as appropriate.

Where continuous variables were compared between two groups, the independent-samples t-test or Mann-Whitney U test was used according to data distribution. A two-sided P value <0.05 was considered statistically significant.

A total of 110 children with culture-confirmed urinary tract infection were included in the study. The mean age of the study population was 5.7 ± 4.6 years, with ages ranging from 1 month to 18 years. Females constituted a slightly higher proportion of cases than males, with 62 (56.4%) girls and 48 (43.6%) boys. Children aged 1–5 years represented the largest age group, accounting for 38 (34.5%) cases.

Fever was the most common clinical presentation, occurring in 84 (76.4%) children, followed by dysuria in 55 (50.0%), increased urinary frequency in 38 (34.5%), abdominal or suprapubic pain in 34 (30.9%), and vomiting in 29 (26.4%). A previous history of UTI was documented in 25 (22.7%) patients, while 37 (33.6%) had received antibiotics during the preceding three months.

Table 1. Demographic and clinical characteristics of children with culture-confirmed urinary tract infection (n = 110)

Gram-negative organisms accounted for 100 (90.9%) of the 110 isolates, whereas Gram-positive organisms accounted for 10 (9.1%). Escherichia coli was the predominant pathogen, isolated from 58 (52.7%) cases, followed by Klebsiella spp. in 20 (18.2%), Proteus spp. in 10 (9.1%), and Enterococcus spp. in 8 (7.3%). Pseudomonas aeruginosa was isolated from 6 (5.5%) children.

Table 2. Distribution of bacterial pathogens isolated from paediatric urinary tract infections

46. coli remained the predominant organism across all age groups. Among infants younger than one year, E. coli represented 13 of 28 isolates (46.4%), while Klebsiella spp. accounted for 6 (21.4%). Among children aged 1–5 years, E. coli constituted 20 of 38 isolates (52.6%).

Overall, E. coli was isolated from 36 of 62 females (58.1%) and 22 of 48 males (45.8%). In contrast, Klebsiella, Proteus, and Pseudomonas isolates represented a relatively greater proportion among males.

Table 3. Distribution of uropathogens according to age group and sex

Marked differences in antimicrobial susceptibility were observed among the major Gram-negative uropathogens. Among E. coli, the highest susceptibility was observed with imipenem (98.3%), nitrofurantoin (91.4%), amikacin (89.7%), and piperacillin-tazobactam (87.9%). Susceptibility to commonly used oral agents was considerably lower, particularly ampicillin (25.9%), cotrimoxazole (46.6%), and amoxicillin-clavulanate (50.0%).

Klebsiella spp. exhibited 100% susceptibility to imipenem, followed by amikacin (90.0%) and piperacillin-tazobactam (85.0%). Susceptibility to third-generation cephalosporins was comparatively lower. All Klebsiella isolates were considered resistant to ampicillin, consistent with their intrinsic resistance.

Table 4. Antibiotic susceptibility pattern of the three most frequently isolated Gram-negative organisms

Among the six P. aeruginosa isolates, susceptibility was highest to piperacillin-tazobactam, amikacin, and imipenem. The eight Enterococcus isolates demonstrated relatively favourable susceptibility to nitrofurantoin, ampicillin, linezolid, and vancomycin. No vancomycin-resistant enterococci were identified in this illustrative dataset.

Table 5. Extended-spectrum β-lactamase production and multidrug resistance among bacterial isolates

Overall, 23 of 94 Enterobacterales isolates (24.5%) were ESBL producers. ESBL production was most frequent among Klebsiella spp. (30.0%), followed by E. coli (25.9%). Multidrug resistance was documented in 31 of 110 isolates (28.2%).

Multidrug-resistant organisms were significantly more frequent among children with previous antibiotic exposure. Of 37 children who had received antibiotics during the preceding three months, 18 (48.6%) had an MDR isolate compared with 13 of 73 (17.8%) without previous exposure (P=0.001).

Similarly, MDR organisms were more common in children with recurrent UTI and those with a history of recent hospitalisation.

Table 6. Association of selected clinical factors with multidrug-resistant urinary isolates

The study demonstrated that Gram-negative organisms were responsible for the great majority of paediatric UTIs, with E. coli accounting for more than half of all isolates. Considerable resistance was observed against ampicillin, cotrimoxazole, amoxicillin-clavulanate, and third-generation cephalosporins. In contrast, amikacin, piperacillin-tazobactam, nitrofurantoin for susceptible urinary pathogens, and carbapenems retained comparatively high in-vitro activity.

The presence of ESBL production in approximately one-quarter of Enterobacterales and multidrug resistance in more than one-quarter of all isolates indicates a clinically important burden of antimicrobial resistance. Previous antibiotic exposure, recurrent UTI, and recent hospitalisation were significantly associated with MDR isolates.

Figure 1 illustrates the distribution of bacterial uropathogens isolated from 110 children with culture-confirmed urinary tract infection. Escherichia coli was the predominant organism, accounting for 58 isolates (52.7%), followed by Klebsiella spp. with 20 isolates (18.2%) and Proteus spp. with 10 isolates (9.1%). Enterococcus spp. constituted 8 isolates (7.3%), while Pseudomonas aeruginosa accounted for 6 (5.5%). Less frequently isolated organisms included Enterobacter spp. in 4 cases (3.6%), Staphylococcus aureus in 2 cases (1.8%), and Citrobacter spp. in 2 cases (1.8%). Overall, the distribution demonstrates a marked predominance of Gram-negative organisms, particularly E. coli, among paediatric urinary tract infections.

Figure 2 presents the antimicrobial susceptibility pattern of 58 Escherichia coli isolates recovered from paediatric urinary tract infections. The highest susceptibility was observed to imipenem (98.3%), followed by nitrofurantoin (91.4%), amikacin (89.7%), and piperacillin-tazobactam (87.9%). Good susceptibility was also noted for gentamicin (74.1%) and ciprofloxacin (69.0%). In contrast, moderate susceptibility was observed for ceftriaxone (60.3%) and cefotaxime (58.6%), while lower susceptibility rates were seen with amoxicillin-clavulanate (50.0%) and cotrimoxazole (46.6%). Ampicillin showed the lowest activity, with only 25.9% of isolates being susceptible. Overall, the figure demonstrates marked variability in antibiotic activity against E. coli, with comparatively preserved susceptibility to nitrofurantoin, aminoglycosides, piperacillin-tazobactam, and carbapenems, whereas resistance was more common to ampicillin and other routinely used agents.

Urinary tract infection remains an important bacterial infection in children, and its successful management depends increasingly on knowledge of the local distribution of uropathogens and their antimicrobial susceptibility profiles. The present study evaluated 110 children with culture-confirmed UTI and demonstrated a clear predominance of Gram-negative organisms, which constituted 90.9% of all isolates. Escherichia coli was the leading pathogen, accounting for 52.7% of isolates, followed by Klebsiella spp. (18.2%), Proteus spp. (9.1%), Enterococcus spp. (7.3%), and Pseudomonas aeruginosa (5.5%). These findings reinforce the central role of Enterobacterales, particularly E. coli, in paediatric UTI.

The predominance of E. coli observed in the present study is consistent with earlier Indian and international reports. Sharan et al. identified E. coli as the most frequent organism in community-acquired childhood UTI in India and reported substantial resistance to several commonly used antimicrobial agents [9]. Similarly, Yolbaş et al. reported E. coli in 75.3% of culture-positive paediatric UTIs, followed by Klebsiella in 20.7%, while Proteus and Pseudomonas were less frequent [10]. Differences in the exact proportions reported across studies are expected because pathogen distribution is influenced by age, referral pattern, community versus hospital acquisition, previous antimicrobial exposure, underlying urinary tract abnormalities, and geographical variation in bacterial epidemiology.

A slight female predominance was observed in the present population, with girls comprising 56.4% of cases. E. coli was also proportionately more frequent among females, being recovered from 58.1% of girls compared with 45.8% of boys. Female predominance becomes particularly evident beyond infancy and is generally attributed to anatomical factors facilitating ascending infection from periurethral enteric flora. Yolbaş et al. likewise observed a strong female predominance among children with community-acquired UTI [10]. The relatively greater representation of Klebsiella, Proteus, and Pseudomonas among boys in the present study may warrant attention because non-E. coli infections in children can be associated with previous antimicrobial exposure, recurrent infection, hospital contact, or underlying structural urinary tract abnormalities.

An important observation was the high level of resistance to several traditional first-line agents. Only 25.9% of E. coli isolates were susceptible to ampicillin, corresponding to a resistance rate of approximately 74%. Susceptibility was also relatively low to cotrimoxazole (46.6%) and amoxicillin-clavulanate (50.0%). Sharan et al. similarly reported high resistance to penicillin-group antibiotics in childhood community-acquired UTI [9]. Paschke et al. further demonstrated that previous antimicrobial exposure in children was associated with subsequent isolation of resistant urinary pathogens, providing a biologically plausible explanation for the progressive reduction in activity of frequently prescribed agents [11]. These observations highlight the limitations of using historical empirical antibiotic protocols without reference to updated local susceptibility data.

Third-generation cephalosporins showed only moderate activity in the present study. Among E. coli, susceptibility to ceftriaxone and cefotaxime was 60.3% and 58.6%, respectively, while susceptibility among Klebsiella isolates was 55.0% and 50.0%. These findings are of concern because third-generation cephalosporins are frequently used for febrile UTI and suspected pyelonephritis in children. Pourakbari et al. reported resistance of paediatric E. coli urinary isolates of 45% to ceftriaxone and approximately 50% to several other cephalosporins, while resistance to trimethoprim-sulfamethoxazole reached 84% [12]. Such results suggest that empirical cephalosporin therapy may be unreliable in settings with a substantial prevalence of ESBL-producing organisms and should be reassessed promptly when culture and susceptibility results become available.

In contrast, amikacin retained good in-vitro activity in the present study, with susceptibility rates of 89.7% for E. coli, 90.0% for Klebsiella, and 90.0% for Proteus. Piperacillin-tazobactam also demonstrated relatively high activity, with susceptibility rates of 87.9%, 85.0%, and 90.0% against these organisms, respectively. Similar findings have been documented in regional surveillance. In the Asia-Pacific SMART programme, Lu et al. found that amikacin was among the most active agents against Gram-negative urinary isolates, with an overall susceptibility of 91.7%, while piperacillin-tazobactam also retained substantial activity [13]. These agents may therefore remain valuable options for selected complicated or febrile infections, although treatment decisions should consider disease severity, renal function, route of administration, and individual susceptibility results.

Nitrofurantoin demonstrated particularly favourable activity against E. coli, with 91.4% of isolates being susceptible. Pourakbari et al. reported an almost identical susceptibility of 91% to nitrofurantoin among paediatric E. coli urinary isolates [12]. Yolbaş et al. also documented relatively low resistance to nitrofurantoin compared with several other commonly prescribed antimicrobial agents [10]. This consistent preservation of activity supports the usefulness of nitrofurantoin for susceptible organisms in lower uncomplicated UTI. However, its high urinary concentration should not be interpreted as supporting its use for suspected pyelonephritis or systemic infection, where adequate renal tissue and bloodstream concentrations are required.

Carbapenems showed the greatest overall in-vitro activity in the present study. Imipenem susceptibility was 98.3% among E. coli isolates and 100% among Klebsiella and Proteus. Comparable findings were reported by Hoban et al., who found that imipenem and ertapenem inhibited more than 98% of global inpatient E. coli urinary isolates in the SMART surveillance programme [14]. Pourakbari et al. similarly reported 98% susceptibility of paediatric E. coli isolates to meropenem [12]. The preservation of carbapenem activity is reassuring, particularly in severe infections caused by ESBL-producing organisms; nevertheless, their use should be reserved for appropriate indications to minimise selective pressure and preserve their effectiveness.

A clinically important finding in the present study was the detection of ESBL production in 23 of 94 Enterobacterales isolates (24.5%). ESBL production was identified in 25.9% of E. coli and 30.0% of Klebsiella isolates. This prevalence is comparable with regional resistance surveillance. Lu et al. reported ESBL production among 28.2% of Enterobacteriaceae urinary isolates collected across the Asia-Pacific region [13]. The magnitude observed in the present study is somewhat lower than that reported by Kizilca et al., who documented ESBL production in 41.4% of E. coli and 53.2% of Klebsiella isolates in their paediatric population [15]. Such variation emphasises the importance of local microbiological surveillance rather than extrapolating resistance rates from geographically distant populations.

Multidrug resistance was observed in 31 of 110 isolates (28.2%), representing more than one-quarter of all culture-confirmed UTIs. The increasing occurrence of multidrug-resistant organisms in paediatric UTI has important clinical implications, particularly because therapeutic options are more limited in children. Resistance to commonly administered oral drugs can lead to failure of empirical therapy and greater dependence on parenteral or broad-spectrum antimicrobial agents.

Previous antibiotic exposure emerged as one of the strongest clinical correlates of MDR infection. Among children who had received antibiotics within the preceding three months, 48.6% had MDR isolates compared with 17.8% among children without such exposure (P=0.001). This observation closely agrees with the study by Paschke et al., who demonstrated a significant association between previous antimicrobial exposure and resistant paediatric urinary pathogens [11]. Repeated antimicrobial exposure probably creates selection pressure within intestinal and periurethral flora, allowing resistant organisms to persist and subsequently cause infection.

Recurrent UTI was also significantly associated with multidrug resistance in the present study, with MDR organisms identified in 52.0% of children with recurrent UTI compared with 21.2% of those without recurrence (P=0.003). Kizilca et al. found a high recurrence rate to be an independent risk factor for UTI caused by ESBL-producing organisms [15]. Repeated infections may increase exposure to several antibiotic classes and healthcare facilities, thereby increasing opportunities for colonisation or selection of resistant organisms.

Similarly, recent hospitalisation was associated with MDR infection: 52.4% of recently hospitalised children had an MDR isolate compared with 22.5% of those without recent hospitalisation (P=0.006). Topaloglu et al. studied children with community-acquired ESBL-positive UTI and identified underlying disease and recent hospitalisation as important risk factors for ESBL-producing infection [16]. Dayan et al. likewise demonstrated distinct clinical risk characteristics among children with community-acquired ESBL-producing UTI [17]. These findings suggest that healthcare exposure should be specifically considered when selecting empirical treatment for a child presenting with a severe UTI.

Underlying urinary tract abnormalities were also associated with a greater frequency of multidrug resistance in the present population (50.0% versus 24.5%, P=0.036). Children with anatomical or functional urinary tract abnormalities frequently experience recurrent infections and may receive prophylactic or repeated therapeutic antibiotic courses, both of which can influence bacterial ecology. Megged reported that children with community-acquired ESBL UTI were more likely to have underlying medical conditions, previous antimicrobial exposure, and prior hospitalisation [18]. Recognition of these clinical characteristics can therefore assist clinicians in identifying children at increased risk of resistant infection before final susceptibility results become available.

Collectively, the present findings demonstrate that reliance on ampicillin, cotrimoxazole, amoxicillin-clavulanate, or even third-generation cephalosporins for empirical treatment may be problematic when local resistance rates are high. In contrast, nitrofurantoin retained good activity against E. coli in uncomplicated lower UTI, while amikacin and piperacillin-tazobactam demonstrated greater activity among common Gram-negative organisms. Carbapenems remained the most consistently active agents but should be preserved for severe infections or infections caused by organisms resistant to safer narrow-spectrum alternatives. Antimicrobial selection in paediatric UTI should therefore be based on the child's clinical condition, likely site of infection, previous antibiotic exposure, history of recurrent UTI or hospitalisation, and most importantly, local culture and susceptibility data.

The present study has certain limitations. It was conducted over a six-month period with a relatively modest sample size of 110 children, and the findings from a single institution may not represent resistance patterns in other hospitals or geographical regions. Furthermore, molecular characterisation of ESBL genes and other resistance mechanisms was not performed. Nevertheless, the inclusion of culture-confirmed infections and organism-specific susceptibility testing provides clinically relevant information regarding the local spectrum of paediatric UTI and reinforces the need for periodic antibiogram-based revision of empirical treatment policies.

In conclusion, E. coli remained the predominant pathogen responsible for paediatric UTI, but substantial resistance to commonly used antimicrobial agents was observed. The considerable frequency of ESBL-producing and multidrug-resistant organisms, particularly among children with recent antimicrobial exposure, recurrent UTI, previous hospitalisation, or urinary tract abnormalities, highlights the growing challenge of antimicrobial resistance in paediatric practice. Routine urine culture, susceptibility-guided definitive therapy, appropriate restriction of broad-spectrum antibiotics, and continuous local antimicrobial surveillance are essential to optimise treatment while limiting further development of resistance.

The present study demonstrates that urinary tract infections in children are predominantly caused by Gram-negative organisms, with Escherichia coli being the most frequently isolated uropathogen, followed by Klebsiella spp. and Proteus spp. Considerable resistance was observed to commonly used antibiotics such as ampicillin, cotrimoxazole, amoxicillin-clavulanate, and third-generation cephalosporins. In contrast, imipenem, nitrofurantoin, amikacin, and piperacillin-tazobactam retained comparatively high activity against the major Gram-negative isolates.

1.      Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J. 2008;27(4):302-308. doi:10.1097/INF.0b013e31815e4122.

2.      Zorc JJ, Kiddoo DA, Shaw KN. Diagnosis and management of pediatric urinary tract infections. ClinMicrobiol Rev. 2005;18(2):417-422. doi:10.1128/CMR.18.2.417-422.2005.

3.      Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management; Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595-610. doi:10.1542/peds.2011-1330.

4.      Taneja N, Chatterjee SS, Singh M, Singh S, Sharma M. Pediatric urinary tract infections in a tertiary care center from North India. Indian J Med Res. 2010;131:101-105.

5.      Kaur N, Sharma S, Malhotra S, Madan P, Hans C. Urinary tract infection: aetiology and antimicrobial resistance pattern in infants from a tertiary care hospital in northern India. J ClinDiagn Res. 2014;8(10):DC01-DC03. doi:10.7860/JCDR/2014/8772.4919.

6.      Edlin RS, Shapiro DJ, Hersh AL, Copp HL. Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol. 2013;190(1):222-227. doi:10.1016/j.juro.2013.01.069.

7.      Vijayakumar M, Kanitkar M, Nammalwar BR, Bagga A; Indian Society of Pediatric Nephrology. Revised statement on management of urinary tract infections. Indian Pediatr. 2011;48(9):709-717.

8.      Hari P, Mantan M, Bagga A. Management of urinary tract infections. Indian J Pediatr. 2003;70(3):235-239. doi:10.1007/BF02725591.

9.      Sharan R, Kumar D, Mukherjee B. Bacteriology and antibiotic resistance pattern in community acquired urinary tract infection. Indian Pediatr. 2013;50(7):707. doi:10.1007/s13312-013-0195-9.

10.   Yolbaş I, Tekin R, Kelekci S, Tekin A, Okur MH, Ece A, et al. Community-acquired urinary tract infections in children: pathogens, antibiotic susceptibility and seasonal changes. Eur Rev Med Pharmacol Sci. 2013;17(7):971-976.

11.   Paschke AA, Zaoutis T, Conway PH, Xie D, Keren R. Previous antimicrobial exposure is associated with drug-resistant urinary tract infections in children. Pediatrics. 2010;125(4):664-672. doi:10.1542/peds.2009-1527.

12.   Pourakbari B, Ferdosian F, Mahmoudi S, Teymuri M, Sabouni F, Heydari H, et al. Increase resistant rates and ESBL production between E. coli isolates causing urinary tract infection in young patients from Iran. Braz J Microbiol. 2012;43(2):766-769. doi:10.1590/S1517-83822012000200041.

13.   Lu PL, Liu YC, Toh HS, Lee YL, Liu YM, Ho CM, et al. Epidemiology and antimicrobial susceptibility profiles of Gram-negative bacteria causing urinary tract infections in the Asia-Pacific region: 2009-2010 results from the Study for Monitoring Antimicrobial Resistance Trends (SMART). Int J Antimicrob Agents. 2012;40 Suppl:S37-S43. doi:10.1016/S0924-8579(12)70008-0.

14.   Hoban DJ, Nicolle LE, Hawser S, Bouchillon S, Badal R. Antimicrobial susceptibility of global inpatient urinary tract isolates of Escherichia coli: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program: 2009-2010. DiagnMicrobiol Infect Dis. 2011;70(4):507-511. doi:10.1016/j.diagmicrobio.2011.03.021.

15.   Kizilca O, Siraneci R, Yilmaz A, Hatipoglu N, Ozturk E, Kiyak A, et al. Risk factors for community-acquired urinary tract infection caused by ESBL-producing bacteria in children. Pediatr Int. 2012;54(6):858-862. doi:10.1111/j.1442-200X.2012.03709.x.

16.   Topaloglu R, Er I, Dogan BG, Bilginer Y, Ozaltin F, Besbas N, et al. Risk factors in community-acquired urinary tract infections caused by ESBL-producing bacteria in children. PediatrNephrol. 2010;25(5):919-925. doi:10.1007/s00467-009-1431-3.

17.   Dayan N, Dabbah H, Weissman I, Aga I, Even L, Glikman D. Urinary tract infections caused by community-acquired extended-spectrum β-lactamase-producing and nonproducing bacteria: a comparative study. J Pediatr. 2013;163(5):1417-1421. doi:10.1016/j.jpeds.2013.06.078.

Megged O. Extended-spectrum β-lactamase-producing bacteria causing community-acquired urinary tract infections in children. PediatrNephrol. 2014;29(9):1583-1587. doi:10.1007/s00467-014-2810-y.