102

Original Article

Risk Factors of Urinary Tract Infection Caused by Extended-

Spectrum Beta-Lactamases-Producing Bacteria in Children
Dr. Md. Hasan Moshiur Shawon 1 *, Prof. Dr. Shanjoy Kumar Paul 2

1. Junior Consultant Paediatrics, District Hospital, Pirojpur, Bangladesh.

2. Former Professor & HoD of Paediatric Nephrology, Sir Salimullah Medical College, Dhaka,
Bangladesh.

* Correspondence: [email protected]

Abstract: Urinary tract infections caused by Extended-spectrum β-lactamases-producing bacteria among children is
a therapeutic challenge because it requires broad-spectrum antibiotics for treatment which further increases
antimicrobial resistance. World health organisation (WHO) has declared ESBL-producing Enterobacterales as critical
priority pathogens. This study determined the risk factors of UTI caused by ESBL-producing bacteria in children and
their antibiotic susceptibility pattern. Urine samples were collected using standard aseptic techniques from children
who were suspected cases of UTI. Urine culture and bacteria isolation were performed following standard
bacteriological techniques. The Kirby-Bauer disk diffusion technique and the Double-disc synergy test were used to
investigate antibiotic susceptibility and presence of ESBL production. The most frequently isolated bacteria was E.
coli in both ESBL and non-ESBL group. Almost all of the ESBL-producing bacteria were resistant to Cephalosporin
group of antibiotics followed by Amoxiclav and Co-trimoxazole. Lowest resistance were found to Colistin followed by
Imipenem and Meropenem. The most predominant risk factor for ESBL-UTI in children was history of prior use of
antibiotics (OR 8.3, 95% CI (3.8-18.5)) followed by previous hospitalization (OR 2.89, 95% CI (1.3-6.6)) and previous
UTI (OR 9.0, 95% CI (1.1-74.2)). However, none of them was found as an independent risk factor. The risk factors for
ESBL-UTI and their antibiotic sensitivity pattern identified in this study will be helpful for selection of an appropriate
empirical antibiotic while awaiting for urine culture report. ESBL testing need to incorporate in the routine clinical
practice and the judicious use of antibiotics should be strengthened to decrease the antimicrobial resistance rate.

Keywords: Extended-Spectrum Beta-Lactamases, Urinary Tract Infections, children, antibiotic resistance

1. INTRODUCTION
Urinary tract infections (UTI) occurs when microorganisms invade and multiply in the urinary tract. Anatomically,
UTIs are upper or lower tract infections. Upper tract UTI causes kidney and ureter inflammation (pyelonephritis).
This causes abdominal pain, loin tenderness, fever, anorexia, vomiting, lethargy, and malaise [1]. Lower tract UTI
causes bladder (cystitis) and urethra infection, causing lower abdominal or suprapubic pain, dysuria, urine
frequency, and urgency [2]. Older children may have infection-related symptoms, younger patients often lack these
typical indications, making upper and lower UTI difficult to distinguish [3]. The third most prevalent illness in
children is UTI, behind respiratory and gastrointestinal infections [4]. Feverish newborns, ill children, and older
children with urinary symptoms account for 6%–8% of UTI cases. Peak prevalence occurs in newborns, toddlers, and
adolescents [5]. UTI is more likely in female and uncircumcised male babies due to bacterial skin flora concentration
under the nappy, shorter female urethral distance, and foreskin surface area [6]. Toddler toilet training can cause
volitional holding and bladder stasis, causing UTIs. When sexual activity upsets bacteria at the urethral entrance,
prevalence rises in adolescent girls [7]. Due to poor sanitation, living methods, undernourishment, and
environmental conditions, this disease is more prevalent in underdeveloped nations. Enterobacterales (previously

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 103

called Enterobacteriaceae) are Gram-negative, non-spore-forming, facultative anaerobic bacilli that cause > 80% of
UTIs [8]. Escherichia coli is the most common, Klebsiella, Enterobacter, and Proteus spp as well [9]. Other Gram-
negative microbes like Pseudomonas aeruginosa can cause UTIs rarely. Enterococcus spp. (patients with a urinary
catheter, urinary tract instrumentation, or anatomical abnormality), Staphylococcus saprophyticus (sexually active
adolescents), and Streptococcus Group B (neonates) are Gram-positive bacterial pathogens [10]. Children rarely get
UTIs from viruses or fungi, save for Candida species in premature neonates. Patients with structural defects may
have several organisms [11]. ESBLs, plasmid-mediated β-lactamases, hydrolyze extended-spectrum Cephalosporins
(Cefotaxime, Ceftriaxone, and Ceftazidime) and Oxyimino-monobactam (Aztreonam), but not Cephamycins
(Cefoxitin and Cefotetan) or Carbapenems (Meropenem and Imipenem). ESBLs transmit resistance to antibiotics and
related Oxyimino-β lactams. Clavulanic acid, Sulbactam, and Tazobactam are ‘classical’ β-lactamase inhibitors that
inhibit these enzymes [12]. ESBLs provide Gram-negative bacteria resistance by preventing β-lactams from reaching
penicillin binding proteins (PBPs), decreasing affinity for PBPs, and destroying the antibiotic through β-lactamases
[13]. The most prevalent resistance mechanism against β-lactam antibiotics is beta-lactamase enzyme synthesis.
Because bacteria share mobile genetic components, ESBL enzymes have spread. Clonal development of ESBL-
producing bacteria, such as E. coli ST131, which is resistant to quinolones, has caused global epidemics [14]. E. coli
and Klebsiella spp. produce ESBLs, but Enterobacter, Proteus, Citrobacter, Morganella, Providencia, Salmonella, and
Serratia can also cause dozens of infections. ESBL-related infections are concerning for various reasons. First,
multidrug resistance makes them hard to treat (Jacoby, 1997). Second, ESBL infections may delay treatment [15].
Third, ESBL infections cause longer hospital stays and higher expenses, fourth, existing identification approaches
may underestimate these organisms' prevalence [16]. Finally, ESBL infections increase the likelihood of clinical
failure and death in adults and children. Poor medication regulatory and control systems in many countries have led
to antibiotic misuse and overuse in humans and animals [17]. These activities promote the spread of resistant
bacterial strains into the community and clinic, lowering treatment outcomes. When infection prevention and
management are lacking, drug-resistant pathogenic bacterial strains can spread anywhere [18]. Inappropriate
prescribing, patient noncompliance with duration, dose, and frequency of antibiotics, and antibiotic use in livestock
and fish farms are known sources of antibiotic resistance. Antibiotic resistance increases in nations where antibiotics
are available without a prescription and self-medication is frequent [19]. In places with heavy antibiotic usage
regardless of history, antibiotic resistance is more likely [20]. Patients under 15 and over 45 are more susceptible to
ESBL, alarmingly, 25% of newborns and young (0–15 year olds) have UTI. Previous antibiotic exposure, UTI,
hospitalization, underlying disease, urinary tract abnormalities, and immunosuppressant drug use have been linked
to ESBL-positive UTIs in children [21].

2. MATERIALS AND METHODS

The study follow the cross-sectional analytical study design, study place was department of Pediatrics and
Department of Microbiology, Sir Salimullah Medical College Mitford Hospital (SSMCMH), Dhaka. On the basis of
inclusion & exclusion criteria, all the patients from 01 month to 12 years of age presented to the pediatric
outpatient department or admitted to pediatric inpatient ward with clinical feature(s) of UTI (fever, abdominal pain,
loin pain, dysuria, frequency, urgency etc.) within the defined period were included. Data has been collected with
the help of purposive sampling technique. Sample size was calculated by following formula:

n = the required sample size

p₁ = anticipated probability of exposure among cases
p₂ = anticipated probability of exposure among control

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 104

p = (p₁ + p₂) ÷ 2
- value of SND at a given level of significance
Zβ = z- value of SND at a given power

Here,
p₁ = 79
p₂ = 52.2
p = (79 + 52.2) ÷ 2
= 65.6

Z𝛽 = 1.28
So calculated sample size:

n = 64

A number of 64 in each group so the total sample (64+64) = 128. Data were collected by interview of the parents or
guardians, clinical examination and laboratory investigations using the research instrument. Sociodemographic data
including age (years), sex and clinical history of participants such as previous use of antibiotic, previous
hospitalization, prior UTI, use of immunosuppressant drug within the past 3 months and associated diseases were
recorded. All patients presented to the pediatric outpatient department or admitted to pediatric inpatient ward,
SSMCMH, fulfilling the inclusion criteria were enrolled for the study. Glans penis and foreskin in male, while
perineum including labia minora and majora in female were cleaned using tap water at room temperature prior to
obtaining the urine sample. Freshly voided early morning mid-stream urine (MSU) from children 2 years and older
and clean catch or sterile, adhesive urine bag specimen from children younger than 2 years were collected into
properly labelled, dry, clean, sterile, transparent, screw-capped, wide-mouth, leak-proof plastic containers. After
labeling the container, samples were transported immediately to the Clinical pathology and Microbiology laboratory
of SSMC with a requisition form for routine examination and culture & antibiotic susceptibility test. The samples
were analyzed and processed according to the standard protocol within 2 hours of collection. Using a calibrated
wire loop of loop diameter 4mm, l0 μl of uncentrifuged urine were inoculated into 5% Blood agar and MacConkey
agar media (Oxoid Ltd. England). Semi quantitative streaking method was used for quantification of bacterial load in
urine. The inoculated plates were incubated at 37⁰C aerobically, after overnight incubation, plates were examined
for growth and colony forming units (cfu) per ml were calculated. A specimen was considered positive for UTI if a
single organism was cultured at a concentration of >105 cfu/ ml. Pure isolates of bacterial pathogen were
preliminarily characterized by their colony morphology and Gram-staining. All positive urine cultures showing
significant bacteriuria were further identified by their characteristic appearance on their respective media and
confirmed by the pattern of biochemical reaction using the standard procedures. Isolated bacteria were E. coli,
Pseudomonas, Klebsiella, Acinetobacter, Providencia, Morganella, Serratia, Citrobacter and Proteus. A single colony

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 105

represents one organism, if an inoculum of 0.01 ml produces 20 colonies, the number of organisms represents in
0.01 ml of urine is 20. So one ml urine contains 2 x 103 organisms. A count of 1 x 105 or more bacteria per ml of urine
were considered as clinically significant [22]. Susceptibility to antimicrobial agents of all isolates were done by Kirby-
Bauer modified disk-diffusion technique. Three to five isolated colonies of the organisms to be tested were picked
from the pure culture plates by a sterile wire loop and suspended in 5 ml of nutrient broth in a screw capped test
tube and mixed gently until it forms a homogenous suspension. In a good light the turbidity of suspension was
matched to 0.5 McFarland standards in order to standardize the inoculums density. A sterile cotton swab was
dipped into the suspension and the excess were removed by gentle rotation of the swab against the surface of the
tube. The swab was then used to distribute the bacteria suspension evenly over the entire surface of Mueller-Hinton
agar (Oxoid Ltd. England). The inoculated plates were left on the flat surface at room temperature to dry for 10-15
minutes. Then the antibiotic discs were placed on the inoculated plates. The antibiotics for disk diffusion testing
were obtained from Oxoid that include: Amoxicillin (20 µg) + Clavulanic acid (10 µg), Ceftriaxone (30 µg),
Ceftazidime (30 µg), Cefotaxime (30 µg), Aztreonam (10 µg), Cefixime (30 µg), Doxycycline (30 µg), Imipenem (10
µg), Meropenem (10 µg), Co-trimoxazole (23.75/1.25 µg), Ciprofloxacin (30 µg), Levofloxacin (5 µg), Gentamicin (10
µg), Amikacin (10 µg), Nitrofurantoin (300μg), Chloramphenicol (30 µg), Tetracycline (30 µg), Nalidixic acid (30 µg)
were used to see the sensitivity patterns of the organism. The plates were then incubated at 37⁰C for 24 hours and
reading was taken using a ruler on the underside of the plate measured the diameter of each zone of inhibition in
mm. Zone of inhibition produced by each was considered into susceptibility categories namely Susceptible (S),
Intermediate (I), and Resistant (R) by CLSI (2015). All the gram-negative isolates were tested for detection of ESBL by
Double-Disc Synergy Test (DDST). Antimicrobial discs (Oxoid Ltd. England) Ceftazidime (CAZ) 30 μg, Cefotaxime (CTX)
30 μg, Ceftriaxone (CRO) 30 μg were used. Mueller Hinton agar plates were prepared and inoculated with
standardized inoculums of the organism with sterile cotton swab. Disc containing 20 μg Amoxicillin and 10 μg
Clavulanic acid was placed in the center of the inoculated plate. Third generation Cephalosporin disc of Ceftazidime,
Ceftriaxone and Cefotaxime were placed about 20 mm distant from Amoxicillin-Clavulanate disc. The plate was
incubated overnight at 37ºC. Extension of the inhibition zone of Ceftazidime, Ceftriaxone and Cefotaxime disc on the
side exposed to the disc containing Amoxicillin and Clavulanic acid was considered positive for ESBLs. Standard
strain of Klebsiella pneumoniae ATCC 700603 was used as ESBL-positive control and E. coli ATCC 25922 was used as
ESBL-negative control. All Statistical analyses were done using Statistical Package for Social Science (SPSS) software
version 27.0.

3. RESULTS AND DISCUSSION

Data were expressed as frequency and percentage and mean ±SD unpaired student t-test and Chi-square test was
done ns = not significant Majority of the patients were age ranges between 1-5 years in both group (p=0.854). There
was male predominance in ESBL-UTI group (p=0.596).

Table 01: Age and sex distribution of the patients with ESBL-UTI and non-ESBL-UTI (N=128)

Variables ESBL Non-ESBL p-value

(n=64) (n=64)
No. (%) No. (%)

Age groups

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1 month-12 months 15(23.4%) 13(20.3%)

1 year-5 years 32(50.0%) 33(51.6%)
6 years-12 years 17(26.6%) 18(28.1%) 0.854ns

Mean±SD 3.76±3.41 3.87±3.25

Range (0.20-12) years (0.10-12.0) years

Sex
Male 34(53.1%) 31(48.4%) 0.596ns

Female 30(46.9%) 33(51.6%)

Male: Female ratio 1.1:1 1:1.1

Figure 01: Bar diagram shows distribution of the bacteria in ESBL-UTI and non-ESBL-UTI group.

E. coli was the commonest organism identified in both ESBL-UTI and non-ESBL-UTI group followed by Pseudomonas,
Providencia and others.

Table 02: Antibiotic susceptibility pattern of the isolated bacteria in ESBL-UTI group (n=64)

Antibiotics Organisms
E.coli Pseudomona Acinetobacte Providenci Citrobacte Morganell Serratia
s r a r a
(n=53) (n=1)
(n=4) (n=1) (n=2) (n=2) (n=1)
Amoxyclav S 3(5.7) 0(0.0) 0(0.0) 0(0.0) 1(50.0) 0(0.0) 0(0.0)
R 50(94.3) 4(100.0) 1(100.0) 2(100.0) 1(50.0) 1(100.0) 1(100.0
)

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 107

Amikacin S 36(67.9) 4(100.0) 1(100.0) 1(50.0) 0(0.0) 0(0.0) 0(0.0)

R 17(32.1) 0(0.0) 0(0.0) 1(50.0) 2(100.0) 1(100.0) 1(100.0
)
Aztreonam S 9(17.0) 1(25.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0)
R 44(83.0) 3(75.0) 1(100.0) 2(100.0) 2(100.0) 1(100.0) 1(100.0
)
Ceftriaxone S 0(0.0) 0(0.0) 1(100.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0)
R 53(100.0 4(100.0) 0(0.0) 2(100.0) 2(100.0) 1(100.0) 1(100.0
) )
Cefixime S 0(0.0) 0(0.0) 1(100.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0)
R 53(100.0 4(100.0) 0(0.0) 2(100.0) 2(100.0) 1(100.0) 1(100.0
) )
Ceftazidime S 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0)
R 53(100.0 4(100.0) 1(100.0) 2(100.0) 2(100.0) 1(100.0) 1(100.0
) )
Cefotaxime S 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0)
R 53(100.0 4(100.0) 1(100.0) 2(100.0) 2(100.0) 1(100.0) 1(100.0
) )
Cephradine S 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0)
R 53(100.0 4(100.0) 1(100.0) 2(100.0) 2(100.0) 1(100.0) 1(100.0
) )
Ciprofloxacin S 13(24.5) 3(75.0) 1(100.0) 2(100.0) 1(50.0) 0(0.0) 1(100.0
)
R 40(75.5) 1(25.0) 0(0.0) 0(0.0) 1(50.0) 1(100.0) 0(0.0)
Chloramphenic S 32(60.4) 3(75.0) 0(0.0) 0(0.0) 1(50.0) 1(100.0) 0(0.0)
ol R 21(39.6) 1(25.0) 1(100.0) 2(100.0) 1(50.0) 0(0.0) 1(100.0
)
Co-trimoxazole S 7(13.2) 1(25.0) 0(0.0) 1(50.0) 0(0.0) 0(0.0) 0(0.0)
R 46(86.8) 3(75.0) 1(100.0) 1(50.0) 2(100.0) 1(100.0) 1(100.0
)
Cefuroxime S 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0)
R 53(100.0 4(100.0) 1(100.0) 2(100.0) 2(100.0) 1(100.0) 1(100.0
) )
Colistin S 52(98.1) 4(100.0) 1(100.0) 1(50.0) 2(100.0) 1(100.0) 1(100.0
)
R 1(1.9) 0(0.0) 0(0.0) 1(50.0) 0(0.0) 0(0.0) 0(0.0)
Doxycycline S 29(54.7) 1(25.0) 1(100.0) 0(0.0) 1(50.0) 1(100.0) 1(100.0
)
R 24(45.3) 3(75.0) 0(0.0) 2(100.0) 1(50.0) 0(0.0) 0(0.0)
Gentamicin S 28(52.8) 3(75.0) 1(100.0) 1(50.0) 0(0.0) 0(0.0) 0(0.0)
R 25(47.2) 1(25.0) 0(0.0) 1(50.0) 2(100.0) 1(100.0) 1(100.0
)
Imipenem S 45(84.9) 4(100.0) 0(0.0) 2(100.0) 0(0.0) 1(100.0) 1(100.0
)
R 8(15.1) 0(0.0) 1(100.0) 0(0.0) 2(100.0) 0(0.0) 0(0.0)

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 108

Levofloxacin S 17(32.1) 3(75.0) 1(100.0) 2(100.0) 1(50.0) 0(0.0) 1(100.0

)
R 36(67.9) 1(25.0) 0(0.0) 0(0.0) 1(50.0) 1(100.0) 0(0.0)
Table-2 continued

Table 02: Antibiotic susceptibility pattern of the isolated bacteria in ESBL-UTI group (n=64)

Antibiotic Organisms
E.coli Pseudomona Acinetobacte Providenci Citrobacte Morganell Serratia
s r a r a
(n=53) (n=1)
(n=4) (n=1) (n=2) (n=2) (n=1)
Meropenem S41(77.4 4(100.0) 0(0.0) 2(100.0) 0(0.0) 1(100.0) 1(100.0
) )
R 12(22.6 0(0.0) 1(100.0) 0(0.0) 2(100.0) 0(0.0) 0(0.0)
)
Nalidixic acid S 10(18.9 2(50.0) 0(0.0) 1(50.0) 0(0.0) 0(0.0) 0(0.0)
)
R 43(81.1 2(50.0) 1(100.0) 1(50.0) 2(100.0) 1(100.0) 1(100.0
) )
Nitrofurantoin S 31(58.5 1(25.0) 1(100.0) 0(0.0) 1(50.0) 0(0.0) 1(100.0
) )
R 22(41.5 3(75.0) 0(0.0) 2(100.0) 1(50.0) 1(100.0) 0(0.0)
)
Pefloxacin S 21(39.6 2(50.0) 1(100.0) 2(100.0) 1(50.0) 0(0.0) 1(100.0
) )
R 32(60.4 2(50.0) 0(0.0) 0(0.0) 1(50.0) 1(100.0) 0(0.0)
)
Tetracycline S 40(75.5 3(75.0) 1(100.0) 0(0.0) 2(100.0) 1(100.0) 0(0.0)
)
R 13(24.5 1(25.0) 0(0.0) 2(100.0) 0(0.0) 0(0.0) 1(100.0
) )
Figures in the parentheses indicate corresponding percentage;

S=sensitive, R=Resistant, Intermediate was counted as sensitive.

Table 03: Antibiotic susceptibility pattern of the isolated bacteria in non-ESBL-UTI group (n=64)

Antibiotics Organisms
E.coli Klebsiella Proteus Pseudomonas

(n=59) (n=1) (n=1) (n=3)

No. (%) No. (%) No. (%) No. (%)

Amoxyclav S 38(64.4%) 0(0.0%) 0(0.0%) 0(0.0%)
R 21(35.6%) 1(100.0%) 1(100.0%) 3(100.0%)
Amikacin S 58(98.3%) 1(100.0%) 1(100.0%) 3(100.0%)
R 1(1.7%) 0(0.0%) 0(0.0%) 0(0.0%)

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 109

Aztreonam S 59(100.0%) 1(100.0%) 1(100.0%) 1(33.3%)

R 0(0.0%) 0(0.0%) 0(0.0%) 2(66.7%)
Ceftriaxone S 59(100.0%) 1(100.0%) 0(0.0%) 2(66.7%)
R 0(0.0%) 0(0.0%) 1(100.0%) 1(33.3%)
Cefixime S 53(89.8%) 1(100.0%) 0(0.0%) 0(0.0%)
R 6(10.2%) 0(0.0%) 1(100.0%) 3(100.0%)
Ceftazidime S 59(100.0%) 1(100.0%) 1(100.0%) 3(100.0%)
R 0(0.0%) 0(0.0%) 0(0.0%) 0(0.0%)
Cefotaxime S 59(100.0%) 1(100.0%) 1(100.0%) 2(66.7%)
R 0(0.0%) 0(0.0%) 0(0.0%) 1(33.3%)
Cephradine S 38(64.4%) 0(0.0%) 0(0.0%) 0(0.0%)
R 21(35.6%) 1(100.0%) 1(100.0%) 3(100.0%)
Ciprofloxacin S 49(83.1%) 0(0.0%) 0(0.0%) 1(33.3%)
R 10(16.9%) 1(100.0%) 1(100.0%) 2(66.7%)
Chloramphenicol S 52(88.1%) 1(100.0%) 1(100.0%) 1(33.3%)
R 7(11.9%) 0(0.0%) 0(0.0%) 2(66.7%)
Co-trimoxazole S 27(45.8%) 1(100.0%) 0(0.0%) 0(0.0%)
R 32(54.2%) 0(0.0%) 1(100.0%) 3(100.0%)
Cefuroxime S 50(84.7%) 1(100.0%) 1(100.0%) 0(0.0%)
R 9(15.3%) 0(0.0%) 0(0.0%) 3(100.0%)
Colistin S 59(100.0%) 1(100.0%) 1(100.0%) 3(100.0%)
R 0(0.0%) 0(0.0%) 0(0.0%) 0(0.0%)
Doxycycline S 42(71.2%) 1(100.0%) 1(100.0%) 1(33.3%)
R 17(28.8%) 0(0.0%) 0(0.0%) 2(66.7%)
Table-3 continued

Table 03: Antibiotic susceptibility pattern of the isolated bacteria in non-ESBL-UTI group (n=64)

Antibiotics Organisms
E.coli Klebsiella Proteus Pseudomonas

(n=59) (n=1) (n=1) (n=3)

No. (%) No. (%) No. (%) No. (%)

Gentamicin S 46(78.0%) 1(100.0%) 0(0.0%) 2(66.7%)
R 13(22.0%) 0(0.0%) 1(100.0%) 1(33.3%)
Imipenem S 59(100.0%) 1(100.0%) 1(100.0%) 1(33.3%)
R 0(0.0%) 0(0.0%) 0(0.0%) 2(66.7%)

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 110

Levofloxacin S 49(83.1%) 1(100.0%) 0(0.0%) 3(100.0%)

R 10(16.9%) 0(0.0%) 1(100.0%) 0(0.0%)
Meropenem S 59(100.0%) 1(100.0%) 1(100.0%) 1(33.3%)
R 0(0.0%) 0(0.0%) 0(0.0%) 2(66.7%)
Nalidixic acid S 12(20.3%) 1(100.0%) 1(100.0%) 0(0.0%)
R 47(79.7%) 0(0.0%) 0(0.0%) 3(100.0%)
Nitrofurantoin S 46(78.0%) 1(100.0%) 0(0.0%) 0(0.0%)
R 13(22.0%) 0(0.0%) 1(100.0%) 3(100.0%)
Pefloxacin S 49(83.1%) 1(100.0%) 0(0.0%) 2(66.7%)
R 10(16.9%) 0(0.0%) 1(100.0%) 1(33.3%)
Tetracycline S 49(83.1%) 1(100.0%) 1(100.0%) 3(100.0%)
R 10(16.9%) 0(0.0%) 0(0.0%) 0(0.0%)
S=sensitive, R=Resistant, Intermediate was counted as sensitive.

Table 04: Pattern of antibiotic resistance between ESBL-UTI and non-ESBL-UTI group (N=128)

Antibiotic ESBL (n=64) Non-ESBL (n=64) p-value

No. (%) No. (%)

Amoxiclav 60(93.8%) 26(40.8%) <0.001s
Amikacin 22(34.4%) 1(1.6%) <0.001s
Aztreonam 54(84.4%) 2(3.1%) <0.001s
Ceftriaxone 63(98.4%) 2(3.1%) <0.001s
Cefixime 63(98.4%) 10(15.6%) <0.001s
Ceftazidime 64(100.0%) 0(0.0%) <0.001s
Cefotaxime 64(100.0%) 1(1.6%) <0.001s
Cephradine 64(100.0%) 26(40.6%) <0.001s
Ciprofloxacin 43(67.2%) 14(21.9%) <0.001s
Chloramphenicol 27(42.2%) 9(14.1%) 0.001s
Co-trimoxazole 55(85.9%) 36(56.3%) <0.001s
Cefuroxime 64(100.0%) 12(18.8%) <0.001s
Colistin 2(3.1%) 0(0.0%) 0.043s
Doxycycline 30(46.9%) 19(29.7%) 0.100ns
Gentamicin 31(48.4%) 15(23.4%) 0.002s
Imipenem 11(17.2%) 2(3.1%) 0.020s
Levofloxacin 39(60.9%) 11(17.2%) <0.001s
Meropenem 15(23.4%) 2(3.1%) 0.002s
Nalidixic acid 51(79.7%) 50(78.1%) 0.473ns
Nitrofurantoin 29(45.3%) 17(26.6%) 0.007s
Pefloxacin 36(56.3%) 12(18.8%) <0.001s
Tetracycline 17(26.6%) 10(15.6%) 0.270ns

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 111

Chi-square test (2) was done to analyze the data. s= significant, ns = not significant, ESBL-producing bacteria were
significantly resistant to commonly used antibiotics.

Table 05: Distribution of the study subjects by Urine examination (N=128)

Urine examination ESBL Non-ESBL p-value

(n=64) (n=64)

No. (%) No. (%)

Pus cell (per HPF)
<5 10(15.6%) 8(12.5%) 0.299ns
5-10 30(46.8%) 28(43.8%)
>10 20(31.3%) 18(28.1%)
Plenty 4(6.3%) 10(15.6%)
RBC (per HPF)
<5 54(84.4%) 57(89.1%) 0.927 ns
5-10 6(9.4%) 4(6.2%)
>10 4(6.2%) 3(4.7%)
Ep cell (per HPF)
<5 59(92.2%) 60(93.8%) 0.193 ns
5-10 5(7.8%) 2(3.1%)
>10 0(0.0%) 2(3.1%)
Albumin
Nil 25(39.1%) 24(37.5%) 0.555 ns
Trace 8(12.5%) 14(21.9%)
1+ 8(12.5%) 5(7.8%)
2+ 5(7.8%) 4(6.2%)
3+ 18(28.1%) 17(26.6%)
pH
<5 3(4.7%) 0(0.0%) 0.080 ns
>5 61(95.3%) 64(100.0%)
Specific gravity
1.0-1.015 8(12.5%) 3(4.7%) 0.115 ns
1.020-1.030 56(87.5%) 61(95.3%)
Nephrotic range proteinuria 21(32.8%) 15(23.4%) 0.555 ns

Chi-square test (2) was done to analyze the data., s= significant, ns = not significant

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 112

None of the urinary findings were statistically significant between two groups.

Table 06: Possible risk factors of study population (N=128)

Possible risk factors ESBL Non-ESBL OR (95% CI) p-value

(n=64) (n=64)

No. (%) No. (%)

Previous hospitalization 24(37.5%) 11(17.2%) 2.89 (1.3-6.6) 0.010s

H/O previous UTI 8(12.5%) 1(1.6%) 9.0 (1.1-74.2) 0.016 s

Previous use of antibiotics 46(71.9%) 15(23.4%) 8.3 (3.8-18.5) <0.001 s

First generation cephalosporin 2(3.1%) 6(9.4%) 0.38 (0.07-2.04) 0.144ns

Second generation cephalosporin 2(3.1%) 1(1.6%) 2.03 (0.18-22.9) 0.559 ns

Third generation cephalosporin 43(67.2%) 10(15.6%) 11.1 (4.7-25.9) <0.001s

Fourth generation cephalosporin 4(6.3%) 0(0.0%) - 0.042s

Immunosuppressant drug 10(15.6%) 3(4.7%) 3.8 (0.98-14.4) 0.041s

Associated diseases 25(39.1%) 16(25%) 1.92(-2.2-30.4) 0.66 ns

Uncircumcised boys 30(88.2%) 26(83.9%) 1.44(-7.92-16.52) 0.611ns

Odds ratio (OR) with 95% CI and Chi-square test were done to analyze the data, s=significant, ns = not significant

Some patient had history of previous use of more than one generation of antibiotics. Previous hospitalization, H/O
previous UTI and previous use of antibiotics (third generation Cephalosporin) were found as risk factors for ESBL-
UTI.

Table 07: Independent risk factors for ESBL-positive UTI

p-value OR 95% C.I

Lower Upper

Previous hospitalization .750 .826 .255 2.675

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 113

H/O previous UTI .320 .308 .030 3.140

Previous use of antibiotic .596 .646 .129 3.242

Third generation cephalosporin .270 .156 .030 1.808

Constant .000 2.840

Multivariate binary logistic regression analysis was done, where none of them was found as an independent risk
factor for ESBL-UTI. E. coli was the most isolated organism in both the ESBL-UTI (84.4%) and non-ESBL-UTI (92.2%)
groups. E. coli was the most commonly isolated bacteria in UTI patients by Afroz, Albaramki, Alim, Awean, Islam,
Kim, Yang, and Kim, Rahman, and Topaloglu. High E. coli ratios cause autoinfection since the bacteria are in the
feces. E. coli can also create a biofilm on the bladder wall that resists the immune system. This study found that
Pseudomonas caused 6.3% of ESBL-UTI and 4.7% of non-ESBL-UTI. Pseudomonas as the second main cause of UTI.
Klebsiella was the second biggest cause and a major risk factor for ESBL development in other investigations.
Different environmental circumstances, host characteristics, healthcare and education programs, socioeconomic
levels, and cleanliness practices in each nation may affect uropathogen kind and distribution. The ESBL-UTI group
had a considerably greater rate of AMR than the non-ESBL-UTI group. ALL ESBL isolates were resistant to
Ceftazidime, Cefotaxime, and Cefuroxime, followed by Ceftriaxone, Cefixime, Amoxiclav, and Co-trimoxazole (p<
Colistin, Imipenem, and Meropenem had the lowest resistance.

3.2 Discussion
A study found that all ESBL isolates were resistant to cefuroxime, ceftazidime, and cefotaxime and 99% to ampicillin
and ceftriaxone. All isolates were sensitive to Meropenem, Imipenem, and Colistin, regardless of ESBL status [23].
ESBL E. coli in India exhibited high resistance to third-generation cephalosporins, quinolones, and co-trimoxazole,
but less resistance to Gentamicin, Levofloxacin, Nitrofurantoin, Netilmicin, and Imipenem [24]. All ESBL isolates in a
Finnish study were resistant to Cephalosporins and susceptible to Meropenem. ESBL-producing bacteria showed
increased resistance to non-β-lactam antibiotics, such as Trimethoprim (76%), Norfloxacin (33%), and
Sulphatrimethoprim (76%) [25]. The only clinically meaningful Trimethoprim resistance in ESBL-negative bacteria
was 27%. In our country, oral third-generation antibiotics like Cefixime are overprescribed [26]. Through antibiotic
selection pressure (ESBLs), this method may increase gram-negative bacteria drug resistance. In this study, 50% of
ESBL-UTI children were 1–5 years old [27]. A recent study found more UTIs among 1-5-year-olds, and most instances
are over 2 [28]. ESBL-UTI risk was independent for children under one year old, a CMH, Dhaka study found that UTIs
were more common in children under 5 (62.5%) [29]. Possibly because younger children aren't toilet-trained. Fecal
flora ascending infection is more common in this age range [30]. In this study, ESBL-UTI members were mostly men
(1.1:1), but not significantly so (p=0.596), a study found no gender correlation however several research have linked
male sex to risk factors [31]. Other research indicated female predominance, as females are more likely to get UTIs
[32]. Short urethras and other factors may make this condition more common in girls. In early infancy, boys are
more prone to congenital deformity, but as they get older, the gender ratio reversesd [33]. Physician visit
preferences may explain male predominance in UTI. Significant risk factors reported in this study by univariate
analysis include prior antibiotic use (p<0.001), past UTI (p=0.016), and prior hospitalization (p=0.010). Children with
antibiotic history had 8.3 times the risk of ESBL-UTI. Third-generation Cephalosporin was 11 times riskier. Different
trials show different effects with prior antibiotic use, multiple studies indicated that antibiotic use was an
independent risk factor for ESBL-UTI [34]. Penicillin, second- and third-generation Cephalosporin, Quinolones,
Carbapenems, and Aminoglycosides, and suppression treatment (TMP/SMX, Nitrofurantoin) were risk factors for

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 114

ESBL-UTI [35]. Previous antibiotic therapy did not increase the risk of ESBL-UTI in children [36]. In a meta-analysis of
five investigations, uropathogens from children who had taken antibiotics were more than 10 times more likely to
be resistant. It increased risk may last up to six months after antibiotic treatment, It also found that restricting third-
generation Cephalosporins can suppress ESBL-producing bacteria in hospitals [37]. Children with a 3-month
hospitalization history had a 3-fold higher risk of ESBL-UTI, findings showed that hospitalization within 3 months was
an independent risk factor for ESBL-UTI in children [38]. Children may acquire ESBL-producing bacteria via
healthcare processes and become reservoirs for them. Returning to the community may cause ESBL-UTI [39]. In this
study, previous UTI in the recent 3 months increased ESBL-UTI risk by 9 times and [40] support this finding as well.
However, [41] observed that children having a history of UTI within 12 months were less likely to contract ESBL-
producing Enterobacteriacea. Multiple hospital stays and broad-spectrum antibiotics may generate ESBL-producing
bacteria [42]. None were independent risk factors for ESBL-UTI in children on multivariate binary logistic regression,
[44] supported this finding. A retrospective Korean investigation found no risk factors in up to 60% of babies with
community-acquired ESBL-producing uropathogens [45].

4. CONCLUSIONS
The Pediatrics and Microbiology departments of Sir Salimullah Medical College Mitford Hospital in Dhaka conducted
a cross-sectional study to investigate the risk factors for urinary tract infections caused by ESBL-producing bacteria
in children ranging in age from one month to twelve years based on the results of the study. In both the ESBL-UTI
(84.4%) and the non-ESBL-UTI (92.2%) groups, E. coli was the bacterium that became the most isolated. As far as
Afroz, Albaramki, Alim, Awean, Islam, Kim, Yang, and Kim, Rahman, and Topaloglu were concerned, the bacteria that
was most frequently isolated from UTI patients was E. coli. Due to the fact that the bacteria are present in the feces,
high E. coli ratios might lead to autoinfection. E. coli has the ability to produce a biofilm on the bladder wall that is
resistant to the immune system. According to the findings of this investigation, Pseudomonas was responsible for
6.3% of ESBL-UTI and 4.7% of non-ESBL-UTI. Pseudomonas was the second most common cause of urinary tract
infections (UTIs). According to the findings of earlier investigations, Klebsiella was the second most significant cause
and a significant risk factor for the development of ESBL. There are a variety of factors that can influence the type of
uropathogen and its dissemination, including the environment, the features of the host, the healthcare and
education programs, the socioeconomic levels, and the cleaning practices of each nation. The ESBL-UTI group had
an antimicrobial resistance rate that was much higher than the non-ESBL-UTI group's rate. There was a high level of
resistance among all ESBL isolates to Ceftazidime, Cefotaxime, and Cefuroxime. The next most resistant isolates
were Ceftriaxone, Cefixime, Amoxiclav, and Co-trimoxazole (p< Colistin, Imipenem, and Meropenem). E. coli was
the most prevalent of the uropathogens that were isolated, and this was true for both the ESBL and the non-ESBL-
UTI groups. The Cephalosporin group of antibiotics was ineffective against almost all of the ESBL-producing bacteria,
followed by Amoxiclav and Co-trimoxazole as the most effective antibiotics. Colistin emerged as the antibiotic with
the least amount of resistance, followed by imipenem and meropenem. Prior hospitalization and a history of urinary
tract infections were the two most important risk factors for urinary tract infections (UTIs) caused by ESBL-
producing bacteria. The most prominent risk factor was a history of antibiotic use in the past. An independent risk
factor for ESBL-positive urinary tract infections was not discovered in any of them. During the process of selecting a
suitable empirical therapy, the risk factors and antibiotic susceptibility pattern that were discovered in this study will
be of great assistance.It is recommended that ESBL testing be incorporated into the standard clinical practice. It is
important for clinicians to use caution while administering antibiotics.

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