PLOS ONE

RESEARCH ARTICLE

Prevalence, etiology and antibiotic resistance

patterns of community-acquired urinary tract
infections in Dhaka, Bangladesh
Mohammad Aminul Islam ID1,2*, Md Rayhanul Islam ID2☯, Rizwana Khan2☯, Mohammed
Badrul Amin2, Mahdia Rahman2, Muhammed Iqbal Hossain2, Dilruba Ahmed3,
Muhammad Asaduzzaman ID2,4, Lee W. Riley5
1 Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University,
a1111111111 Pullman, Washington, United States of America, 2 Laboratory of Food Safety and One Health, Laboratory
a1111111111 Sciences and Services Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b),
a1111111111 Dhaka, Bangladesh, 3 Clinical Microbiology Laboratory, Laboratory Sciences and Services Division,
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh, 4 Centre
a1111111111
for Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway, 5 Division of Infectious
a1111111111 Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, United
States of America

☯ These authors contributed equally to this work.

* amin.islam@wsu.edu
OPEN ACCESS

Citation: Islam MA, Islam MR, Khan R, Amin MB,

Rahman M, Hossain MI, et al. (2022) Prevalence, Abstract
etiology and antibiotic resistance patterns of
community-acquired urinary tract infections in Urinary tract infection (UTI) accounts for a significant morbidity and mortality across the
Dhaka, Bangladesh. PLoS ONE 17(9): e0274423. world and is a leading cause for antibiotic prescriptions in the community especially in devel-
https://doi.org/10.1371/journal.pone.0274423
oping countries. Empirical choice of antibiotics for treatment of UTI is often discordant with
Editor: Dwij Raj Bhatta, Tribhuvan University, the drug susceptibility of the etiologic agent. This study aimed to estimate the prevalence of
NEPAL
community-acquired UTI caused by antibiotic resistant organisms. This was a cross-sec-
Received: June 24, 2022 tional study where urine samples were prospectively collected from 4,500 patients at the
Accepted: August 30, 2022 icddr,b diagnostic clinic in Dhaka, Bangladesh during 2016–2018. Urine samples were ana-
Published: September 15, 2022 lyzed by standard culture method and the isolated bacteria were tested for antibiotic suscep-
tibility by using disc diffusion method and VITEK-2. Descriptive statistics were used to
Copyright: © 2022 Islam et al. This is an open
access article distributed under the terms of the estimate the prevalence of community acquired UTI (CA-UTI) by different age groups, sex,
Creative Commons Attribution License, which and etiology of infection. Relationship between the etiology of CA-UTI and age and sex of
permits unrestricted use, distribution, and patients was analyzed using binary logistic regression analysis. Seasonal trends in the prev-
reproduction in any medium, provided the original
alence of CA-UTI, multi-drug resistant (MDR) pathogens and MDR Escherichia coli were
author and source are credited.
also analyzed. Around 81% of patients were adults (�18y). Of 3,200 (71%) urine samples
Data Availability Statement: All relevant data are
with bacterial growth, 920 (29%) had a bacterial count of �1.0x105 CFU/ml indicating UTI.
within the paper and its Supporting Information
files. Women were more likely to have UTI compared to males (OR: 1.48, CI: 1.24–1.76). E. coli
(51.6%) was the predominant causative pathogen followed by Streptococcus spp. (15.7%),
Funding: This work was supported by the National
Institutes of Health (NIH), grant number: Klebsiella spp. (12.1%), Enterococcus spp. (6.4%), Pseudomonas spp. (4.4%), coagulase-
[R01AI116471] which was awarded to MAI. The negative Staphylococcus spp. (2.0%), and other pathogens (7.8%). Both E. coli and Klebsi-
funders had no role in study design, data collection ella spp. were predominantly resistant to penicillin (85%, 95%, respectively) followed by
and analysis, decision to publish, or preparation of
macrolide (70%, 76%), third-generation cephalosporins (69%, 58%), fluoroquinolones
the manuscript.
(69%, 53%) and carbapenem (5%, 9%). Around 65% of patients tested positive for multi-
Competing interests: The authors have declared
drug resistant (MDR) uropathogens. A higher number of male patients tested positive for
that no competing interests exist.

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 1 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Abbreviations: UTI, Urinary tract infection; CA- MDR pathogens compared to the female patients (p = 0.015). Overall, 71% of Gram-nega-
UTIs, community-acquired UTIs; CLSI, Clinical and tive and 46% of Gram-positive bacteria were MDR. The burden of community-acquired UTI
Laboratory Standards Institute; ESBL, extended
spectrum beta-lactamase; MDR, multi-drug
caused by MDR organisms was high among the study population. The findings of the study
resistant; 3GCr, third-generation cephalosporin- will guide clinicians to be more selective about their antibiotic choice for empirical treatment
resistant; icddr,b, International Centre for of UTI and alleviate misuse/overuse of antibiotics in the community.
Diarrhoeal Disease Research, Bangladesh.

Introduction
Urinary tract infections (UTIs) in both community and hospital settings are estimated to affect
around 405 million people globally and nearly 0.23 million people died of UTIs, contributing
to 5.2 million disability-adjusted life years (DALYs) in 2019 [1]. Treatment of UTI begins
empirically often with different broad-spectrum antibiotics [2]. The incidence of UTIs caused
by multidrug-resistant uropathogens has been increasing at an alarming rate worldwide. Such
common infections can turn into life-threatening illnesses, especially in developing countries
[3, 4]. The frequency, spectrum, and antibiotic resistance in uropathogens differ according to
geographical locations and time, which necessitates a thorough understanding of the epidemi-
ology of community-acquired UTIs (CA-UTIs) [5].
The predominant organism causing both complicated and uncomplicated UTI is uropatho-
genic Escherichia coli followed by Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabi-
lis, and group B Streptococcus (GBS) [6]. Further, multi-drug resistant E. coli and K.
pneumoniae are increasingly recognized to cause both CA-UTIs and hospital-acquired UTIs
[7, 8]. Because of these two pathogens, empirical treatment for acute pyelonephritis frequently
involves a third-generation cephalosporin [9]. However, inappropriate use of antibiotics is
very common in the management of CA-UTI. In developing countries, the scenario is debili-
tating as a significant proportion of UTI patients purchase antibiotics directly from commu-
nity pharmacies without prescription or any expert consultation [10, 11]. Consequently,
common antibiotics become ineffective. Although UTI can occur in any age and sex groups,
female children, women in their reproductive age, and older women are more vulnerable to
infections [12].
UTI is a significant public health problem in Bangladesh, which accounts for considerable
morbidity [13], health care cost [14] due to frequent treatment failure, and recurrent infec-
tions. UTI is also one of the main reasons for misuse of antibiotics in the community leading
to the escalating burden of antimicrobial resistance [11]. A study carried out in 2012 among
443 suspected UTI patients in a regional medical college hospital in Bangladesh showed that
43% of patients had significant bacterial growth of uropathogens in their urine samples [15]. A
recent study has shown that more than 75% of E. coli causing UTI are resistant to third-genera-
tion cephalosporin [16]. Existing reports are based on either a small sample size, targeting only
a specific population or age group, analysis of retrospective data from hospital registry, or
characterization of convenience samples of bacterial isolates obtained from urine samples of
UTI patients [17, 18]. The proportion of multi-drug resistant uropathogens is likely to have
increased over time. There is no large-scale prospective survey of UTIs in Bangladesh that can
provide an up-to-date information on the burden of infections in the community. Continuous
monitoring of the etiology of infections and antibiotic resistance pattern is essential not only
for selecting appropriate antibiotics for empirical therapy but also for reducing the overuse/
misuse of antibiotics. We carried out a community-based study to investigate the etiologies of
UTI along with antibiotic resistance profiles for 2 years in Dhaka, Bangladesh.

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 2 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Methods
Ethical approval
All participants provided written informed consent before taking part in the study. Written
informed consent was obtained from the parents/guardians of the minors (<16 years of age)
included in this study. The research team explained the background and objectives of the
study clearly to the participants. This study was approved by the Institutional Review Board
(IRB) of icddr,b (protocol number: PR 16071).

Study design
This study is a cross-sectional survey of patients from communities who visited the clinical
diagnostic center of the International Centre for Diarrhoeal Disease Research, Bangladesh
(icddr,b) from 1st September 2016 to 30th November 2018. The icddr,b clinical diagnostic cen-
ter serves as reference laboratories for clinical diagnostic analysis of human diseases cohorts
and control subjects. Approximately 1500 patients and individuals avail diagnostic services
each day from the diagnostic outpatient department. The diagnostic laboratories are the only
accredited laboratories under ISO15189 (quality) and ISO15190 (safety) in Bangladesh for as
many as 160 different tests and parameters. The diagnostic center only offers on-payment clin-
ical diagnostic services and does not provide any consultancy services to the patient. During
the study period, patient’s consents were taken every day from 9 am to 5 pm except for the
weekends and government holidays. Study physicians approached only those patients at the
diagnostic center who ordered for urine culture and sensitivity analysis and requested for their
willingness to allow the study team to use culture-sensitivity results of their urine sample and
use the resulting bacterial isolates for further characterization. In Bangladesh, it is not required
to show physician’s order to the diagnostic clinics for urine culture and sensitivity test and
patients can order for the test by themselves. We did not assess whether they had any urinary
tract complaints or had any symptoms of UTI but we used the following exclusion criteria for
enrolment of the patients: 1) patients having any medical or surgical device in their bodies
(e.g., catheter, cannula) 2) patients having renal stone 3) patients admitted to hospital. Enrolled
patients were segregated into three age groups: adults (�18y), adolescents (11-17y) and chil-
dren (0-10y).

Sample collection and processing

Clean catch midstream urine was collected in a sterile urine container by the patient or by the
caregiver of the patient (in case of children). Samples from the consented patients were labeled
with a green color sticker containing our study name for tracking. Urine culture was done in
the clinical microbiology lab of icddr,b following standard procedure within 1 h of collection
[19]. Briefly, a loopful (~10μl) of urine samples were streaked on MacConkey agar (Oxoid
Ltd., UK) and blood agar (Oxoid Ltd., UK) by a semi-quantitative method using a calibrated
loop. Plates were incubated at 35˚C aerobically and examined at 18–24 hours and they were
further incubated for another 24 hours before a negative report was issued. Cultures were
quantitated, and ‘significant’ bacteriuria was defined as a case of UTI in specimen containing
bacterial species �1.0x105 CFU/ml of urine according to the standard guideline [20]. Patients
with non-significant bacteriuria (<1.0x105 CFU/ml) were excluded from further analysis.

Identification of bacterial species

Isolates obtained from 1st September 2016 to 17th December 2017 were identified based on
Gram’s stain reaction, culture characteristics and biochemical properties as described earlier

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 3 / 13

PLOS ONE Community-acquired UTI in Bangladesh

[21], while the isolates obtained from 18th December 2017 to 30th November 2018 were identi-
fied using VITEK-2 system.

Antibiotic susceptibility tests

Antibiotic susceptibility testing of uropathogens isolated during the period from 1st September
2016 to 17th December 2017 was performed by the disk diffusion method following the Clinical
and Laboratory Standards Institute (CLSI) guidelines using commercially available antibiotic
disks (Oxoid Ltd., UK) [22]. Susceptibility testing for isolates obtained between 18th December
2017 to 30th November 2018 was done with VITEK 2 system. Antibiotic susceptibility tests were
performed against 37 commonly prescribed antibiotics from 13 different classes of which amino-
glycoside (gentamycin 10μg), macrolide (azithromycin 15μg), cephalosporins (ceftriaxone 30 μg;
cefotaxime 30μg; ceftazidime 30μg; cefepime 30μg; cefixime 5μg), penicillin (ampicillin 10μg),
penicillin/beta lactamase inhibitor combination(piperacillin-tazobactam 110μg), phenicols (chlor-
amphenicol 30μg), tetracycline (tetracycline 30 μg), linezolid (linezolid 30μg), (fluoro)quinolone
(nalidixic acid 30μg; ciprofloxacin 5μg), carbapenem (imipenem 10μg, meropenem, 10μg), nitro-
furans (nitrofurantoin 300μg), glycylcyclines (vancomycin 30μg) and sulfonamides (sulfamethox-
azole-trimethoprim 25μg) were tested against both Gram-positive and Gram-negative bacteria. In
addition, polymyxin (polymyxin-B 300μg) and glycopeptide (vancomycin 30μg) antibiotics were
tested only against Gram-negative and Gram-positive organisms, respectively. Isolates were cate-
gorized as sensitive, intermediate, or resistant according to the CLSI guideline. All third-genera-
tion cephalosporin-resistant E. coli isolates were tested for ESBL production by combination disk
diffusion test as described by CLSI using cefotaxime (CTX 30 μg), ceftazidime (CAZ, 30 μg) alone
and in combination with clavulanic acid (CLA, 10 μg) [22]. Isolates were considered as ESBL-pro-
ducer if the inhibition zone diameter was 5 mm larger with CLA than without [22]. If an organism
was resistant to at least one agent in three or more classes of antibiotics, it was categorized as mul-
tidrug resistant (MDR) [23]. All MDR E. coli isolates were subcultured on fresh MacConkey plates
and isolated colonies were stored at -80˚C for further analysis.

Data analysis
We entered data into SPSS 20.0 (IBM Inc., Chicago, USA). Data cleaning, statistical analyses,
and data visualization were done in Stata 13.0 (College Station, Texas, USA) and MS Office
Excel 2010 (Microsoft, Washington, USA). Descriptive statistics including frequency distribu-
tion, percentage, and cross-tabulation were done among different age groups, sex, and etiology
of infection. Percent of resistance to different antibiotics and resistance to multiple antibiotics
in each organism was determined. Data were analyzed to determine the association between
the proportion of samples that tested positive for MDR, non-MDR, third-generation cephalo-
sporin-resistant, and carbapenem-resistant organisms, with age and sex by Chi-square test and
Fisher exact test where applicable. Binary logistic regression was done by considering a sample
positive for MDR as a dependent variable and age, sex as independent variables. Seasonal
trends in the prevalence of CA-UTI, MDR pathogens, MDR, and non-MDR E. coli were ana-
lyzed to see the changing patterns of infection over two years (September 2016-November
2018). Statistical significance was determined at alpha = 0.05 for all tests.

Results
Prevalence of community acquired UTIs
During the period from September 2016 to November 2018, around 39,000 patients visited the
icddr,b diagnostic center in Dhaka for doing culture and sensitivity analysis of their urine

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 4 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Table 1. Characteristics of patients according to their age, sex and urine culture status.
Covariates Male (N = 1,237) n (%) Female (N = 3,263) n (%) Total (N = 4,500) n (%)
Age group
Adult (18 & above) 895 (72) 2,748 (84) 3,643 (81)
Adolescent (11–17) 48 (4) 95 (3) 143 (3)
Child (0–10) 294 (24) 420 (13) 714 (16)
Growth status
Growth positive 747 (60) 2,453 (75) 3,200 (71)
Significant growth (�105 CFU/ml of urine) 199 (27) 721 (29) 920 (29)
Insignificant (<105 CFU/ml of urine) 548 (73) 1,732 (71) 2,280 (71)
No growth 477 (39) 720 (22) 1,197 (27)
Collection Contamination (� 3 organisms) 13 (1) 90 (3) 103 (2)
https://doi.org/10.1371/journal.pone.0274423.t001

samples. In this study we enrolled 4,500 patients of which 3,643 (81%) were adults and 3,263
(73%) were females. Of these urine samples, 3,200 (71%) tested positive for microbial growth
on culture plates, of which 920 (29%) had a significant bacterial count (�1.0x105 CFU/ml of
urine), defined as cases of UTI (Table 1). According to this criterion, the prevalence of
CA-UTI cases among samples tested was 20% (920 of 4,500). The prevalence of CA-UTI was
significantly higher among adult patients compared to adolescents and children (OR: 1.86, CI:
1.48–2.34) (Table 2). The prevalence of CA-UTI was also significantly higher among female
patients (OR: 1.48, CI: 1.24–1.76) (Table 2). However, age-adjusted female patients and sex-
adjusted age showed a lower risk of CA-UTI than the crude rate (Table 2).

Etiologies of CA-UTI
Culture of urine samples from 920 patients yielded significant growth of uropathogens includ-
ing 849 (92%) monomicrobial (single bacterial species) and 71 (8%) polymicrobial (pair of two
different bacterial species) growths. A total of 991 [849+ (71� 2)] isolates were obtained from
920 patients of which 989 were bacterial isolates and 2 were identified as Candida spp. Among
bacterial isolates, E. coli was the predominant (51.6%), followed by Streptococcus spp. (15.7%),
Klebsiella spp. (12.1%), Enterococcus spp. (6.4%), Pseudomonas spp. (4.4%), coagulase negative
Staphylococcus spp. (2.0%), Enterobacter spp. (1.8%), Proteus spp. (1.6%), Acinetobacter spp.
(1.0%), Staphylococcus saprophyticus (1.1%), Staphylococcus aureus (0.6%), Corynebacterium
spp. (0.3%), Serratia spp. (0.3%), and Sphingomonas paucimobilis (0.3%). A significant propor-
tion of Streptococcus spp. and Enterococcus spp. were Streptococcus agalactiae (52%), and
Enterococcus faecalis (59%), respectively. Due to some limitations of conventional culture-

Table 2. Prevalence of community-acquired UTI among patients according to different age and sex groups.
Characteristics No (%) of UTI patients Age (Mean±SD) COR (CI) AOR (CI)
Age
Adult (n = 3,643) 808 (22) 45.96±16.11 1.86 (1.48,2.34) 1.76 (1.40,2.22)
Adolescent (n = 143) 17 (12) 14.33±4.56 0.88 (0.51,1.52) 0.86 (0.49, 1.49)
Child (n = 714) 95 (13) 4.70±5.25 1.00 1.00
Sex
Male (n = 1,237) 199 (16) 37.00±24.43 1.00 1.00
Female (n = 3,263) 721 (22) 38.95±20.18 1.48 (1.24,1.76) 1.39 (1.17, 1.66)

COR, crude odds ratios; AOR, adjusted odds ratios, CI, confidence intervals, SD, standard deviation

https://doi.org/10.1371/journal.pone.0274423.t002

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 5 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Fig 1. Prevalence of major bacterial pathogens causing community-acquired UTI among patients from 2016 to
2018.
https://doi.org/10.1371/journal.pone.0274423.g001

based methods in identifying organisms at species level we report the prevalence of some
organisms at genus level. Distribution of isolates over two years showed almost similar trends
with E. coli being the predominant organism in year 1 (52%) and year 2 (50%), followed by
Streptococcus spp. (15%, 17%, respectively), Klebsiella spp. (12%, 12%), Enterococcus spp. (7%,
5%), coagulase negative Staphylococcus spp. (5%, 4%), Pseudomonas spp. (2%, 2%), and other
pathogens (7%, 10%) (Fig 1). Of 71 polymicrobial infections, 39 (55%) tested positive for only
Gram-negative bacteria, 17 (24%) tested positive for only Gram-positive bacteria and 15 (21%)
tested positive for a mix of Gram-positive and Gram-negative bacteria. The predominant pair
of organisms (13 of 71) included lactose fermenting and non-fermenting E. coli followed by a
pair of E. coli and Klebsiella spp.

Antibiotic resistance patterns of uropathogens

Among Gram-negative bacteria, E. coli and Klebsiella spp. were resistant to different classes of
antibiotics with the highest rate of resistance to penicillin (85%, 95%, respectively) followed by
macrolide (70%, 76%), third-generation cephalosporins (69%, 58%), fluoroquinolone (69%,
53%) and sulfonamide (56%, 41%). The difference in the prevalence of resistance in E. coli and
Klebsiella spp. was significant for several antibiotics including third-generation cephalospo-
rins, fluoroquinolones, nitrofurantoin, and sulphonamide (Fig 2). For both E. coli and Klebsi-
ella spp. no significant variation in resistance frequency was observed between the two years
(Fig 2). Carbapenem resistance was the least prevalent in both E. coli (5%) and Klebsiella spp.
(9%) (Fig 2). Overall, 454 (71%) Gram-negative isolates were multidrug-resistant and E. coli
and Klebsiella spp. were the predominant with a prevalence of 74% and 68%, respectively. Of
510 E. coli isolates, 350 (69%) were third-generation cephalosporins resistant (3GCr) and 233
(67%) of 3GCr E. coli were positive for ESBL.

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 6 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Fig 2. Antibiotic resistance profiles of four major pathogens causing community-acquired UTI from 2016 to
2018. Only those antibiotics were included in the analysis for which the minimum number of isolates tested was 10.
https://doi.org/10.1371/journal.pone.0274423.g002

Of 260 Gram-positive bacterial isolates, antibiotic susceptibility test results were available
for 194 (75%) isolates. Among the prevalent Gram-positive organisms, both Streptococcus spp.
and Enterococcus spp. were predominantly resistant to macrolide (59%, 65%, respectively).
Only a small proportion (9%) of Streptococcus spp. was resistant to third-generation cephalo-
sporin (Fig 2). Overall, 46% of Gram-positive isolates were identified as MDR, Streptococcus
spp. and Enterococcus spp. were predominant with a prevalence of 37% and 35%, respectively.

Distribution of uropathogens according to age and sex

A significantly higher number of female patients (n = 721) had an infection with both Gram-
negative and Gram-positive bacteria (p<001). Male to female ratio among laboratory-con-
firmed CA-UTI patients were 1:3 (age-adjusted odds ratio: 1.39, CI: 1.17–1.66). E. coli was the
predominant uropathogen among adult female patients followed by Streptococcus spp., Klebsi-
ella spp., and Enterococcus spp. We observed similar trends among adult male patients except
that coagulase negative Staphylococcus spp. was more prevalent than Enterococcus spp. (Fig 3).

Distribution of MDR uropathogens according to age and sex

The prevalence of MDR-UTIs did not differ significantly in patients of different age groups.
However, a significantly higher proportion of male patients (73%) tested positive for MDR
organisms compared to their female counterparts (63%) (p = 0.015). The difference was prom-
inent among child patients. Male children had 72% (CI: 22%-90%) higher odds of being
infected with MDR organisms compared to their female counterparts (Table 3). However, the
difference was not statistically significant among patients positive for 3GCr and carbapenem
resistant organisms at any age group, although higher proportions of male adult and child
patients were positive for 3GCr organisms compared to their female counterparts (Table 4).

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 7 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Fig 3. Distribution of the prevalence of major pathogens causing CA-UTI among patients by age and sex.
https://doi.org/10.1371/journal.pone.0274423.g003

Temporal distribution of antibiotic-resistant uropathogens among patients

We analyzed the distribution of antibiotic resistance in 991 isolates over two years to find the
trends across years. There were no significant fluctuations in the prevalence of resistance to
any particular antibiotic over the years among major uropathogens such as E. coli, Klebsiella
spp., Streptococcus spp., and Enterococcus spp. (Fig 2). Overall, more than 50% of all Gram-
negative isolates (range: 53% to 95%) were found consistently resistant to penicillin, third-gen-
eration cephalosporins and fluoroquinolones. Prevalence of ESBL-producing E. coli has signif-
icantly increased over the years (p<0.05).

Discussion
Increased resistance to multiple antibiotics among pathogens causing CA-UTI leads to fre-
quent treatment failure and complications. Drug-resistant CA-UTI has become a major global

Table 3. Prevalence of MDR community-acquired UTI among patients according to different age and sex groups.
Covariates (n = 892)� MDR (n = 575) Age (yrs) (Mean±SD) Non-MDR (n = 317) Age (yrs) (Mean±SD) OR (CI)
Adult (n = 781) n (%) n (%)
Male (n = 157) 109 (69) 57.11±13.68 48 (31) 51.79±17.75 1
Female (n = 624) 393 (63) 51.99±15.33 231 (37) 46.25±16.37 0.75 (0.51, 1.09)
Adolescent (n = 17)
Male (n = 2) 1 (50) - 1 (50) - 1
Female (n = 15) 9 (60) 13.18±2.41 6 (40) 14.33±3.32 1.50 (0.07, 28.89)
Child (n = 94)
Male (n = 35) 29 (83) 2.66±2.66 6 (17) 1.42±1.24 1
Female (n = 59) 34 (58) 4.44±3.07 25 (42) 4.35±3.03 0.28 (0.10, 0.78)
�
Antibiotic susceptibility results were available for 892 out of 920 patients

https://doi.org/10.1371/journal.pone.0274423.t003

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 8 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Table 4. Prevalence of 3GCr and carbapenem-resistant pathogens among patients with community-acquired UTI.
Covariates� 3GCr n (%) Age (yrs) (Mean±SD) OR (CI) Covariates� CarbR n (%) Age (yrs) (Mean±SD) OR (CI)
Adult (n = 521) Adult (n = 521)
Male (n = 107) 77 (72) 58.88±12.97 1 Male (n = 107) 5 (5) 62.40±7.64 1
Female (n = 414) 271 (65) 53.27±14.17 0.74 (0.46–1.18) Female (n = 414) 20 (5) 53.15±16.58 1.04 (0.38–2.83)
Adolescent (n = 8) Adolescent (n = 8)
Male (n = 2) 1 (50) - 1 Male (n = 2) 1 (50) - -
Female (n = 6) 4 (67) 14.00±3.46 2 (0.07–51.59) Female (n = 6) 0 - -
Child (n = 58) Child (n = 58)
Male (n = 21) 15 (71) 2.00±1.85 1 Male (n = 21) 2 (10) 1.23±0.86 1
Female (n = 37) 24 (65) 4.67±3.03 0.74 (0.23–2.36) Female (n = 37) 2 (5) 8±1.41 0.54 (0.07–4.17)

CarbR, carbapenem resistant; n, number; 3GCr, 3rd generation cephalosporin resistant

�
One isolate represents one patient. A total of 587 Gram-negative isolates were tested for susceptibility against third-generation cephalosporin and carbapenem
antibiotics.

https://doi.org/10.1371/journal.pone.0274423.t004

health problem, especially in developing countries like Bangladesh. However, longitudinal sur-
veillance of CA-UTI estimating the burden of infection, etiology and antibiotic susceptibility
patterns of uropathogens in Bangladesh is largely missing except for a few small observational
studies among specific population groups such as pregnant women, children, and hospitalized
patients [15, 17, 24, 25]. We conducted this study to fill this critical knowledge gap. Among
4,500 patients enrolled in this study during the 2 years, the prevalence of laboratory-confirmed
CA-UTI cases (as defined by CFU �1.0x105 CFU/ml from urine culture) was 20% with
women bearing the greater burden (78%), similar to most studies of CA-UTI [26].
Although the majority of UTI cases were caused by a single pathogen, we found a small pro-
portion of patients had polymicrobial growth in their urine culture mostly E. coli coupled with
lactose non-fermenting E. coli or Klebsiella spp. In general, polymicrobial infections are less
common in young, healthy, sexually active females [27]. In our study, we found that polymi-
crobial cases were predominant among female adult patients (52.3 ± 15 years), and there was
no significant difference in prevalence among different age groups. Studies on polymicrobial
cases of UTI in Bangladesh are limited, one study reported that 5% patient had polymicrobial
growth in urine samples [15]. It is more likely that polymicrobial infections often go untreated
or treated with inappropriate antibiotics leading to the development of antibiotic resistance in
uropathogens [28].
Among monomicrobial cases, we found that Streptococcus spp. was the most prevalent
cause of CA-UTI after E. coli, which is in agreement with a previous study among adult
women in Dhaka slums [29]. However, two studies carried out with patients attending tertiary
level hospitals outside of Dhaka (in Rajshahi and Mymensingh), reported that Staphylococcus
saprophyticus was the second leading cause of UTI after E. coli [15, 18] while another study (in
Comilla) reported Klebsiella pneumoniae as the second leading cause [30]. There might be
some geographical variations in the etiology of UTI in Bangladesh, which might also be depen-
dent on the age, sex, sexual activity (for female), clinical features and demographic characteris-
tics of patients. However, irrespective of all variations among patients, E. coli appears to be the
most common cause of UTI, and thus combating E. coli infections would largely reduce the
burden of CA-UTI in the community. Among all Streptococcus spp. cases S. agalactiae or
Group B Streptococcus (GBS) accounted for 52% (n = 80) and around 9% of the total number
of patients with UTI; 92% (n = 74) of women were infected with GBS. In a previous study
among pregnant women in rural Bangladesh, only a small proportion of (5.3%) patients were
infected with GBS [24].

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 9 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Around 65% of the patients in our study tested positive for an MDR pathogen comprising
both Gram-positive and Gram-negative organisms, which is higher than the report from a
neighboring country Nepal [31, 32]. There is scarcity of data on the overall prevalence of MDR
pathogens in CA-UTI in Bangladesh and neighboring countries. The majority of studies
focused on resistance patterns of the predominant bacterial pathogen causing UTI, such as E.
coli or ESBL-producing E. coli. Among neighboring countries, a study in Kathmandu, Nepal
reported that 41% of bacterial pathogens from UTI cases were MDR [32]. A similar study from
Alighar, India reported that 42% of uropathogens were ESBL-producing, while another study
from Pakistan showed that 66% of uropathogens were ESBL-producing [33]. Studies from
India and Pakistan reported the occurrence of MDR E. coli as 43% and 59%, respectively [31,
34, 35]. In this study, we found that 74% of E. coli isolates were MDR and 69% of isolates were
resistant to third-generation cephalosporins, which is higher than the prevalence of MDR E.
coli (58%) reported earlier from Bangladesh [29]. Overall, 50% of all isolates were consistently
resistant to macrolide, and penicillin, and 80% of isolates were sensitive to carbapenem, glyco-
peptides and rifampicin. In the case of E. coli, a significant proportion (70%) was sensitive to
aminoglycosides, nitrofurantoin and carbapenem, which corroborates with data from other
countries [36–40].
We found that male patients were more likely to be infected with MDR organisms than
female patients. Similarly, prevalence of 3GCr and carbapenem-resistant organisms was higher
among adult male compared to adult females. This finding correlates with the results of a large
study conducted in Portugal where the prevalence of MDR uropathogens was higher in men
than in women (35% vs. 22%) [41]. However, among adolescents and children, the difference
in prevalence was not statistically significant. One of the reasons for the higher prevalence of
MDR organisms among adult male in our study could be the older age as we found mean ages
of the male adults with 3GCr and carbapenem-resistant infections were 58.9 (±13.0) and 62.4
(±7.6) years, respectively which is higher than the mean age for female adults with 3GCr (53.3
±14.2) and carbapenem (53.1±16.6) resistant infections. Older males usually develop UTIs as a
result of bladder outlet obstruction from prostate enlargement, which is often associated with
a higher prevalence of resistance due to recurrence and prolonged antibiotic treatment with
higher therapeutic doses [42, 43].
There were some limitations in our study. We carried out the surveillance among patients
who came to icddr,b diagnostic facility to test their urine samples for culture and sensitivity
analysis. A large proportion of patients receiving diagnostic services from icddr,b are the resi-
dents of Dhaka city and therefore the data may not be representative of the whole country.
icddr,b diagnostic facility only provides clinical diagnostic services and does not offer any out-
patient services and therefore, we could not estimate the proportion of patients with and with-
out symptomatic infection. Nevertheless, our study provides a recent insight into the etiology
of CA-UTI along with trends in antibiotic resistance among uropathogens over 2 years in a
large sample size for the first time in Bangladesh.

Conclusions
The burden of CA-UTI caused by MDR pathogens is high among the study participants and
there was no significant difference in prevalence and etiology of infection over two years. The
findings of the study can serve as an evidence base for updating guidelines for improved man-
agement of CA-UTI in Bangladesh and other developing countries with similar settings. It also
provides a basis to conduct epidemiologic studies to investigate risk factors for the acquisition
of antibiotic-resistant CA-UTI.

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 10 / 13

PLOS ONE Community-acquired UTI in Bangladesh

Supporting information
S1 Data. Data file for Figs 1–3 and the frequency of polymicrobial infections.
(XLSX)
S1 File. PLOS’ questionnaire on inclusivity in global research.
(DOCX)

Acknowledgments
We acknowledge the contribution of Dr. Progga Paromita and Dr. Refaya Noor for their sup-
port in enrolling patients during the first phase of the study. We are grateful for the invaluable
assistance of all the patients participated in the project.

Author Contributions
Conceptualization: Mohammad Aminul Islam, Lee W. Riley.
Data curation: Md Rayhanul Islam, Rizwana Khan, Muhammed Iqbal Hossain, Muhammad
Asaduzzaman.
Formal analysis: Mohammad Aminul Islam, Md Rayhanul Islam, Rizwana Khan, Mohammed
Badrul Amin, Mahdia Rahman, Muhammed Iqbal Hossain, Muhammad Asaduzzaman.
Funding acquisition: Mohammad Aminul Islam, Lee W. Riley.
Investigation: Mohammad Aminul Islam, Mahdia Rahman, Dilruba Ahmed, Muhammad
Asaduzzaman.
Methodology: Mohammad Aminul Islam, Mohammed Badrul Amin, Mahdia Rahman,
Muhammed Iqbal Hossain, Dilruba Ahmed.
Project administration: Mohammad Aminul Islam, Rizwana Khan, Mohammed Badrul
Amin, Muhammed Iqbal Hossain, Muhammad Asaduzzaman.
Supervision: Mohammad Aminul Islam.
Writing – original draft: Mohammad Aminul Islam.
Writing – review & editing: Mohammad Aminul Islam, Md Rayhanul Islam, Mohammed
Badrul Amin, Dilruba Ahmed, Muhammad Asaduzzaman, Lee W. Riley.

References
1. Zeng Z, Zhan J, Zhang K, Chen H, Cheng S. Global, regional, and national burden of urinary tract infec-
tions from 1990 to 2019: an analysis of the global burden of disease study 2019. World J Urol. 2022; 40
(3):755–63. https://doi.org/10.1007/s00345-021-03913-0 PMID: 35066637
2. Bryce A, Hay AD, Lane IF, Thornton HV, Wootton M, Costelloe C. Global prevalence of antibiotic resis-
tance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of
antibiotics in primary care: systematic review and meta-analysis. BMJ (Clinical research ed). 2016; 352:
i939. https://doi.org/10.1136/bmj.i939 PMID: 26980184
3. Mazzariol A, Bazaj A, Cornaglia G. Multi-drug-resistant Gram-negative bacteria causing urinary tract
infections: a review. J Chemother. 2017; 29(sup1):2–9. https://doi.org/10.1080/1120009X.2017.
1380395 PMID: 29271736
4. Gupta A, Bansal N, Houston B. Metabolomics of urinary tract infection: a new uroscope in town. Expert
Rev Mol Diagn. 2012; 12(4):361–9. https://doi.org/10.1586/erm.12.27 PMID: 22616701
5. Tandogdu Z, Wagenlehner FM. Global epidemiology of urinary tract infections. Curr Opin Infect Dis.
2016; 29(1):73–9. https://doi.org/10.1097/QCO.0000000000000228 PMID: 26694621

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 11 / 13

PLOS ONE Community-acquired UTI in Bangladesh

6. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mecha-
nisms of infection and treatment options. Nat Rev Microbiol. 2015; 13(5):269–84. https://doi.org/10.
1038/nrmicro3432 PMID: 25853778
7. Kim YH, Yang EM, Kim CJ. Urinary tract infection caused by community-acquired extended-spectrum
β-lactamase-producing bacteria in infants. J Pediatr. 2017; 93(3):260–6. https://doi.org/10.1016/j.jped.
2016.06.009 PMID: 27842212
8. Nai-Chia F, Hsin-Hang C, Chyi-Liang C, Liang-Shiou O, Tzou-Yien L, Ming-Han T, et al. Rise of commu-
nity-onset urinary tract infection caused by extended-spectrum β-lactamase-producing Escherichia coli
in children. J Microbiol Immunol Infect. 2014; 47:399–405. https://doi.org/http%3A//dx.doi.org/10.1016/
j.jmii.2013.05.006 PMID: 23834784
9. Albaramki JH, Abdelghani T, Dalaeen A, Khdair Ahmad F, Alassaf A, Odeh R, et al. Urinary tract infec-
tion caused by extended-spectrum β-lactamase-producing bacteria: Risk factors and antibiotic resis-
tance. Pediatr Int. 2019; 61(11):1127–32. https://doi.org/10.1111/ped.13911 PMID: 31206219
10. Leski TA, Taitt CR, Bangura U, Stockelman MG, Ansumana R, Cooper WH 3rd, et al. High prevalence
of multidrug resistant Enterobacteriaceae isolated from outpatient urine samples but not the hospital
environment in Bo, Sierra Leone. BMC Infect Dis. 2016; 16:167. https://doi.org/10.1186/s12879-016-
1495-1 PMID: 27090787
11. Auta A, Hadi MA, Oga E, Adewuyi EO, Abdu-Aguye SN, Adeloye D, et al. Global access to antibiotics
without prescription in community pharmacies: A systematic review and meta-analysis. J Infect. 2019;
78(1):8–18. https://doi.org/10.1016/j.jinf.2018.07.001 PMID: 29981773
12. Minardi D, d’Anzeo G, Cantoro D, Conti A, Muzzonigro G. Urinary tract infections in women: etiology
and treatment options. Int J Gen Med. 2011; 4:333. https://doi.org/10.2147/IJGM.S11767 PMID:
21674026
13. Noor R, Munna MS. Emerging diseases in Bangladesh: Current Microbiological Research Perspective.
Ci Ji Yi Xue Za Zhi. 2015; 27(2):49–53. https://doi.org/10.1016/j.tcmj.2015.01.003 PMID: 32288426
14. Rahman MM, Zhang C, Swe KT, Rahman MS, Islam MR, Kamrujjaman M, et al. Disease-specific out-
of-pocket healthcare expenditure in urban Bangladesh: A Bayesian analysis. PLoS One. 2020; 15(1):
e0227565. https://doi.org/10.1371/journal.pone.0227565 PMID: 31935266
15. Haque R, Akter ML, Salam MA. Prevalence and susceptibility of uropathogens: a recent report from a
teaching hospital in Bangladesh. BMC Res Notes. 2015; 8:416. https://doi.org/10.1186/s13104-015-
1408-1 PMID: 26342570
16. Acherjya GK, Tarafder K, Ghose R, Islam DU, Ali M, Akhtar N, et al. Pattern of antimicrobial resistance
to Escherichia coli among the urinary tract infection patients in Bangladesh. Am J Intern Med. 2018; 6
(5):132–7. https://doi.org/10.11648/j.ajim.20180605.17
17. Majumder MI, Ahmed T, Hossain D, Begum SA. Bacteriology and antibiotic sensitivity patterns of uri-
nary tract infections in a tertiary hospital in Bangladesh. Mymensingh Med J. 2014; 23(1):99–104.
PMID: 24584381
18. Parvin US, Hossain MA, Musa AK, Mahamud C, Islam MT, Haque N, et al. Pattern of aerobic bacteria
with antimicrobial susceptibility causing community acquired urinary tract infection. Mymenshingh Med
J. 2009; 18(2):148–53. PMID: 19623138
19. Murray PR, Barron EJ, Jorgensen JH, Pfaller MA, Yolken RH. Manual of Clinical Microbiology. 8th ed.
Washington DC: ASM Press; 2003.
20. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious diseases society of Amer-
ica guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis.
2005; 40(5):643–54. https://doi.org/10.1086/427507 PMID: 15714408
21. Isenberg HD. Essential procedures for clinical microbiology. Washington DC, ASM press,; 1998.
22. CLSI. Performance standards for antimicrobial susceptibility testing. 27th ed. CLSI supplement M100.
Wayne, PA, Clinical and Laboratory Standards Institute; 2017.
23. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant,
extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim
standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18(3):268–81. https://doi.org/
10.1111/j.1469-0691.2011.03570.x PMID: 21793988
24. Lee AC, Mullany LC, Koffi AK, Rafiqullah I, Khanam R, Folger LV, et al. Urinary tract infections in preg-
nancy in a rural population of Bangladesh: population-based prevalence, risk factors, etiology, and anti-
biotic resistance. BMC Pregnancy Childbirth. 2019; 20(1):1. https://doi.org/10.1186/s12884-019-2665-
0 PMID: 31892316
25. Das R, Ahmed T, Saha H, Shahrin L, Afroze F, Shahid AS, et al. Clinical risk factors, bacterial aetiology,
and outcome of urinary tract infection in children hospitalized with diarrhoea in Bangladesh. Epidemiol
Infect. 2017; 145(5):1018–24. https://doi.org/10.1017/S0950268816002971 PMID: 28029092

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 12 / 13

PLOS ONE Community-acquired UTI in Bangladesh

26. Linhares I, Raposo T, Rodrigues A, Almeida A. Frequency and antimicrobial resistance patterns of bac-
teria implicated in community urinary tract infections: a ten-year surveillance study (2000–2009). BMC
Infect Dis. 2013;13–19. https://doi.org/10.1186/1471-2334-13-19 PMID: 23327474
27. Kline KA, Lewis AL. Gram-positive uropathogens, polymicrobial urinary tract infection, and the emerg-
ing microbiota of the urinary tract. Microbiol Spectr. 2016; 4(2):10. https://doi.org/10.1128/
microbiolspec.UTI-0012-2012 PMID: 27227294
28. Croxall G, Weston V, Joseph S, Manning G, Cheetham P, McNally A. Increased human pathogenic
potential of Escherichia coli from polymicrobial urinary tract infections in comparison to isolates from
monomicrobial culture samples. J Med Microbiol. 2011; 60(Pt 1):102–9. https://doi.org/10.1099/jmm.0.
020602–0
29. Rahman SR, Ahmed MF, Begum A. Occurrence of urinary tract infection in adolescent and adult
women of shanty town in Dhaka city, Bangladesh. Ethiop J Health Sci. 2014; 24(2):145–52. https://doi.
org/10.4314/ejhs.v24i2.7 PMID: 24795516
30. Majumder MMI, Ahmed T, Ahmed S, Khan AR, Saha CK. Antibiotic resistance in urinary tract infection
in a tertiary care hospital in Bangladesh-A follow-up study. Med Today. 2019; 31(1):9–14.
31. Awasthi TR, Pant ND, Dahal PR. Prevalence of multidrug resistant bacteria in causing community
acquired urinary tract infection among the patients attending outpatient department of Seti zonal hospi-
tal, Dhangadi, Nepal. Nepal J Biotechnol. 2015; 3(1):55–9.
32. Baral P, Neupane S, Marasini BP, Ghimire KR, Lekhak B, Shrestha B. High prevalence of multidrug
resistance in bacterial uropathogens from Kathmandu, Nepal. BMC Res Notes. 2012; 5:38. https://doi.
org/10.1186/1756-0500-5-38 PMID: 22260454
33. Sohail M, Khurshid M, Saleem HG, Javed H, Khan AA. Characteristics and antibiotic resistance of uri-
nary tract pathogens isolated from Punjab, Pakistan. Jundishapur J Microbiol. 2015; 8(7):e19272.
https://doi.org/10.5812/jjm.19272v2 PMID: 26421129
34. Kulkarni SR, Peerapur BV, Sailesh KS. Isolation and antibiotic susceptibility pattern of Escherichia coli
from urinary tract infections in a tertiary care hospital of north eastern Karnataka. J Nat Sci Biol Med.
2017; 8(2):176–80. https://doi.org/10.4103/0976-9668.210012 PMID: 28781483
35. Ali I, Rafaque Z, Ahmed S, Malik S, Dasti JI. Prevalence of multi-drug resistant uropathogenic Escheri-
chia coli in Potohar region of Pakistan. Asian Pac J Trop Biomed. 2016; 6(1):60–6.
36. Zhang H, Kong H, Yu Y, Wu A, Duan Q, Jiang X, et al. Carbapenem susceptibilities of Gram-negative
pathogens in intra-abdominal and urinary tract infections: updated report of SMART 2015 in China.
BMC Infect Dis. 2018; 18(1):493. https://doi.org/10.1186/s12879-018-3405-1 PMID: 30268102
37. Kabugo D, Kizito S, Ashok DD, Graham KA, Nabimba R, Namunana S, et al. Factors associated with
community-acquired urinary tract infections among adults attending assessment centre, Mulago hospi-
tal Uganda. Afr Health Sci. 2016; 16(4):1131–42. https://doi.org/10.4314/ahs.v16i4.31 PMID:
28479906
38. Dehbanipour R, Rastaghi S, Sedighi M, Maleki N, Faghri J. High prevalence of multidrug-resistance
uropathogenic Escherichia coli strains, Isfahan, Iran. J Nat Sci Biol Med. 2016; 7(1):22–6. https://doi.
org/10.4103/0976-9668.175020 PMID: 27003964
39. Maraki S, Mantadakis E, Michailidis L, Samonis G. Changing antibiotic susceptibilities of community-
acquired uropathogens in Greece, 2005–2010. J Microbiol Immunol Infect. 2013; 46(3):202–9. https://
doi.org/10.1016/j.jmii.2012.05.012 PMID: 22795650
40. Tillekeratne LG, Vidanagama D, Tippalagama R, Lewkebandara R, Joyce M, Nicholson BP, et al.
Extended-spectrum ß-lactamase-producing Enterobacteriaceae as a common cause of urinary tract
infections in Sri Lanka. Infect Chemother. 2016; 48(3):160–5. https://doi.org/10.3947/ic.2016.48.3.160
PMID: 27704730
41. Linhares I, Raposo T, Rodrigues A, Almeida A. Incidence and diversity of antimicrobial multidrug resis-
tance profiles of uropathogenic bacteria. BioMed Res Int. 2015; 2015:354084. https://doi.org/10.1155/
2015/354084 PMID: 25834814
42. Nicolle LE. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol. 2005; 16
(6):349–60. https://doi.org/10.1155/2005/385768 PMID: 18159518
43. Lipsky BA. Urinary tract infections in men. Epidemiology, pathophysiology, diagnosis, and treatment.
Ann Intern Med. 1989; 110(2):138–50. https://doi.org/10.7326/0003-4819-110-2-138 PMID: 2462391

PLOS ONE | https://doi.org/10.1371/journal.pone.0274423 September 15, 2022 13 / 13