|Year : 2022 | Volume
| Issue : 1 | Page : 13-18
Multidrug-resistant organisms in urinary tract infections in Bangladeshi children: Where are we?
Md Ziaur R Chowdhury1, Md Benzamin2, Mohsina Khatoon3, Tuhin B Tamal1
1 Department of Pediatrics, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh
2 Department of Pediatric Gastroenterology and Nutrition, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh
3 Microbiology Department, Sylhet Women’s Medical College, Sylhet, Bangladesh
|Date of Submission||12-Jan-2022|
|Date of Acceptance||06-Mar-2022|
|Date of Web Publication||31-May-2022|
Dr. Md Benzamin
Pediatric Gastroenterology and Nutrition, Sylhet MAG Osmani Medical College Hospital, Sylhet
Source of Support: None, Conflict of Interest: None
Background: The incidence of antibiotic-resistant urinary tract infections (UTIs) in children, particularly multidrug-resistant (MDR) UTIs, is increasing day by day. Aims: The aim of this article is to describe the incidence of MDR UTIs in a pediatric population of Bangladesh. Materials and Methods: This retrospective, observational study was carried out by the Microbiology Department of Sylhet Women’s Medical College, Sylhet and Department of Pediatrics, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh. We reviewed the data record software of Microbiology Department of Sylhet Women’s Medical College and Popular Diagnostic Centre, Sylhet from April 2021 to October 2021 and collected all the urine culture-positive reports with symptom (UTI) and without symptom (asymptomatic bacteriuria) of children (0–18 years) and antibiotic sensitivity to different organisms. Patients with incomplete data were excluded from this study. A total of 39 patients were evaluated, and data were entered into Microsoft Excel and analyzed by SPSS software. This study got ethical approval from Departmental Review Board of Sylhet Women’s Medical College, Sylhet, Bangladesh. Results: Thirty-nine patients, including 13 (33.3%) males and 26 (66.7%) females, were included in this study, with a 1.92:1 female-to-male ratio. The mean age was 100.5 months (SD 90.5 months). MDR organism was identified in 23 patients (55%). Escherichia coli was the most common organism, found in 23 (59%) of the cultures, with the next being Klebsiella spp. 12 (30.8%), Enterococcus spp. 2 (5.1%), Pseudomonas aeruginosa 1 (2.6%), and Staphylococcus aureus 1 (2.6%). About 48% of E. coli, 75% of Klebsiella, 100% of Enterococcus, and 100% of Pseudomonas were MDR. Imipenem is 100% sensitive and linezolid is 100% resistant. Among the oral drugs, nitrofurantoin had less resistance. Conclusion: The majority of UTIs in children are MDR, with E. coli being the most common organism.
Keywords: Bangladeshi, children, multidrug-resistant, urinary tract infections (UTIs)
|How to cite this article:|
Chowdhury MZ, Benzamin M, Khatoon M, Tamal TB. Multidrug-resistant organisms in urinary tract infections in Bangladeshi children: Where are we?. Paediatr Nephrol J Bangladesh 2022;7:13-8
|How to cite this URL:|
Chowdhury MZ, Benzamin M, Khatoon M, Tamal TB. Multidrug-resistant organisms in urinary tract infections in Bangladeshi children: Where are we?. Paediatr Nephrol J Bangladesh [serial online] 2022 [cited 2023 Oct 4];7:13-8. Available from: http://www.pnjb-online.org/text.asp?2022/7/1/13/346346
| Introduction|| |
Antibiotic resistance (ABR) is a global threat to human health and international institutions such as the World Health Organization (WHO), the World Organization for Animal Health (OIE), and the Food and Agriculture Organization of the United Nations (FAO) create global action for this. International consensus now defines multidrug resistance as non-susceptibility to at least one antimicrobial in three or more classes, based on in vitro antibiotic susceptibility testing. Extensively drug-resistant (XDR) organisms are defined as isolates with susceptibility to only one or two antimicrobial classes, with resistance to agents in all the remaining categories. Pan-drug resistance is resistant to all agents in all antimicrobial classes.
Globally, antibiotic-resistant bacteria are being recorded at increasing rates. To understand the relevance of the threat posed by ABR, the WHO estimated that every year in the world, infections caused by multidrug-resistant (MDR) bacteria result in 700,000 deaths across all ages, of which around 200,000 are newborns. ABR is believed to be largely caused by the inappropriate use of antibiotics in both humans and animals. Although high-income countries continue to consume the most antibiotics in humans and animals, there has been a significant increase in low- and middle-income countries (LMICs) in recent decades.,[6-8] Within LMICs, most inappropriate use of antibiotics by humans probably results from the inappropriate prescribing and sale of antibiotics, mainly via poorly regulated private providers, for conditions that do not require antibiotics.,
Urinary tract infections (UTIs) represent one of the most frequent infectious diseases affecting humans, as well as an important public health issue with a significant economic burden. UTIs represent one of the most common bacterial infections in children and one of the main reasons for fever and antibiotic prescriptions.,
A minimum of 10 colony-forming units (CFUs) for catheter specimens and 105 CFUs for midstream clean catch specimens or 5 × 104 CFUs and significant pyuria in a patient with fever or other clinical symptoms was found. The incidence of the disease reaches 3% in neonates and is around 0.7% in infants up to 1 year. The prevalence of UTI in febrile infants is around 5%. The reported incidence of UTI is 7% among girls and 2% among boys during the first 6 years of life. A recurrence of infection is common in up to 11% of girls and 7% of boys, by the age of 16, and a recurrence of infection is common.
UTIs are primarily caused by Gram-negative bacteria. The main pathogen responsible for uncomplicated cystitis and pyelonephritis is Escherichia coli, followed by other species of Enterobacteriaceae, such as Proteus mirabilis and mostly Klebsiella pneumoniae, and by Gram-positive pathogens, such as Enterococcus faecalis and Staphylococcus saprophyticus.
The main goals in the treatment of childhood UTIs are rapid recovery from complaints and prevention of related complications such as urosepsis, urolithiasis, and renal abscess, as well as the prevention of permanent renal parenchymal damage. To achieve these aims, empirical antibiotic prescription is often endorsed even before the culture results are available.
ABR in pediatric patients is increasing. Currently, there is an alarming level of antimicrobial resistance that has developed in UTI pathogens as a result of improper and widespread use of antibiotics., Approximately 50% of all pediatric UTIs are susceptible to commonly used antibiotics., Antibiotic-resistant infections are most likely to be associated with greater morbidity and mortality and are associated with increased healthcare costs. The increasing ABR trends are likely to have important clinical implications for the empirical use of antibiotics. For this reason, knowledge of the etiological pathogens of UTIs and their antimicrobial resistance patterns in specific geographical locations may aid clinicians in choosing the appropriate antimicrobial empirical treatment.
Prior to this study, bacteria causing UTIs and their susceptibility patterns to most commonly used antibiotics had not been previously determined in Sylhet, Bangladesh, so the aim of this study was to characterize these factors in this region of Bangladesh.
| Materials and Methods|| |
This retrospective, observational study was carried out by the Microbiology Department of Sylhet Women’s Medical College, Sylhet and Department of Pediatrics, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh. We reviewed the data record software of Microbiology Department of Sylhet Women’s Medical College and Popular Diagnostic Centre, Sylhet from April 2021 to October 2021 and collected all the urine culture-positive reports with symptom (0–18 years) and antibiotic sensitivity to different organisms. In both centers, the mid-stream urine sample was collected in a sterile container without touching the skin and sent to the laboratory cautiously to prevent contamination. Patients’ age, sex, culture-positive organism, and sensitivity were the variables. Patients with incomplete data were excluded from this study. A total of 39 patients were evaluated and data were entered into Microsoft Excel and analyzed by SPSS software. This study got ethical approval from Departmental Review Board of Sylhet Women’s Medical College, Sylhet, Bangladesh.
| Results|| |
A total of 39 children with UTIs were included, 13 (33.3%) males and 26 (66.7%) females, with a 1.92:1 male-to-female ratio. The mean age was 100.5 months (SD 90.5 months), ranging from 28 days to 216 months of age. About 28% of children were between 1 and 12 months, 33.3% were between 13 and 60 months, and 38% between 61 and 216 months [Table 1].
[Table 2] shows the distribution of the isolated uropathogens. E. coli was the most common organism, found in 23 (59%) of the cultures, with the next being Klebsiella spp. 12 (30.8%), Enterococcus spp. 2 (5.1%), Pseudomonas aeruginosa 1 (2.6%), and Staphylococcus aureus 1 (2.6%).
[Table 3] shows the resistance patterns of the uropathogens in the study samples. Here we found that imipenem is 100% sensitive and linezolid is 100% resistant. Amikacin and gentamicin show less resistance. Among the oral drugs, nitrofurantoin had less resistance.
[Table 4] shows the extent of ABR. About 55% of the organisms were MDR. None of them was XDR or pan-drug resistant. About 48% of E. coli, 75% of Klebsiella spp., 100% of Enterococcus spp., and 100% of Pseudomonas were MDR.
[Figure 1] shows the ABR pattern of E. coli. Here, linezolid was 100% resistant and amikacin and imipenem were 100% sensitive.
| Discussion|| |
UTIs are commonly observed in children. Infection generally occurs with the colonization of the lower urinary tract by Gram-negative microorganisms. It may extend up to the bladder and kidneys depending on the pathogen’s characteristics. UTI is of major clinical importance owing to considerably high morbidity and mortality rates among children.
In this study, children with UTI were 33.3% male and 66.7% female, with a female-to-male ratio of 1.92:1. Similar findings with female predominance were observed by Islam et al. and Vazouras et al. Samancı et al. found 80% female with a male-to-female ratio of 1:4. In our study, the mean age was 100.5 months (SD 90.5 months), ranging from 28 days to 216 months. In other studies, mean age was variable, for example, Duicu et al. found a mean age of 4.13±4.48 years, Lutter et al. found a mean age of 31 months, and Samancı et al. found a mean age of 10.7±4.3 months.
In the present study, the most frequently isolated bacteria included E. coli (59%), followed by Klebsiella spp. 12 (30.8%), Enterococcus spp. 2 (5.1%), P. aeruginosa 1 (2.6%), and S. aureus 1 (2.6%).
Islam et al. found E. coli (70%), followed by Klebsiella spp. (13.6%), P. aeruginosa (4.2%), and Enterococcus spp. (3.40%). E. coli (87%), K. pneumoniae (3%), P. aeruginosa (2%), and Enterococcus species (2%) were identified as common organisms by Lutter et al. Mirsoleymani et al. found that the predominant agents of UTIs were successively E. coli (65.2%), Klebsiella spp. (26%), P. aeruginosa (3.6%), Staphylococcus coagulase-positive (3.7%), Citrobacter (0.9%), Enterobacter spp. (0.4%), and Proteus mirabilis (0.2%). Vazouras et al. found E. coli (79.2), followed by Klebsiella sp. (7.2%), Proteus sp. (5.1%), P. aeruginosa (4.7%), Enterobacter sp. (1.7%), Citrobacter sp. (0.4%), and Gram-positive cocci (1.7%). Samancı et al. found E. coli (85.8%) and this was followed by Klebsiella spp. (5.3%), Enterobacter spp. (3.3%), and Proteus spp. (2.1%). So in all studies, E. coli is the most common organism, followed by Klebsiella sp.
In our study, the resistance patterns of the uropathogens of study samples were found to be imipenem 100% sensitive and linezolid 100% resistant. Amikacin and gentamicin showed less resistance. Among the oral drugs, nitrofurantoin had less resistance. Islam et al. found that the most resistant drugs were colistin (94.55%), followed by cefradine (79.59%), cotrimoxazole (SXT) (69.39%), nalidixic acid (NA) (66.67%), and ceftazidime (CTM) (48.98%). Samancı et al. found high rates of amoxicillin-clavulanate, cefuroxime axetil, and TMP-SMX resistance in all microorganisms, whereas resistance to amikacin, meropenem, imipenem, ertapenem, fosfomycin, and nitrofurantoin was found at a low rate.
In the present study, about 55% of the organisms were MDR. None of them was XDR or pan-drug resistant. About 48% of E. coli, 75% of Klebsiella, 100% of Enterococcus, and 100% of Pseudomonas were MDR. Duicu et al. showed that 34.13% of the uropathogens were MDR, with E. coli infection at 39.74% MDR. Roberts et al. found MDR organisms in 12% of the patients. At the time of the MDR, the most common MDR organisms were E. coli (61%), Enterobacter species (25%), and Citrobacter species (17%). Esposito et al.’s findings are lower than all other studies with only 6.7% MDR and 0.2% XDR bacteria, and the most frequent MDR pathogens were E. coli (57.1%), P. aeruginosa (10.1%), K. pneumoniae (5.9%), and Proteus mirabilis (5.0%). The XDR pathogens were E. coli (3/4) and K. pneumoniae (1/4).
In the present study, E. coli was 100% resistant to linezolid and amikacin, whereas imipenem was 100% sensitive. There were variable percentages of resistance such as amoxyclav 33.3%, co-trimoxazole 27.1%, nitrofurantoin 4.1%, meropenem 4.5%, cefuroxime 52.2%, cephradine 70.6%, ceftazidime 66.7%, cefixime 69.6%, ciprofloxacin 30.4%, and levofloxacin 30.4%. It is 12.2% resistant to ampicillin, 12.2% resistant to amoxicillin/clavulanic acid, 19.3% resistant to ampicillin/sulbactam, 12.1% resistant to piperacillin-tazobactam, 26.5% resistant to trimethoprim-sulfamethoxazole, 5.9% resistant to gentamicin, and only 0.9% resistant to amikacin. Samanci et al. found the highest rates of resistance against ampicillin (61.2%) and TMP-SMX (38.7%); resistance to cefuroxime (30.2%), cefixime (28.9%), and ceftriaxone (27.2%) was found with lower frequencies for E. coli. The lowest rates of resistance were found against meropenem (2%), amikacin (0.4%), colistin (0.6%), ertapenem (1.5%), and imipenem (1.7%). Mirsoleymani et al. reported that E. coli specimens were 52.2% and 56.2% resistant to ceftriaxone and cefotaxime. Farajnia et al. reported a resistance rate of 90.7% to ampicillin, 51.8% to co-trimoxazol, and 26.5% to cefalexin, whereas the highest percentages of susceptibility were seen for amikacin (96.6%) and gentamicin (92.9%).
These significantly higher bacterial resistance rates to antibiotics in our country due to inappropriate use of antibiotics by humans probably result from the inappropriate prescribing and sale of antibiotics, mainly via poorly regulated private providers, for conditions that do not require antibiotics and also the inappropriate use of antibiotics in household-based, domestic, or “backyard” animal farming, e.g., domestic/household poultry farming.
| Conclusion|| |
MDR organisms account for a significant proportion of pediatric UTIs, and E. coli is the most common organism. Imipenem is 100% sensitive and linezolid is 100% resistant. Among the oral drugs, nitrofurantoin had least resistance. We suggest that empirical antibiotic selection should be based on knowledge of the local prevalence of bacterial organisms and antibiotic sensitivities rather than on universal or even national guidelines.
Benz and Associates Research Group, Bangladesh is acknowledged.
Financial support and sponsorship
The authors received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Health Organization, Food and Agriculture Organization of the United Nations & World Organisation for Animal Health. Antimicrobial Resistance: A Manual for Developing National Action Plans, Version 1. Geneva: World Health Organization; 2016.
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;18:268-81.
Van Boeckel TP, Pires J, Silvester R, Zhao C, Song J, Criscuolo NG, et al
. Global trends in antimicrobial resistance in animals in low- and middle-income countries. Science 2019;365:eaaw1944.
Fight Antimicrobial Resistance: Protect Mothers and Newborns. 4th Global Conference of Women Deliver. Copenhagen, Denmark: WHO Regional Office for Europe. 2016. Available from: http://who.int/drugresistance/activities/Women-Deliver-AMRside-event-Handout-May2016.pdf?ua=1
(accessed on March 19, 2021).
Holmes AH, Moore LS, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, et al
. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016;387:176-87.
Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, et al
. Global antibiotic consumption 2000 to 2010: An analysis of national pharmaceutical sales data. Lancet Infect Dis 2014;14:742-50.
Klein EY, Van Boeckel TP, Martinez EM, Pant S, Gandra S, Levin SA, et al
. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci USA 2018;115:E3463-70.
Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, et al
. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci USA 2015;112:5649-54.
Shallcross LJ, Davies DS Antibiotic overuse: A key driver of antimicrobial resistance. Br J Gen Pract 2014;64:604-5.
Knowles R, Sharland M, Hsia Y, Magrini N, Moja L, Siyam A, et al
. Measuring antibiotic availability and use in 20 low- and middle-income countries. Bull World Health Organ 2020;98:177-87C.
Mazzariol A, Bazaj A, Cornaglia G Multi-drug-resistant Gram-negative bacteria causing urinary tract infections: A review. J Chemother 2017;29:2-9.
Falup-Pecurariu O, Leibovitz E, Bucur M, Lixandru R, Bleotu L, Falup-Pecurariu C High resistance rates to 2nd and 3rd generation cephalosporins, ciprofloxacin and gentamicin of the uropathogens isolated in young infants hospitalized with first urinary tract infection. Biomed Res 2017;28:8774-9.
Ismaili K, Wissing KM, Lolin K, Le PQ, Christophe C, Lepage P, et al
. Characteristics of first urinary tract infection with fever in children: A prospective clinical and imaging study. Pediatr Infect Dis J 2011;30:371-4.
NICE. Urinary Tract Infection in Under 16s: Diagnosis and Management, Clinical Guideline CG54. National Institute for Health and Care Excellence, 2017. Available from: https://www.nice.org.uk/guidance/cg54/resources/urinary-tract-infection-in-under-16s-diagnosis-and-management-pdf-975507490501
Edlin RS, Shapiro DJ, Hersh AL, Copp HL Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol 2013;190:222-7.
Larcombe J Urinary tract infection in children: Recurrent infections. BMJ Clin Evid 2015;0306:1-9.
Beetz R, Westenfelder M Antimicrobial therapy of urinary tract infections in children. Int J Antimicrob Agents 2011;38(suppl.):42-50.
Abdullah FE, Memon AA, Bandukda MY, Jamil M Increasing ciprofloxacin resistance of isolates from infected urines of a cross-section of patients in Karachi. BMC Res Notes 2012;5:696.
Bonkat G, Bartoletti R, Bruyère F, Cai T, Geerlings SE, Köves B, et al
. EAU Guidelines on Urological Infections, 2017. p. 247-69. ISBN 978-90-79754-91-5.
Saperston KN, Shapiro DJ, Hersh AL, Copp HL A comparison of inpatient versus outpatient resistance patterns of pediatric urinary tract infection. J Urol 2014;191:1608-13.
Prabhu A, Taylor P, Konecny P, Brown MA Pyelonephritis: What are the present day causative organisms and antibiotic susceptibilities? Nephrology (Carlton) 2013;18:463-7.
Bryce A, Hay AD, Lane IF, Thornton HV, Wootton M, Costelloe C Global prevalence of antibiotic resistance 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 2016;352:i939.
Farajnia S, Alikhani MY, Ghotaslou R, Naghili B, Nakhlband A Causative agents and antimicrobial susceptibilities of urinary tract infections in the northwest of Iran. Int J Infect Dis 2009;13:140-4.
Kashef N, Djavid GE, Shahbazi S Antimicrobial susceptibility patterns of community-acquired uropathogens in Tehran, Iran. J Infect Dev Ctries 2010;4:202-6.
Samancı S, Çelik M, Köşker M Antibiotic resistance in childhood urinary tract infections: A single-center experience. Turk Arch Pediatr 2020;55:386-92.
Mortazavi F, Shahin N Changing patterns in sensitivity of bacterial uropathogens to antibiotics in children. Pak J Med Sci 2009;25: 801-5.
Islam MA, Begum S, Parul SS, Bhuyian AT, Islam MT, Islam MK Antibiotic resistance pattern in children with UTI: A study in a tertiary care hospital, Dhaka, Bangladesh. Am J Pediatr 2019;5: 191-5.
Vazouras K, Velali K, Tassiou I, Anastasiou-Katsiardani A, Athanasopoulou K, Barbouni A, et al
. Antibiotic treatment and antimicrobial resistance in children with urinary tract infections. J Glob Antimicrob Resist 2020;20:4-10.
Duicu C, Cozea I, Delean D, Aldea AA, Aldea C Antibiotic resistance patterns of urinary tract pathogens in children from Central Romania. Exp Ther Med 2021;22:748.
Lutter SA, Currie ML, Mitz LB, Greenbaum LA Antibiotic resistance patterns in children hospitalized for urinary tract infections. Arch Pediatr Adolesc Med 2005;159:924-8.
Mirsoleymani SR, Salimi M, ShareghiBrojeni M, Ranjbar M, Mehtarpoor M Bacterial pathogens and antimicrobial resistance patterns in pediatric urinary tract infections: A four-year surveillance study (2009–2012). Int J Pediatr 2014;1-6.
Kang KT, Ng K, Kendrick J, Tilley P, Ting J, Rassekh SR, et al
. Third-generation cephalosporin-resistant urinary tract infections in children presenting to the pediatric emergency department. Paediatr Child Health 2020;25:166-72.
Esposito S, Maglietta G, Costanzo MD, Ceccoli M, Vergine G, Scola CL, et al
. Retrospective 8-year study on the antibiotic resistance of uropathogens in children hospitalised for urinary tract infection in the Emilia-Romagna Region, Italy. Antibiotics 2021;10:1207.
Hicks JP, Latham SM, Huque R, Das M, Newell J, Abdullah SM, et al
. Antibiotic practices among household members and their domestic animals within rural communities in Cumilla district, Bangladesh: A cross-sectional survey. BMC Public Health 2021;21:406.
[Table 1], [Table 2], [Table 3], [Table 4]