Abstract
Background
Urinary tract infections (UTIs) are the most prevalent infections, with a variety of etiologic agents, a high number of occurrences, relapses, and complications; also, antibiotic resistance of the pathogenic bacterium is a hugely significant challenge for physicians.
Objective
The goal of this research was to identify the common bacterial uropathogens as well as their susceptibility to commonly used antibiotics.
Materials and Methods
During the first six months of 2018, a descriptive cross-sectional study was conducted on urine samples of 1780 patients at FMIC based on culture. Bacterial typing was performed using cystine lactose electrolyte deficient agar and blood agar, and Kirby–Bauer disc diffusion was employed to assess the sensitivity of the bacteria to various antibiotics.
Results
Among 1780 patients in 341 (19.15%) samples, uropathogens were isolated. E. coli (63.9%), Enterococcus (11.1%), Serratia species (10.8%), Staphylococcus species (8.2%), Klebsiella (2.9%), Proteus species (1.8%), and Pseudomonas aeruginosa (1.2%) were the most common bacterial uropathogens. More than two-thirds of patients were female (69.6%), with the remaining 30.4% male. Ampicillin, amoxicillin, and erythromycin were the antibiotics with the highest resistance rates in bacterial uropathogens, at 92.6%, 82.9%, and 82.1%, respectively. Furthermore, ceftriaxone, ceftazidime, cefixime, and sulfamethoxazole were antibiotics with resistance rates exceeding 70%. The antibiotics pristinamycin and ticarcillin were the most sensitive, with a TRR of zero. Ertapenem, imipenem, amikacin, tazobactam, fosfomycin, vancomycin, and nitrofurantoin were the antibiotics with the lowest resistance rates (less than 10%).
Conclusion
E. coli was the most common bacterial uropathogen isolated in this study, followed by Enterococcus species. Our findings suggest that physicians, particularly in FMIC, consider E. coli, Enterococcus, Serratia and Staphylococcus as the most common bacteria, and use pristinamycin, ticarcillin, ertapenem, imipenem, amikacin, tazobactam, fosfomycin, vancomycin, and nitrofurantoin as sensitive antibiotics in empirical UTI treatment.
Keywords: antibiotic, bacterial, prevalence, susceptibility, uropathogen, UTI
Introduction
Urinary tract infections (UTIs) are the most common bacterial infection. Currently, they are one of the most frequent diseases which occur at any ages from the neonate to adult.1 Data shows that worldwide 150 million people are suffering from UTIs in developing countries.2,3 According to a 1997 assessment of National Ambulatory Medical Care and National Hospital Ambulatory Medical Care, UTIs account for approximately 7 million OPD visits, 1 million cases in emergency departments, and 100,000 hospital admissions. The incidence of UTIs is higher in women than men. By the age of 24, nearly one-third of women will have had at least one episode of a UTI that necessitates the use of antibiotics.2,3 Approximately 50% of women will experience at least one episode of a UTI at some point in their lives, and nearly 20% to 40% of women will have recurring infections.1,4 Infants, pregnant women2,5 and the elderly, and patients with spinal cord injuries, diabetes mellitus, multiple sclerosis, AIDS/HIV, and urologic abnormalities or catheters are all at higher risk of UTIs. Long-term catheterization increases the risk of UTIs, resulting in over 1 million UTI cases reported each year in hospitals and nursing homes.3,5 UTIs are the second most common infection in elderly, accounting for approximately one-quarter of all infections.2,3
The bacterial uropathogens differ according to factors such as gender, age, hospitalization, catheterization, and previous antibiotic exposure.6 According to various studies, Escherichia coli and other Enterobacteriaceae, Staphylococcus, and Enterococcus are the most prevalent uropathogens. Other etiological agents of UTIs include Klebsiella pneumoniae, Klebsiella oxytoca, Streptococcus agalactiae, Streptococcus viridans, Proteus mirabilis, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae, and Staphylococcus aureus.7
Drug resistance of bacterial uropathogens is a major issue in medical settings today,8 particularly in developing countries, where the issue is exacerbated by poverty, poor hygiene, and illiteracy.1,9 Although antibiotic resistance is a global health issue,6 developing countries are heavily involved in this problem due to the high prevalence of infectious diseases and the possibility that patients with resistant infections will not have access to the appropriate medications. On the other hand, factors such as poor sanitation, contaminated water, internal conflicts, and an increase in the number of immunocompromised HIV-infected individuals promote the emergence and rapid spread of resistant pathogens.9,10
Due to lack of hospital surveillance systems and computerized records in hospitals in developing countries such as Afghanistan, it is difficult to assess accurate incidences of UTI and bacterial resistance. As a result, the purpose of this study was to determine the prevalence of UTIs among patients at the French Medical Institute for Children, to identify the bacteria causing the infection and to investigate their antimicrobial resistance patterns, which may be of epidemiological significance given the prevalence of multidrug-resistant bacteria in Afghanistan.
Materials and Methods
This descriptive cross-sectional study was conducted at the French Medical Institute for Children from January to July 2018. The urine cultures of the 341 patients included in the study were evaluated for isolated microorganisms by culture. Patient information such as age, gender, as well as laboratory records on their susceptibility, antibiotic resistance and culture results, were collected.
This study was conducted in accordance with the Declaration of Helsinki and it was approved by the Ethical Board of the French Medical Institute for Children on September 14, 2017, proposal no: 09. All participants provided their consent before joining the study, and the consent of individuals under the age of 18 was taken from their parents or legal guardians.
Microbiological Methods for Bacteria Identification
Following the sample collection, urine samples with a clinical diagnosis of UTI were sent to the microbiology laboratory, after which they were cultured in cystine lactose electrolyte deficient agar and 5% sheep blood agar mediums. Uropathogenic bacteria was identified by standard conventional procedure in urine cultures, where a significant colony was detected by incubation at 37°C for 18–24 hours. Urinary tract infection was confirmed as a result of urine culture, with samples containing 100,000 CFU/mL and a single bacterial growth.
Antibiotic Susceptibility Method
The disk diffusion method was used to assess the in-vitro susceptibility of positive samples to the most commonly used antimicrobial drugs for UTI treatment, including ceftriaxone (30µg), amoxicillin-clavulanic acid (20/10µg), ceftazidime (30µg), aztreonam (30µg), ciprofloxacin (5µg), cefixime (5µg), trimethoprim-sulfamethoxazole (5/250µg), ertapenium (10µg), imipenem (10µg), amikacin (30µg), piperacillin/tazobactam (100/10µg), fosfomycin (200µg), ampicillin (10µg), gentamicin (10µg), pristinamycin, penicillin (10µg), and nitrofurantoin (300µg).
Statistical Analysis
Analysis of this study was performed using SPSS version 22.0. For continuous variables, the descriptive statistics were shown as mean and standard deviation. Nominal variables were presented as the number of cases and percentages. The overall resistance rate is calculated by adding the resistance rates of all tested cases to a specific antibiotic.
Results
In the first half of 2018, out of 1780 patients registered in FMIC, 341 (19.15%) of them had uropathogenic infection and 1439 (80.85%) of them were negative for uropathogenic infection. Among those with positive infection, 239 (70.1%) were female and 102 (29.9%) were male (Table 1). The mean age of participants was 25.9 years, with a standard deviation of 17.2 years.
Table 1.
Distribution of Patients in FMIC in the First Six Months of 2018 According to Uropathogenic Status by Sex
| Uropathogenic Status | Male | Female | Total | |||
|---|---|---|---|---|---|---|
| n | % | n | % | N | % | |
| Non-uropathogenic | 440 | 30.58 | 999 | 69.42 | 1439 | 80.85 |
| Uropathogenic | 102 | 29.9 | 239 | 70.1 | 341 | 19.15 |
| Total | 542 | 30.4 | 1238 | 69.6 | 1780 | 100.0 |
Among 341 patients who tested positive for bacteria in urine culture, bacterial microorganisms were isolated. The most common uropathogenic bacteria was E. coli, which counts for more than 60% of all cases. P. aeruginosa, Proteus spp., and Klebsiella spp. were the least common uropathogenic bacteria, with rates of less than 5%. The percentages of Enterococcus spp., Serratia spp., and Staphylococcus spp., were (11.1%, 38), (10.8%, 37), and (8.2%, 28), respectively (Figure 1).
Figure 1.
Distribution of microorganisms in positive samples of urine at the French Medical Institute for Children.
Ampicillin, amoxicillin, and erythromycin had the highest rates of antibiotic resistance among bacterial uropathogens, at 92.6%, 82.9%, and 82.1%, respectively. Antibiotics having a resistance rate of more than 70% included ceftriaxone, ceftazidime, and cefixime sulfamethoxazole. Furthermore, pristinamycin and ticarcillin were the most sensitive antibiotics, with a TRR of zero. The antibiotics with resistance rates below 10% were ertapenem, imipenem, amikacin, tazobactam, fosfomycin, vancomycin, and nitrofurantoin. Ampicillin, erythromycin, sulfamethoxazole and amoxicillin were the most resistant antibiotics for E. coli, Enterococcus spp., Staphylococcus spp., Serratia spp., Proteus spp., and Klebsiella spp. In addition, amoxicillin, ceftazidime, and ampicillin were the most resistant antibiotics for P. aeruginosa (Table 2 and Figure 2).
Table 2.
Antibiotic Resistance of UTI Isolated Bacteria at the French Medical Institute for Children
| Antibiotics | Uropathogenic Isolated Bacteria and Resistance Rate to Antibiotics | ||||||
|---|---|---|---|---|---|---|---|
| E. coli | Enterococcus spp. | Staphylococcus spp. | Serratia spp. | Proteus spp. | P. aeruginosa | Klebsiella spp. | |
| Ceftriaxone (N=272) | 165(77.4%) | 4(40.0%) | 0(0.0%) | 21(65.6%) | 1(20.0%) | 1(100%) | 5(50%) |
| Amoxicillin (N=281) | 182(84.2%) | 8(80%) | 0(0.0%) | 28(77.7%) | 5(83.3%) | 4(100%) | 6(75.0%) |
| Ceftazidime (N=269) | 163(77.9%) | 1(33.3%) | 0(0.0%) | 21(56.7%) | 2(33.3%) | 4(100%) | 4(50%) |
| Aztreonam (N=127) | 55(56.7%) | 0(0.0%) | 0(0.0%) | 9(42.8%) | 1(50%) | 1(50%) | 1(33.3%) |
| Ciprofloxacin (N=243) | 114(70.8%) | 22(75.8%) | 8(36.3%) | 11(57.8%) | 0(0.0%) | 2(100%) | 2(33.3%) |
| Cefixime (N=51) | 34(87.1%) | 0(0.0%) | 2(100%) | 2(50.0%) | – | – | 1(20.0%) |
| Sulfamethoxazole (N=186) | 97(81.5%) | 15(57.6%) | 12(80.0%) | 10(71.4%) | 2(50%) | 1(100%) | 2(28.5%) |
| Ertapenem (N=12) | 0(0.0%) | – | – | – | – | – | 1(25%) |
| Imipenem (N=115) | 1(1.1%) | 0(0.0%) | 0(0.0%) | 1(5.2%) | 0(0.0%) | 1(33.3%) | 0(0.0%) |
| Amikacin (N=330) | 6(2.7%) | 21(65.6%) | 0(0.0%) | 3(8.1%) | 0(0.0%) | 1(25%) | 0(0.0%) |
| Tazobactam (N=276) | 7(3.2%) | 0(0.0%) | 0(0.0%) | 0(0.0%) | 1(16.6%) | 1(33.3%) | 0(0.0%) |
| Fosfomycin (N=246) | 7(3.8%) | 4(28.5%) | 0(0.0%) | 0(0.0%) | 3(50.0%) | 2(100%) | 1(11.1%) |
| Ampicillin (N=284) | 202(93.9%) | 6(60.0%) | 4(80.0%) | 35(97.2%) | 5(100%) | 4(100%) | 7(77.7%) |
| Gentamicin (N=330) | 69(33.8%) | 23(71.8%) | 6(22.2%) | 12(37.5%) | 1(16.6%) | 1(25%) | 4(44.4%) |
| Pristinamycin (N=3) | – | 0(0.0%) | – | – | – | – | – |
| Fusidic acid (N=51) | – | 4(16%) | 5(19.2%) | – | – | – | – |
| Clindamycin (N=52) | 1(100%) | 12(42.8%) | 2(8.6%) | – | – | – | – |
| Rifampicin (N=52) | – | 5(19.2%) | 0(0.0%) | – | – | – | – |
| Ticarcillin (N=5) | – | 0(0.0%) | 0(0.0%) | – | – | – | – |
| Vancomycin (N=40) | 0(0.0%) | 1(100%) | 0(0.0%) | – | – | – | – |
| Penicillin (N=43) | – | 10(47.6%) | 13(59.0%) | – | – | – | – |
| Cefoxitin (N=29) | – | 5(55.5%) | 1(5%) | – | – | – | – |
| Erythromycin (N=56) | 2(66.6%) | 26(81.2%) | 18(75%) | – | – | – | – |
| Nitrofurantoin (N=244) | 16(8.2%) | 1(14.2%) | 0(0.0%) | 1(3.7%) | 2(40%) | – | 2(28.5%) |
Note: – means that this bacteria did not test for that antibiotic.
Figure 2.
Total resistance rate in UTI isolated bacteria at the French Medical Institute for Children.
Discussion
Urinary tract infections (UTIs) are the most common infections in society and hospitals. UTIs are known as a challenging issue for physicians due to their high rate of occurrence, relapse, complications, various etiologic agents and increasing drug resistance. Due to antibiotic misuse, which can present substantial therapeutic issues, bacterial resistance to antibiotics is a significant problem not only in UTIs but also in other diseases.
The prevalence of UTIs was found to be 19.15% in this study, while it was 13.9% in studies for isolating the etiologic agents and evaluating their resistance to antimicrobials conducted at Messalata Central Hospital, Libya.11 A study from Pakistan on the frequency and antimicrobial susceptibility of bacterial uropathogens on 1512 samples discovered that the frequency of culture-based uropathogens was 17.9%.12 However, research from Ethiopia discovered that, out of 687 urine samples, 28.38% of the patients had uropathogens. As a result, the prevalence of UTIs in Afghanistan is higher than in Libya and Pakistan, owing to poor adherence to hygiene and sanitation measures, as well as a lack of access to safe drinking water. The majority of patients in the current study, like many other studies,12–15 were female because their urethra is considerably shorter and closer to the anus than it is in men; making it easier for bacteria from the anus to enter the urinary tract. The most common uropathogen in UTIs has been identified as E. coli in the current study, which was also concluded in various countries around the world at different times.14–17 The second isolated uropathogen was Enterococcus, while some studies placed Klebsiella11,14,16 as the second uropathogen in the general factor sequence. Moreover, in some studies Enterococcus13 is reported as the second isolated uropathogen. Similar to that, Enterococcus (9.4%) came in second in the general factor in our study, followed by Serratia (9.1%). In the current study, isolated E. coli had the highest susceptibility to ertapenem, imipenem, amikacin, tazobactam, fosfomycin, and nitrofurantoin and the highest resistance to amoxicillin, cefixime, and ampicillin, with rates above 80%, because these three antibiotics are widely used in empirical therapy of UTI by physicians and patients in Afghanistan. E. coli isolates were 65.8%, 64.0%, 65.1%, and 66.4% susceptible to ciprofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and fosfomycin, respectively, compared to other studies such as research in Poland14 and a study in Turkey that revealed high resistance to ampicillin (87.3%), cefuroxime (71.6%) and trimethoprim/sulfamethoxazole (60.8%). The lowest resistance to nitrofurantoin (21.4%), tazobactam (19.1%), imipenem (8.6%), meropenem (8.8%), amikacin (6.2%) and cefoperazone/sulbactam (4.7%) was seen for all microorganisms.16 A study from Libya showed that amikacin had the highest susceptibility followed by imipenem and meropenem, with 0%, 0.6%, and 2.5% resistance rates, respectively, while cephalothin and ampicillin had the lowest sensitivity, with 80.6% and 90.0% resistance rates, respectively.11 In a study in Isfahan, bacterial uropathogens were relatively highly susceptible to imipenem (79.2%), ciprofloxacin (78.0%), and nitrofurantoin (70.8%) while sensitivity to cefotaxime (53%), cephalexin (39.8%) and trimethoprim/sulfamethoxazole (26.1%) was low; resistance to imipenem, cefotaxime, and cephalexin was more common in recurrent cases as well as in patients who had previously used antibiotics before being affected by a UTI.15 The sensitive antibiotics in isolated uropathogens in a study from Ethiopia18 and Pakistan12 were amikacin, gentamicin and nitrofurantoin. Additionally, nitrofurantoin, fosfomycin, and amikacin were found to be highly sensitive antibiotics in a study conducted in Mexico by Lagunas-Rangel.13 These antibiotics have also been shown to be highly sensitive in the current study.
In Afghanistan, there are geographical, social, economic, and lifestyle factors that influence drug resistance, particularly in UTIs. Geographically and socially, the majority of UTI patients lack access to medical facilities and thus utilize over-the-counter medications, which cause the resistance. Economically, most people do not have the opportunity to undertake urine culture and are treated empirically, which also increases the resistance rate. Regarding lifestyle, most people practice low sanitation and hygiene standards and consume contaminated water, which are additional variables that are thought to contribute to the rising rate of UTIs and resistance among UTI patients.
Conclusions
E. coli and Enterococcus spp. were the most frequently isolated UTI bacteria in this study in Afghanistan. Based on our research, it is recommended that physicians, particularly those working in the FMIC, use sensitive antibiotics such as pristinamycin, ticarcillin, ertapenem, imipenem, amikacin, tazobactam, fosfomycin, vancomycin, and nitrofurantoin in the empiric treatment of UTIs when they are suspected to be caused by E. coli, Enterococcus, Serratia and Staphylococcus.
Funding Statement
This study has been done without funding.
Ethical Considerations
The research proposal was approved by the Ethical Committee of the French Medical Institute for Children [project no: 14.09.2017/09].
Disclosure
The authors report no conflicts of interest in relation to this work.
References
- 1.Subramanian M, Ganesapandian S, Singh M, Kumaraguru A. Antimicrobial susceptibility pattern of urinary tract infection causing human pathogenic bacteria. Asian J Med Sci. 2011;3(2):56–60. [Google Scholar]
- 2.Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon. 2003;49(2):53–70. PMID: 12601337. doi: 10.1067/mda.2003.7 [DOI] [PubMed] [Google Scholar]
- 3.Foxman B, Brown P. Epidemiology of urinary tract infections: transmission and risk factors, incidence, and costs. Infect Dis Clin North Am. 2003;17(2):227–241. PMID: 12848468. doi: 10.1016/s0891-5520(03)00005-9 [DOI] [PubMed] [Google Scholar]
- 4.den Heijer CD, Donker GA, Maes J, Stobberingh EE. Antibiotic susceptibility of unselected uropathogenic Escherichia coli from female Dutch general practice patients: a comparison of two surveys with a 5 year interval. J Antimicrob Chemother. 2010;65(10):2128–2133. PMID: 20682565. doi: 10.1093/jac/dkq286 [DOI] [PubMed] [Google Scholar]
- 5.Emiru T, Beyene G, Tsegaye W, Melaku S. Associated risk factors of urinary tract infection among pregnant women at Felege Hiwot Referral Hospital, Bahir Dar, North West Ethiopia. BMC Res Notes. 2013;6:292. PMID: 23885968; PMCID: PMC3750516. doi: 10.1186/1756-0500-6-292 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Laxminarayan R, Chaudhury RR. Antibiotic resistance in India: drivers and opportunities for action. PLoS Med. 2016;13(3):e1001974. PMID: 26934098; PMCID: PMC4775002. doi: 10.1371/journal.pmed.1001974 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Bitew A, Molalign T, Chanie M. Species distribution and antibiotic susceptibility profile of bacterial uropathogens among patients complaining urinary tract infections. BMC Infect Dis. 2017;17(1):654. PMID: 28962545; PMCID: PMC5622472. doi: 10.1186/s12879-017-2743-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Serretiello E, Folliero V, Santella B, et al. Trend of bacterial uropathogens and their susceptibility pattern: study of single academic high-volume center in Italy (2015–2019). Int J Microbiol. 2021;2021:5541706. PMID: 34035817; PMCID: PMC8116166. doi: 10.1155/2021/5541706 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Seifu WD, Gebissa AD. Prevalence and antibiotic susceptibility of Uropathogens from cases of urinary tract infections (UTI) in Shashemene referral hospital, Ethiopia. BMC Infect Dis. 2018;18(1):30. PMID: 29320984; PMCID: PMC5763535. doi: 10.1186/s12879-017-2911-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Laxminarayan R, Heymann DL. Challenges of drug resistance in the developing world. BMJ. 2012;344:e1567. doi: 10.1136/bmj.e1567 [DOI] [PubMed] [Google Scholar]
- 11.Mohammed MA, Alnour TM, Shakurfo OM, Aburass MM. Prevalence and antimicrobial resistance pattern of bacterial strains isolated from patients with urinary tract infection in Messalata Central Hospital, Libya. Asian Pac J Trop Med. 2016;9(8):771–776. PMID: 27569886. doi: 10.1016/j.apjtm.2016.06.011 [DOI] [PubMed] [Google Scholar]
- 12.Malik N, Ahmed M, Ur Rahman M. Prevalence and antimicrobial susceptibility of uropathogens in patients reporting to a tertiary care facility in Peshawar, Pakistan. J Microbiol Antimicrob. 2015;7(1):6–12. doi: 10.5897/JMA2014.0323 [DOI] [Google Scholar]
- 13.Lagunas-Rangel FA. Antimicrobial susceptibility profiles of bacteria causing urinary tract infections in Mexico: single-centre experience with 10 years of results. J Glob Antimicrob Resist. 2018;14:90–94. PMID: 29581074. doi: 10.1016/j.jgar.2018.03.004 [DOI] [PubMed] [Google Scholar]
- 14.Stefaniuk E, Suchocka U, Bosacka K, Hryniewicz W. Etiology and antibiotic susceptibility of bacterial pathogens responsible for community-acquired urinary tract infections in Poland. Eur J Clin Microbiol Infect Dis. 2016;35(8):1363–1369. PMID: 27189078; PMCID: PMC4947106. doi: 10.1007/s10096-016-2673-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Karimian M, Kermani R, Khaleghi M, Kelishadi R, Ataei B, Mostafavi N. Antibiotic susceptibility patterns of isolates from children with urinary tract infection in Isfahan, Iran: impact on empirical treatment. J Glob Antimicrob Resist. 2017;9:3–7. PMID: 28232229. doi: 10.1016/j.jgar.2016.12.014 [DOI] [PubMed] [Google Scholar]
- 16.Demir M, Kazanasmaz H. Uropathogens and antibiotic resistance in the community and hospital-induced urinary tract infected children. J Glob Antimicrob Resist. 2020;20:68–73. PMID: 31340182. doi: 10.1016/j.jgar.2019.07.019 [DOI] [PubMed] [Google Scholar]
- 17.Sierra-Díaz E, Hernández-Ríos CJ, Bravo-Cuellar A. Antibiotic resistance: microbiological profile of urinary tract infections in Mexico. Cir Cir. 2019. 87(2):176–182. English. PMID: 30768071. doi: 10.24875/CIRU.18000494 [DOI] [PubMed] [Google Scholar]
- 18.Tesfa T, Baye Y, Sisay M, Amare F, Gashaw T. Bacterial uropathogens and susceptibility testing among patients diagnosed with urinary tract infections at Hiwot Fana Specialized University Hospital, Eastern Ethiopia. SAGE Open Med. 2021;9:20503121211001162. PMID: 33796299; PMCID: PMC7970184. doi: 10.1177/20503121211001162 [DOI] [PMC free article] [PubMed] [Google Scholar]