Antibiotic Resistance Trends Among Out-patients With Urinary Tract Infections In North Western Tanzania

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Magembe , S. Mapunjo , E. Mayenga , J. Shao , C. Lubega , K. Makhaola , I. Lumu , Tanzania Fleming Fund Fellowship consortium doi: https://doi.org/10.1101/2025.05.14.25327543 E. Magembe 1 National Public Health Laboratory, Tanzania Find this author on Google Scholar Find this author on PubMed Search for this author on this site S. Mapunjo 3 Ministry of Health Tanzania Find this author on Google Scholar Find this author on PubMed Search for this author on this site E. Mayenga 1 National Public Health Laboratory, Tanzania Find this author on Google Scholar Find this author on PubMed Search for this author on this site J. Shao 4 African Society of Laboratory Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site C. Lubega 5 Makerere university Find this author on Google Scholar Find this author on PubMed Search for this author on this site K. Makhaola 4 African Society of Laboratory Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site I. Lumu 2 University of Edinburgh 5 Makerere university Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ivanlumu{at}outlook.com Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF ABSTRACT BACKGROUND Urinary tract infections (UTIs) are among the most common infections in the community and hospital settings and Enterobacteriaceae , are responsible for most infections. This study determined the prevalence and resistance trends of E. coli and K. pneumoniae to fluroquinolones and cephalosporins among out-patients diagnosed with urinary infections at a Zonal tertiary hospital in Tanzania METHODS This was a prospective cross sectional time series conducted in northern Tanzania and enrolled all out patients presenting with UTI symptoms. The study conducted for a period of six months between march 2021 to September 2021. RESULTS During the study period1582 patients were enrolled, the mean age was 20.2(SD 22.2) years and 883(55.8%) were female. The prevalence of E. coli was higher in female patients at 12.0% compared 6.7% in male. Both E. coli and K. pneumoniae were most prevalent in patients over >45 years at 13.3% and 3.2% respectively. E . coli resistance to Ceftriaxone, cefepime, and ciprofloxacin was 41.0%, 36.8% and 51.0% respectively. Resistance K. pneumoniae to ceftriaxone, cefepime, and ciprofloxacin was shown to be 52.8%, 47.4% and 28.2% respectively. Meanwhile, 76/192(39.6%) isolates were identified as ESBL. CONCLUSIONS In this setting empirical treatment of urinary tract infections with ciprofloxacin a commonly prescribed antibiotics for this diagnosis may not work in over half of patients when E,coli is the causative pathogen. Moreover, E. coli , resistance of 43% to ceftriaxone implies that patients who do not respond to initial therapy with ciprofloxacin, are at a risk of not responding to subsequent therapy necessitating the use of reserve antibiotics. INTRODUCTION Antimicrobial resistance is an emerging global public health and economic problem ( 1 , 2 , 3 ), associated with significant mortality and morbidity ( 4 , 5 ). It is estimated that by 2050, global mortality from antimicrobial resistance will reach 10 million deaths annually ( 5 , 6 ), and cost the global economy over 100 trillion dollars each year ( 6 ). Worldwide, E. coli and K. pneumoniae are the major causes of community infections, such as urinary tract and intra-abdominal infections. Antibiotic-resistant strains of Klebsiella pneumoniae , are prevalent worldwide, posing substantial challenges as they are often implicated in severe and life-threatening infections ( 7 ). Urinary tract infections (UTIs) rank among the most frequently encountered bacterial infections in community and hospital settings ( 8 ) UTIs, particularly uncomplicated cystitis in women, are a frequent cause of antibiotic use in the community and in hospital setting ( 9 ). Enterobacteriaceae, particularly E. coli, are the main pathogens, responsible for >80% of episodes of UTIs where a pathogen is identified and thus emphasizing their importance in antimicrobial surveillance ( 9 , 10 ). According to WHO, resistance E. coli isolates from urine samples to ceftriaxone ranged from 6% to 80%, while K. pneumoniae resistance to ceftriaxone ranged between 4 % and 90% in similar samples ( 11 ). In Tanzania, the AMR epidemiological landscape mirrors global trends, with studies indicating high resistance rates among E. coli and K. pneumoniae to commonly prescribed antibiotics, notably cephalosporins and fluoroquinolones ( 12 ). The Global Antimicrobial Resistance Partnership (GARP)-Tanzania Working Group AMR situation analysis reported that E. coli from urinary tract infections showed a 90% resistance to Ampicillin and 30-50% resistance to other common antibiotics. Extended-Spectrum Beta Lactamase (ESBL), which causes resistance to all beta lactam antibiotics, was found in 25-40% of E. coli (community and hospital sources) with more than 50% in children ( 13 ). Fluoroquinolones, cephalosporins and β lactamase inhibitor combinations have been commonly used as first-line treatment options for these pathogens. Third-generation cephalosporins are now used widely, due to an increase in fluoroquinolone resistance in many countries ( 11 , 15 ). In addition, Enterobacteriaceae that produce extended-spectrum beta-lactamases (ESBL) have become endemic in many parts of the world, including Tanzania (10.) thereby limiting available treatment options and heightening the risk of therapeutic failure ( 16 ).The 2017 edition of Standard Treatment Guidelines (STG/NEMLIT) recommended the use of ciprofloxacin, amoxicillin +clavulanic acid and ceftriaxone in managing UTIs (14.) but there are concerns about the emergence and spread of resistance strains This study, therefore, was conducted to determine the prevalence and resistance trends of E. coli and K. pneumoniae to fluroquinolones and cephalosporins among out-patients diagnosed with urinary infections at a Zonal tertiary hospital in Tanzania. METHODOLOGY This was a prospective cross-sectional time series study conducted for seven months between March and September 2021. The study included all outpatients diagnosed with Urinary tract infections (UTIs) at Bugando Medical Centre (BMC). BMC is a specialist and university teaching hospital for the Lake and Western zones of the United Republic of Tanzania. BMC is a tertiary referral hospital for eight regions and serves a catchment population of over 14 million people. The microbiology laboratory at BMC an ISO 15189 accredited laboratory and participates as a sentinel site for ARM surveillance. Sample collection and Laboratory procedures Midstream urine samples were collected by the patients after instructions, following local procedures, and submitted to the laboratory within 2 hours after collection. Caretakers of children under the age of 5 years were given instructions to collect the urine sample of children and submit it to the testing laboratory within the same time. All samples were processed following local Standard operating procedures (SOPs) for urine culture, inoculating 10 microliters on Blood Agar and MacConkey Agar (Himedia, India) at BMC laboratory. In this study, urine samples with >10 5 CFU/ml growth were considered positive (significant growth), a positive culture with one organism was considered a pure culture, and a growth of 2 pathogens, one or both with ≥10 5 CFU/ml growth, was also considered as positive. Both isolates were subsequently sub-cultured separately to obtain pure culture. A negative urine culture was defined as any growth <10 5 CFU/ml (no significant growth) and those without any bacterial growth. A urine sample showing more than two pathogens growth was considered contaminated, and the patient was instructed to provide another sample. Conventional biochemical identification method (Triple Sugar Iron (TSI), Sulfide Indole Motility (SIM), Citrate, Oxidase and Urease test) (Himedia, India) were done on appropriate quality controlled in-house prepared media by using established SOPs. Antibiotic susceptibility testing for ciprofloxacin 5μg, ceftriaxone 30μg, cefipime 30μg, ceftazidime 30μg, and amoxacillin/clavulanic acid 20/10μg, (Himedia, India) was performed to all identified isolates based on Clinical Laboratory Standard Institute guidelines ( 17 ) and 0.5 McFarland inoculum on Mueller Hinton agar (Himedia, India). Phenotypic ESBL production was determined based on the disc approximation method where ceftriaxone 30μg, ceftazidime 30μg and Amoxicillin/Clavulanic acid 20/10μg placed 20mm apart on Mueller Hinton Agar to estimate ESBL prevalence in E. coli and K. pneumoniae . A zone difference of >5mm was considered as ESBL positive. ATCC bacterial strains E. coli ATCC 25922 (Susceptible wild type B-lactamase negative), and K. pneumoniae ATCC 700603 (ESBL producing strain, SHV-18) were used as control strains for media quality assurance, biochemical identification, AST, and ESBL testing. The E. coli and K. pneumoniae isolates identified from urine samples collected from outpatients at BMC in Mwanza city were transported in cold chain to NPHL in Dar es Salaam for further confirmation and storage. Data management and statistical analysis We collected information on age, sex, specimen date, presenting symptoms, and a history of infection in the last three months. Clinical and demographic information, and microbiology data were entered into WHONET Software. Frequencies, percentages, and standard deviations were used to summarize the clinical characteristics of outpatients presenting with UTI. The proportion for K. pneumoniae and E. coli isolates recovered from urine samples, and along with the antibiotic susceptibility profile, was calculated. In some cases we combine intermediate and resistant results into a single group and report as non-susceptibility. The resistance percentage and 95% confidence interval of K. pneumoniae and E. coli against Fluoroquinolones and cephalosporins derived. The data presented is presented according to the CLSI guides( 18 ) and analysis was done using WHONET and R studio software. Ethical Consideration Ethical clearance for the study was issued by the National Institute for Medical Research-Reference code (NIMR/HQ/R.8a/Vol.IX/3554. RESULTS During the study period (March to September 2021), a total of 1582 patients were enrolled and 1582 non-repetitive urine samples were analysed. The mean age was 20.2 years (SD 22.2). Most samples 883(55.8%) were from Female patients (See Table 1 ). Out of 1582 processed specimens during the study period, 400 (25.2%) samples were culture positive and 1182 (74.7%) were culture negative or showed no significant growth. E. coli was isolated from 153 (9.7%) and K. pneumoniae from 39 (2.5%) while 208(13.1%) were identified as others isolates (supplementary table 1). The prevalence of E. coli was higher in female patients at 12.0% compared 6.7% in male. Meanwhile, the prevalence of K. pneumoniae was similar in both sexes. Both E. coli and K. pneumoniae were the most prevalent in patients aged over 45 years at 13.3% and 3.2% respectively (supplementary table 1) View this table: View inline View popup Download powerpoint Table 1. Demographic and Clinical characteristics of outpatients Patients presenting at BMC with suspected UTI, March - April 2022 Susceptibility patterns and trends Of 153 E. coli isolates, 151 were tested for susceptibility to third-generation cephalosporins (ceftriaxone), 152 to fourth-generation cephalosporins (cefepime), and 153 were tested for fluoroquinolones (ciprofloxacin). Resistance to Ceftriaxone was 41.0%, cefepime resistance was observed in 36.8% and for ciprofloxacin, 51.0% resistance ( Table 2 ). Of the 39 K. pneumoniae isolates 36 were tested for third-cephalosporins (ceftriaxone), 38 isolates tested for fourth-generation cephalosporins (cefepime), and all 39 isolates were tested against fluoroquinolones (ciprofloxacin), for which resistance was shown to be 52.8%, 47.4% and 28.2% respectively. View this table: View inline View popup Download powerpoint Table 2. Resistance profiles E. coli and K. pneumoniae for ceftriaxone, cefepime and ciprofloxacin, BMC, March – September 2021 Higher resistance was observed in both K. pneumoniae isolates from female patients compared to isolates from male patients ( Figure 1 ) Up to 36.2% of E . coli were resistant to Cefepime and 52.8% to Ciprofloxacin while for K. pneumoniae 54.5% resistance to cefepime(Table1). Meanwhile, 76/192(39.6%) isolates were ESBL phenotypes of which 57/192 (29.6%) were E. coli and 19/192 (9.9%) were K. pneumoniae isolated. Figure 2 shows the resistance trend of E . coli to ciprofloxacin, ceftriaxone and cefepime over 7 months. Generally, the resistance of E. coli to ciprofloxacin remained higher compared to ceftriaxone and cefepime the entire period. Download figure Open in new tab Figure 1. Resistance of E. coli and K. pneumoniae by sex, BMC, March – September 2021 Download figure Open in new tab Figure 2. Resistance trends of E. coli isolates by month, BMC, March – September 2021 DISCUSSION This study was conducted to investigate the prevalence and trends of resistance in uropathogens isolated from patients presenting with UTIs, with the ultimate goal of extrapolating this data to guide policymaking. Moreover, the investigators hoped to, highlight the need and demonstrate the feasibility of, a routine surveillance program at a sentinel in Tanzania. This study has shown that among UTI cases, at a tertiary referral hospital, E. coli was the most common causative pathogen in 9.7% (153) of cases, making it a representative uropathogen in AMR surveillance. We observed a high incidence of E . coli associated infection in female patients 12004/100,000 samples which was higher compared to male patients 6723/100,000. This finding is in agreement with other studies explaining that UTI is more prevalent in female patients than in male patients ( 19 ). Also, the prevalence for E. coli and K . pneumonie (13.3% vs 3.2%) was higher in patients between patients >45 years compared to other age groups. This implies that of the 100000 patients aged >45 years that attend BMC with signs of UTI, this will translate to patients will 13333/samples and 3157/ be diagnosed with UTI due to E. coli and K . pneumoniae respectively. This observation would be due to anatomical differences in females that predispose women to UTI and also age-related change as UTI become more common with advancing age in both sexes ( 20 ). Additionally, we observed a high incidence of ESBL (48718/100000 isolate) in K . pneumoniae isolate compared to E. coli isolate(37253/100000 isolates). The high proportion of ESBL would be due to recurrent and frequent UTIs, especially in females and older patients necessitating frequent use of antibiotics. E. coli and K. pneumoniae were the most common pathogen found in urine highlighting the need to continuously monitor their prevalence. These findings show high resistance rates to one of the second-line treatment options, according to the National Treatment Guidelines, and commonly used antibiotic for UTI treatment. A resistance rate of 51% for ciprofloxacin was shown among E. coli isolates, while this was 28.2% for K . pneumoniae isolates among patients treated for UTI. These findings imply that one in two of E. coli associated UTIs may not be responsive to empirical treatment of ciprofloxacin, while almost one-third of K. pneumoniae associated-UTIs may not be treated with Ciprofloxacin. The high resistance observed may be due to overuse of ciprofloxacin which until recently was the first line treatment for UTI according to National Guidelines ( 14 ). Additionally, urinary tract infections are more common in females than in males ( 19 , 20 ), leading to frequent use of antibiotics in this population group and consequently resulting in the high resistance rates of K. pneumonia observed in this study. We observed a generally high resistance to ciprofloxacin throughout the study period followed by ceftriaxone this would be due to the increased use of these antibiotics in routine care. Additionally, Ciprofloxacin is easily accessible in the community and this could be a driving factor for its misuse, and subsequently driving factor to AMR ( 21 ). The rise of ciprofloxacin resistance in June is difficult to explain but the observation period was equally short to shade sufficient light on this. Although cefepime is not commonly used in routine care the resistance trends are concerning and may be a result of cross resistance to other generations of cephalosporins which are more readily available. The study provided a sufficient number of isolates to highlight the AMR situation in Northern Tanzania among patients diagnosed or investigated for UTI. Moreover, this study was a prospective cross-sectional time series of ARM trends over 7 months. To our knowledge, this was the first time series conducted during the peak of the COVID-19 pandemic to investigate the resistance trends of ceftriaxone and ciprofloxacin in an outpatient settings. The current study highlights the significance of culture-guided therapy to improve patient care and antibiotic stewardship in an attempt to curb AMR in low and middle-income countries. On the other hand, the results this study should be interpreted with caution since the study was performed at a single tertiary referral hospital and there may be variations across the region. Additionally, the Zonal hospital receives patients with complicated medical histories, or that have been previously treated with antibiotics, thus overestimating the level of resistance. Lastly, no information on treatment outcomes was included in the current study. Of interest for future exploration could be a program investigating patient treatment outcome, as a measure to monitor effectiveness of empirical antibiotic treatment, and its effect on AMR in the indicator pathogens E. coli and K. pneumoniae . In summary, in this setting empirical treatment of urinary tract infections with ciprofloxacin a commonly prescribed antibiotic for this diagnosis may not work in over half of patients where E . coli is isolated. Moreover, the E. coli , non-susceptibility rate of 43% to ceftriaxone -the second-line option, means that patients not responding to initial therapy with ciprofloxacin, may not respond to subsequent therapy necessitating the use of reserve antibiotics. Data Availability The data is available via reasonable requests directed to the Tanzania Fleming Fund Fellowship consortium. Tanzania Fleming Fund consortium Nyambura Moremi., Kolader Marion., Schultsz Constance., Shumba.Edwin., Ondoa Pascale., Richard Walemwa., Beverly Egyir., Neema Kamala., Kayuni Gibbonce., Oskam Linda. Acknowledgement ME, LI, conceptualised and designed the study and drafted the first manuscript. LC LI, ME., Analysed and interpreted the data. MS, SJ, LI, ME Wrote sections of the manuscript LI, MK: supervised the writing of the manuscript and critically reviewed the manuscript We thank the study staff at Bugando Medical centre, Igembe Zechariah, and Peter Peter. Conflict of Interest: No conflict of interest to declare The data is available via reasonable requests directed to the Tanzania Fleming Fund Fellowship consortium. Footnotes Source of funds: This work was supported by the Department of Health and Social Care (DHSC)’s Fleming Fund using UK aid. The views expressed in this publication are those of the authors and not necessarily those of the UK DHSC or its management Agent. References 1. ↵ WHO ( 2015 ) Global antimicrobial resistance surveillance system (GLASS): manual for early implementation . Geneva: WHO 2. ↵ Jonas OB , Irwin A , Berthe FC , Le Gall FG , Marquez PV . Drug-resistant infections: a threat to our economic future . World Bank Rep . 2017 ; 2 : 1 – 32 . OpenUrl 3. ↵ Founou RC , Founou LL , Essack SY . Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis . PloS one . 2017 Dec 21; 12 ( 12 ): e0189621 . 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Gender and age-dependent etiology of community-acquired urinary tract infections . The scientific world journal . 2012 ; 2012 ( 1 ): 349597 . OpenUrl PubMed 21. ↵ Tchesnokova V , Larson L , Basova I , Sledneva Y , Choudhury D , Solyanik T , Heng J , Bonilla TC , Pham S , Schartz EM , Madziwa LT . Increase in the community circulation of ciprofloxacin-resistant Escherichia coli despite reduction in antibiotic prescriptions . Communications Medicine . 2023 Aug 12; 3 ( 1 ): 110 . OpenUrl PubMed View the discussion thread. Back to top Previous Next Posted May 16, 2025. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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