Abstract
Type 2 diabetes mellitus (T2DM) is a known risk factor for recurrent urinary tract infections (rUTIs), which impacts the response to antimicrobial therapy due to glycemic variability. This study aimed to evaluate the association between glycemic control and antimicrobial treatment response in T2DM patients with rUTIs.
A prospective observational comparative cohort study was conducted in the Wasit province of Iraq at Al-Zahraa Teaching Hospital and private internal medicine clinics from October 2024 to June 2025. Patients with rUTIs were enrolled, including patients with T2DM. Patients underwent structured follow-up at Days 1, 3, 7, and 30. Laboratory testing, urine cultures, antibiotic sensitivity tests, and antimicrobial prescriptions were assessed. Outcomes included clinical cure (Day 14) and recurrence (Day 30).
Among the 99 patients who participated, 58 (58.6%) had diabetes, while the remaining 41 (41.4%) were non-diabetic. The most frequently identified bacteria in this study were Escherichia coli (32%), Staphylococcus aureus (20%), Enterococcus species (15%), Pseudomonas aeruginosa (17%), and Proteus spp. (7%). The study results demonstrate a significant association between diabetes status and the age of patients (p-values of <0.001). Furthermore, there was a significant association between UTI recurrence and RBS, the HbA1c variable (p-value=0.001). Patients with poor glycemic control demonstrated substantially higher recurrence rates within 30 days following treatment (65%) compared with patients with good glycemic control (22.2%), whereas no recurrence was observed among non-diabetic patients. Resistance patterns were more prominent in the uncontrolled group. Poor glycemic control was associated with increased UTI recurrence despite adequate initial antimicrobial response, underscoring the importance of glycemic optimization for sustained treatment success.
Plain Language Summary
Urinary tract infections (UTIs) occur more frequently in people with type 2 diabetes and often recur after treatment. This study investigated how blood glucose control and disease severity influence the response to antimicrobial therapy and the likelihood of infection recurrence. A prospective study was conducted among patients with type 2 diabetes who experienced recurrent UTIs. Clinical data, laboratory findings, and antimicrobial susceptibility patterns of the isolated bacteria were evaluated. Patients were categorized according to their glycemic status to assess whether blood sugar control affected treatment outcomes. The results suggest that better glycemic control is associated with improved response to antimicrobial therapy and may reduce the risk of recurrent infections. The study also highlights variations in antimicrobial susceptibility among the bacterial isolates, emphasizing the importance of culture-guided therapy. These findings may help clinicians optimize the management of recurrent UTIs in diabetic patients by considering both glycemic control and appropriate antimicrobial selection.
Keywords
Introduction
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder marked by persistent hyperglycemia resulting from the body’s impaired response (insulin resistance). 1 In Iraq, almost 90% of global diabetes cases are categorized as T2DM. The estimated overall incidence of diabetes in Iraq is 2.18%, with a greater prevalence among urban residents compared to their rural counterparts. Moreover, the incidence rates of diabetes are higher in the southern part of Iraq than in the Kurdistan region. All of these rates increase markedly with advancing age, especially after 50. Consequently, there is a growing burden of disease associated with T2DM. 2
Individuals suffering from diabetes have a higher risk of developing infections because their bodies do not effectively fight off infection-causing bacteria due to a reduction in the immune system’s ability to respond. Urinary tract infections (UTIs) have become a common complication among diabetic patients, leading to increased morbidity and poor glucose level control. Numerous studies have established the significance of glycemic control concerning the incidence of UTIs, with uncontrolled glycemia increasing both the likelihood and severity of these infections, particularly in women aged 40 and above. 3 T2DM patients have been identified as being of greater interest to researchers in the past since they have been shown through numerous research studies to have UTIs more frequently than non-T2DM patients. 4 Annually, UTIs affect approximately 150 million people worldwide. This burden compounds a massive global metabolic crisis; the International Diabetes Federation reported 451 million diabetic adults globally in 2017, a figure projected to climb to 693 million by 2045. The prevalence of UTIs among DM patients varies significantly across regions. Studies report a prevalence of 29.82% in Romania, 11% in India, 51.3% in hospitals in Egypt and 15.97% in Ethiopia. 5 Of these people, 79% live in middle- and low-income nations. 6 In the Middle East, A systematic review and meta-analysis indicated an overall UTI prevalence of 11.5% in type 2 diabetic patients, with variations based on age and research duration 7 In Iraq, specific studies reveal even higher rates; for instance, a study in Misan Province reported a UTI prevalence of 65% among diabetic patients, with Escherichia coli being the most common pathogen 8 Recurrent urinary tract infection (rUTI) is defined as ≥2 episodes within 6 months or ≥3 episodes within 1 year. 9 rUTIs pose a major obstacle to the treatment of patients with diabetes, as the levels of antimicrobial resistance (AMR) and persistence of infections are elevated. 10 Several pathophysiological mechanisms contribute to this increased risk, including impaired leukocyte function, reduced immune response, autonomic neuropathy leading to incomplete bladder emptying, and glycosuria that promotes bacterial growth. 11 In addition, certain therapeutic agents such as sodium–glucose cotransporter-2 (SGLT2) inhibitors have been associated with an increased risk of genitourinary infections due to enhanced urinary glucose excretion. 12 The incidence of UTIs varies depending on the agent used and the population characteristics and is reported to range from 3% to 9%. This clinical safety concern, in light of SGLT2 inhibition glucosuria, may provide an environment for microorganisms to prosper and promote pathogen infections’ initiation and progress. 13 The patient exhibiting bacterial persistence should be evaluated for an anatomical anomaly that facilitates bacterial survival. 14 Factors that may facilitate bacterial persistence include calculi, foreign bodies, urethral diverticula, or a unilaterally affected kidney 15 Importantly, poor glycemic control has been consistently linked to increased infection recurrence and antimicrobial resistance, making metabolic control a key determinant of treatment outcomes. 16 Despite these associations, there is a lack of prospective studies from Middle Eastern countries, particularly Iraq, evaluating the relationship between glycemic status, antimicrobial response, and recurrence in patients with rUTIs. Consequently, this study seeks to assess the response to antimicrobial therapy in patients with rUTIs based on glycemic status in individuals with T2DM compared to non-diabetic patients in order to evaluate the patterns of antimicrobial resistance. Additionally, the study aims to assess recurrence rates following treatment.
Methods
Study design and setting
This study was a prospective, observational, comparative cohort study conducted in a clinical setting without randomization or intervention allocation. The study was conducted in a period between October 2024 and June 2025 during their visits to AL Zahraa Teaching Hospital and the private clinic of internal medicine seeking treatment. A convenience sampling technique was used to recruit eligible patients during the study period. The sample size (n = 99) was determined based on feasibility and patient availability during the study duration. A convenience sampling approach was adopted due to the limited availability of eligible patients with rUTIs who fulfilled the predefined inclusion criteria during the study period. In addition, the feasibility-based sample size was considered appropriate for this prospective clinical investigation because of the restricted study duration, available clinical resources, and the exploratory nature of the study.
Inclusion criteria
Participants were eligible for enrollment according to the following group-specific eligibility criteria:
General eligibility criteria for all participants included: 1. Age ≥ 18 years, of either sex. 2. A documented diagnosis of T2DM for at least one year prior to enrollment. 3. Diagnosis of rUTI, confirmed through clinical history, urinary symptoms, positive general urine examination findings, and urine culture results when available, according to established clinical guidelines. 4. Ability to communicate effectively and provide accurate responses to the study questionnaire.
Additional eligibility criteria for the diabetic group included: 1. A documented diagnosis of type 2 diabetes mellitus (T2DM) for at least one year before enrollment. 2. Availability of HbA1c measurements for assessment of glycemic control status.
Eligibility criteria for the non-diabetic comparator group included: 1. Absence of a prior diagnosis of diabetes mellitus. 2. Presence of rUTI meeting the same clinical diagnostic criteria applied to the diabetic group
Exclusion criteria
Participants were excluded if any of the following conditions were present: 1. Diagnosis of type 1 diabetes mellitus or exclusive insulin-dependent diabetes. 2. Use of SGLT2 inhibitors, due to their known association with genitourinary and renal adverse effects. 3. Receipt of systemic antimicrobial therapy within 72 hours prior to enrollment. This timeframe was selected to minimize the potential influence of recent antimicrobial exposure on urine culture results, bacterial isolation, and antimicrobial susceptibility testing, thereby allowing a more accurate baseline microbiological assessment before study enrollment. 4. Female patients with recurrent vaginitis or urinary incontinence. 5. Male patients with benign prostatic hyperplasia (BPH) or overflow incontinence as an underlying cause of rUTI. 6. Presence of chronic comorbid conditions other than T2DM that may predispose to rUTIs, including chronic kidney disease, spinal cord injury, or nephrolithiasis. 7. Pregnant and lactating women, postmenopausal women were not excluded from the study and were included if they fulfilled the eligibility criteria. Although menopause is recognized as an independent risk factor for rUTIs, menopausal status was not analyzed separately in the present study.
Study groups
A total of 99 patients were divided into two major groups and two subgroups as follows: Group 1: The (control) group included (41) patients present with rUTI. Group 2: The (active) group, including (58) T2DM patients presented with rUTI, is sub-divided into two subgroups: Group 2A: included (18) T2DM patients presented with good glycemic control (HbA1c level ≤7%) and rUTI. Group 2B: included (40) T2DM patients presented with poor glycemic control (HbA1c level >7%) and rUTI.
Data collection
For each patient in the study, the following information was documented: Demographic characteristics: Age, sex, body mass index, smoking status, place of residence. Variables associated with diabetes: Duration, familial history, current regimen, and medication history for additional conditions if applicable. Comprehensive baseline investigations were performed include GUE, urine culture and sensitivity (UC), HbA1c for T2DM patients, random blood glucose (RBG) or fasting blood glucose (FBG). Body weight and height were measured according to standardized protocols, and body mass index (BMI) was computed as weight in kg divided by height in meter squared (kg/m2). Body mass index (BMI) was classified according to World Health Organization (WHO) criteria. 17
In the microbiological evaluation phase of this study, patients who consented underwent a microbiological evaluation using midstream clean catch urine samples collected under aseptic conditions prior to initiating any antimicrobial therapy. The urine samples were processed immediately and cultured on the appropriate media (blood agar, MacConkey agar) and incubated at 35-37 degrees Celsius for 18-24 hours under aerobic conditions. Significant bacteriuria for this study was defined as isolation of a single uropathogen at a concentration of ≥107colony-forming units per milliliter (CFU/mL), according to established microbiological and urological guidelines. 18 The bacteria were identified using biochemical testing methods that adhered to the criteria set forth in routine clinical laboratory protocols for microbiology.
The severity of recurrent urinary tract infection was categorized as mild, moderate, or severe based on clinical presentation and physician assessment. Classification was determined according to symptom severity, presence of fever, flank pain, systemic manifestations, and laboratory findings at the time of evaluation. Mild cases included localized lower urinary tract symptoms without systemic involvement, moderate cases included more pronounced urinary symptoms with clinical evidence of infection, whereas severe cases were characterized by significant systemic manifestations or complicated infection requiring intensive clinical management, according to established clinical assessment approaches reported in previous literature19.
Antimicrobial susceptibility testing was done on the urine isolates using the disk diffusion method according to the clinical standards for microbiology testing (e.g., CLSI). The results of the antimicrobial susceptibility testing were used to classify the isolated uropathogens as the following: Sensitive, Intermediate, Resistant. Uropathogen presence and their antimicrobial resistance patterns were recorded and compared for differences between the study groups within the context of glycemic control.
The microbiological response was assessed by repeating formal microbiological evaluation by urinalysis, having negative results (indicative of microbiological clearance) 7-14 days after antimicrobial therapy was initiated. As molecular typing techniques were not used in this study, there is no definitive way of determining whether recurrent infection was caused by the same strain or by a different strain from that already present in the subject. This limitation has been noted.
Statistical analysis
Statistical analyses were performed by using the Statistical Package for the Social Sciences (SPSS) software for Windows, version 25 (IBM Corp., Armonk, NY, USA). Data were summarized with descriptive statistics. Frequencies and percentages were used to present the categorical variables. Continuous variables are expressed as mean ± standard deviation (SD) when they follow a normal distribution, or median and range when they do not follow a normal distribution. Data from normally distributed continuous variables were compared between study groups using one-way analysis of variance (ANOVA), while the Mann–Whitney U test or Kruskal–Wallis test was used for non-parametric data, as appropriate. When multiple group comparisons were performed, Bonferroni-adjusted post hoc analyses were applied to control for type I error. Associations between categorical variables were assessed using the chi-square test. Fisher’s exact test was employed when expected cell counts were less than five. A two-sided p value < 0.05 was considered statistically significant. Univariate and multivariate binary logistic regression analyses were performed to identify predictors associated with rUTIs among diabetic patients. Variables demonstrating clinical relevance or statistical significance in univariate analysis were entered into the multivariate regression model to determine independent predictors of recurrence. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and a p-value<0.05 was considered statistically significant.
Results
Presented the basic characteristics of the study patients.
Subscript letter denotes a subset of groups categories whose column proportions differ significantly from each other at the .05 level by Bonferroni post hoc test. p ≥ 0.05 is considered non –significant, p < 0.01 is considered significant.
†P value for ANOVA Test.
‡P value for Chi Square Test.
▪P value for Kruskal Wallis test.
Baseline investigations.
P value for Kruskal Wallis test; subscript letter denotes a subset of groups categories whose column proportions differ significantly from each other at the 0.05 level by Bonferroni post hoc test. p < 0.01 is considered significant.
Causative bacterial species in study groups.
Data presented as number (N) and percentage (%), P-value by Fisher's Exact Tes. p ≥ 0.05 is considered non-significant.
Severity of the rUTI among study groups.
Data presented as number (N) and percentage (%), P-value by Fissure’s Exact Test. p ≥ 0.05 is considered non–significant.
Antibacterial sensitivity across study groups.
Data presented as number (N) and percentage ( %), P-value by Chi Square Test.or Fissure’s Exact Test p ≥ 0.05 is considered non -significant p < 0.01 is considered significant.

Sensitivity and resistance of antibacterial across study groups.
For the GUE results for the three study groups following 7–14 days of antibiotic treatment that are shown in Figure 2, most patients in all three groups had negative urine results after 7–14 days of antibiotic medication, indicating a satisfactory microbiological response. Group 2B had the highest clearance rate, while the percentage of negative GUE values varied per group. The results for Group 1 and Group 2A were almost the same, with roughly 27% positive and 73% negative GUE. This resemblance suggests that diabetes patients react to antibiotic treatment in a manner comparable to that of non-diabetic people when blood glucose levels are adequately managed. Interestingly, group 2B had the highest clearance rate (90%) and the lowest rate of positive GUE (10%). General urine examination results 7-14 days after commencing of antibiotics treatment.
As illustrated in Figure 3, none of the patients in Group 1 experienced recurrence of UTIs during the follow-up period. In contrast, UTI recurrence within 30 days post-treatment was observed in 26 patients (65.0%) in Group 2B and in 4 patients (22.2%) in Group 2A. Rate of UTI recurrence among study groups.
Factors associated with UTI recurrence.
Datapresented as number (N) and percentage (%), P-value by Chi Square/Fisher’s exact Tests. p ≥ 0.05 is considered non –significant, p < 0.01 is considered significant.
†P value by independent T test.
‡P value by Mann Whitney test.
Factors predicting UTI recurrence among diabetic patients.
P value by Binary regression test. p ≥ 0.05 is considered non–significant, p < 0.01 is considered significant.
Discussion
In the current study, advanced age was highly associated among patients with recurrent UTIs compared to those without recurrence. This suggests that, although older patients tend to have more recurrent infection, age alone was not an independent determinant in this cohortp‑value (0.4). This study was consistent with a recent study that revealed the prevalence of rUTI increased with age. Similarly, female predominance was evident in both groups (approximately 76%), reflecting the general higher susceptibility of women to UTIs due to anatomical and hormonal factors, yet no significant gender-based difference in recurrence was detected. A similar finding had been stated by many studies with the same result, where women were much more prone to UTIs than men.20,21
In the present study, glycemic indices were significantly higher in patients with recurrent infection; these findings clearly demonstrate that poor glycemic control is a major contributor to UTI recurrence. Chronic hyperglycemia impairs host immune response, reduces leukocyte chemotaxis and phagocytic function, and enhances bacterial adherence and biofilm formation in the urinary tract. 20 A study reported that rUTI was more prevalent in patients with high glycemic indices22. Moreover, the current finding was inconsistent with that of Sara B. et al. in 2023, who stated that the prevalence of rUTI was higher in poor glycemic control than in optimal glycemic control. 23
In the present study, all study groups presented with complete clinical symptom relief within 7 to 14 days, and no patients had any symptoms that persisted. This suggested that the antibiotic regimens were largely successful in attaining early clinical cure. However, some observed variation in the microbiological response based on the GUE results. The current results showed negative GUE indicators as epithelial and pus cells revealed complete bacterial clearance, which was noticed more among the poorly controlled diabetes group with a higher tendency toward improvement. The microbiological and clinical reactions indicate that, at least during the 14-day short-term follow-up, antimicrobial treatment was generally successful across glycemic groups. This finding was in agreement with prior investigation, which indicated elevated early cure rates among both diabetic and non-diabetic women when suitable antibiotics were used.11,24
The results of the current study, the univariate and multivariate models, revealed that glycemic status was the major predictor for recurrence rate, particularly among poorly controlled diabetes. Additionally, in the univariate analysis only, patient age and a longer duration of disease were found to be significant risk indicators. Older age increased recurrence risk by approximately 5% per year in univariate analysis, consistent with prior reports demonstrating that aging reduces bladder immunity, increases post-void residual volume, and is associated with higher comorbidity burden.25,26 The duration of diabetes was longer in patients with poor glycemic control (median 3 years, range 1–17) compared to those with good control (median 2 years, range 0–15). This observation is consistent with reports from Pakistan in 2025, where longer diabetes duration worsens metabolic control and is associated with increased frequency and severity of UTI. 10 Longer disease duration increases microvascular and neurogenic bladder dysfunction, creating a favorable environment for recurrence. 27 Finally, in the present study, smoking status and residence (urban vs. rural) were not important predictors of recurrent infection.
According to the present study, the antibiotic combination didn’t affect the rate of recurrence rates across single, double, or triple-drug regimens among diabetics. This is consistent with previous studies in 2023, where combination antimicrobial therapy did not demonstrate superiority over single-agent targeted therapy for preventing recurrence, and recurrence in diabetics was primarily linked to hyperglycemia, biofilm persistence, and host factors, not regimen breadth. 23 Also stated in substantial modern literature is that recurrence is mostly influenced by metabolic dysregulation (elevated HbA1c, RBS), host immunity, and pathogen features, rather than the quantity of antibiotics used. 28
Although current findings revealed microbiological cures following antimicrobial therapy, it is important to consider resistance to certain types, as previous literature indicates that the average resistance of AMDs across different classes is significantly higher in diabetic patients compared to non-diabetic patients. 29 Regarding susceptibility patterns, Amikacin had the highest sensitivity rates across all research groups, achieving total susceptibility in Group 2A and over 90% in Group 2B. This observation aligns with global studies indicating that aminoglycosides retain efficacy owing to their limited use and parenteral delivery. 30 In line with the findings of the current investigation, Mohammad et al. determined that amikacin has strong action against 91% of bacteria, including Pseudomonas, Klebsiella, and all other species that cause UTIs in Iraqi hospitals. 31 The sensitivity of E. coli to amikacin was reported to be 90.6% in India, 93.7% in Saudi Arabia, 99.4% in South Korea, and 100% in Taiwan, according to the majority of investigations that produced results similar to the current findings. 32 Similarly, fluoroquinolones, especially ciprofloxacin and levofloxacin, showed relatively high sensitivity, indicating their continued efficacy against dominant uropathogens like E. coli, the most commonly isolated organism in the current study. This is consistent with other recent studies that have shown strong sensitivity to fluoroquinolones. 33
Nitrofurantoin exhibited considerable sensitivity across all groups, with resistance levels remaining insignificantly low. Topa A et al. stated that nitrofurantoin is the optimal selection for uncomplicated UTI, including in those with diabetes, because of its limited systemic absorption and low propensity for resistance development. 34 Conversely, gentamicin exhibited significant resistance across all groups, a result that conflicts with previous reports; however, it corresponds with recent data indicating rising cross-resistance within the aminoglycoside class. For example, a study in China reported most E. coli isolates were resistant to gentamicin (95.1%). 35 In contrast, significantly higher resistance rates were noted for frequently prescribed oral β-lactam antibiotics, such as cefixime, amoxicillin, amoxicillin-clavulanate, and methoprim. These findings reflect regional resistance patterns observed in Iraq and Saudi Arabia, where widespread empirical prescribing and over-the-counter availability of antibiotics have exacerbated resistance among uropathogen. 36 the current findings generally align with reports from several LMIC and Middle Eastern countries, including Oman, Saudi Arabia, Iran, Egypt, Pakistan, Bangladesh, and India, where nitrofurantoin and amikacin retained relatively high activity against uropathogenic E. coli. 37 In the present Iraqi cohort, amikacin demonstrated the highest sensitivity rates, whereas cefixime, amoxicillin-clavulanate, and trimethoprim showed markedly higher resistance patterns. These findings emphasize that recurrent UTIs among diabetic patients represent an important and growing antimicrobial resistance challenge in Middle Eastern LMIC healthcare settings. Factors such as mild endothelial dysfunction, reduced neutrophil activity, or subclinical glycosuria could contribute to bacterial persistence among diabetics. The highest recurrence rate among poorly controlled diabetics underscores that hyperglycemia is a key factor for reinfection. Other national studies revealed that 66% of participants with T2DM suffer from rUTI38. The previously reported recurrence rate of UTI was 38.6% of diabetic patients.
Study limitation
This study was performed at a single clinical center, potentially constraining the generalizability of the results to other populations exhibiting distinct microbial patterns or treatment methodologies. The 30-day follow-up period may not adequately capture the long-term recurrence rate or number of recurrent episodes, as many recurrent infections develop over several months. In addition, the study did not perform molecular typing to distinguish between relapse and reinfection, which restricts interpretation of treatment outcomes and pathogen dynamics. Additionally, the use of convenience sampling and a relatively small feasibility-based sample size may have introduced selection bias and limited the generalisability of the findings to broader populations. Therefore, the study results should be interpreted cautiously, and larger multicenter studies are recommended to validate the current findings across different clinical settings and populations.
Conclusion
Moderate-severity rUTI was the most common clinical presentation across all study groups and was observed proportionately more often in patients with poorly controlled T2DM. The findings show that E. coli and Staphylococcus spp. are the most common bacteria causing rUTIs in T2DM patients in Wasit Province, Iraq. There is significant resistance to the beta-lactam antibiotics currently used to treat these infections, so the most reliable empirical treatment options for physicians are ciprofloxacin and amikacin, which should be reserved for cases of documented rUTI due to the risk of unnecessary exposure to developing resistant pathogens.
All study groups demonstrated a high short-term clinical response, with complete symptom resolution within 7–14 days, including patients with poor glycemic control, who also showed post-treatment improvement in urine examination parameters. Despite this satisfactory initial response, UTI recurrence was significantly more frequent in patients with poorly controlled diabetes (42.2% vs. 10.4%). In univariate analysis, poor glycemic status was the strongest independent predictor of recurrence. Increasing age and a longer duration of diabetes also added to the risk.
Footnotes
Acknowledgment
Ethical considerations
Ethical approval for this study was obtained from the Scientific and Ethical Committee of the College of Pharmacy, Mustansiriyah University, Baghdad, Iraq (Approval No.: 80). Written informed consent was obtained from all participants before enrollment. Participant confidentiality and data privacy were maintained throughout the study. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.
Author contributions
The authors were responsible for developing the hypothesis, conducting literature research, performing experiments, and preparing and reviewing the manuscript.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
Data available on reasonable request.
