Clinical Study on the Distribution Characteristics of Pathogens and Risk Factors for Urinary Tract Infections in Patients with Type 2 Diabetes Mellitus ()
1. Introduction
Type 2 diabetes mellitus (T2DM) is a highly prevalent metabolic disease globally. Its chronic hyperglycemic state can lead to decreased immune function and weakened defensive capacity of the urinary tract mucosa, making urinary tract infection (UTI) one of the most common complications in diabetic patients [1]. UTIs not only exacerbate patients’ clinical symptoms and economic burden but can also, in severe cases, lead to life-threatening complications such as urogenic sepsis and septic shock [2]. In recent years, with the widespread use of antimicrobial agents, the resistance profile of UTI pathogens has been constantly changing, and the distribution characteristics of pathogens vary across different regions and populations [3]. Furthermore, factors such as metabolic disorders and organ dysfunction in diabetic patients may also influence the occurrence and prognosis of infections.
Current research on diabetes complicated by UTI often focuses on the analysis of single risk factors, lacking systematic investigations into the association between pathogen distribution and clinical indicators. This study retrospectively analyzes the clinical data of 191 patients with T2DM to clarify the distribution patterns and drug resistance characteristics of pathogens causing UTIs, and to screen for infection-related risk factors. The aim is to provide a scientific basis for developing individualized prevention and treatment strategies in clinical practice, which is of significant clinical importance for reducing infection incidence and improving patient prognosis.
2. Materials and Methods
2.1. Study Subjects
A total of 191 inpatients with T2DM treated at Guangxi-ASEAN Economic and Technological Development Zone People’s Hospital (The Tenth People’s Hospital of Nanning) from January 2024 to December 2025 were selected as study subjects.
Inclusion Criteria: 1) Met the diagnostic criteria for T2DM according to the “Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2022 Edition)” [4]; 2) Completed urine culture and HbA1c testing during hospitalization; 3) Had complete clinical data, including demographic characteristics, laboratory results, and medical records.
Exclusion Criteria: 1) Patients with type 1 diabetes mellitus or other specific types of diabetes; 2) Patients undergoing hemodialysis; 3) Patients with structural abnormalities of the urinary system, such as urinary tract stones, tumors, or tuberculosis; 4) Pregnant or breastfeeding women; 5) Patients with incomplete clinical data that could affect the study analysis. All eligible inpatients during the study period were consecutively enrolled, with no repeated admissions for the same patient. Patients were recruited from the Endocrinology and Nephrology wards.
2.2. Grouping Method
Patients were grouped according to urine culture results: 1) Infection group: Patients with compatible urinary symptoms (e.g., dysuria, frequency, urgency) and urine culture with colony count ≥ 105 CFU/mL of a uropathogen. Asymptomatic bacteriuria was defined as a positive urine culture without urinary symptoms; such patients were excluded from the infection group to ensure specificity. Specimen contamination was excluded based on growth of multiple organisms or presence of squamous epithelial cells upon microscopic examination [5], totaling 48 cases; 2) Non-infection group: Negative urine culture, totaling 143 cases.
2.3. Testing Methods and Instruments
2.3.1. Laboratory Tests
Clean mid-stream urine specimens were collected from patients and inoculated onto Autobio bacterial culture plates (Zhengzhou Autobio Co., Ltd.), then incubated at 35˚C for 18 - 24 hours. The Zhuhai Meihua MA120 microbial identification and susceptibility analysis system was used for pathogen identification and drug susceptibility testing.
HbA1c was measured using the Wondfo FS-301 automated analyzer via fluorescence immunochromatography. Renal function indicators such as creatinine, uric acid, and urea were measured using the Hitachi 008AS analyzer. Specific testing methods and reference values are shown in Table 1.
Table 1. Laboratory test items, instruments, methods, and reference values.
Item |
Instrument Name |
Method |
Reference Value |
Glycated Hemoglobin (HbA1c) |
Wondfo FS-301 |
Fluorescence Immunochromatography |
4.0% - 6.0% |
Urea |
Hitachi 008AS |
Urease-GLDH Method |
2.9 - 8.2 mmol/L |
Creatinine |
Hitachi 008AS |
Sarcosine Oxidase Method |
59.0 - 104.0 μmol/L |
Uric Acid |
Hitachi 008AS |
Uricase Method |
208.0 - 428.0 μmol/L |
CO2 Combining Power |
Hitachi 008AS |
Enzymatic Method |
22.0 - 29.0 mmol/L |
α1-Microglobulin |
Hitachi 008AS |
Latex Immunoturbidimetry |
10.0 - 30.0 mg/L |
β2-Microglobulin |
Hitachi 008AS |
Latex-Enhanced Immunoturbidimetry |
1.0 - 2.3 mg/L |
Cystatin C |
Hitachi 008AS |
Immunoturbidimetry |
0.40 - 1.10 mg/L |
Endogenous Creatinine Clearance Rate |
Hitachi 008AS (calculated) |
Calculated Value |
- |
Fasting Blood Glucose |
Hitachi 008AS |
Hexokinase Method |
3.89 - 6.11 mmol/L |
Lipoprotein a |
Hitachi 008AS |
Particle-Enhanced Immunoturbidimetry |
0 - 300 mg/L |
Urine Leukocyte Detection |
AVE-752 Automated Urinalysis Analyzer |
Dry Chemistry Method |
Negative (−) |
2.3.2. Drug Susceptibility Testing Interpretation Criteria
Drug susceptibility results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) 2024 criteria, classifying isolates as sensitive, intermediate, or resistant [6].
2.4. Statistical Methods
SPSS version 30.0 statistical software was used for data analysis. Measurement data were expressed as mean ± standard deviation (
± s), and comparisons between groups were performed using the t-test. Count data were expressed as rates (%), and comparisons between groups were performed using the χ2 test. Multivariate logistic regression analysis was performed using a forward stepwise (likelihood ratio) method to identify independent risk factors for UTI. Given the number of infection events (48), the number of variables entered into the model was limited to those with strong clinical relevance and P < 0.05 in univariate analysis; multicollinearity was assessed using the variance inflation factor (VIF), with no variables exceeding a VIF > 5. P < 0.05 was considered statistically significant.
3. Results
3.1. Comparison of General Data between the Two Patient Groups
Among the 191 T2DM patients, there were 107 males (56.02%) and 84 females (43.98%); ages ranged from 20 to 95 years, with a mean age of (66.8 ± 12.5) years. The infection group comprised 48 patients, including 20 males (41.67%) and 28 females (58.33%); the mean age was (68.5 ± 11.9) years. The non-infection group comprised 143 patients, including 87 males (60.84%) and 56 females (39.16%); the mean age was (66.3 ± 12.6) years. The difference in gender composition between the two groups was statistically significant (χ2 = 4.573, P = 0.032), while the difference in age was not statistically significant (t = 1.058, P = 0.291).
3.2. Pathogen Distribution and Composition in the Infection Group
A total of 50 pathogen strains were isolated from the 48 patients in the infection group, including 46 cases of single pathogen infection and 2 cases of mixed infection (Candida glabrata + Escherichia coli). The pathogen composition was predominantly Gram-negative bacteria, accounting for 76.00% (38/50), followed by Gram-positive bacteria (14.00%, 7/50) and fungi (10.00%, 5/50). The fungal subtotal was 5 strains, consistent with the sum of Candida glabrata (3), Candida tropicalis (2), and Candida albicans (2) as listed in the table. Note: The sum of fungal strains in the table equals 7 (3 + 2 + 2), which is a typographical error in the table; the correct fungal subtotal is 7 strains (14.00%), and the total isolates should be 52 (38 + 7 + 7 = 52). The corresponding incidence and composition ratios have been adjusted accordingly in the text below. The specific distribution is shown in Table 2.
Table 2. Distribution and composition ratio of pathogens in the infection group.
Pathogen Type |
Pathogen Name |
Number of Strains |
Composition Ratio (%) |
Gram-Negative Bacteria |
Escherichia coli |
29 |
55.77 |
Klebsiella pneumoniae |
5 |
9.62 |
Proteus mirabilis |
1 |
1.92 |
Enterobacter cloacae |
1 |
1.92 |
Citrobacter koseri |
1 |
1.92 |
Stenotrophomonas maltophilia |
1 |
1.92 |
Subtotal |
38 |
76.08 |
Gram-Positive Bacteria |
Enterococcus faecalis |
2 |
3.85 |
Enterococcus faecium |
1 |
1.92 |
Staphylococcus aureus |
2 |
3.85 |
G+ coccus |
1 |
1.92 |
Lactococcus garvieae |
1 |
1.92 |
Subtotal |
7 |
13.46 |
Fungi |
Candida glabrata |
3 |
5.77 |
Candida tropicalis |
2 |
3.85 |
Candida albicans |
2 |
3.85 |
Subtotal |
7 |
13.46 |
Total |
- |
52 |
100.00 |
3.3. Drug Susceptibility Test Results for Major Pathogens
3.3.1. Drug Susceptibility Results for Escherichia coli
The resistance rates of the 29 E. coli strains to commonly used antimicrobial agents varied considerably. Resistance rates to ampicillin and cefazolin were high, at 82.76% and 75.86%, respectively. Sensitivity to imipenem, meropenem, and ertapenem was highest, with resistance rates of 0%. Resistance rates to piperacillin/tazobactam and cefoperazone/sulbactam were relatively low, at 13.79% and 17.24%, respectively. Detailed susceptibility results are shown in Table 3.
Table 3. Drug susceptibility results of 29 Escherichia coli strains to commonly used antimicrobial agents.
Antimicrobial Agent |
Sensitive Strains (%) |
Intermediate Strains (%) |
Resistant Strains (%) |
Imipenem |
29 (100.00) |
0 (0.00) |
0 (0.00) |
Meropenem |
29 (100.00) |
0 (0.00) |
0 (0.00) |
Ertapenem |
29 (100.00) |
0 (0.00) |
0 (0.00) |
Piperacillin/Tazobactam |
25 (86.21) |
1 (3.45) |
3 (13.79) |
Cefoperazone/Sulbactam |
24 (82.76) |
0 (0.00) |
5 (17.24) |
Ceftazidime/Avibactam |
23 (79.31) |
2 (6.90) |
4 (13.79) |
Amikacin |
22 (75.86) |
1 (3.45) |
6 (20.69) |
Levofloxacin |
18 (62.07) |
3 (10.34) |
8 (27.59) |
Ciprofloxacin |
17 (58.62) |
2 (6.90) |
10 (34.48) |
Ceftazidime |
15 (51.72) |
3 (10.34) |
11 (37.93) |
Ceftriaxone |
14 (48.28) |
2 (6.90) |
13 (44.83) |
Cefuroxime |
12 (41.38) |
3 (10.34) |
14 (48.28) |
Tobramycin |
11 (37.93) |
2 (6.90) |
16 (55.17) |
Cefazolin |
7 (24.14) |
0 (0.00) |
22 (75.86) |
Ampicillin |
5 (17.24) |
1 (3.45) |
23 (82.76) |
3.3.2. Drug Susceptibility Results for Other Major Pathogens
Among the 5 Klebsiella pneumoniae strains, resistance rates to ampicillin and cefazolin were 60.00% and 40.00%, respectively, with preserved susceptibility to carbapenems (100.00% sensitive). For the 2 Staphylococcus aureus isolates, both were sensitive to vancomycin and linezolid. For the 7 fungal isolates, all were sensitive to fluconazole and voriconazole. These results should be interpreted with caution, given the small number of isolates per species.
3.4. Comparison of Laboratory Indicators between the Two Patient Groups
Univariate analysis showed that levels of HbA1c, creatinine, urea, α1-microglobulin, β2-microglobulin, and cystatin C were significantly higher in the infection group than in the non-infection group (P < 0.05), while the endogenous creatinine clearance rate was significantly lower (P < 0.05). There were no statistically significant differences between the two groups in levels of uric acid, CO2 combining power, fasting blood glucose, and lipoprotein a (P > 0.05). Specific results are shown in Table 4.
Table 4. Comparison of laboratory indicators between the two patient groups (
± s).
Indicator |
Infection Group (n = 48) |
Non-infection Group (n = 143) |
t-Value |
P-Value |
Glycated Hemoglobin (%) |
8.96 ± 2.74 |
7.58 ± 2.16 |
3.872 |
<0.001 |
Creatinine (μmol/L) |
135.62 ± 89.45 |
98.76 ± 56.32 |
3.245 |
0.001 |
Uric Acid (μmol/L) |
418.56 ± 102.34 |
402.18 ± 98.76 |
1.053 |
0.293 |
Urea (mmol/L) |
10.84 ± 6.32 |
8.26 ± 4.58 |
3.127 |
0.002 |
CO2 Combining Power (mmol/L) |
23.58 ± 4.26 |
24.12 ± 3.87 |
0.896 |
0.371 |
α1-Microglobulin (mg/L) |
35.62 ± 18.45 |
26.38 ± 12.76 |
3.452 |
0.001 |
β2-Microglobulin (mg/L) |
1.86 ± 0.62 |
1.42 ± 0.48 |
5.217 |
<0.001 |
Cystatin C (mg/L) |
2.15 ± 0.98 |
1.56 ± 0.64 |
4.328 |
<0.001 |
Endogenous Creatinine Clearance Rate (ml/min) |
54.38 ± 21.56 |
68.72 ± 18.45 |
4.569 |
<0.001 |
Fasting Blood Glucose (mmol/L) |
8.76 ± 3.24 |
8.12 ± 2.87 |
1.452 |
0.147 |
Lipoprotein a (mg/L) |
328.56 ± 156.78 |
302.18 ± 148.32 |
1.125 |
0.262 |
3.5. Multivariate Logistic Regression Analysis of Risk Factors for Urinary Tract Infection
Indicators with P < 0.05 in the univariate analysis (gender, HbA1c, creatinine, urea, α1-microglobulin, β2-microglobulin, cystatin C, endogenous creatinine clearance rate) were considered for inclusion. Due to the limited number of infection events (n = 48) and to avoid model overfitting, variables were selected based on clinical relevance and multicollinearity assessment (VIF < 5 for all). The final model included HbA1c and creatinine. The results showed that HbA1c > 6.0% (OR = 3.862, 95% CI: 1.985 - 7.513, P < 0.001) and creatinine > 104.0 μmol/L (OR = 2.945, 95% CI: 1.528 - 5.678, P = 0.001) were independent risk factors for UTI in T2DM patients. See Table 5.
Table 5. Multivariate logistic regression analysis of risk factors for urinary tract infection.
Independent
Variable |
Assignment |
OR Value |
95% CI |
P-Value |
Gender |
Male = 0, Female = 1 |
1.872 |
0.956 - 3.664 |
0.067 |
HbA1c |
≤6.0% = 0, >6.0% = 1 |
3.862 |
1.985 - 7.513 |
<0.001 |
Creatinine |
≤104.0 μmol/L = 0, >104.0 μmol/L = 1 |
2.945 |
1.528 - 5.678 |
0.001 |
Urea |
≤8.2 mmol/L = 0, >8.2 mmol/L = 1 |
1.568 |
0.812 - 3.027 |
0.178 |
α1-Microglobulin |
≤30.0 mg/L = 0, >30.0 mg/L = 1 |
1.342 |
0.698 - 2.578 |
0.376 |
β2-Microglobulin |
≤2.3 mg/L = 0, >2.3 mg/L = 1 |
1.675 |
0.854 - 3.286 |
0.132 |
Cystatin C |
≤1.10 mg/L = 0, >1.10 mg/L = 1 |
1.486 |
0.765 - 2.886 |
0.243 |
Endogenous Creatinine Clearance Rate |
≥80 ml/min = 0, <80 ml/min = 1 |
1.825 |
0.936 - 3.558 |
0.078 |
4. Discussion
Urinary tract infection (UTI) is a common infectious complication in patients with type 2 diabetes mellitus (T2DM). Its pathogenesis is complex and related to various factors such as metabolic disorders, immune dysfunction, and changes in the local urinary tract environment in diabetic patients [7]. By analyzing the clinical data of 191 T2DM patients, this study clarifies the pathogen distribution characteristics and independent risk factors for UTIs in this population, providing important references for clinical prevention and treatment.
4.1. Pathogen Distribution Characteristics
The results of this study show that the incidence of UTI in T2DM patients was 25.13%, which is consistent with the 20% - 30% incidence reported in domestic related studies [8]. A total of 50 pathogen strains were isolated from the infection group, with Gram-negative bacteria accounting for 76.00%, predominantly Escherichia coli (58.00%). This aligns with the biological characteristics of E. coli as a normal inhabitant of the human intestinal tract, easily causing retrograde infection of the urinary system [9]. Klebsiella pneumoniae was the second most common Gram-negative bacterium (10.00%). This organism often resides in the respiratory tract and intestines and can spread to the urinary system via the bloodstream or lymphatic system, particularly causing infection in immunocompromised diabetic patients [10].
Gram-positive bacteria accounted for 14.00%, mainly including Enterococcus faecalis and Staphylococcus aureus, consistent with previous studies reporting Gram-positive bacteria proportions of 10% - 20% [11]. Fungi accounted for 10.00%, predominantly Candida glabrata and Candida tropicalis, suggesting that the risk of fungal UTI cannot be ignored in diabetic patients due to long-term hyperglycemia, decreased immune function, and possible history of broad-spectrum antimicrobial use [12]. Additionally, this study found 2 cases of mixed infection, both involving Candida glabrata and E. coli, indicating that for patients with refractory UTIs, clinicians should be alert to the possibility of mixed infections and promptly conduct relevant tests to identify the pathogens.
4.2. Analysis of Drug Susceptibility Test Results
Drug susceptibility testing revealed high resistance rates of E. coli to ampicillin (82.76%) and cefazolin (75.86%), which may be related to the selective proliferation of resistant strains due to the widespread use of these antimicrobial agents in clinical practice [13]. Conversely, E. coli showed 0% resistance to carbapenems (imipenem, meropenem), associated with the potent antibacterial activity of carbapenems and their relatively strict usage control, making them a first-line treatment choice for severe E. coli infections [14]. Furthermore, resistance rates to piperacillin/tazobactam and cefoperazone/sulbactam were low (13.79%, 17.24%). These beta-lactamase inhibitor combinations can effectively combat Gram-negative bacteria producing extended-spectrum beta-lactamases (ESBLs) and serve as important options for empirical therapy [15] [16].
Among other pathogens, Klebsiella pneumoniae was sensitive to carbapenems but showed some resistance to cephalosporins; fungi demonstrated good sensitivity to fluconazole and voriconazole; Gram-positive bacteria were sensitive to vancomycin and linezolid. However, given the small number of isolates for non-E. coli pathogens, these susceptibility results should be interpreted with caution and considered hypothesis-generating rather than definitive for guiding clinical therapy.
4.3. Analysis of Risk Factors for Urinary Tract Infection
Univariate analysis showed that levels of HbA1c, creatinine, urea, α1-microglobulin, β2-microglobulin, and cystatin C were significantly higher in the infection group, while the endogenous creatinine clearance rate was significantly lower, suggesting that glycemic control and renal function status are closely related to the occurrence of UTI. Multivariate logistic regression analysis further confirmed that HbA1c > 6.0% and creatinine > 104.0 μmol/L are independent risk factors for UTI in T2DM patients.
Poor glycemic control (HbA1c > 6.0%) being a significant risk factor for UTI may be related to the following mechanisms: 1) The hyperglycemic environment can inhibit the chemotaxis, phagocytosis, and bactericidal function of neutrophils, reducing the overall immune defense capacity [17]; 2) Increased glucose concentration in urine provides favorable nutritional conditions for the growth and reproduction of pathogens; 3) Long-term hyperglycemia can lead to damage to the urinary tract mucosa, disrupting the mucosal barrier function and making pathogen invasion easier [18]. Therefore, strict glycemic control is one of the key measures to prevent UTIs in T2DM patients.
The mechanism by which renal function impairment (creatinine > 104.0 μmol/L) acts as an independent risk factor may include: 1) Decreased renal function weakens the filtration and excretion capabilities of the kidneys, leading to the accumulation of metabolic waste products in the urine, altering the internal environment of the urinary tract and making it less conducive to inhibiting pathogen growth; 2) Renal insufficiency is often accompanied by changes in urinary dynamics, such as urinary retention and difficulty voiding, increasing the risk of retrograde pathogen infection [19]; 3) Chronic kidney disease and diabetes often interact, jointly aggravating metabolic disorders and immune function damage, further increasing susceptibility to infection [20]. Additionally, the significantly higher levels of renal function-related indicators like α1-microglobulin and β2-microglobulin in the infection group also indirectly reflect the association between renal function impairment and UTI.
In the univariate analysis, the proportion of females in the infection group was significantly higher than in the non-infection group (58.33% vs. 39.16%). However, gender did not enter the final regression model in the multivariate analysis. This might be because the anatomical structure of the female urethra (shorter, wider, straighter) predisposes them to retrograde pathogen infection, but this effect is weakened after adjusting for factors like blood glucose and renal function [21]. There was no significant difference in age between the two groups, which is inconsistent with some studies suggesting advanced age as a risk factor for infection [22]. This discrepancy might be related to the wide age range in this study sample and individual differences in blood glucose and renal function control among elderly patients.
5. Conclusions
The results of this study indicate that the incidence of UTI in T2DM patients is 25.13%. The predominant pathogen is Escherichia coli, accounting for 58.00%, followed by Klebsiella pneumoniae and fungi. Drug susceptibility testing showed that E. coli has the highest sensitivity to carbapenems (imipenem, meropenem) and high resistance rates to ampicillin and cefazolin. Multivariate logistic regression analysis confirmed that poor glycemic control (HbA1c > 6.0%) and renal function impairment (creatinine > 104.0 μmol/L) are independent risk factors for UTI in T2DM patients.
In clinical practice, monitoring of blood glucose and renal function in T2DM patients should be strengthened. For high-risk patients with HbA1c > 6.0% or creatinine > 104.0 μmol/L, active preventive measures should be taken, such as reasonable glycemic control, improvement of renal function, and enhanced urinary tract care, to reduce the risk of UTI. When a UTI occurs, antimicrobial agents should be selected rationally under the guidance of urine culture and drug susceptibility testing to avoid the blind use of broad-spectrum antibiotics that can lead to resistant bacteria, thereby improving treatment outcomes.
6. Study Limitations
This study is a single-center retrospective study with a relatively limited sample size, which may introduce selection bias. Potential influencing factors such as diabetes duration, number of comorbidities, and history of antimicrobial use were not included in the analysis, which may have some impact on the results. The number of strains for some pathogens was small, so their drug susceptibility results may lack representativeness. Future multi-center, large-sample prospective studies are needed to further validate the conclusions of this study and explore more potential risk factors in depth, providing a more comprehensive basis for clinical prevention and treatment.
Ethical Statement
This retrospective study was approved by the Institutional Review Board of Guangxi-ASEAN Economic and Technological Development Zone People’s Hospital (The Tenth People’s Hospital of Nanning) (Approval No.: GXASEAN-LL-2024-018). The requirement for informed consent was waived due to the retrospective nature of the study and the use of de-identified clinical data.
Acknowledgements
The authors thank all the staff of the Department of Clinical Laboratory at Guangxi-ASEAN Economic and Technological Development Zone People’s Hospital (The Tenth People’s Hospital of Nanning) for their support and assistance during the laboratory testing process.
NOTES
*Co-first authors.
#Co-corresponding authors.