International Journal of Academic Medicine

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 7  |  Issue : 4  |  Page : 212--219

Clinical characteristics and complications of symptomatic bacteriuria in patients with Type 2 diabetes


Tauseef Nabi 
 Consultant, Department of Endocrinology, MMIMSR, Ambala, Haryana, India

Correspondence Address:
Dr. Tauseef Nabi
E 32, MMIMSR, Mullana, Ambala, Haryana
India

Abstract

Introduction: Patients with Type 2 diabetes have a higher prevalence of symptomatic bacteriuria, which may predispose to various complications. The aim was to study the clinical characteristics and complications of symptomatic bacteriuria in patients with Type 2 diabetes and factors associated with Escherichia coli symptomatic bacteriuria. Materials and Methods: This was a single-center observational study done on 200 Type 2 diabetes patients admitted with symptomatic urinary tract infection (UTI). Various clinical, biochemical parameters, and urine examination and culture were studied. Results: The prevalence of symptomatic bacteriuria was 69% in Type 2 diabetes patients admitted with UTI. E. coli (55%) was the most commonly isolated organism. Postmenopausal state, longer duration of diabetes, chronic kidney disease, hypertension, and history of symptomatic UTI in a prior year increase the risk of symptomatic bacteriuria. Severe hyperglycemia and acute kidney injury (AKI) occurred more frequently in bacteriuria patients as compared to without bacteriuria (P < 0.001). Upper UTI was significantly associated with symptomatic bacteriuria. Complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar state, and multiorgan dysfunction syndrome were not associated with symptomatic bacteriuria. Poor glycemia, leukocytosis, glycosuria, proteinuria, renal cyst, and renal calculi correlated with symptomatic bacteriuria. Female gender, obesity, and poor glycemia were associated with E. coli symptomatic bacteriuria. Conclusions: Complications do not frequently occur in symptomatic bacteriuria except AKI. Severe hyperglycemia and uncontrolled glycemia need consideration in reducing symptomatic bacteriuria. The following core competencies are addressed in this article: Medical knowledge, Patient care, Practice-based learning and improvement, and Systems-based practice.



How to cite this article:
Nabi T. Clinical characteristics and complications of symptomatic bacteriuria in patients with Type 2 diabetes.Int J Acad Med 2021;7:212-219


How to cite this URL:
Nabi T. Clinical characteristics and complications of symptomatic bacteriuria in patients with Type 2 diabetes. Int J Acad Med [serial online] 2021 [cited 2022 Jan 26 ];7:212-219
Available from: https://www.ijam-web.org/text.asp?2021/7/4/212/333405


Full Text



 Introduction



Diabetes has reached a pandemic level and become a major health challenge. Worldwide, around 415 million people have diabetes. As per the International Diabetes Federation 2019 report, India is having 77 million patients with diabetes and is expected to be 134.2 million by 2045.[1] Patients with Type 2 diabetes are at increased risk of urinary tract infection (UTI) and complications. UTI is the second most common of sepsis in diabetes and good diabetic control reduces the risk of infection.[2]

The presence of bacteria in the urine in significant numbers is defined as bacteriuria. Bacteriuria can be symptomatic or asymptomatic. Symptomatic bacteriuria is defined as bacteriuria in the presence of UTI symptoms. Bacteriuria is common among diabetes patients and may lead to serious complications if not properly managed.[3] Bacteriuria is more common in diabetic women compared with nondiabetic women.[4] Consequently, diabetic women are also at higher risk for morbidity and mortality from UTI.[5] UTI varies dramatically in their presentation and sequelae.[6] Several complications of UTI such as emphysematous pyelonephritis (EPN), emphysematous cystitis, and renal abscess occur more frequently in Type 2 diabetes and are mostly accompanied by bacteriuria.[7]

Factors affecting the risk for UTI in diabetic patients include age, presence of chronic diabetic complications, mainly diabetic nephropathy and cystopathy, and metabolic control.[8] UTI in patients with Type 2 diabetes usually presents with severe hyperglycemia, hyperglycemic hyperosmolar state (HHS), or even diabetic ketoacidosis (DKA).[9] Hyperglycemia presenting as glycosuria promotes the growth of uropathogens.[10] Dysfunctional voiding and urinary retention as a result of autonomic neuropathy involving the genitourinary tract lead to a decrease in bacterial clearance through micturition, thereby promoting bacterial growth.[11]

Facultative anaerobes are the most organisms causing UTI in diabetes and usually originate in bowel flora. Escherichia coli is the most common cause of UTI, accounting for around 85% of community-acquired and 50% of hospital-acquired infections. Other microorganisms include Klebsiella pneumoniae, Proteus, Enterococcus faecalis, and Staphylococcus saprophyticus.[12] Resistant uropathogens and fungal UTI are also frequently found in diabetic patients.[12],[13]

All diabetic patients with suspected UTI should have a urine culture done, before treatment initiation, with exceptions of presumed acute cystitis (lower UTI) in patients without urinary tract abnormality.[10] Interpretation of urine culture in diabetes patients should be made with caution. UTI in patients with diabetes should be treated aggressively.

The role of glycemic control and diabetic micro- and macrovascular complications in the development or augmentation of symptomatic bacteriuria in Type 2 diabetes patients or vice versa has received little attention.[14] Therefore, with this study, we analyzed the prevalence, clinical and biochemical characteristics, and complications of symptomatic bacteriuria in patients with Type 2 diabetes, admitted as inpatient and factors associated with E. coli symptomatic bacteriuria.

 Materials and Methods



Study design and setting

This was a single-center observational study of adult Type 2 diabetes patients with symptomatic UTI attending a tertiary care hospital in North India. The institutional ethical committee approved the study (IEC/SKIMS/2015-235). Informed consent was obtained from all the recruited subjects.

Sample size and study subjects

The study recruited consecutive 200 symptomatic UTI patients admitted in the department of endocrinology. This study was conducted for 3 years, from December 2015 to December 2018. At baseline, all patients were interviewed using a standardized questionnaire regarding the number of UTIs within the previous year, urinary tract surgery, and menopausal status in females. A detailed physical examination of the subjects was carried based on a study protocol. The eligibility criteria for including the subject in the study were both male and female Type 2 diabetes patient having age >30 years. The exclusion criteria were (i) other types of diabetes, (ii) recent hospitalization, (iii) antibiotic use within the previous 2 weeks, (iv) immunocompromised states-HIV, patients on steroids, malignancy, and transplant recipients, and (v) recent urinary instrumentation.

Detailed study design

Clinical and biochemical parameters

Demographic and clinical profile regarding the duration of diabetes, complications of diabetes, drug therapy, UTI symptomatology and comorbidities (hypertension [HTN], obesity, hypothyroidism, chronic kidney disease [CKD], coronary artery disease, and others) were recorded. Complete blood count, renal function test (KFT), fasting blood glucose (FBG) and 2-h postprandial blood glucose (PP), 24-h urinary protein estimation, and glycosylated hemoglobin (HbA1c) were estimated at baseline. Ultrasonography (USG) of abdomen was done in all patients. Blood culture and noncontrast computed tomography (NCCT) abdomen were done as per requirement.

Urine examination and culture sensitivity

Voided, clean-catch, and midstream urine samples were collected from patients for routine urine analysis and culture sensitivity at baseline. Antimicrobial sensitivity testing was interpreted according to Clinical and Laboratory Standards Institute criteria.[15] Symptomatic UTI patients were divided into lower UTI (cystitis) who had frequency of urination, urgency, dysuria, and/or abdominal discomfort. Acute pyelonephritis was defined when the patients presented with fever (>38.3°C), nausea/vomiting, flank pain and USG showing features suggestive of the enlarged kidney, presence of collection, and/or perinephric stranding. The diagnosis of EPN was based on clinical features and documentation of gas within collecting system, renal parenchyma, or perinephric tissue on NCCT abdomen.

Definitions of symptomatic bacteriuria

Symptomatic bacteriuria in women was diagnosed when a urine count was ≥105 CFU/ml in the presence of UTI symptoms. Whereas in men, the diagnosis of symptomatic bacteriuria was reported when a urine colony count was ≥104 CFU/ml.[12] The presence of ≥3 different microorganisms in urine specimen was considered contamination.

Definitions

Pyuria (defined as ≥10 leukocytes/mm3) and hematuria (defined as ≥3 red blood cell/HPF) were detected by microscopic examination. Obesity was defined as body mass index ≥25 kg/m2. Systolic blood pressure (BP) of ≥140 or diastolic BP of ≥90 mmHg was defined as uncontrolled HTN. Proteinuria was defined as 24-h urinary protein ≥150 mg, leukocytosis as total leukocyte count more than the normal upper limit for the laboratory (4–10 × 103/μL), acute kidney injury (AKI) when creatinine increased by 0.3 mg/dl from baseline. DKA and HHS defined as per American Diabetes Association guidelines. Severe hyperglycemia was defined when blood glucose was >300 mg/dl and cystopathy, when the patient has decreased bladder sensation with postvoid residual urine >150 ml. Shock and multiorgan dysfunction syndrome (MODS) were defined as per Infectious Disease Society of America guidelines. CKD-EPI was used to calculate estimated glomerular filtration rate.

Statistical analysis

Quantitative variables were expressed as means ± standard deviation, while qualitative variables were expressed in terms of proportion. Descriptive and univariate analytic techniques were used to analyze the data. Chi-square test or Fisher's exact tests were used to compare categorical variables, whereas Student's t-test for independent observations was used for continuous variables. To study the joint effects and interactions of various independent variables, binary logistic regression analysis was carried out to calculate multivariate P value. P < 0.05 was considered statistically significant. All the analyses were performed by the statistical software SPSS Version 21 (IBM SPSS Statistics for Windows, version 21 Armonk, NY, USA: IBM Corp.).

 Results



[Table 1] shows the microbiological outcome of symptomatic bacteriuria in patients with Type 2 diabetes. Bacteriuria was present in 138 (69%) of patients, out of which females were 111 (68.5%) and males 27 (71.1%). E. coli 110 (55%) was the most commonly isolated organism in symptomatic UTI patients, followed by Enterococcus faecalis (6%). In females and males, the most common isolate was E. coli.{Table 1}

The demographic and clinical characteristics associated with symptomatic bacteriuria in patients with Type 2 diabetes are shown in [Table 2]. The mean age was similar in patients with and without bacteriuria. Most of the patients in both groups were females. Postmenopausal state significantly associated with symptomatic bacteriuria. The diabetes duration was longer in patients with bacteriuria than without bacteriuria, with a mean duration of 11.65 ± 6.75 and 9.42 ± 5.51 years, respectively (P = 0.023). With respect to diabetic microvascular complications, only nephropathy was significantly (P = 0.028) associated with bacteriuria. HTN and CKD were significant associated with symptomatic bacteriuria (P < 0.05). The presence of previous UTI was significantly associated with symptomatic bacteriuria (P < 0.001). Uncontrolled BP and obesity were associated with symptomatic bacteriuria (P < 0.05).{Table 2}

[Table 3] reveals the complications associated with symptomatic bacteriuria among patients with Type 2 diabetes. With regard to the type of UTI; pyelonephritis and EPN were significantly associated with symptomatic bacteriuria. Complications such as DKA, HHS, MODS, and hypotension were not associated with symptomatic bacteriuria among patients with Type 2 diabetes. Severe hyperglycemia and AKI occurred more frequently in symptomatic bacteriuria patients as compared to without bacteriuria (P < 0.001).{Table 3}

[Table 4] reveals the laboratory and biochemical parameters associated with symptomatic bacteriuria. Symptomatic bacteriuria patients had higher mean FBG, blood glucose PP, and HbA1c than UTI without bacteriuria with FBG of 268 ± 104 mg/dl and 219 ± 69 mg/dl and HbA1c of 11.52 ± 2.29 and 9.99% ± 1.75%, respectively (P < 0.05). 100% of symptomatic bacteriuria patients had uncontrolled glycemia (P = 0.034). Renal parameters were comparable between the two groups. Renal cyst and renal calculi correlated with symptomatic bacteriuria (P < 0.05).{Table 4}

[Table 5] shows the factors associated with E. coli symptomatic bacteriuria in Type 2 diabetes patients. There were 138 cases of symptomatic bacteriuria in Type 2 diabetes, of which 110 (70.7%) were E. coli induced and rest 28 (29.3%) were non-E. coli induced. On multivariate analysis, the factors associated with E. coli symptomatic bacteriuria in Type 2 diabetes were female gender, obesity, and poor glycemic control.{Table 5}

 Discussion



Patients with uncontrolled Type 2 diabetes are at increased risk of UTI and its complications, which can be reduced with optimal glycemic control. Symptomatic bacteriuria may increase morbidity and mortality in patients with diabetes.

In this study, we analyzed the prevalence, clinical and biochemical characteristics, and complications of symptomatic bacteriuria in patients with Type 2 diabetes admitted as inpatient and factors associated with E. coli symptomatic bacteriuria. We analyzed 138 symptomatic bacteriuria patients with Type 2 diabetes and 62 UTI patients without bacteriuria for comparison.

Prevalence of symptomatic bacteriuria

In our study, the prevalence of symptomatic bacteriuria was 69% in Type 2 diabetes patients admitted with community-acquired UTI. E. coli (55%) was the most commonly isolated microorganism, followed by Enterococcus faecalis and Candida spp. E. coli is the most common cause of UTI in diabetes from Western and Indian studies.[9],[16],[17],[18] Sharma et al.[19] reported the prevalence of bacteriuria in 43% of elderly Type 2 diabetes patients. The study by Kumar et al.[17] revealed bacteriuria in about 88% of upper UTI, which is higher than our results. In our study, symptomatic bacteriuria was present in 68.5% of females and 71.1% of males, whereas other studies[20],[21] showed that bacteriuria was common in females. Fungus causing UTI in diabetic population is more common in patients having prolonged parenteral antibiotic use, catheterization, and more extended hospital stay.[2] In the present study, six patients had UTI due to Candida, whereas another study[16] also reported similar finding. The relative higher percentage of E. faecalis could be because the patients were hospitalized and higher rates of Enterococcus have been reported in hospitalized patients with UTI.[22]

Factors related to symptomatic bacteriuria

Postmenopausal state significantly correlated with symptomatic bacteriuria. The diabetes of longer duration, presence of previous UTI, diabetic nephropathy, HTN, and CKD were significantly associated with symptomatic bacteriuria in our study. Adeyeba et al.[23] also found a positive correlation between bacteriuria in UTI and duration of diabetes. Al-Rubeaan et al.[24] found UTI related to females gender and obesity. The association of obesity with symptomatic bacteriuria in our study could be because of coincidence, as obesity is common in women. Uncontrolled HTN leads to angiopathic changes in kidney, which causes CKD and predisposes to infections. In our study, symptomatic bacteriuria patients had poor glycemic control than UTI without bacteriuria. Vaishnav et al.[25] demonstrated a higher incidence of bacteriuria in uncontrolled diabetic patients. Severe hyperglycemia occurred more frequently in symptomatic bacteriuria patients as compared to those without bacteriuria. Severe hyperglycemia with alter the immune response and with glycosuria will provide the favorable environment for bacterial growth. This emphasizes the importance of strict glycemic control in preventing symptomatic bacteriuria. Proteinuria was a risk factor for symptomatic bacteriuria in our as well in another study.[14] Glycosuria and pyuria occurred more frequently in patients with symptomatic bacteriuria in our study and in the study by Yeshitela et al.[26] Renal cyst and renal calculi significantly increased the risk of symptomatic bacteriuria by acting as a nidus for bacterial growth. Pyelonephritis, EPN, and AKI were significantly higher in symptomatic bacteriuria patients. The significantly higher prevalence of nephropathy and proteinuria in the patients with symptomatic bacteriuria than in those without bacteriuria suggests either the role of bacteriuria in increasing the risk of microangiopathic complications or a predisposing role in producing symptomatic bacteriuria.

Escherichia coli symptomatic bacteriuria

In our study, the factors associated with E. coli symptomatic bacteriuria in Type 2 diabetes were female gender, obesity, and poor glycemic control. E. coli remains the most common cause of bacteriuria, so demonstration of demographic and clinical factors associated with E. coli symptomatic bacteriuria will help in predicting its consequences. E. coli is the common cause of recurrent UTI.[18] Virulence factors of bacterial strains play an essential role in pathogenesis of UTI. Strains of E. coli expressing Type 1 fimbriae adhere better to urinary endothelial cells of women with diabetes.[27] Further understanding involved in uropathogenesis with respect to E. coli genes is required.[28]

The present study had some limitations. First, it was a single-center study; second, other risk factors such as virulence factors of bacterial strains were not identified. Third, the clinical factors associated with extended spectrum beta-lactamases producing E. coli was not studied, which could help in predicting the resistant microorganism before culture results are available.

 Conclusions



The prevalence of symptomatic bacteriuria was 69% in Type 2 diabetes. E. coli remains the most common isolated microorganism in symptomatic bacteriuria. Postmenopausal state, longer duration of diabetes, and presence of nephropathy increase the risk of symptomatic bacteriuria. The higher degree of hyperglycemia could be either the result of symptomatic bacteriuria or be responsible for its perpetuation. Complications do not frequently occur in symptomatic bacteriuria except AKI. E. coli symptomatic bacteriuria was associated with female gender; obesity had poor glycemic control. UTI in Type 2 diabetes should be treated aggressively, more so E. coli bacteriuria. Long-term prospective studies on the effect of symptomatic bacteriuria in Type 2 diabetes patients are required and to identify virulence factors shared by bacterial strains.

Acknowledgment

The authors would like to express their greatest gratitude to all participating patients, health professionals, and community support group members, who provided assistance for this study. I am thankful to Dr. Hifz Ur Rahman for helping me in statistical analysis of the data. I am also thankful to Dr. Nayeem U Din Wani, Lecture of Department of Microbiology for helping me in the analysis of the urine culture reports. I also thank the technical department of microbiology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Research quality and ethics statement

Appropriate approval was obtained from institutional ethics committee of SKIMS vide number IEC/SKIMS/2015-235. Clinical trials registration was not done as it was observational study. The authors declare that they followed applicable EQUATOR Network (http://www.equator-network.org/) research reporting guidelines.

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