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ORIGINAL ARTICLE
Year : 2022 | Volume
: 9
| Issue : 1 | Page : 41-46
Asymptomatic and symptomatic bacteriuria in patients with type 2 diabetes
Tauseef Nabi
Department of Endocrinology, All is Well Multi-Speciality Hospital, Burhanpur, Madhya Pradesh, India
Correspondence Address:
Dr. Tauseef Nabi
All is Well Multi-Speciality Hospital, Burhanpur, Madhya Pradesh
India
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/iahs.iahs_98_20
Aim: Asymptomatic bacteriuria (ASB) and symptomatic bacteriuria with antibiotic-resistant organisms are common in patients with type 2 diabetes. The aim was to study the prevalence, bacterial profile and antibiotic susceptibility pattern in ASB and symptomatic bacteriuria and the factors associated with Escherichia coli bacteriuria in type 2 diabetes. Materials and Methods: This was an observational case-control study done on 400 asymptomatic type 2 diabetes patients, 200 symptomatic urinary tract infection (UTI), and 200 nondiabetic controls. Various clinical, biochemical parameters and urine examination and culture were studied. Results: The prevalence of ASB and symptomatic bacteriuria in type 2 diabetes was 17.5% and 69%, respectively, and were significantly higher as compared to controls (10%). E. coli was present in 52.9% of ASB cases of type 2 diabetes and 70% of nondiabetic control ASB. E. coli (55%) was most commonly isolated in symptomatic bacteriuria. Majority of the Gram-negative bacteria isolates in ASB and symptomatic bacteriuria with type 2 diabetes and controls were sensitive to amikacin, imipenem, piperacillin/tazobactam, and nitrofurantoin. E. coli were more resistant to quinolones in ASB and symptomatic bacteriuria than controls. Most of the Gram-positive bacteria were sensitive to vancomycin, linezolid, and amoxiclav. The factors associated with E. coli bacteriuria in type 2 diabetes were female gender, long duration of diabetes, past history of symptomatic UTI, poor glycemic control, and renal function. Conclusions: E. coli remains the most common isolated microorganism in asymptomatic and symptomatic bacteriuria. E. coli were more resistant to quinolones in patients with type 2 diabetes.
Keywords: Asymptomatic bacteriuria, symptomatic bacteriuria, type 2 diabetes, urinary tract infection, urine culture sensitivity
As per the International Diabetes Federation 2019 report, India is harboring 77 million patients with diabetes.[1] Urinary tract infections (UTI) are more common and severe and carry worse outcomes in patients with type 2 diabetes and good diabetic control is recommended to mitigate this risk.[2] UTI is a common cause of morbidity and mortality.[3] The spectrum of UTI ranges from asymptomatic bacteriuria (ASB) to lower UTI (cystitis), and pyelonephritis, emphysematous pyelonephritis (EPN), emphysematous cystitis, and renal abscesses.[4] UTI in diabetes is imposing a significant burden on health care expenditure[5] and the high rates of antibiotic prescription may further induce the development of antibiotic-resistant uropathogens.[6] Uncontrolled diabetes causing glycosuria may promote the growth of pathogenic bacteria.[7] Impairments in the immune system and the multiple effects of diabetes contribute to the pathogenesis of UTI in diabetes.[8]
Escherichia More Details (Escherichia coli) is the most common cause of UTI, accounting for 85% of community-acquired and 50% of hospital-acquired infections. Other pathogens isolated include Enterobacteriaceae such as Klebsiella spp, Proteus spp, Enterobacter spp, and Enterococci.[9] Patients with diabetes are more prone to have resistant pathogens as the cause of their UTI.
There is geographical variation in microbiological isolates and also antibiotic susceptibility pattern is changing. In the present study, we looked at the prevalence, bacterial profile, and antibiotic susceptibility pattern in asymptomatic and symptomatic bacteriuria in patients with type 2 diabetes and controls and the factors associated with E. coli bacteriuria in patients with type 2 diabetes.
Materials and MethodsThis was a hospital-based observational case-control study of adult type 2 diabetes patients attending the tertiary care center in North India. The institutional ethical committee approved the study. Informed consent was obtained from all the recruited subjects.
Study subjects
The study recruited alternate (i.e., every 3rd) 400 type 2 diabetes patients with no symptoms of UTI attending the Endocrine clinic and consecutive 200 symptomatic UTI patients. We also recruited 200 randomly selected healthy controls without diabetes standardized for age and gender for the comparison. The study was conducted for 3 years. All patients were interviewed and detailed physical examination was carried out. The eligibility criteria for including subjects in the study were: Both male and female type 2 diabetes patients aged > 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-patients on steroids, and (v) recent urinary instrumentation.
Clinical parameters including duration of diabetes, complications of diabetes, drug therapy, clinical symptomatology especially urinary complaints and comorbidities were recorded. Fasting blood glucose and 2-h postprandial blood glucose, kidney function test, and glycosylated hemoglobin (HbA1c) were estimated.
Urine examination and culture sensitivity
Voided, clean-catch and midstream urine samples were collected. Urine specimens were inoculated on Hichrome agar media and plates were incubated at 37°C aerobically for 24 h colony-forming unit (CFU) count was determined. The organisms were identified using standard cultural, morphological, and biochemical techniques.[10] The standard strain number for E. coli used was ATCC 25922, Klebsiella pneumoniae was ATCC 700603, Pseudomonas aeruginosa was ATCC 27853, Enterococcus faecalis was ATCC 51299, Staphylococcus aureus was ATCC 29213 and Staphylococcus saprophyticus was ATCC 19701. Antimicrobial sensitivity testing was carried out on Mueller–Hinton agar (plates with commercially available discs by the Kirby-Bauer disc diffusion method and interpreted according to Clinical and Laboratory Standards Institute criteria.[11] Nitrofurantoin (NFT) with disc content (300 mcg), ceftriaxone (30 mcg), levofloxacin (5 mcg), norfloxacin (10 mcg), ciprofloxacin (5 mcg), amikacin (30 mcg), gentamicin (120 mcg), tetracycline (30 mcg), cotrimoxazole (1.25/23.75 mcg), vancomycin (30 mcg), linezolid (30 mcg), amoxiclav (30 mcg), piperacillin/tazobactam (100/10 mcg), imipenem (10 mcg), cefixime (5 mcg), cefpodoxime (10 mcg), and ampicillin/sulbactam (10/10 mcg) were the biograms used, which were manufactured by Microxpress, a division of tulip diagnostics (P) LTD. ASB in females was diagnosed if culture grew the same organism within 2 weeks, but if repeat culture was sterile, then they were taken as non-ASB. Symptomatic UTI patients were divided into lower UTI (cystitis), acute pyelonephritis and EPN based on clinical symptomatology and imaging finding.
Definitions of symptomatic and asymptomatic bacteriuria
ASB is diagnosed in females when two consecutive urine specimens yielding the same bacterial strain in quantitative counts of ≥105 CFU/ml in the absence of urinary symptoms, while in males single urine specimen is sufficient for diagnosis.[12] Symptomatic bacteriuria in women was diagnosed when a urine count was ≥105 CFU/ml in the presence of urinary symptoms, while in men the urine count ≥104 CFU/ml is required.[12]
Statistical analysis
Quantitative variables were expressed as means ± standard deviation, while qualitative variables were expressed in terms of proportion. Categorical variables were compared employing Chi-square test or Fischer's exact tests, whereas continuous variables were compared by using Student's t-test for independent observations. 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).
ResultsThe prevalence of ASB in type 2 diabetes was 17.5% as compared to 10% in controls (P = 0.015). ASB was significantly higher (P = 0.049) in females as compared to males. [Table 1] shows the microbiological isolates from asymptomatic and symptomatic bacteriuria in patients with type 2 diabetes and control ASB. E. coli was the most common organism isolated from urine culture. E. coli was followed by E. faecalis. In symptomatic UTI, pyelonephritis was present in 44.5%, cystitis in 55.5% and EPN in 9.5%. Urine culture was positive in 69% of patients. E. coli (55%) was most common isolated organism in symptomatic bacteriuria patients followed by E. faecalis and others. E. coli was again the most common in all types of symptomatic bacteriuria, as shown in [Table 2]. Most of the Gram-negative bacteria were sensitive to amikacin, imipenem, gentamicin, piperacillin/tazobactam and NFT, as shown in [Table 3]. E. coli in ASB of type 2 diabetes, and controls and symptomatic bacteriuria were sensitive to amikacin > imipenem > gentamicin > piperacillin/tazobactam > NFT. E. coli were more resistant to quinolones (levofloxacin and ciprofloxacin) in ASB and symptomatic bacteriuria as compares to control ASB. [Table 4] shows the antimicrobial susceptibility pattern of Gram-positive bacteria isolates. Most of the Gram-positive bacteria were sensitive to vancomycin, linezolid, NFT, and amoxiclav.
Table 1: Microbiological isolates from asymptomatic and symptomatic bacteriuria in patients with type 2 diabetes in comparison to control asymptomatic bacteriuria
Table 2: Microbiological isolates from symptomatic bacteriuria (pyelonephritis, cystitis and emphysematous pyelonephritis) in patients with type 2 diabetes
Table 3: Antimicrobial susceptibility pattern of gram-negative bacteria isolated from type 2 diabetes patients (asymptomatic bacteriuria and symptomatic bacteriuria) and control asymptomatic bacteriuria
Table 4: Antimicrobial susceptibility pattern of gram-positive bacteria isolated from type 2 diabetes patients (asymptomatic bacteriuria and symptomatic bacteriuria) and control asymptomatic bacteriuria[Table 5] shows the factors associated with E. coli bacteriuria in type 2 diabetes patients. There were 208 cases of bacteriuria in type 2 diabetes, of which 147 (70.7%) were E. coli induced and rest 61 (29.3%) were non-E. coli induced. The factors which predicted E. coli UTI on multivariate analysis were female gender, long duration of diabetes, history of symptomatic UTI in the year before study entry, poor glycemic control, and lower estimated glomerular filtration rate (eGFR).
Table 5: Factors associated with: Escherichia coli bacteriuria in type 2 diabetes patients Discussion Patients with type 2 diabetes are at increased risk of UTI and its complications. The prevalence of ASB in type 2 diabetes was 17.5% as compared to 10% in the control group (P = 0.015). Our results are comparable to previous studies, which showed a prevalence of ASB in people with diabetes as 17%–21%.[13],[14],[15] The prevalence of ASB was 19.9% and 10.7% in females and males patients with type 2 diabetes, respectively, in our study. Meiland et al.[14] reported the prevalence of ASB in diabetic women as 17% while another study[16] also showed female as a risk factor for ASB. In our study, E. coli causing ASB was present in 52.9% of type 2 diabetes and 70% of ASB controls. The results are consistent with the majority of reports where E. coli is the major pathogen in ASB.[15],[17],[18],[19] We noted a lower percentage of E. coli in patients with diabetes versus controls, which confirms the results of a study by Geerlings et al.[20]
In our study, symptomatic bacteriuria was present in 69% of type 2 diabetes patients. E. coli is the commonest organism responsible for UTI in literature, both from western and Indian studies, similar to our study.[17],[21],[22],[23] 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.[24] In our study, E. coli was by far the most common causative organism for EPN, literature reports E. coli isolation in 47%–90% followed by Proteus mirabilis, K. pneumoniae, Enterococcus species, and P. aeruginosa.[21],[25]
In our study, most of the E. coli in type 2 diabetes ASB were sensitive to Amikacin (100%), Imipenem (94.6%), Piperacillin/tazobactam (86.5%), Gentamicin (83.8%), and NFT (81.1%) which were comparable to control ASB except that E. coli in ASB type 2 diabetes patients had higher resistance to quinolones. We observed that the isolated E. coli strains were resistant to ciprofloxacin, cephalosporins, cotrimoxazole, and ampicillin/sulbactam in type 2 diabetes patients and controls [Table 3], which are comparable with other studies.[17],[19] The high sensitivity of E. coli to carbapenems and amikacin in both type 2 diabetes and controls may be due to their broad spectra on bacteria, which is comparable to other studies.[17] The sensitivity of E. coli in this study is in agreement with previous reports.[16],[18]Enterococcus fecalis antibiotic sensitivity was also comparable between type 2 diabetes ASB and control ASB except controls were more susceptible to penicillin, ampicillin and amoxiclav. Study reported that the high prevalence of resistance to some of the commonly used antibiotics such as ampicillin and tetracycline might be due to their abuse and low cost of purchase.[18]
In our study, most of the E. coli in symptomatic bacteriuria were sensitive to Amikacin (95.5%), Imipenem (91.8%), Gentamicin (87.3%), Piperacillin/tazobactam (80.9%), and NFT (77.3%) as shown in [Table 3]. Other studies[17],[26] showed similar antibiotic susceptibility pattern. Studies have demonstrated that E. coli are highly sensitive to carbapenems in symptomatic UTI with diabetes.[17],[27] In our study, levofloxacin sensitivity was better than ciprofloxacin, pointing toward escalating ciprofloxacin resistance reported in other studies.[28] Our study reported excellent sensitivity to imipenem among Enterobacteriaceae, which is comparable to study by Banerjee et al.[28] but contrast to study by Kumarasamy et al.[29]
In our study, the factors associated with E. coli bacteriuria were female gender, long duration of diabetes, history of symptomatic UTI in the year before study entry, poor glycemic control, and lower eGFR. The study revealed UTI in the prior year predicted E. coli UTI subsequently.[30] The association between clinical characteristics and E. coli bacteriuria has not been studied previously. The identification of the clinical characteristics before the culture results are available help in selecting the presumptive antibiotic. A study has shown that E. coli correlated with the risk of a decline in renal function and certain virulence factors of E. coli might contribute to a decline in renal function.[31] The study has also show that E. coli bacteriuria is a risk factor for recurrent UTI.[32] Virulence factors shared by bacterial strains direct them through a particular pathogenesis process. The current understanding of genetic defining the pathotypes is limited. Discovery of additional E. coli genes involved in uropathogenesis requires further understanding.[33]
ConclusionsE. coli was the most commonly isolated microorganism in asymptomatic and symptomatic bacteriuria. E. coli were more resistant to quinolones in patients with type 2 diabetes. The factors associated with E. coli bacteriuria in type 2 diabetes were female gender, long duration of diabetes, history of symptomatic UTI in the year before study entry, poor glycemic control, and renal function. Long-term prospective studies on the effect of bacteriuria in type 2 diabetes patients are required and to identify virulence factors shared by bacterial strains.
Acknowledgments
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. Feroz Ahmad for helping me in statistical analysis of the data. I also thank the technical department of microbiology.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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