Samreen Riaz1*, Abdullah Mohsin2, Saima Shokat3 and Saba Shamim2*
1Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan
2Institue of Molecular Biology and Biotechnology, University of the Lahore, Lahore, Pakistan
33Department of Zoology, Government College University Lahore, Pakistan
*Corresponding Author: Samreen Riaz, Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
Received: February 26, 2021; Published: March 26, 2021
Introduction: The (UTI) ―Urinary Tract Infection‖ was most prevalent common disease that involves in all humans. The diabetes mellitus patients having greater chances to sickness while comparison to the non-diabetic patients. In the current research work, different parameters of microbiology in UTI having patients suffering from type 2 diabetes mellitus have been studied.
Method: Total 1000 diabetes type1 and type 2 patients with age > 18 years with or without symptoms of UTI with significant bacteriuria were enrolled in the study. Identification of the UTI that was according to the clinical history, symptoms and detailed clinical examination and confirmed by urine examination. Other investigations (CBC, serum creatinine, blood urea, HBA1C, fasting and post meal blood sugar and USG abdomen with pelvis) were also done. In the patient’s samples of the urine culture, patterns of antibiotic sensitivity have been observed.
Results: The highest numbers of patients were of fever 105 (46.67%) followed by asymptomatic UTI [98; 43.56%]. The presence of anemia and leucocytosis had statistically no significant association with UTI while poor glycaemic control has statistically significant association with UTI in diabetic patients. E. coli (32.14%) was commonest microorganism isolated in urine culture. Gram negative organisms were mostly sensitive to ―Imipenem, Piperacillin-tazobactam and Nitrofurantoin‖ while gram positive bacteria were mostly sensitive to ―Linezolid, Nitrofurantoin, Vancomycin, Tetracyclin, Clindamycin and Azithromycin‖ and showed increased resistance to Fluroquinolones and Cotrimoxazole. Candida sp. was sensitive to Fluconazole, Itraconazole.
Conclusions: E. coli is the Universal common bacterial isolate. To treat the UTI with diabetes or without diabetes, aminoglycoside or nitrofurantoin have been used previously from long time. For treatment and prevention of UTI among patients there must be check of antimicrobial sensitivity and its resistance pattern.
Keywords: Type 2 Diabetes Mellitus; UTI; Bacteriuria; Pakistan; Clinical Profile
UTI that consist of the diagnostic operation which involve asymptomatic bacteriuria, urethritis, cystitis, phylonephritis. It is not prevalent in children and older people, there were more cases of women in UTI as compare to men. Data showed 50 percent females are more pronounce in having UTI or unproblematic cystitis in their life. In the non-pregnant females, UTI approximately focusing on the anatomy while top UTI or bottom UTI and both. ― UTI can be symptomatic or asymptomatic, but is defined as presence of bacteriuria with a quantitative count of more than or equal to 105 colony forming unit of bacteria per milliliter. In E. coli is the most common disease causing microorganism in UTIs both types complicated and uncomplicated. ― There are some microorganisms that produce UTI Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus saprophyticus, group B Streptococcus, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus and Candidaspp. National Ambulatory Medical Care Survey which has been described that the UTI is still prevalent microbial disease throughout the global. There are many risk factors in UTI like anatomy of female’s body, sexual activity, abnormalities in urinary tract, vesicoureteral reflux, blockage in urinary tract, and use of the catheter or a low immunity condition while in diabetes mellitus [1-7]Organisms causes UTI
Most prevalent microorganism which causing UTI e.g. E. coli and Proteus, Klebsiella, Streptococcus and Staphylococcus epidermis are also pathogens. In the hospitals and local population area high rate of antimicrobial resistance can be seen among uropathogens that can produce UTI. The mostly used antibiotic medicine that have been found better prevention for treatment involve like ― penicillins, cotrimoxazole, older quinolones such as nalidixic acid and cephalosporins and Newer fluorinated quinolone (ofloxacin, cipro- floxacin), gentamicin, amikacin and imipenum”. It is very difficult to treat the UTI in the current year where the most bacteria are antibiotic resistance. ―Microbes that are multi drug resistance (MDR) for example Enterobacteriaceae that including E. Coli or K. Pneumonia”. As u Know in the hospitals community clinics and other health care practice, there is much emphasis is given to T2DM or its complications. There are a lot of researches who have been done work on the diabetes but there is lack of epidemiological information regarding to diabetes and its complications. In clinical diagnostic, UTI results in highly expressed morbidity and increase medical costs. There is scarcity of research work despite of the clinical or health importance in public. In the current study of diabetic and non-diabetic UTIs, different parameters of clinical presentation, predisposing conditions, pathogens caused UTIs have been observed in their susceptibility to antimicrobial drugs [8-17]. In Figure 1 the risk of diabetes and UTI has been shown (Figure 1).Diabetes mellitus (DM)
Diabetes mellitus (DM) is a group of metabolic disorder that is characterized by high blood sugar levels over a prolonged period. Diabetes which is divided into the 2 types for example type 1 or type 2. Diabetes type 1 is caused by the breakdown of pancreas that produce hormone like insulin. The type 2 is deficiency of insulin through beta cells of the human body. All types of the diabetes mellitus which have acute (short term) and chronic (long term) problems. There are few acute or the short term problems that are hyperosmolar hyperglycemia, coma or death, diabetic ketoacidosis, or long term problems like nephropathy, foot ulcers, opthalmopathy, and cardiovascular diseases. In the previous study, it has been noted that the global prevalence of diabetes is about 415 million humans and only 90% of have T2DM. There number is calculated and increase about 552 millions in the 2030 year. It has been observed that every year people were dying from this disease as per 1.5 to the 5 million. The economic funds of world cost is about 612 billion dollars that is used for his managements and prevention. “Diabetes Mellitus (DM)” is worldwide serious strength problem and it has considered important socio demographic load for the progress like Pakistan. Around the world in 2019 data showed the 451 million of people were diabetics but in 2045 number is increased round about 693 millions. According to latest Pakistan national diabetes survey about 26.3% of the local population age over 19 is diabetic. People having diabetes mellitus type 2 are more chances of Urinary tract infection. Others are the poor bladder function, obstruction in urinary flow or incomplete voiding are also considered as new factors that are mostly present in patients which has diabetes mellitus and have shown increase chances to UTI among them. In expecting females, asymptomatic bacteriuria is associated with pre term birth, perinatal mortality and pyelonephritis in mother [18-27].
Figure 1: Risk of UTI in Diabetes Mellitus.
Countless study that declared the overall incidence of the UTI beyond patients with diabetes mellitus. All the patients in UK with universal method research database seen that incidence ratio of UTI was the 46.9 per thousand person years beyond the diabetic patients as compared with 29.9 that patients except diabetes. American knowledgebase examine throughout 2014 discovered that UTI testing was many prevalence in filed along the diabetes or except diabetes (9.4% vs 5.7%). About 70,000 patients in America with diabetes type two that discovered 8.2% were testing UTI in the 1 year “(12.9 percent females or 3.9% of males, along rising rate with the life group)”. Previous study explained that the diabetic women were more than 15 times regularly hospitalized for the short term pyelonephritis than the non-diabetic women. The diabetic men were hospitalized less than 15 or greater then non diabetic patient’s men populations. Asymptomatic bacteriurea” has been noted that it is grater for example eight to twenty five percent in diabetics. It also increase significantly in that patients who have diabetes with the long period of time [28-35].Pathogens that involve in UTI patients who have diabetes mellitus
UTI begin when its microbial disease causing microorganism that usually present in the “gastrointestinal tract (GTI)” that contaminate the environment of periurethral region which have ability to produce colonies in urethra. “After that pathogens migrated in the urinary bladder or invaded, colonized the external umbrella cells through the high appearance of the pili and adhesins”. “In the host inflammatory feedback or neutrophil infiltration has been functional and few microbe which get free from the immune system of human body”.
Microorganism which occupy host cell or by the help of morphological changes their result showed that support to the cells of the neutrophils. Then disease causing microbes is multiply or create the biofilm. Enzymes like “proteases or toxins” has been formed with the help of this microbe that promote damage of the host. They delivered most important essential nutrients which has been more promoted the microbial survival or then entered into kidneys and which make colonies that emerge into pyelonephritis. In that case if they leave them unprocessed then microbes will damaged that “tubular kidney or epithelial barrier” which can finally finish while the bacteremia [36-40]. As shown in figure 2.
Figure 2: Top Countries with diabetes.
The higher risk of UTI in diabetes type 2 that understand through different process. Diabetic neuropathy produces the defective bladder and also create more chances of UTI. It also involve dysfunction of its retention that causes low bacterial clearance by micturition and promoting the microbial growth. The urinary bladder decayed that may present for example 26%-85% of the diabetic women. As the glucose level increase in the urine sample in patient with the diabetes mellitus enhances the bacterial reproduction and creates a positive environment for the infections. There are many studies that usually showed the group among HbA1c level and glycosuria, that causing threat factors of the UTI with in diabetic case. In the condition pyelonephritis, it increase renal parenchymal glucose levels” that produce friendly atmosphere which help microbe to grow and reproduce. It also lead to kidney complications like emphysematous and pyelonephritis. Impaired immune responses (humoral, cellular, and innate immunity has important character into diabetes mellitus case. It also lower the capacity of defend against the microbe proliferation. “Low level of urinary interleukin six or eight was observed in diabetes cases with asymptomatic bacteriurea as match up with those who having no diabetes”. ―Dapagliflozin‖ is that medicine which is utilized by patients who have diabetes mellitus and it linked with the little bit higher in UTI. Patients having diabetes mellitus is severe and most prevalent in UTI. They are regularly caused by the resistant disease causing pathogens. They examined that the impact of diabetes mellitus on spectrum of the uropathogens or antimicrobial drugs that susceptibility in the patients along with UTI in our regions. E. coli was predominant uropathogens, that followed by the streptococci in diabetes mellitus or non-diabetic groups. As increasing number of isolates that are sensitive to nitrofurantoin in the either groups or MDR ratio were increasing in diabetes mellitus patients along with the chronic disease status. Patients that having high HbA1c levels or greater duration of diabetes mellitus pronounced more risk of UTI. Increase kidney paremchymal level of glucose that provide a familiar atmosphere for growth of microbes. Limitless diabetes mellitus is higher prevalent that associated along with the complicated UTI for example pyelonephritis and emphysematous cystitis. In another study meta-analysis on asymptomatic bacteriuria that are in patients with the diabetes mellitus. It observed that duration of diabetes mellitus was higher in patients with asymptomatic bacteriuria. In another meta-analysis that HbA1c was present little bit increase in the diabetes mellitus with asymptomatic bacteriuria and the difference is not statistically more significant. In one study it has been concluded that patients of diabetes mellitus HbA1c above 8.1% have increase prevalence risk of UTI. In addition there is HbA1c below 6.5% is also appeared to significantly down the risk of UTI. It also has been found that the most UTI cases have showed the uncontrolled glycemia. It is also very famous that patients with the greater duration of diabetes mellitus have greater prevalence of diabetes mellitus with chronic complications. It may lead to a high presence of UTI in diabetes. In many of other patients there is autonomic neuropathy that results in the dysfunctional voiding or urinary retention. The mean of HbA1c was 9.3% in some other study. Many of other diabetic patients had long duration of diabetes mellitus. Patients with the diabetes mellitus can have an increased risk of the UTI, particularly among women. Age of human very matter in bacteriuria as risk agent. UTI in the diabetic and non-diabetic groups and showed the mean age group was the greater in the diabetes groups only [41-44].
It some study it had been noted have same observation. The result explained risk element that linked with UTI are senior age humans, women’s, sex, or higher HbA1c values. Gram-negative bacteria, for example E. coli, are most prevalent and common uropathogen that has been isolated in the patients with the UTI and diabetes. In one study, the most common microorganism isolated was E. coli. The clinical profile of isolated microorganisms from some patients’ urine sample were same in both groups. Same result have been observed research work previously. Widely use of the antimicrobial agent that cause lead to emergence of the drug resistant microorganism. It has been developing higher resistance to the antimicrobial agents. It has been seen that microorganism which causing UTI. It is very necessary that pattern of antibiotic susceptibility of the isolated microorganism. In other study it has been observed that there is no difference between the susceptible bacterial organisms and patterns of antibiotic resistance in the UTI of patients having diabetes and normal healthy controls. In another research work it is noted the susceptibility patterns of antimicrobial agents that may assist to use appropriate and proper therapeutic choices and techniques in diabetic patients. Both of the two groups of diabetes showed the increase level of resistance of ampicillin and a sensitivity to the drug of nitrofurantoin. Taking the techniques of gram staining of the microorganism, Gram-negative microbial isolates like ―E. coli and Klebsiella pneumoniae‖ both of them increase level protection of the ―ampicillin‖ in the diabetic or non-diabetic groups as observed in the some previous studies. As some other data shows, many isolated microorganisms were very sensitive to the drug nitrofurantoin, regardless of having diabetes status. Similarly, a greater percentage of some Gram+ve isolates were also sensitive to the nitrofurantoin. These findings have been reported elsewhere also. Depending on this data available and validated information, it can be thought that the “nitrofurantoin may be used as the medicine for empiric analysis and therapy for UTI in that patients along diabetes” Although the fluoroquinolones have also been recommended as this drug of choice may be empirical treatment”. and therapy of community who has acquired UTI. It also reported that higher trend of the drug fluoroquinolone resistance is a vital problem for the diabetic patients. In some other research, ciprofloxacin resistance was also observed as %42.9 of total microbial isolates. This is very high rate when it was compared with the other studies by done other scientists. Patients have longer diabetes duration have greater prevalence of diabetes with the chronic complications, which can lead to up-regulation in UTI that caused by resistant bacterial pathogens. It also has been found that the highest increase in MDR risk present among the diabetic patients with longer duration of more than 10 years. This retrospective design study can also be considered as some of its limitation. However, the strict exclusion and inclusion patient selection criteria can be used and the inclusion of outdoor patients with a relatively greater number can help to counter that limitation [45-48]. See figure 3.
Figure 3: Data of Pakistani UTI in Diabetes Mellitus.
The treatment of the UTI should be identify in each patient of the diabetes mellitus that present along with the symptoms dependable with the UTI, that are ―frequency, dysuria, or suprapubic pain” which are less for the UTI and the symptoms or sign for higher UTI that involve that of UTI have fever, tendemess, cost vertebral angle pain and chills. The patients with the diabetes mellitus type 2 or UTI which found with ―hypo or hyperglycemia, non ketotic hyperosmolar state, or even the ketoacidosis” that need immediate removal of the virulent agent, that consist UTI. The ―midstream urine‖ sample should investigated, for the leukocytes count from the patient who are suspicious. Urine dip stick method were used to check the pyruvia in the patient of UTI, it can be seen by microscope. From the microscopic study of the pyruvia can be explained colonization. Presence of positive test of urinary nitrite showed presence of the microbe. A negative test explained absence of microbe and it can also indicate gram positive bacteria which don’t have ability to low the nitrate level. Usually hematuria or protein urea that can also common judgment. When obtain the urine culture that must be managed in all the cases of the imagined UTI in the diabetes mellitus patients. The good purpose is from the voided, mid-stream urine and clean catch. A culture which obtain is through the sterile urinary catheter inserted, or by suprapubic aspiration in a patient for whom specimen cannot be collected, such as in patients with altered sensorium or neurologic/urologic. In those patients with chronic stages of indwelling catheters, the preferred protocol of having a urine +sample for the culturing is taking a sample from catheter who freshly put, to the patient as there is production of the biofilm on catheter. The most usual pathogens microbe which is took from urine of diabetes mellitus patients for example Escherichia coli, other Enterobacteriaceae such as Klebsiella spp., Enterobacter spp., Proteus spp., and Enterococci. Infected person suffering from diabetes mellitus type two showed more result of microbial resistant organisms that can cause the UTI with the ―extended-spectrum β-lactamase-positive Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, fluoroquinolone-resistant uropathogens, or vancomycin-resistant Enterococci”. .Management and prevention of UTI in diabetes
Treatment and prevention of UTI in the patients suffering from type 2 diabetes vary on many factors for example the ―existence of the symptoms; whether infection is localized only in the bladder as in lower UTI, or also comprises the kidney as well, making it upper UTI; severity of systemic symptoms, presence of urologic abnormalities, renal function, and accompanying metabolic alterations.‖ Frequently, prevention and treatment of UTI in the type 2 diabetic people is compatible with UTI in healthy normal. Antibiotic selection must also advised through clinical patterns of susceptibility in uropathogens. Therapy must be include the correct metabolic problems that produced by the method of infectious. There are some cases of symptomatic should be treatment as ―asymptomatic bacteriurea” is frequent risk factor or antibiotic therapy should be given in these cases. It may also not give much benefit as it serves mainly to raise the bacterial resistance. Prevention and therapy must addressed accordingly to the severity of disease and with culturing data. As people having with diabetes is also taken some other medicines for the long term, the choice of right antibiotics in these person must take into notice because of the drug interactions between the diabetics and antihypertensive drugs have the antimicrobials agents. Many antibiotics can also produce impaired glucose homeostasis that leads the worse condition of the patient. Many long term diabetic patients were also damaged kidneys. Thus the dose adjustment should be necessary in these patients in the kidney impairment of the antimicrobials drugs are very necessary. Aminoglycosides is one of right example. These drugs must use with great precaution and care in the patients with kidney damage because of their side effects of nephrotoxicity. Drug nitrofurantoin must also be prevented for the patients having diabetes and kidney failure because of having peripheral neuropathy that is linked with the accumulation of drugs in the kidneys . See figure 4.
Figure 4: Methodology of UTI in Diabetes Mellitus.
Diabetes mellitus is main risk factor of urinary tract infections UTI or it also have great risk of some complications of UTI for example like emphysematous pyelitis (EP), emphysematous pyelonephritis (EPN), xanthogranulomatous pyelonephritis (XGP), emphysematous cystitis (EC), renal or perirenal abscess, and renal papillary necrosis (RPN).‖ Regretless, diabetic person have bad results of UTI usually when it correlate to that people which have no diabetes. ―Diabetes mellitus‖ is coupled with ―longer hospitalization, azotemia, bacteremia, and septic shock.‖ ―Diabetes mellitus‖ has also been noted to higher threat factor for the before clinical damage after 3 days of antibiotic therapy in females with ―acute pyelonephritis.‖ The death rate of UTI is five times higher in patients that have more life span. ―Relapse and reinfection” are mostly seen in that person which having diabetes. More than ―sixty seven percent of emphysematous cystitis and ninety percent cases of emphysematous pyelonephritis that were occurred in people with diabetes mellitus.‖ ―Kidney and ―perinephric abscesse, Urosepsis and bacteremia” are occurred in patients with diabetes. ―Emphysematous‖ create problems in the kidney or the urinary bladder because microrganisms present in it and they do fermentation glucose and generate the carbon dioxide. ―Impaired tissue perfusion that present in diabetic peoples and have impaired transport of the metabolic end products.‖ ―Diabetes mellitus is major risk factor for progression of the renal abscess that linked with the ascending infection‖ .
One study showed that bacteriuria was more common in female as compare to male and patient above 50 year of age are more affected then younger one. People with type ii diabetes mellitus and diagnosis with oral hypoglycaemic agent are effected more frequently. Bacteriuria was more common in patient whose glycocylated haemoglobin was more than 10% and fasting plasma glucose was more than 200mg/dl. Patients having neuropathy are more prone to UTI. Most common organism an association between UTI and DM was first noted in an autopsy series in 1940's. Many autopsy is prevalent UTI in diabetic’s peoples. Those women which have diabetes are more chances 3 times to have microbes in their urinary bladders than those females who have no diabetes. The same result does not found to be right for male. There are also showed to be higher risk of the microbial infection spreading upregulation into the kidneys of the diabetic people and females with UTI are also more need become hospitalization than those of non-diabetic females. Diabetes disturb many organ systems that save us from the infection generally also against the urinary tract infections specific. Bad circulation in diabetics, reduced ability of leukocytes to fight against infection, dysfunctiona urinary bladders that contract in poor manner. All these factors promote to the higher prevalence of UTI in diabetics. Asymptomatic bladder infections detected by a positive urine culture are also common among diabetics without any clinical evidence of UTI. Recurrent UTI are common in diabetics .
UTI is more frequently associated in the elderly diabetic patients with higher risk in women gender. Asymptomatic bacteriuria was prevalent in diabetic patient. Fever is the most common symptom has been seen for UTI in diabetics, because any of patient of fever, having with or no urinary symptom should be studied for the presence of UTI. Poor diabetic control (Hba1c>7%) and longer duration of diabetes (>10 yrs) are linked with more risk of UTI in diabetics. E. coli is the major prevalent pathogenic micro-organism and most of microbe’s isolated microorganisms were very sensitive to antimicrobial drugs. Thus drug Imipenam can be used for the empirical therapy for UTI in diabetic’s reports. Piperecillin-tazobactam is second most drug that can be used for the empirical treatment of UTI in diabetics, however ceftriaxone and ampicillin showed wide resistance and hence should not be given for empirical treatment of UTI in diabetics. Good control of diabetes mellitus must be obtained to lower the risk of UTI in diabetic. ―Urinary tract infection (UTI) is the most frequent and prevalent medical cases that has been observed in all age groups of diabetes. Diabetic people are more susceptible to UTI as compared to normal healthy people. Complex UTI and linked diabetic complications may be significant cause of morbidity and mortality. However, UTI is linked with the high medical cost associated with its prevention. Possible method and methodology of the UTI in diabetes may be neuropathy that produced by the hyperglycemia resulting in neurogenic bladder, urinary stasis and increasing probability of infection. Other possible reasons may as reduced ―neutrophil activity, low urinary cytokines, and leukocyte concentrations that could facilitate the adhesion of microbes to uroepithelial cells. Therefore; hyperglycemia also facilitate the colonization, production and growth of variety of micro-organisms. Research data supported that E. coli is the most frequent and prevalent microbial isolate and others microbes are klebsiella pneumoniae, enterococci, pseudomonas, citrobacter, serratia, gram positive cocci . See figure 5.
Figure 5: Demographic data of Diabetes and UTI.
Urinary tract infections (UTI) mostly has been occurred in the diabetes mellitus cases due to because of having an impaired immune conditions in which glucose volume higher in urine. There are many complicated cases in the UTI that may be rare but are more prevalent in the diabetic’s peoples along with severe complications that need to be addressed in future. The proper ad right management and prevention of UTI in the diabetes is very crucial, as there is need of prompt diagnosis with right use of antibiotics that is very necessary for its therapy. Future research in the related work will be hopefully lower the burden of UTI in the diabetic population. When women age was increasing with passage of time they show some diagnostic aspects like ―high urinary frequency, dysuria, flank pain, hematuria or urinary incontinence that consequently increased in those people who have diabetes with having UTI”. ―Some other state like incline the UTI between males and females, ICCU admission, Benign Prostatic Hypertrophy, Renal Calculi and indwelling catheter were common.‖ Last year studies showed the incidence of UTI was greater in the diabetic patients. Type 2 patients that use insulin therapy, and their history of neglect medicine with the less glycemic control that increase cases of UTI in previous study. ―Escherichia coli” was universally most prevalent and in which we isolate microbe from urine culture of diabetic type’s patients. However we still used medicine to diagnose UTI of diabetes patients in the Hospitals
Ethics committee approval was obtained from the University and concerned Hospitals. Authors are thankful to the concerned University of the Punjab, Hospitals and laboratories for the providing data and samples.
The author(s) declare that the publication of this article has no conflict of interest.
Citation: Samreen Riaz., et al. “Molecular Level Microbiological and Clinical Profile of Urinary Tract Infection in Diabetes Mellitus". Acta Scientific Microbiology 4.4 (2021): 157-166.
Copyright: © 2021 Samreen Riaz., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.