Taufiq Shaikh1 and Ranan Dasgupta2
Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London, W6 8RF, UK
Department of Urology, Imperial College Healthcare NHS Trust, St Mary’s Hospital, Praed Street, London, W2 1NY, UK
Certain groups of patient are at higher risk of UTI, for example, diabetics. We discuss the reasons why they are more prone in this chapter. We also touch upon the more severe complications, which the reader should be aware of, such as emphysematous pyelonephritis. Some of these cases require urgent surgery, and therefore it is essential that the clinician has a low threshold of suspicion in cases of urosepsis in diabetics, and therefore early involvement of urological input is justified.
DiabeticDiabetes mellitusUrinary tract infectionEmphysematous pyelonephritisPapillary necrosis
Are UTIs More Common in Diabetics?
UTI is one of the most common infections in diabetic patients. Patients with diabetes have an increased risk of urinary tract infection as compared to nondiabetic population . This is true for both asymptomatic bacteriuria (ASB) and symptomatic UTI.
The rate of asymptomatic bacteriuria is three to four times higher in diabetic women as compared to nondiabetic women [2, 3]. However, there is not much difference in the prevalence of asymptomatic bacteriuria in diabetic and nondiabetic men . The relative risk of symptomatic UTI in diabetics is about 1.39–1.43 times more as compared to nondiabetics .
What Course Does UTI Run in Diabetic Patients?
In diabetic patients, UTI has a higher chance to run a complicated course as compared to nondiabetic patients. Diabetes predisposes to more severe infections which are difficult to treat and recur more often. The chances of bacteremia and need for hospital admission also are higher in diabetic patients with UTI.
What Is the Pathogenesis of Development of UTI in Diabetic Patients?
As in nondiabetic patients, the essential step in the pathogenesis of UTI is the adherence of pathogenic microbes to the bladder mucosal lining. In most gram-negative uropathogens, this is achieved by various virulence factors such as H antigen, fimbriae, or adhesins. In the case of E. coli (the most commonly studied organism), virulence factors are fimbriae. Type 1 fimbriae bind to glycoprotein receptors in uroepithelium, whereas Type 2 fimbriae bind to glycolipid receptors in the kidney .
Once the bacteria are bound, urothelial cells internalize bacteria by an active process similar to endocytosis and require tyrosine phosphorylation . This is followed by an inflammatory response from the host immune system. The inflammatory response consists of steps involving uroepithelial cell activation associated with transmembrane signaling, resulting in the production of distinct inflammatory mediators. Usually, this is followed by the direction of the innate immune cells to the infectious focus which leads to local destruction and elimination of the invading bacteria . This process involves the complement system, Toll-like receptors (TLRs), urinary Tamm-Horsfall proteins (THPs), cytokines, and adhesion molecules . Bacteria can also invade uroepithelium where they replicate and form quiescent intracellular reservoirs, which may serve as a possible source for recurrent UTIs.
What Is the Reason for Higher Prevalence of UTI in Diabetics?
The presence of glucosuria and impairment of the granulocyte function in the diabetic patients, although long suggested as the reason for increased risk of UTI, have not been conclusively proven in vivo [9–11]. Some studies have suggested that decreased urinary levels of IL-6 and IL-8 in diabetic patients contribute to increased incidence of UTI . It has also been suggested that there is increased adherence of bacteria to the urothelium in diabetic patients. This is due to decreased ability of THP to bind type 1 fimbriated organisms, possibly because of an additional glycosylation of THP in diabetic patients, and a positive correlation with poorly controlled diabetes [13, 14].
What Are the Risk Factors That Predispose to UTI in Diabetes Mellitus (DM)?
As in nondiabetic patients, host factors tend to be either urinary tract obstruction, stasis, reflux, instrumentation, or sexual intercourse . Additional factors in diabetic patients that might predispose them to UTI include age, glycemic control, duration of DM, diabetic cystopathy, frequent hospitalization, vaginitis, and vascular complications .
What Is the Clinical Presentation and in What Way Can It Present Differently?
The clinical presentation of UTI in diabetic patients can range from asymptomatic bacteriuria to severe life-threatening sepsis. The incidence of symptomatic UTI in the form of dysuria, frequency, abdominal discomfort, and urgency is higher in diabetic patients . Occasionally, UTI in this group of patients might also be associated with hematuria.
In diabetic patients, there are increased chances of UTI running a complicated course and presenting with acute pyelonephritis. The risk of hospital admission for acute pyelonephritis can increase 20–30 times in diabetic patients less than 44 years of age. The risk is 30–50 times in diabetics over 44 years of age . Bilateral pyelonephritis is more common in diabetic patients . Papillary necrosis, renal abscess, emphysematous pyelonephritis, and systemic sepsis may also occur .
What Is Emphysematous UTI?
Emphysematous UTI is a severe necrotizing infection and, as the name suggests, it is characterized by gas formation along the urinary tract. It mainly can be in the form of emphysematous pyelonephritis or emphysematous cystitis. Emphysematous pyelonephritis (EPN) can involve the collecting system, renal parenchyma, and the perirenal tissues, whereas emphysematous cystitis involves the bladder wall. The infection has a severe and fulminant course and can be life-threatening if not recognized and treated early. Gas formation is thought to occur as a result of mixed acid fermentation of glucose . A high degree of suspicion is required for diagnosis, which is made by a radiological demonstration of gas formation along the renal tract. A CT KUB is the investigation of choice and delineates the localization or the extent of gas formation, thus helping formulate an optimal management plan .
Treatment comprises active resuscitation, electrolyte and blood glucose monitoring, and correction and administration of antibiotics targeting gram-negative bacteria. Any associated obstruction along the urinary tract, if present, should be relieved, and if there is extensive gas formation with renal destruction, a nephrectomy may be warranted .
What Is Renal Papillary Necrosis?
Renal papillary necrosis is an important complication of UTI in diabetics. Symptoms include chills, fever, and acute renal insufficiency. The pathogenesis is not well understood but is presumed to be due to the marginal vascular supply at the papilla, which becomes further compromised by infection, leading to infarction and sloughing of the papillae .
What Are the Main Organisms Implicated for UTI in Diabetes, and Is There Any Difference Compared to UTI in Nondiabetics?
The causative microorganisms of UTIs in patients with DM are similar to those found in nondiabetic patients with complicated UTI. The same is true for the antibiotic resistance and sensitivity patterns . The most common causative organism for UTI is E. coli. Other pathogenic microbes include Klebsiella sp., Group B streptococci, Enterococcus spp., and Pseudomonas. Diabetes mellitus, per se, is not considered to be a risk factor for the development of antibiotic resistance.
Should ASB Be Treated in Diabetics?
ASB is a risk factor for symptomatic UTI in nondiabetic patient population  and increases the risk of recurrent UTI, progressive renal failure, and hypertension . The limited number of studies in diabetic patients show that ASB increases the risk of symptomatic UTI in type II diabetics, as compared to type I diabetics . There is no relationship between ASB and deterioration in renal function , as was previously thought . The risk of complications is not reduced by antimicrobial therapy of ASB and, therefore, should not be an indication to screen for or treat ASB .
Is the Treatment of UTI in DM Different from Nondiabetics and What Important, or Special, Considerations Should Be Given to Such Patients?
As the causative microbes and their antimicrobial sensitivity in diabetics are similar to nondiabetic patients, the choice of antimicrobial treatment should be similar and based on the local resistance patterns of the common uropathogens . Treatment protocols should avoid nephrotoxic agents as much as possible. A 2-week treatment regime is as effective as a 6-week regime. Any recurrence seen 4–8 weeks after treatment is a reinfection rather than a relapse .
Even though there is no general agreement, UTI in diabetics is treated as “complicated” by most clinicians [31, 32]. Preferred drugs are fluoroquinolones and amoxicillin-clavulanic acid, which achieve high levels in urine and urinary tissues on administration . Trimethoprim/sulfamethoxazole is usually avoided as it can lead to hypoglycemia .
Although evidence is lacking, the duration of antimicrobial therapy is longer (7–14 days) than in the nondiabetic population, particularly with frequent upper tract involvement and increased risk of serious complications. The treatment of uncomplicated pyelonephritis does not differ from that of nondiabetic patient group. In these cases, a 7-day regime of oral fluoroquinolones is considered to be a better choice than 2 weeks of trimethoprim . For more severe infections requiring hospital admission and those with sepsis, a combination of intravenous agents based on local policy need to be administered. These agents include fluoroquinolones, aminoglycosides, ceftriaxones, Tazocin, and meropenems.
For recurrent symptomatic infections, such as those in nondiabetics, antibiotic prophylaxis can be initiated in diabetic group as well.
What Non-antimicrobial and Preventative Strategies Can Be Adopted by Such Patients?
The non-antimicrobial strategies to prevent UTI are essentially similar to those that help in prevention of UTI in the nondiabetic patient group. General advice includes sufficient fluid intake, complete emptying of the bladder, less frequent use of catheters, and avoidance of spermicides in women . Other strategies include ingestion of cranberry juice [37, 38] and oral or vaginal administration of lactobacillus . Cranberry tablets are considered a better alternative to cranberry juice in diabetic patients. Estrogen administration can be beneficial in the reduction of recurrence rates of UTI in postmenopausal diabetic women . Two types of vaccines for prevention of UTI have been developed, but both have been withdrawn; although safe, these vaccines were effective in only about a third of patients they were administered to.
· Diabetic patients are at higher risk of developing a UTI.
· UTI has a higher risk of complications, and in diabetics, involvement of the upper tract requiring hospital admission is greater.
· The complications to carefully be aware of include emphysematous pyelonephritis, renal papillary necrosis, renal abscess, and septicemia.
· The most common causative organism for UTI in diabetics is E. coli.
· Asymptomatic bacteriuria is not an indication for antimicrobial treatment in diabetics.
· The choice of antibiotics should be based on local resistance and sensitivity patterns and does not differ much from the nondiabetic group.
· Antibiotic prophylaxis can be initiated in patients with recurrent UTIs.
· Nephrotoxic antimicrobials should be avoided in diabetic patients.
· Cranberry tablets are considered a better alternative to cranberry juice in diabetic patients.
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