Urinary Tract Infection in Diabetics

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Provisional chapter
Urinary Tract Infection in Diabetics
Ajay Kumar Prajapati
Additional information is available at the end of the chapter
© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Ajay KumarPrajapati
Additional information is available at the end of the chapter
Abstract
Diabetes is a metabolic disease with increase blood sugar level. A large population of
world is aected by diabetes. The patients suering from diabetes have many other com-
plications like cardiovascular disease, kidney disease, retinopathy, diabetic foot, diabetic
neuropathy, urinary tract infection, etc. The patients with diabetes are more prone to get
urinary tract infection due to frequent urination and high blood sugar level. The high
sugar level gives favorable growth environment to the pathogens. Early diagnosis and
proper medication are necessary for management of urinary tract infection in diabetic
patients. The diagnosis of urinary tract infection is dependent on urine culture reports.
The treatment should preferably be started after antimicrobial susceptibility reports. The
misuse or overuse of antibiotics may lead to antimicrobial resistance. The antimicrobial
resistance is another challenge in management of urinary tract infection.
Keywords: diabetes mellitus, urinary tract infection, Gram-negative bacilli, antibiotic,
antimicrobial resistance
1. Introduction
Diabetes is a global threat that aects the quality of life, and it is estimated that it will aect
220 million people by the year 2020 worldwide. Morbidity and mortality in diabetic patients
are caused by infections. Evidence suggests that, urinary tract infection (UTI) is the most
common bacterial infections among diabetic patients. According to American Diabetes
Association (ADA) report, patients suering from type 2 diabetes are more likely to have
a urinary tract infection (UTI) and repeat UTI than patients without diabetes. Symptomatic
bacteriuria in patients with diabetes is serious and warrants proper clinical aention for diag-
nosis and treatment. High glucose concentration in the urine can provide a rich source of
nutrients for bacteria. Therefore, bacteria can multiply and make foundation for infection also.
© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

High glucose concentration in the urine can allow urinary colonization by microorganisms.
Moreover, multiple mechanisms were involved in UTI patients with diabetes. Diabetic female,
diabetic overweight, and diabetic obese patients are having the highest risk of UTI. In general
diabetic population, other risk factors associated with urinary tract infection were found to
be diabetic nephropathy, diabetes with hypertension, and insulin therapy. Emphysematous
pyelonephritis, emphysematous cystitis, renal and perinephric abscesses, urosepsis, and bac-
teremia are the complications of diabetes-associated UTI. Longer hospitalization, recurrence
of UTI, relapse and re-infection, bacteremia, azotemia, and septic shock are the outcomes of
diabetes-associated UTI [1].
2. Diabetes
Diabetes is a persistent disease. This disease is characterized by increase of blood glucose
level. The reasons of increase of blood glucose level may be either insucient production of
insulin, a hormone that regulates the blood glucose level, or the insulin produced cannot be
used properly. Frequent urination, increased thirst, and increased hunger are the common
symptoms of diabetes. Uncontrolled blood sugar level can cause many complications. These
complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers,
damage to the eyes, diabetic ketoacidosis, etc. Diabetes mellitus can be described as group of
metabolic disorders causing increase in blood sugar level due to defect in insulin secretion,
insulin action, or both [2]. The digestive system breaks carbohydrates, sugars, and starches
found in many foods into glucose, which is a type of sugar that enters the bloodstream [3].
By the action of the hormone insulin, cells throughout the body absorb glucose and use it for
energy. Diabetes develops when the body does not produce enough insulin or is unable to use
insulin eectively or both. Insulin is produced in the pancreas. Clusters of cells found in the
pancreas are called islets. Pancreas having islets, which contain beta cells, produces insulin
and releases it into the blood.
3. Types of diabetes
• Type 1 diabetes also called as insulin-dependent diabetes mellitus (type I diabetes occurs
due to β-cell destruction, usually leading to absolute insulin deciency).
• Type 2 diabetes also called as noninsulin-dependent diabetes mellitus (type II diabetes
occurs due to a progressive loss of insulin secretion).
• Gestational diabetes mellitus (GDM) (diabetes detected in the second or third trimester of
pregnancy that is not clearly overt diabetes).
• Specic types of diabetes due to other reasons, for example, monogenic diabetes syn-
dromes (such as maturity-onset diabetes of the young [MODY] and neonatal diabetes),
Microbiology of Urinary Tract Infections: Microbial Agents and Predisposing Factors2

diseases associated with exocrine pancreas (such as cystic brosis), and drug- or chemical-
induced diabetes (such as use of glucocorticoid, in the treatment of HIV/AIDS or after
organ transplantation).
Type 1 diabetes occurs in childhood, mainly due to destruction of pancreatic β-cell islets
through autoimmune-mediated, causing complete insulin deciency. Type 2 is more associated
with adults and elderly people, which are mainly due to insulin resistance or abnormal insulin
production. The exact reason of pancreatic failure and insulin resistance is unknown, but they
are associated with disease condition, food habit, and environmental impact. Diabetic patients
are more susceptible to various type of infection such as skin diseases and carbuncles [4].
Gestational diabetes is other type of diabetes, which is mainly associated with pregnancy. It
occurs in the 4% of pregnancies in US, usually during the third trimester. It causes increased
perinatal morbidity and mortality unless properly diagnosed or managed. Genetic defects
of β-cell function or insulin action is also a type of diabetes mellitus commonly called matu-
rity onset diabetes. Neonatal diabetes mellitus is also a type of diabetes, in which rst 3
months of life insulin is required for the maintenance of blood glucose level in. It may be
caused by intrauterine growth retardation and defects of chromosome. The heart, blood
vessels, eyes, kidneys, and nerves can be damaged by diabetes, leading to disability and
premature death.
4. Urinary tract infection in diabetics
Infections are frequent causes of morbidity and mortality in diabetic patients. Evidence sug-
gesting that urinary tract infection (UTI) is the most common bacterial infections among dia-
betic patients. High glucose concentration in the urine can provide a rich source of nutrients
for bacteria [5, 6]. Therefore, bacteria can multiply and make foundation for infection; also,
high glucose concentration in the urine can allow urinary colonization by microorganisms.
Moreover, some of the immunological defects like impaired neutrophil function, reduced T
cell-mediated immune response, low levels of prostaglandin E, thromboxane B2, and leukot-
riene B4 may contribute to the increased risk for infection. Other conditions such as bladder
dysfunction (incomplete bladder emptying) caused by autonomic neuropathy also may con-
tribute to the increased risk for infection [7, 8]. UTI in diabetes can lead to severe complica-
tions including bacteremia, renal abscess, and renal papillary necrosis. In some cases, diabetes
modies the genitourinary system and may cause damage to the organ, which leads to pyelo-
nephritis. This type of UTI occurs 15 times more frequently in diabetic patients. Therefore,
early diagnosis and correct treatment are very important for diabetes patients with UTI [9,
10]. Molecular reasons for an increased frequency of UTI in diabetic patients include depres-
sion in the function of polymorphonuclear leucocytes especially during acidosis, dysfunction
of chemotaxis, and phagocytosis [10]. High blood glucose levels may cause nerve damage,
aecting the ability of the bladder to sense the presence of urine and thus allowing urine to
stay for a long time in the bladder and increasing probability of infection [11].
Urinary Tract Infection in Diabetics 3

Various types of UTI in patients with diabetes include
• Asymptomatic bacteriuria
• Acute cystitis
• Complicated lower UTI (including catheter-associated UTI)
• Uncomplicated pyelonephritis
• Complicated pyelonephritis/urosepsis
5. Pathogenesis of UTI in diabetics
The chance of occurrence of UTIs in diabetic patients used to increase many folds due to
several factors. Multiple potential mechanisms unique to diabetes may cause increased risk of
UTI in diabetic patients. Elevated renal parenchymal glucose levels create a positive environ-
ment for the growth and multiplication of microorganisms, which is one of the precipitating
factors of pyelonephritis and renal problem such as emphysematous pyelonephritis. Several
problems in the immune system, including humoral, cellular, and innate immunity, may help
in the pathogenesis of UTI in diabetic patients [12–14]. Lower urinary interleukin-6 and inter-
leukin-8 levels were found in diabetic patients with UTI. An outline of process involved in
pathogenesis of urinary tract infection in diabetic patients is mentioned in Figure 1.
Some suggested host related mechanisms include [15]:
i. Presence of glycosuria
ii. Increased adherence to uroepithelial cells
iii. Immune dysfunction
5.1. Presence of glycosuria
The presence of glycosuria is responsible for the growth of dierent microbial strains. Among all
E. coli is the major cause for the condition of UTI [15]. The bacteria isolated from diabetic patients
with a UTI are similar to the bacteria found in nondiabetic patients with a complicated UTI. As
in uncomplicated UTIs, E. coli causes the majority of infections. For example, one study reported
E. coli to be the causative uropathogen in 47% of the UTIs in diabetic patients and in 68% of the
UTIs in nondiabetic patients. Non-E. coli uropathogens found in patients with diabetes, include
Enterobacter spp., Klebsiella spp., Proteus spp., Group B Streptococci, and Enterococcus faecalis [16].
Geerlings et al. [17] in their study reported that urine samples with glucose concentrations
between 100 and 1000 mg/dL, which comes in the range of moderate to severe glucosuria,
were responsible for enhanced bacterial growth after 6 h, compared with normal urine.
E. coli gain access to the urinary tract by the mechanism which reects an exceptional ability to
adapt to an environment very dierent from the gut. They need to alter their metabolism [18],
Microbiology of Urinary Tract Infections: Microbial Agents and Predisposing Factors4

Figure 1. Process involved in pathogenesis of UTI in patients with diabetes.
Urinary Tract Infection in Diabetics 5

ascend against the ow of urine, and adhere to the epithelial layer. E. coli that successfully invade
the urinary tract harbor a specic factor that enables them to survive. These strains of E. coli are
commonly named uropathogenic E. coli (UPEC). Flagellae are thread-like structures which pro-
vide E. coli with the ability to move. It has been found to bind to TLR5 [19] and is of importance
for the immune response to E. coli in UTI in mice [20]. A critical step for UPEC is adhesion to
avoid being washed out with the urine and the rst step in a series of events leading to infection.
The type-1 mbriae are adhesion factors studied in great detail and are critical for adhesion and
invasion of UPEC into bladder cells [21, 22]. They are equipped with a protein on the tip called
FimH, which is responsible for the interaction with the host cell [23]. It binds to several struc-
tures on uroepithelial cells, the most important being uroplakin IA that coats the facet cells of the
bladder [24]. They also bind to β-integrin, which triggers cytoskeleton rearrangement leading to
bacterial internalization [25]. In renal epithelial cells, complement factor 3, which is secreted by
epithelial cells during infection, can link with type 1 mbriae to form a complex that interacts
with CD46 to promote internalization. Other mbriae like P mbriae are connected with kidney
infection, since they bind to glycosphingolipids on kidney epithelial cells [26].
Flagella provide the bacteria with mobility and may interact with the supercial bladder cell
through TLR5. Further adhesion is provided by type 1 mbriae binding to uroplakin 1A or
β1-integrin, which also promote internalization into the cell. Complement secreted upon bac-
terial infection binds to the bacteria and promotes interaction with the bladder through CD46.
In the kidney, P mbriae of the bacteria bind to glycosphingolipids on the surface of renal
epithelial cells. Bacterial invasion is further promoted by TLR4 and TLR5.
5.2. Increased adherence to uroepithelial cells
The uroepithelium is having a very important property of exibility by which it will allow ll-
ing and emptying of the bladder and at the same time impermeable to uid and able to cope
with the varying pH, osmolality, and toxicity, for example, high ammonium concentration.
It is composed of dierent layers of cells with the umbrella or facet cells lining the lumen are
multinuclear, large cells with uroplakin facing the urine. Uroplakins are proteins contributing
to the impermeability of the epithelium but can also act as a receptor for type 1 mbriae on
the uropathogenic E. coli [27].
The important step in the pathogenesis of UTIs is the adherence of uropathogens to the bladder
mucosa. Therefore, adhesins (mbriae) are important virulence factors. Although virulence
factors have been distinguished best in E. coli (the most common uropathogen), many same
principles may be applicable to other Gram-negative uropathogens, for example, Klebsiellae.
Type 1 mbriae mediate the adherence of glycoprotein receptors (uroplakins) on the uroepi-
thelial cells to E. coli, whereas P mbriae bind to glycolipid receptors in the kidney [25].
5.3. Immune dysfunction
It is observed that hyperglycemic environment alters immune function in patients with dia-
betes. Several aspects of immunity may be aected, including polymorphonuclear leukocyte
function and adhesion, phagocytosis, and chemotaxis. This may play a part in the patho-
genesis of urinary tract infections in patients with diabetes. Lower urinary concentrations of
Microbiology of Urinary Tract Infections: Microbial Agents and Predisposing Factors6

interleukin-8 and interleukin-6 in women suering from diabetes have been shown to corre-
late with a lower urinary WBCs count that may contribute to the increased incidence of UTIs
in this patient group [28].
If UPEC comes in contact with the epithelium, within minutes, the antimicrobial peptide
cathelicidin is secreted and acts on the bacteria. Within hours, cytokines and chemokines are
produced and their signaling will start to x professional immune cells to the site of infection.
The bacteria on the other hand will try to circumvent the immune defense in dierent ways.
One is to enter the cell cytoplasm and form intracellular bacterial communities (IBCs) in order
to “hide” from the immune response [29]; another is to down regulate the immune response
with dierent modes of signaling. Depending on the number of bacteria, the host status, and
the virulence factors they carry, the bacteria will either survive in the urinary tract or be
eliminated and washed out with the urine [29].
If this rst line of defense against pathogens entering the urinary tract fails, an inammatory
response is initiated. Aachment to the bladder uroepithelial cells by bacterial mbriae allows
for close contact between host and pathogen. Trans-membrane signaling through TLRs leads
to the production of inammatory mediators such as chemokines with subsequent recruit-
ment of professional immune cells to the infectious focus. Chemokine IL-8 is required for
neutrophil recruitment and activation in the urinary tract [30].
When the inammatory response subsides, bacteria may still be left in the bladder epithe-
lium. Bacteria that form IBCs can escape the dierent steps in host defense and treatment
with antibiotics will be less ecient because of poor antibiotic penetration into the IBCs. From
the IBC, bacteria can be expelled from the cells by a TLR4 mediated mechanism or in mature
IBCs, and bacteria form lamentous structures and then separate from the cell to colonize
adjacent cells. The cells may also be exfoliated, allowing the underlying immature cells to be
exposed to further UPEC invasion. Here, they can turn into quiescent intracellular reservoirs
(QIRs) for weeks, only to re-emerge to cause recurrent infections. Pyelonephritis may develop
if the bacteria ascend further in the urinary tract. In the kidney, bacteria may cause damage of
tissue and reach the blood circulation, causing septicemia, commonly called urosepsis. This
increases the mortality from 0.3% in pyelonephritis to 7.5–30% in urosepsis [31].
6. Classication of urinary tract infection
UTIs are classied based on laboratory data, clinical symptoms, and microbiological ndings.
Practically, UTIs have been divided into uncomplicated and complicated UTIs and sepsis.
The present guidelines give an outline of a tentative improved system of classication of
UTI based on various factors as follows: (Guidelines on Urological Infections by European
Association of Urology)
i. Classication based on grade of severity of infections and symptoms
ii. Classication based on underlying risk factors
iii. Classication based on anatomical level of infection
Urinary Tract Infection in Diabetics 7

iv. Classication based on microbiological ndings
v. Classication based on complications
7. Diagnosis of urinary tract infection in diabetics
Upper and lower UTI can be suspected in diabetic patients with most common symptoms.
Symptoms vary in upper and lower UTI. Table 1 highlights the symptomatic dierence
between upper and lower UTI.
Diagnosis of urinary tract infection can be done by following methods.
• Examination of midstream urine specimen: After the symptomatic identication, a mid-
stream urine sample should be examined for the presence of WBCs, as pyuria is present in
almost all cases of UTI.
• Pyuria detection: Pyuria can be detected either by microscopic examination (dened as >10
leukocytes/mm3) or by dipstick leukocyte esterase test (sensitivity of 75–96% and specic-
ity of 94–98%).
• Colonization: An absence of pyuria on microscopic assessment can suggest colonization,
instead of infection, when there is bacteriuria [32].
• Microscopic examination: Allows for visualizing bacteria in urine.
• Dipstick: Tests for the presence of urinary nitrite.
○Positive test: Indicates the presence of bacteria in urine.
○Negative test: is the product of low count bacteriuria or bacterial species that lack the
ability to reduce nitrate to nitrite (mostly Gram-positive bacteria).
• Urine culture: Should be done in all cases of suspected UTI in diabetic patients, prior to
initiation of treatment (preferred method of obtaining a urine sample for culture is from
voided, clean-catch, and midstream urine) [33].
7.1. Diagnosis of UTI in women patients
All women with recurrent UTI should undergo a physical examination to evaluate urogenital
anatomy and vaginal tissues estrogenization. Postvoid residual urine volume also should
Lower UTI Upper UTI
• Frequency
• Urgency
• Dysuria
• Suprapubic pain
Costovertebral angle pain/tenderness fever and chills, with or without lower urinary
tract symptoms
Table 1. Symptomatic dierence between upper and lower UTI.
Microbiology of Urinary Tract Infections: Microbial Agents and Predisposing Factors8

be measured. Diabetes screening is indicated in patients with other risk factors like family
history and obesity. Most women do not need extensive urologic investigations. However,
women who suer infection with organisms which is not common causes of UTI, such as
Proteus, Klebsiella, Enterobacter, and Pseudomonas, may have structural abnormalities or renal
calculi. They would benet from imaging studies of the upper urinary tract and cystoscopy.
Women who have persistent hematuria after recovery of their infection also require a com-
plete urologic workup. Although empirical therapy based on symptoms is generally accurate
and cost-eective, women who are thought to be in the early stages of a problem with recur-
rent UTI should have documented cultures. Urine culture serves as the gold standard for
diagnostic accuracy. The standard denition of a UTI on culture is >100,000 colony forming
units per HPF. This value has excellent specicity but a sensitivity of only 50% [34].
8. Complications of urinary tract infection in diabetics
Emphysematous pyelonephritis (EPN) is a severe and necrotizing form of multifocal bacterial
nephritis along with gas formation within parenchyma of the kidney. So far, more than 200
cases have been reported in literature. Underlying poorly controlled diabetes mellitus is pres-
ent in up to 90% of aected patients [28].
The commonest oending organisms are Klebsiella and Escherichia coli followed by Proteus.
The clinical manifestations are nonspecic and not dierent from the classic triad of upper
UTI (i.e., fever, ank pain and pyuria); due to this, the diagnosis of EPN is often delayed.
Disseminated intravascular coagulopathy, acute respiratory distress syndrome, disturbance
of consciousness, acute renal failure, and shock can reveal some severe forms. Diabetic keto-
acidosis is a very uncommon presentation, and only few cases have been reported so far.
EPN needs a radiological diagnosis. Conventional radiography may indicate gas bubbles over-
lying the renal fossa. Ultrasonography (US) characteristically shows an enlarged kidney that
contains high amplitude echoes within the renal parenchyma. Computed tomography (CT) is
the imaging procedure of choice, which conrms the presence and extent of parenchymal gas.
9. Pathogens of UTI in diabetes
A descriptive, cross sectional study was conducted on UTI and antibiotic sensitivity paern
among diabetic patients in National Academy of Medical Sciences (NAMS), Mahabouddha,
Kathmandu, Nepal. According to this study, E. coli is the most common organism followed by
Klebsiella, Proteus, and Pseudomonas. Most of the urinary isolates were sensitive to Ceftriaxone,
Ciprooxacin, and Cotrimoxazole, whereas resistance was high for ampicillin [35].
A study was conducted to nd out the prevalence of UTI in diabetic patients. A total of
1470 diabetic patients (847 women and 623 men) were included in the study, admied to
the Diabetes Clinic of the Emergency Clinical County Hospital Timişoara between January
and December 2012. According to this study, 10.7% in overall population had positive urine
Urinary Tract Infection in Diabetics 9

cultures. In this population, almost 78% of patients were having asymptomatic bacteriuria.
The most frequent bacteria involved in UTI are Escherichia coli (68.9%) [9].
About 10.5% of type 2 and 12.8% of type 1 diabetic patients had UTI. There is no signicant
dierence between type 1 and type 2 diabetes (p = 0.45); 4.5% of men and 15.3% of women
developed UTI, an extremely signicant dierence (p < 0.0001)
Chiţă et al. concluded that urinary tract infections are more prevalent in diabetic patients.
Because of the high proportion of asymptomatic forms among diabetic patients, the urine
culture should be done in all hospitalized patients with diabetes.
The pathogens involved in causing urinary tract infection in diabetic patients and their fre-
quency are mentioned in Table 2.
10. Management of urinary tract infections in diabetics
Generally, treatment of UTI is similar in both diabetic patients and nondiabetic patients [5];
however, the choice of antibiotics in UTI patients with diabetes is one of the important consid-
erations in the therapeutic management. Possible drug interactions between antimicrobials
and antidiabetics or certain antibiotics may lead to impaired glucose homeostasis.
UTI treatment in diabetes patients depends on various factors including [5];
• Presence of symptoms
• Presence of infection in the bladder (lower UTI) or also involves the kidney (upper UTI)
• Presence of urologic abnormalities
• Severity of systemic symptoms
• Occur with metabolic alterations and renal function
Moreover, UTI treatment varies based on patient’s age, sex, infecting agent, underlying dis-
ease, and whether there is lower or upper urinary tract involvement. Several clinical trials
revealed that increasing trends of resistance to many antimicrobials with the increasing trend
Gram-negative microorganisms Frequency (%) Gram-positive microorganisms Frequency (%)
Escherichia coli 56.75 Alpha Streptococci 33.33
Klebsiella pneumonia 21.62 Staphylococcus aureus 66.66
Pseudomonas aeruginosa 9.54 S. epidermidis 0
Enterobacter aerogenes 4.05 — —
Proteus mirabilis 4.05 — —
Citrobacter freundii 4.05 — —
Table 2. Pathogens of UTI in diabetes.
Microbiology of Urinary Tract Infections: Microbial Agents and Predisposing Factors10

of antibiotic resistance in E. coli, with limited therapeutic options, the management of urinary
tract infections is likely to become complicated.
10.1. Treatment recommendations for UTI in diabetes according to Infectious
Diseases Society of America (IDSA)
10.1.1. Acute cystitis management in patients with type II diabetes
Acute cystitis treatment should be tailored according to culture results, if obtained. Apart
from proper glucose control, one of the following UTI treatments is mandatory for acute cys-
titis management [36]. First line treatment management: Nitrofurantoin 100 mg three times
daily for 5 days or fosfomycin trometamol 3 g single dose, or trimethoprim-sulfamethoxazole
960 mg twice daily for 3 days (can be used empirically only if resistance prevalence is known
to be less than 20% and medication was not used in previous 3 months). Second line manage-
ment: Quinolones and β-lactams.
10.1.2. Pyelonephritis management in patients with type II diabetes
Hospitalization should be done for the patients with severe symptoms for initial intravenous anti-
biotic therapy [5, 36]. Empiric antibiotics treatment: broad-spectrum cephalosporins, aminoglyco-
sides, uoroquinolones, piperacillin-tazobactam, or carbapenems should be started [37]. Severe
sepsis presenting patients or those known to harbor-resistant uropathogens or the patients who
have received multiple antibiotic courses should receive broad-spectrum coverage, guided by
current urinary culture report. Treatment should be tailored when culture reports are available.
11. Antimicrobial agents
There are several types of antimicrobial agents such as antibiotics, antifungals, antivirals,
antimalarials, and anthelmintics. Likewise, there are several types of microorganisms such
as bacteria, fungi, viruses, and parasites. Microorganisms are responsible for various infec-
tious diseases and sometimes leading to death. Antimicrobial agents play an essential role in
decreasing morbidity and mortality associated with infections. Antimicrobial agents increased
the life expectancy and quality of life. Dierent antimicrobial agents and their mechanism of
action are mentioned in Table 3.
11.1. Benets of antimicrobial agents
• Prevent and treat infection
• Increased the expected life spans of human being
• Prevent or treat infection after surgery (C section, organ transplants, joint replacements, etc.)
• Prevent or treat infection at the time of chemotherapy treatments
• Antimicrobial drugs decrease the morbidity and mortality caused by food-borne, water-
borne, and other poverty-related infections
Urinary Tract Infection in Diabetics 11

12. Antimicrobial resistance
Resistance to antibiotics and other types of antimicrobial agents is growing and represents
the single greatest challenge in the treatment of infectious diseases today. According to WHO,
“AMR occurs when microorganisms change when they are exposed to antibiotic and antimi-
crobial drugs.” Due to anti microbial resistance, antimicrobial agents turning ineective and
infections persist in the body, increasing the risk of spread to others. AMR aects the eective
prevention, and treatment of infections caused by bacteria, parasites, viruses, and fungi. WHO
says that AMR is a growing and alarming threat to global public health that requires lot of
action from the government. Moreover, people should get a lot of awareness message regarding
antimicrobial resistance. An antimicrobial resistance developing microorganisms are sometimes
called as “superbugs” [38].
As per WHO cost analysis data, health care cost of resistant infections is higher than nonre-
sistant infections because of
• Longer duration of illness
• Additional tests
• Use of more expensive drugs
Global WHO statistics says that a total of 480,000 people develop multidrug resistant TB each
year, and drug resistance is starting complication in treatment of HIV and malaria as well.
12.1. Emergence of drug-resistant bacteria
Emergence of penicillinase-producing Staphylococcus aureus and emergence and spread of
multidrug-resistant S. aureus in the early 1960s, emergence of MRSA in 1961, emergence
of PISP in 1967, emergence of penicillinase-producing H. inuenzae in 1974, emergence of
PRSP in 1977, emergence of BLNAR H. inuenzae in 1980, emergence of ESBL-producing
Antimicrobial agents Eect on bacteria Mechanism
Penicillins, cephalosporins, carbapenems, polypeptide
antibiotics
Bactericidal Inhibition of cell wall synthesis
Lincosamides, aminoglycosides, macrolides,
tetracyclines, chloramphenicol
Bacteriostatic Inhibition of protein synthesis
Quinolones, metronidazole Bactericidal Inhibits DNA synthesis
Rifamycins Bactericidal Inhibitions of RNA transcription
Sulfonamides Bacteriostatic Competitive inhibition
Table 3. Dierent antimicrobial agents and its mechanism of action.
Microbiology of Urinary Tract Infections: Microbial Agents and Predisposing Factors12

Gram-negative bacilli in 1983, emergence of VRE in 1986, increased infections with MRSA,
PRSP, BLNAR, etc. and increase of resistant gonococci in 1990s, increase of MDRP, and increase
of quinolone-resistant E. coli in 2000s are the emergence of drug resistance bacteria.
Major reasons for increasing antimicrobial resistance:
• Ineective infection-control practices
• Noncompliance with infection-control practices
• Using sub-optimal dose of antibiotics for prophylaxis and treatment of infection
• Multiple comorbidities in hospitalized patients
• Prolonged hospitalization
• Increased number and duration of intensive care unit stays
• Colonized patients transfer from hospital to hospital
• Grouping of colonized patients in long-term-care facilities
Major mechanisms for acquired antimicrobial resistance:
• Enzyme that degrades the antimicrobial agent
• Enzyme that alters the antimicrobial agent
• Mutation in the antimicrobial agent’s target which reduces the antimicrobial agent binding.
• Posranslational or posranscriptional modication of the antimicrobial agent’s target,
which reduces binding of the antimicrobial agent
• Reduced uptake of the antimicrobial agent
• Active eux of the antimicrobial agent
• Antimicrobial agent target overproduction
13. Conclusion
Urinary tract infections are more common in the diabetic patients. Diabetic patients are
severely aected with urinary tract infection. Treatment of UTI without proper diagnosis may
lead to antimicrobial drug resistance. Treatment with antimicrobial agents should be started
on the basis of culture reports. Only bacteriuria with symptoms of UTI should be treated with
antibiotics to avoid the spread of drug resistant pathogens in the society. This practice can
reduce the morbidity and mortality in diabetic patients suering from urinary tract infection.
The multidrug resistant pathogens are a challenge to society.
Urinary Tract Infection in Diabetics 13

Author details
Ajay Kumar Prajapati
Address all correspondence to: ajay_prajapati2000@yahoo.co.in
Bharathiar University, Coimbatore, India
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