08:40 18/02/2023 Urinary Tract Infections (UTI) in Diabetes Mellitus: Overview, Renal Emphysema, Emphysematous Cystitis

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Urinary Tract Infections (UTI) in

Diabetes Mellitus
Updated: Apr 05, 2021
Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...

OVERVIEW

Overview
This section will focus primarily on the emphysematous class of diabetic urinary tract infections (UTIs).

Diabetic UTIs are usually multifactorial in origin. Risk for infection is associated with longer duration or greater severity
of the disease. [1]  Elevated serum and urine glucose levels, as well as defective host immune factors, are major
predisposing factors. Hyperglycemia impedes neutrophil diapedesis and phagocytosis. The urinary retentiom of
diabetic neuropathy, nephropathy, vesicourethral reflux and renal papillary necrosis are additional factors in the
development of diabetic UTIs.

There has been concern about an increased risk for UTIs posed by the hyperglycosuria of SGLT2 inhibitors. With the
possible exception of dapagliflozin, the incidence of urinary tract infections has not increased.These patients do
appear to be at a 3- to 5-fold increase in genital infections. [2, 3]  diabetic topathy include vesicourethral reflux and
recurrent UTIs. As many as 30% of women with diabetes may  develop a cystocoele cystourethrocele, or rectocele. All
of these increase the frequency and severity of UTIs in female diabetics.

Other complications of diabetic UTIs include renal and perirenal abscess, emphysematous pyelonephritis,
emphysematous cystitis, fungal infections, xanthogranulomatous pyelonephritis, and papillary necrosis.
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08:40 18/02/2023 Urinary Tract Infections (UTI) in Diabetes Mellitus: Overview, Renal Emphysema, Emphysematous Cystitis

Diabetes mellitus and obstruction of the urinary tract are the predominant risk factors for developing emphysematous
UTIs. The exact mechanism for developing these distinctive infections is not completely identified. It appears that
associated vascular thrombosis of the kidney produces a more fulminant infection because of necrosis and
hemorrhagic infarction. [4] Emphysematous pyelonephritis carries a mortality rate of up to 80%. Ninety percent of
cases are associated with diabetes mellitus. There is a significant rate of associated urinary tract obstruction. [5]

Upper tract emphysematous UTIs are divided into pyelonephritis and pyelitis. Emphysematous cystitis occurs less
frequently.Emphysematous infection can involve one or all 3 of these processes. Emphysematous pyelonephritis is
necrotizing infection of the body of the kidney that may spread to the pararenal areas. Emphysematous pyelitis is
limited to the collecting system and emphysematous cystitis to the bladder.The organisms involved most commonly
are Escherichia coli, Klebsiella pneumoniae, and Candida. [6]

Emphysematous upper tract infections may be classified into 4 prognostic categories based on CT scan appearance.
These range from gas that is isolated to the collecting system (class I ) to the appearance of gas that is limited to the
body of the kidney (class 2) to extension of the gas or abscess to the perinephric space or to adjacent tissue (class 3A
and class 3B, respectively). Class 4 denotes involvement of both kidneys.

For more information on this topic, see the Medscape Reference article Urinary Tract Infections in Females.

Renal Emphysema
Emphysematous pyelonephritis
Emphysematous pyelonephritis represents a severe, necrotizing form of multifocal bacterial nephritis with gas
formation within the renal parenchyma. From 70-90% of cases develop in patients with diabetes. Sixty percent of
infections are secondary to E coli. Enterobacter aerogenes and Klebsiella, Proteus, Streptococcus, and Candida
species also may play a role.

Three factors must be present for the development of renal emphysema—excess tissue glucose, impaired tissue
perfusion, and a gas-producing bacterium. The gas may result from fermentation of necrotic tissue or from mixed acid
fermentation by Enterobacteriaceae. Predisposing factors include diabetes mellitus, remote or recent kidney infection,
and obstruction.

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08:40 18/02/2023 Urinary Tract Infections (UTI) in Diabetes Mellitus: Overview, Renal Emphysema, Emphysematous Cystitis

Patients with renal emphysema may present with fever, chills, and nausea or vomiting. Half of patients have evidence
of a flank mass on examination. Rarely, patients have crepitus over the thigh or flank.

Laboratory findings include leukocytosis, hyperglycemia, pyuria, and an elevated blood urea nitrogen (BUN) and
creatinine. A plain film of the abdomen may reveal gas in the kidneys in 85% of infections. Renal ultrasonography may
also help establish the diagnosis. If gas is visualized, then a CT scan should be performed to reveal if the gas is in the
parenchyma (emphysematous pyelonephritis) or the collecting system (emphysematous pyelitis).

The mortality rate is 60% in cases in which the gas is localized to the renal parenchyma, regardless of treatment. The
mortality rate is 80% if the gas has spread in the perinephric space and the patient is treated with antibiotics alone. [7]

Emphysematous pyelitis

Emphysematous pyelitis  describes the presence of gas localized to the renal collecting system. Emphysematous
cystitis is defined as detecting air in the urinary tract. More than 50% of these patients have diabetes. Obstruction of
the collecting system generally is generally present. The left kidney is involved twice as often as the right. The most
common isolate is  E. coli. gram-negative organisms, S aureus, Clostridium perfringens, and Candida species also
may be responsible.

Patients with emphysematous pyelitis most commonly present with fever, chills, nausea and vomiting, and abdominal
pain.

The most common symptoms of ephysematous cystitis are frequency, urgency,abdominal pain, and dysuria.  Gross
hematuria and pneumaturia are occasionally observed.

Leukocytosis and pyuria are observed in most patients. along with, azotemia and hyperglycemia are present.
Abdominal imaging may reveal gas outlining the renal pelvis and in the ureters; air in the bladder wall or lumen. Renal
ultrasonography may detect diffuse thickening of the bladder wall and echogenicity. CT scans may documentgas in
the bladder wall with extension into the lumen. Blebs of the bladder mucosa may detectable by ultrasonography

Despite administration of appropriate antibiotic and relief of obstruction,the mortality rate  may be as high 20%.

Emphysematous Cystitis
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08:40 18/02/2023 Urinary Tract Infections (UTI) in Diabetes Mellitus: Overview, Renal Emphysema, Emphysematous Cystitis

Emphysematous cystitis (cystitis emphysematosa) involves gas that is localized to the bladder secondary to a bladder
infection. Gas in the bladder is more frequently related to a fistula between the bladder and the colon or vagina than to
a gas-producing infection. As many as 80% of patients with emphysematous cystitis are diabetic. [8]

The presentation is similar to that ofpyelonephritis. Plain radiographs may demonstrate gas in the bladder wall or
lumen, an air-fluid level in the bladder, or a cobblestone appearance to the bladder wall. CT scan is the study of
choice to help localize the gas to the proper organ. Treatment involves intravenous antibiotics and relief of any outlet
obstruction. This condition is not as life-threatening as emphysematous pyelonephritis or pyelitis.

Treatment and Consultations

In any type of emphysematous UTI, coverage for multiple for antibiotic–resistant organisms (eg, Pseudomonas
aeruginosa, extended spectrum beta-lactamase [ESBL]–producing Enterobacteriaceae) must be stronglyconsidered.It
should be kept in mind that  diabetics are at greater risk for complications from aminoglycosides. An infectious disease
consultation may be helpful in selecting the appropriate antimicrobial agent.

Urologic consultation is essential in patients with UTIs complicated by obstruction, renal cysts, perinephric abscess,
renal carbuncle, or unknown renal masses. Other consultations depend on the patient's underlying state of health and
may include an endocrinologist, as well as an obstetrician, gynecologist, endocrinologist, nephrologist, neurologist, or
neurosurgeon.

Cases that do not have evidence for abscess formation and/or obstruction and are limited to the collecting system
(uncomplicated pyelitis) often can be successfully treated with intravenous antibiotics alone.

Pyelitis that has associated obstruction and/or abscess and emphysematous pyelonephritis that is limited to the body
of the kidney is best managed with percutaneous catheter drainage and surgery if obstruction is present.

When infection has spread beyond the body of the kidney (class and class B), nephrectomy is usually indicated. If the
patient is hemodynamically stable and without acute renal failure, decreased level of consciousness, and
thrombocytopenia, it is reasonable to try percutaneous catheter drainage and intravenous antibiotics.

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08:40 18/02/2023 Urinary Tract Infections (UTI) in Diabetes Mellitus: Overview, Renal Emphysema, Emphysematous Cystitis

When the infectious process involves both kidneys (class 4) or there only one kidney present, nephrectomy-sparing
approaches should be considered. [7]

Medical therapy, combined with vigorous bladder irrigation if blood clots are present, is usually adequate for treatment
of emphysematous cystitis; however, 10% of cases require a combination of medical and surgical therapy that ranges
from partial to, rarely, total cystectomy. [8]

Coverage of ESBL-producing organisms must be strongly considered in the initial empiric choice of antibiotics. Risk
factors for infections with ESBL-producing gram-negative organisms include diabetes mellitus; recent travel to Asia,
the Middle East, or Africa; male gender; residence in a nursing home; previous hospitalization; surgical or urologic
procedures; chronic renal failure; and freshwater swimming. The recent use of fluoroquinolones, especially as
prophylaxis for transrectal biopsies, is becoming a major risk factor for ESBL-producing Enterobacteriaceae. [9, 10, 11,
12, 13]  In such cases Fosfomycin may be the " go to" antibiotic. At this time, the parenteral form is not yet availabe in
this country.

Awareness of the local antibiogram, especially that of a specific patient, is proving to be more and more helpful in the
empirical choice of antibiotics. [14]

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