Pyelonephritis

Definition

Pyelonephritis is an infection of the kidney and the ureters, the ducts that carry urine
away from the kidney.

Alternative Names

Urinary tract infection - complicated; Infection - kidney; Complicated urinary tract

infection; Kidney infection

Causes

Pyelonephritis most often occurs as a result of urinary tract infection , particularly when
there is occasional or persistent backflow of urine from the bladder into the ureters or an
area called the kidney pelvis. See: Vesicoureteric reflux

Pyelonephritis can be sudden (acute) or long-term (chronic).

• Acute uncomplicated pyelonephritis is the sudden development of kidney

inflammation.
• Chronic pyelonephritis is a long-standing infection that does not go away.

Pyelonephritis occurs much less often than a bladder infection, although a history of such
an infection increases your risk. You're also at increased risk for a kidney infection if you
have any of the following conditions:

• Backflow of urine into the ureters or kidney pelvis

• Kidney stones
• Ostructive uropathy
• Renal papillary necrosis

You are also more likely to get a kidney infection if you have a history of chronic or
recurrent urinary tract infection , especially if the infection is caused by a particularly
aggressive type of bacteria.

Acute pyelonephritis can be severe in the elderly and in people who are
immunosuppressed (for example, those with cancer or AIDS ).

Symptoms

• Back pain orflank pain

• Chills with shaking
• Severe abdominal pain (occurs occasionally)
 • Fatigue
• Fever
o Higher than 102 degrees Fahrenheit
o Persists for more than 2 days
• General ill feeling
• Chills with shaking
• Mental changes or confusion*
• Skin changes
o Flushed or reddened skin
o Moist skin (diaphoresis )
o Warm skin
• Urination problems
o Blood in the urine
o Cloudy or abnormal urine color
o Foul or strong urine odor
o Increased urinary frequency or urgency
o Need to urinate at night (nocturia)
o Painful urination
• Vomiting, nausea

* Mental changes or confusion may be the only signs of a urinary tract infection in the
elderly.

Exams and Tests

A physical exam may show tenderness when the health care provider presses (palpates )
the area of the kidney.

• Blood culture may show an infection.

• Urinalysis commonly reveals white or red blood cells in the urine.
• Other urine tests may show bacteria in the urine.

An intravenous pyelogram (IVP) or CT scan of the abdomen may show swollen kidneys.
These tests can also help rule out underlying disorders.

Additional tests and procedures that may be done include:

• Kidney biopsy
• Kidney scan
• Kidney ultrasound
• Voiding cystourethrogram

Treatment

The goals of treatment are to:

 • Control the infection
• Relieve symptoms

Due to the high death rate in the elderly population and the risk of complications, prompt
treatment is recommended. Sudden (acute) symptoms usually go away within 48 to 72
hours after appropriate treatment.

Your doctor will select the appropriate antibiotics after a urine culture identifies the
bacteria that is causing the infection. In acute cases, you may receive a 10- to 14-day
course of antibiotics.

If you have a severe infection or cannot take antibiotics by mouth, you may be given
antibiotics through a vein (intravenously) at first.

Chronic pyelonephritis may require long-term antibiotic therapy. It is very important that
you finish all the medicine.

Commonly used antibiotics include the following:

• Amoxicillin
• Cephalosporin
• Levofloxacin and ciprofloxacin
• Sulfa drugs such as sulfisoxazole/trimethoprim

Outlook (Prognosis)

With treatment, most kidney infections get better without complications. However, the
treatment may need to be aggressive or prolonged.

Pregnant women and persons with diabetes or spinal paralysis should have a urine culture
after finishing antibiotic therapy to make sure that the bacteria are no longer present in
the urine.

In rare cases, permanent kidney damage can result when:

• Chronic kidney infections occur in a transplanted kidney

• Many kidney infections occur during infancy or childhood

Acute kidney injury (acute renal failure) may occur if a severe infection leads to
significantly low blood pressure (shock). The elderly, infants, and persons with a
weakened immune system have an increased risk for developing shock and a severe
blood infection called sepsis . Often, such patients will be admitted to the hospital for
frequent monitoring and IV antibiotics, IV fluids, and other medications as necessary.

Severe episodes of acute kidney injury may result in permanent kidney damage and lead
to chronic kidney disease.
Possible Complications

• Acute kidney failure

• Kidney infection returns
• Infection around the kidney (perinephric abscess)
• Severe blood infection (sepsis)

When to Contact a Medical Professional

Call your health care provider if you have symptoms of pyelonephritis.

Call your health care provider if you have been diagnosed with this condition and new
symptoms develop, especially:

• Decreased urine output

• Persistent high fever
• Severe flank pain or back pain

Prevention

Prompt and complete treatment of bladder infections may prevent development of many
cases of pyelonephritis. Chronic or recurrent urinary tract infection should be treated
thoroughly.

You can help preventing kidney infections by taking the following steps:

• Keep the genital area clean. Wiping from front to back helps reduce the chance of
introducing bacteria from the rectal area to the urethra.
• Urinating immediately after sexual intercourse. This may help eliminate any
bacteria that may have been introduced during sexual activity.
• Drink more fluids (64 to 128 ounces per day). This encourages frequent urination
and flushes bacteria from the bladder.
• Drink cranberry juice. Doing so prevents certain types of bacteria from attaching
to the wall of the bladder and may lessen your chance of infection.
RODUCTION — Acute pyelonephritis is a urinary tract infection that has progressed
from the lower urinary tract to the upper urinary tract. Most episodes of acute
pyelonephritis are uncomplicated but hospitalization may be required [1].

Acute uncomplicated pyelonephritis typically occurs in healthy, young women and must
be distinguished from acute complicated pyelonephritis and from chronic pyelonephritis:

* Acute complicated pyelonephritis is progression of upper urinary tract infection to

emphysematous pyelonephritis, renal corticomedullary abscess, perinephric abscess, or
papillary necrosis. (See 'Acute complicated pyelonephritis' below.)

* Chronic pyelonephritis is an uncommon cause of chronic tubulointerstitial disease

due to recurrent infection, such as infection in association with a chronically obstructing
kidney stone (possibly producing xanthogranulomatous pyelonephritis) or vesicoureteral
reflux. Affected patients can present with weeks to months of insidious symptoms. (See
"Xanthogranulomatous pyelonephritis" and "Presentation, diagnosis, and clinical course
of vesicoureteral reflux".)

The clinical features, diagnosis, and treatment of acute uncomplicated and complicated
pyelonephritis will be reviewed here. The microbiology and pathogenesis of acute
pyelonephritis are discussed separately. (See "Microbiology and pathogenesis of acute
pyelonephritis".)

ACUTE UNCOMPLICATED PYELONEPHRITIS

Clinical manifestations — The clinical manifestations of acute uncomplicated

pyelonephritis include flank pain, abdominal or pelvic pain, nausea, vomiting, fever
(≥37.8ºC), and/or costovertebral angle tenderness. Fever has been strongly correlated
with the diagnosis of acute pyelonephritis; thus, patients with clinical manifestations of
acute pyelonephritis in the absence of fever should be evaluated for alternative diagnoses
[2]. Symptoms of cystitis may or may not be present [3]. In some cases, the presentation
may mimic pelvic inflammatory disease. Rarely, patients with acute pyelonephritis
present with sepsis, multiple organ system dysfunction, shock, and/or acute renal failure.

Diagnosis — The diagnosis of acute uncomplicated pyelonephritis can usually be made

from the history, physical examination, and laboratory evaluation. The physical
examination should focus on vital signs and evaluation of the abdomen, pelvis, and the
costovertebral angles. In the setting of vaginal symptoms or poorly localized tenderness,
a pelvic examination should be performed to distinguish pelvic inflammatory disease
from acute uncomplicated pyelonephritis. Pregnancy testing is also appropriate. (See
"Clinical features and diagnosis of pelvic inflammatory disease".)

A urinalysis should be performed to evaluate for pyuria, which is present in virtually all
patients with acute pyelonephritis. The absence of pyuria strongly suggests an alternative
diagnosis or the presence of an obstructing lesion [4]. White cell casts indicate a renal
origin for the pyuria. Other urinalysis parameters lack adequate sensitivity for evaluation
of pyelonephritis. Nitrite testing, for example, has a sensitivity of 35 to 80 percent; it is
not useful for detecting presence of organisms unable to reduce nitrate to nitrite, such as
enterococci and staphylococci.

Urine culture and antimicrobial susceptibility testing of uropathogens should be

performed in the setting of acute pyelonephritis. Up to 95 percent of episodes of
pyelonephritis are associated with >10(5) CFU per mL of organisms, although some
patients with pyelonephritis have colony counts of 10(3) to 10(4) CFU per mL [5]. If the
urine sample for culture is obtained through a newly-inserted catheter, some clinicians
consider a colony count of ≥10(2) CFU per mL sufficient for diagnosis of pyelonephritis.
The lower colony counts are extrapolated from studies of cystitis but have not been
systematically evaluated in the setting of pyelonephritis. (See "Urine sampling and
culture in the diagnosis of urinary tract infection in adults".)

Urine gram stain may be helpful for rapid preliminary diagnostic purposes and for
guiding the choice of empiric therapy pending culture results.

Imaging studies are not routinely required for diagnosis of acute uncomplicated
pyelonephritis but can be helpful in certain circumstances. (See "Radiologic evaluation in
acute pyelonephritis".)

Microbiology — Escherichia coli is the most common cause of acute pyelonephritis. In a

report of over 2700 uropathogens isolated from patients with acute pyelonephritis,
Escherichia coli accounted for about 82 percent of isolates in women and about 73
percent in men [6]. Klebsiella pneumoniae was next in frequency, accounting for 2.7
percent of isolates in women and 6.2 percent in men. Staphylococcus saprophyticus
accounted for less than 3 percent of isolates. (See "Microbiology and pathogenesis of
acute pyelonephritis".)

Treatment — Initial treatment includes supportive care and initiation of empiric antibiotic
therapy. Inpatient management is appropriate in the following circumstances:

* Severe illness with high fevers, pain, and marked debility

* Inability to maintain oral hydration or take oral medications
* Pregnancy
* Concerns about patient compliance

Outpatient management is safe and effective for patients with mild to moderate illness
who can be stabilized with rehydration and antibiotics in an outpatient facility and
discharged on oral antibiotics under close supervision. In an emergency department
report of 44 patients with pyelonephritis, for example, a 12 hour observation period with
parenteral antibiotic therapy, followed by completion of outpatient oral antibiotics was
effective management for 97 percent of patients [7].

Empiric antibiotics — Empiric antibiotic selection should be guided by knowledge of the

epidemiology of antimicrobial susceptibility when available, since rates of antibiotic
resistance fluctuate with patterns of antibiotic use in the community. In a report of 4342
urine isolates from patients with cystitis in the mid 1990s, the prevalence of resistance to
trimethoprim-sulfamethoxazole rose from 9 to 18 percent over a five year period [8]. In
comparison, resistance to ciprofloxacin and aminoglycosides was very low.

However, a subsequent study in this region demonstrated that antibiotic resistance trends
had reversed [6]. Among E. coli isolates from over 3200 patients in the late 1990s, there
was a decrease in trimethoprim-sulfamethoxazole resistance together with an increase in
the rate of ciprofloxacin resistance (24 to 13 percent and 1.7 to 3.4 percent, respectively)
[6]. These changes paralleled a reduction in the use of trimethoprim-sulfamethoxazole
and an increase in the use of a fluoroquinolone for management of outpatient urinary tract
infections (53 to 32 percent and 35 to 61 percent, respectively).

Risk for pyelonephritis due to an organism resistance to trimethoprim-sulfamethoxazole

or fluoroquinolones appears to vary substantially by region, and risk stratification cannot
reliably predict patients at for infection with resistant organisms [9,10]. Recent antibiotic
use should be considered in the selection of an empiric regimen pending culture and
susceptibility data.

Oral antibiotics — We favor an oral fluoroquinolone such as levofloxacin (500 to 750 mg

orally once daily) or ciprofloxacin (500 mg orally twice daily) for initial empiric
treatment of acute pyelonephritis (table 1) [11,12]. The newer fluoroquinolone
moxifloxacin should be avoided because of uncertainty regarding effective
concentrations in urine.

Trimethoprim-sulfamethoxazole (1 double strength tablet orally twice daily), or

trimethoprim (200 mg orally once daily) can be used if the infecting strain is known to be
susceptible. If gram-positive cocci are observed on Gram stain, enterococcus or S.
saprophyticus should be suspected and amoxicillin (500 mg orally three times daily or
875 mg orally twice daily) should be added to the treatment regimen until the causative
organism is identified. Ampicillin and sulfonamides should not be used for empiric
therapy because of the high rate of resistance among causative pathogens.

Cefpodoxime (200 mg orally twice daily) or cefixime (400 mg orally once daily) may
also be effective for the treatment of acute uncomplicated pyelonephritis, although
published data are limited. Cefixime likely has limited activity against S. saprophyticus.

Parenteral antibiotics — We favor ceftriaxone or fluoroquinolones (in areas where

fluoroquinolone resistance is relatively low) for initial empiric treatment of hospitalized
patients with acute uncomplicated pyelonephritis (table 2). Some clinicians favor
fluoroquinolones over ceftriaxone given their excellent genitourinary penetration.

Patients with penicillin allergy may be treated with a fluoroquinolone. Patients with
fluoroquinolone resistance may be treated with ceftriaxone. Paitents unable to take beta-
lactam or fluoroquinolone agents (due to hypersensitivity and/or resistance) may be
treated with aztreonam (1 g IV every 8 to 12 hours).
Routine follow-up management — Patients initially treated with parenteral therapy who
improve clinically and can tolerate oral fluids may transition to oral antibiotic therapy.
Fluoroquinolone serum levels achieved with oral and intravenous dosing are equivalent,
and the modes of delivery are equally effective clinically [13].

We favor a 7-day course of antibiotics for mild to moderately ill patients with a prompt
response to treatment and with infecting strains that are susceptible to the chosen
antibiotic [11]:

* In a study of 255 women with uncomplicated pyelonephritis comparing a 7-day

course of ciprofloxacin to a 14-day course of trimethoprim-sulfamethoxazole, patients
treated with ciprofloxacin had a more favorable clinical cure rate than those treated with
trimethoprim-sulfamethoxazole (96 versus 83 percent ) [14].
* A five-day course of oral levofloxacin 750 mg once daily was as effective as a ten-
day course of ciprofloxacin [15]. This levofloxacin regimen has FDA approval for
uncomplicated pyelonephritis only and is not appropriate for complicated pyelonephritis.

However, beta lactam regimens should be administered for a full 14-day course given
failure rates with a shorter duration of therapy [16].

The duration of antibiotic therapy need not be extended in the setting of bacteremia in the
absence of other complicating factors; there is no evidence that bacteremia portends a
worse prognosis [13]. Surveillance blood cultures to demonstrate clearance of bacteremia
are appropriate, although follow-up urine cultures are not needed in patients with acute
pyelonephritis whose symptoms resolve on antibiotics.

Persistent symptoms — Patients with persistent clinical symptoms on antibiotic therapy

should be evaluated for complicated pyelonephritis with radiographic imaging and
additional laboratory investigation. (See 'Acute complicated pyelonephritis' below.)

Patients with delayed response to therapy should receive a longer course of antibiotics
(14 to 21 days), even in the absence of evidence for complicated disease.

Patients with recurrent symptoms within a few weeks of treatment for pyelonephritis
should have repeat urine culture and antimicrobial susceptibility testing. If the pathogen
isolated is the same isolate as in the initial episode with the same susceptibility profile, a
repeat course of treatment with another antibiotic agent should be instituted. In addition,
radiographic studies should be performed to evaluate for complicated pyelonephritis.

Imaging — Patients with persistent fever or clinical symptoms after 48 to 72 hours of

appropriate antimicrobial therapy for uncomplicated pyelonephritis should undergo
radiologic evaluation of the upper urinary tract with ultrasound or computed tomography
(CT) scan. These modalities are useful for evaluating obstruction, abscess, or other
complications of pyelonephritis [17-19]. Resolution of radiographic hypodensities may
lag behind clinical improvement by up to three months [20]. (See "Radiologic evaluation
in acute pyelonephritis".)

ACUTE COMPLICATED PYELONEPHRITIS — Complicated pyelonephritis is

progression of upper urinary tract infection to renal corticomedullary abscess, perinephric
abscess, emphysematous pyelonephritis, or papillary necrosis. Risk factors for
progression to complicated pyelonephritis include urinary tract obstruction, urologic
dysfunction, antibiotic resistant pathogen(s), and diabetes (particularly for
emphysematous pyelonephritis and papillary necrosis) (table 3). (See "Renal and
perinephric abscess" and "Emphysematous urinary tract infections".)

Clinical manifestations — In addition to the clinical manifestations of uncomplicated

pyelonephritis discussed above, complicated pyelonephritis may be associated with
weeks to months of insidious, nonspecific signs and symptoms such as malaise, fatigue,
nausea, or abdominal pain.

Patients with complicated pyelonephritis due to urolithiasis may present with renal colic
and gross or microscopic hematuria. These findings should prompt consideration of
xanthogranulomatous pyelonephritis, a variant of chronic pyelonephritis that may be
confused with renal cell carcinoma. (See "Xanthogranulomatous pyelonephritis".)

Diagnosis — Acute complicated pyelonephritis is associated with pyuria and bacteriuria,

although these findings may be absent if the infection does not communicate with the
collecting system or if the collecting system is obstructed.

Urine culture with antimicrobial susceptibility testing should be performed. Parameters

for interpretation of urine colony counts are as outlined above for acute uncomplicated
pyelonephritis (see 'Diagnosis' above.

Microbiology — E. coli is the most common cause of complicated pyelonephritis. Other

pathogens including Citrobacter sp, Enterobacter sp, Pseudomonas aeruginosa,
enterococci, Staphylococcus aureus, and fungi account for a higher proportion in
complicated than uncomplicated pyelonephritis [21]. S. saprophyticus is an uncommon
cause of complicated UTI. (See "Microbiology and pathogenesis of acute
pyelonephritis".)

Treatment — Patients with complicated pyelonephritis should be managed initially as

inpatients. Underlying urinary tract anatomic or functional abnormalities (such as
obstruction or neurogenic bladder) should be addressed in consultation with an urologist
[21]. Antibiotics alone may not be successful unless such underlying conditions are
corrected.

Broad-spectrum parenteral antibiotics should be used for empiric treatment of

complicated pyelonephritis as outlined in the Table (table 2). Antimicrobial therapy
subsequently must be tailored to individual patient circumstances with consideration of
the results of susceptibility testing and prior recent antibiotic therapy. Transitioning to
oral antibiotic therapy is as outlined above for acute uncomplicated pyelonephritis (table
1) and (see "Renal and perinephric abscess") and "(see 'Routine follow-up management'
above.

Antibiotics should be administered for at least 10 to 14 days, although a longer duration

of therapy may be warranted for patients with underlying complicating factors. The five-
day regimen of levofloxacin 750 mg once daily has FDA approval for uncomplicated
pyelonephritis only and is not appropriate for complicated pyelonephritis.

PREGNANCY — Acute pyelonephritis in pregnant women is discussed separately. (See

"Urinary tract infections and asymptomatic bacteriuria in pregnancy".)

INFORMATION FOR PATIENTS — Educational materials on this topic are available

for patients. (See "Patient information: Kidney infection (pyelonephritis)".) We
encourage you to print or e-mail this topic review, or to refer patients to our public web
site, www.uptodate.com/patients, which includes this and other topics.

SUMMARY AND RECOMMENDATIONS

* Acute uncomplicated pyelonephritis is a urinary tract infection that has progressed

from the lower urinary tract to the upper urinary tract. (See 'Acute uncomplicated
pyelonephritis' above.)

* Acute complicated pyelonephritis is progression of acute pyelonephritis to

emphysematous pyelonephritis, renal corticomedullary abscess, perinephric abscess, or
papillary necrosis. It is frequently associated with an underlying condition such as
obstruction, urologic dysfunction, diabetes, or infection with an antibiotic-resistant
pathogen. (See 'Acute complicated pyelonephritis' above.)

* Clinical manifestations of pyelonephritis include flank pain, nausea, vomiting, fever

(≥37.8ºC) and/or costovertebral angle tenderness. (See 'Clinical manifestations' above.)

* Laboratory evaluation should include urinalysis (to evaluate for pyuria), urine culture
and antimicrobial susceptibility testing. Most episodes of pyelonephritis are associated
with >10(5) CFU per mL of organisms, although some patients with pyelonephritis have
colony counts of 10(3) to 10(4) CFU per mL. (See 'Diagnosis' above.)

* For patients able to tolerate oral antibiotics, we suggest an oral fluoroquinolone for
initial empiric treatment of acute uncomplicated pyelonephritis (table 1) (Grade 2B). (See
'Oral antibiotics' above.)

* For patients unable to tolerate oral antibiotics, we suggest intravenous ceftriaxone or

a fluoroquinolone for initial empiric parenteral treatment of acute uncomplicated
pyelonephritis (table 2) (Grade 2B). (See 'Parenteral antibiotics' above.)
 * For patients with complicated pyelonephritis, we suggest broad-spectrum parenteral
antibiotics as outlined in the Table (table 2) (Grade 2B).
* Subsequent choice and duration of antibiotic therapy must be tailored to
antimicrobial susceptibility findings and clinical circumstances. (See 'Routine follow-up
management' above.)

* Imaging (ultrasonography or computed tomography) is warranted in the setting of

persistent fever or clinical symptoms after 48 to 72 hours of appropriate antimicrobial
therapy to evaluate for obstruction, abscess, or other complications of pyelonephritis.
(See 'Imaging' above.)
Background

Urinary tract infections (UTIs) are relatively common infections in children. Cystitis
(lower-tract infection) is characterized by voiding-related symptoms with or without
fever and often without other systemic signs. Findings on nuclear renal scans suggest that
the vast majority of infants and young children with febrile UTIs have acute
pyelonephritis (APN), which is an upper tract infection.

Early recognition and prompt treatment of UTIs is important to prevent late sequelae,
such as renal scarring, hypertension, and renal failure. When assessing the pediatric
patient with UTI, one may encounter few specific symptoms. Older children are most
likely to have symptoms attributable to the urinary tract. Differentiating cystitis from
pyelonephritis in the pediatric patient may be difficult and sometimes impossible. Febrile
UTI should be assumed to be pyelonephritis and treated accordingly.
Pathophysiology

UTIs are generally ascending in origin and caused by perineal contaminants, usually
bowel flora. However, in neonates, infection is assumed to be hematogenous in origin
rather than ascending. This feature may explain the nonspecific symptoms associated
with UTI in these patients. After the neonatal period, bacteremia is generally not the
source of infection; rather, UTI or pyelonephritis is the cause of the bacteremia.

Bacterial colonization of the bladder is most likely to develop into infection if urinary
stasis or low-flow conditions are present. Some causes of these conditions include
infrequent voiding, incomplete voiding, obstruction or other urinary tract abnormalities.
Vesicoureteral reflux (VUR) has been reported in as many as 33% of children with acute
pyelonephritis. Even in the absence of urinary tract abnormalities, cystitis may result in
VUR or worsen preexisting VUR and lead to pyelonephritis. Chronic or recurrent
pyelonephritis results in renal damage, scarring, and, if severe, chronic renal failure.

Host genetic factors that promote inflammation contribute to renal scarring. Interleukin
(IL)-8 and CXCR1 polymorphisms, ACE insertion/deletion (ACE I/D) gene
polymorphism, and tumor necrosis factor-[alpha] polymorphism have been identified as
potential mediators to tissue fibrosis and subsequent renal scarring following acute
pyelonephritis.