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DISEASE OVERVIEW

Pyelonephritis
Ferri's Clinical Advisor 2021 Conn's Current Therapy 2020

Ferri, Fred F., MD, FACP

Pyelonephritis
Definition

Genetics

Etiology

Diagnosis

Differential Diagnosis

Treatment

Copyright © 2021 by Elsevier, Inc. All rights reserved.

Definition
Ascending infection of a bacterial pathogen that infects the renal pelvis and kidney. It primarily
presents as a urinary tract infection (UTI) characterized by painful urination (dysuria) with
associated flank pain/tenderness, nausea, vomiting, and/or fever. The elderly may also present with

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failure-to-thrive, unexplained anorexia, other organ system decompensation, or generalized

deterioration.

Consists of two groups

• Uncomplicated: Can be treated as an outpatient with oral antibiotics.

• Complicated: Inpatient treatment with intravenous antibiotics is required. Hospitalization

is indicated for persistent vomiting, progression of uncomplicated UTI, suspected sepsis,
immunosuppression, or urinary tract obstruction. This is a potentially life-threatening
infection that can lead to renal parenchymal damage. Timely diagnosis and management can
significantly impact patient outcomes.

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Genetics
Congenital urologic structural disorders associated with vesicoureteral reflux predispose to infections
at an early age (<5 yr) and produce renal scarring in most males and some females. Pyelonephritis
may produce an Ask-Upmark kidney (segmental renal hypoplasia) which is found more often in
young females with severe hypertension.

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Etiology
Ascending infections from intestinal bacteria that colonize the perineum and vulva in women account
for most infections. Less commonly, bacteria, viruses, or fungal pathogens may produce
hematogenously induced pyelonephritis.

• Gram-negative bacilli cause 95% of cases (e.g., E. coli and Klebsiella species).

• Less common gram-negative bacteria may produce infection, particularly after urinary tract
instrumentation (e.g., Enterobacter, Serratia, and Proteus mirabilis, Pseudomonas , among
others).

• Resistant gram-negative organisms or fungi such as Candida may colonize indwelling

catheters.

• Gram-positive organisms such as enterococci and rarely, Staphylococcus saprophyticus.

• Staphylococcus aureus indicates hematogenous spread to the kidneys.

• Viruses generally are limited to the lower urinary tract.

• Urea-splitting organisms generate alkaline urine, which fosters production of staghorn

calculi. These stones may grow to large size and cause infection, obstruction, or both.

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In the elderly, E. coli is less common (60%). Diabetics develop infections from Klebsiella species,
Enterobacteriaceae, Clostridia species, or Candida species.

During the past decade, community-acquired bacteria (particularly E. coli ) that produce extended-
spectrum beta-lactamases have emerged as a cause of acute pyelonephritis worldwide. The most
common risk factors for these uropathogens include frequent visits to health care centers, recent use
of antimicrobials (e.g., cephalosporins and fluoroquinolones), older age, immunosuppression,
recurrent pyelonephritis, nephrolithiasis, and comorbid conditions such as diabetes mellitus and
recurrent UTIs.

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Diagnosis
Differential Diagnosis
Differential diagnosis includes the following:

• Abdominal abscess

• Acute abdomen

• Appendicitis

• Basilar pleural process

• Diverticulitis

• Endometriosis

• Herpes zoster

• Lower rib fracture

• Metastatic disease

• Musculoskeletal disorders

• Nephrolithiasis

• Pancreatitis

• Papillary necrosis

• Pelvic inflammatory disease

• Prostatitis

• Pulmonary infarctions

• Renal corticomedullary necrosis

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• Renal vein thrombosis

• Retroperitoneal hemorrhage or abscess

• Splenic abscess or infarct

• Urinary tract obstruction

• Vascular pathology

Workup
Evaluation includes prostate health assessment in older males.

Urinalysis
Conducted on a clean-catch voided or catheterized specimen, if unable to void or cooperate. Dipstick
and microscopic examination must be performed on a fresh specimen for preservation of formed
elements (e.g., cells, casts, and microorganisms). Most cases demonstrate pyuria and positive
leukocyte esterase in association with a positive blood reaction and microhematuria. Leukocyte casts
are generally of renal origin but may be absent.

Urine Culture
Historically, clean, midstream cultures are obtained from all patients suspected of having acute
pyelonephritis to guide antibiotic therapy. However, a clean-catch specimen may not be necessary
because recent evidence demonstrates no significant difference in the number of contaminated or
unreliable culture results when collected with or without preparatory cleansing. Obtain a catheterized
urine sample if the patient is unable to void, is uncooperative, or has a change in mental status. There
is no difference in colony counts or organisms between catheterized and midstream voiding samples.

More than 95% of acute pyelonephritis cases exhibit more than 10 5 colony-forming units of a single
bacterium per ml of urine. However, it is important to obtain an accurate history regarding the
timing of culture acquisition and prior antibiotic administration. A negative culture with classic
clinical and radiological findings does not rule out acute pyelonephritis as proven in a prospective
study in which only 23.5% of 196 patients with clinical and radiological evidence of acute
pyelonephritis demonstrated positive urine cultures. A urine Gram stain may aid in the choice of
empiric antimicrobial therapy pending urine culture. If gram-positive cocci are seen, one should
consider Enterococcus species or Staphylococcus saprophyticus as causative.

Post-treatment urinalysis and culture are unnecessary if symptomatic improvement occurs, but these
studies should be obtained if symptomatic improvement does not occur within 2 to 3 days of
antibiotic treatment, or symptoms recur within 2 wk of treatment. Urinary tract imaging is
recommended in these cases.

Blood Cultures
Cultures are obtained from hospitalized patients, but may not be routinely required in uncomplicated
cases. Approximately 15% to 30% of patients with acute pyelonephritis are bacteremic. The elderly
and individuals with complicated acute pyelonephritis are more likely to develop bacteremia and
sepsis.
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Urine cultures yield a causative organism in nearly all cases of acute pyelonephritis. Therefore, a
positive blood culture may be diagnostically redundant. However, in unclear cases, or when an
alternative diagnosis to acute pyelonephritis is considered, endometriosis, intraabdominal or psoas
abscess, or cholangitis, blood cultures should be obtained.

Radiology
Most uncomplicated cases of acute pyelonephritis do not require imaging studies, unless symptoms
do not improve or recurrence occurs or patient has prolonged fever (>72 hours) or persistent
bacteremia. Abdominal radiographs (i.e., kidney, ureter, and bladder x-ray [KUB]) are of limited use
in acute pyelonephritis, unless staghorn calculi are present. Retrograde or antegrade pyelography
may be helpful in severe obstruction that is not evident after noninvasive evaluations. Voiding
cystourethrography demonstrates vesicoureteral reflux and is generally performed routinely only in
children.

Recommendations for radiologic tests:

• Healthy patients with uncomplicated pyelonephritis typically do not require radiologic

evaluation when therapeutic responses occur within 72 hours of antibiotic therapy.

• If no response to therapy occurs within 72 hours, abdominal CT is the study of choice.

• Diabetics and immunocompromised patients should undergo precontrast and postcontrast

abdominal and pelvic CT scans ( Fig. 1 (f0010) ) within 24 hours of diagnosis when the response
to therapy is not prompt.

• Ultrasound ( Fig. E2 (f0015) ) is reserved for patients in whom exposure to contrast or

radiation is considered hazardous. There is a high false-negative rate for renal abscess with
ultrasound. In a prospective study of acute pyelonephritis of 213 patients submitted for
CT/NMR study, 50 patients (23.5%) had a renal abscess, yet only two were detected by
ultrasound.

• All other adults with complicated cases (i.e., history of stones or other urologic conditions,
prior urologic surgery, repeated episodes of pyelonephritis) should be evaluated early by CT.

• Helical CT detects calculi with high sensitivity.

• Urologic imaging studies should be conducted in all young men and boys.

FIG. E2
Acute pyelonephritis.
A, Subtle focal increased echogenic areas are seen in the anterior cortex of the right kidney. B, Single focal hypoechoic area is seen in
the upper pole of the kidney in another patient.
From Rumack CM et al: Diagnostic ultrasound , ed 4, Philadelphia, 2011, Elsevier.

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Although the risk of contrast nephropathy has declined substantially, exert caution during contrast
administration to patients with chronic kidney disease or for those taking metformin. When
evaluating kidney function, diagnostic decision-making must include eGFR trends, not serum
creatinine, especially in the elderly. Patients with acute pyelonephritis and acutely elevated baseline
serum creatinine may warrant CT imaging to rule out obstruction. If the risk of radiocontrast media
administration outweighs its benefits, consider retrograde or antegrade pyelography.

The purpose of imaging is to identify underlying structural abnormalities, such as occult obstruction
from a stone or abscess and serious complications such as emphysematous pyelonephritis. In a
prospective study of 213 patients with acute pyelonephritis, there were no differences in frequency of
fever, leukocytosis, C-reactive protein, pyuria, urine cultures, and duration of symptoms before
hospitalization for positive or negative CT. Accordingly, systematic CT or magnetic resonance
imaging is not required to exclude an anatomical abnormality. Such abnormalities cannot be
predicted based on clinical, biochemical, or culture parameters.

Emphysematous pyelonephritis is a necrotizing infection that produces intraparenchymal kidney gas

identifiable by renal imaging that is associated with high mortality. Risk factors include diabetes
mellitus and/or urinary tract obstruction. Gas-forming bacteria, most commonly E. coli , produce gas
that is usually restricted within Gerota fascia. If gas is localized to the kidney, mortality is 60%. If gas
spreads to the perinephric space, mortality is 80%. In emphysematous pyelitis, the mortality is 20%.
This must be differentiated from a renal abscess that can also be associated with a gas collection.
With drainage and antibiotic treatment, a renal abscess has a favorable prognosis.

FIG. 1
Acute pyelonephritis: Contrast material–enhanced computed tomographic (CT) scan.
The heterogeneous CT nephrogram shows the diffuse involvement of the right kidney. Stranding and some fluid are visible in the
perinephric space with thickening of Gerota fascia.
From Skorecki K et al: Brenner & Rector’s the kidney , ed 10, Philadelphia, 2016, Elsevier.

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Laboratory Tests
A basic metabolic profile and CBC with differential count are required for all patients with suspected
acute pyelonephritis to estimate renal function. If the diagnosis is in doubt, other laboratory tests
may be appropriate to clarify the differential diagnosis (e.g., lipase, transaminase, and β-HCG levels).

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Differential Diagnosis
Differential diagnosis includes the following:

• Abdominal abscess

• Acute abdomen

• Appendicitis

• Basilar pleural process

• Diverticulitis

• Endometriosis

• Herpes zoster

• Lower rib fracture

• Metastatic disease

• Musculoskeletal disorders

• Nephrolithiasis

• Pancreatitis

• Papillary necrosis

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• Pelvic inflammatory disease

• Prostatitis

• Pulmonary infarctions

• Renal corticomedullary necrosis

• Renal vein thrombosis

• Retroperitoneal hemorrhage or abscess

• Splenic abscess or infarct

• Urinary tract obstruction

• Vascular pathology

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Treatment
Acute General Rx
Uncomplicated Acute Pyelonephritis
Close outpatient follow-up is possible with minimal gastrointestinal symptoms and the ability to
maintain fluid intake and oral medications. Prompt antibiotic therapy prevents progression of
infection and must be initiated following acquisition of appropriate cultures. Begin empiric therapy
based on risk of adverse effects, local community bacterial profiles, and resistance rates. Antibiotics
are revised after urine culture results are available.

The concept of requiring long-term treatment of acute pyelonephritis has been questioned. Women
with acute pyelonephritis were randomized to oral treatment with ciprofloxacin 500 mg twice daily
for 7 days or 14 days, and 27% of these patients experienced bacteremia from E. coli . No differences
in the cure rates were found (87% and 96%, respectively).

Outpatient regimens:

• Fluoroquinolones are preferred in communities where the local prevalence of resistant E.

coli is ≤10%.

• Ciprofloxacin 500 mg by mouth twice daily or a single, 1000-mg dose in the extended-
release form by mouth daily for 7 days.

• Levofloxacin 750 mg by mouth daily for 5 days.

• The initial dose may be administered intravenously (ciprofloxacin 400 mg or levofloxacin

500 mg).

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• When a fluoroquinolone is contraindicated, alternative treatment with

trimethoprim/sulfamethoxazole 160/800 mg PO twice daily for 10 to 14 days may be
administered if the pathogen is susceptible. Recent data suggest that stopping treatment at 7
days may be equally effective.

Because of the high prevalence of resistance to oral beta-lactam antibiotics and

trimethoprim/sulfamethoxazole, these agents usually are reserved for cases where susceptibility
results are known. Additional factors (e.g., allergy history, potential drug–drug interactions, drug
availability) may require empiric treatment with these agents before susceptibility results are known.
For such cases, a long-acting, broad-spectrum parenteral drug (e.g., ceftriaxone 1 g or gentamicin 5
mg/kg) may be administered as a one-time dose or longer, until sensitivities of the organism are
known. If the local prevalence of fluoroquinolone resistance to E. coli exceeds 10%, an initial
intravenous dose of ceftriaxone or gentamicin is recommended, followed by an oral fluoroquinolone
regimen.

Significant clinical improvement during appropriate empiric antibiotic therapy should occur within
48 to 72 hours. If improvement does not occur, a complication of acute pyelonephritis or an
alternative diagnosis such as an abscess, emphysematous pyelonephritis, or an obstructing calculus
should be considered. Any unexpected change in the clinical picture warrants immediate
investigation with a CT scan, and with potential for surgical intervention.

Complicated Acute Pyelonephritis

Hospitalization is indicated for the following reasons:

• Toxic patients

• Complicated infections

• Diabetes or otherwise immunosuppressed

• Suspected bacteremia

Inpatient care includes supportive care, monitoring of culture results, adjustment of antibiotic
regimen, and intravenous volume repletion as required. Intravenous antibiotics are continued until
defervescence occurs and clinical improvement occurs. Next, there is conversion to an oral antibiotic
regimen for a total duration of 10 to 14 days.

• Intravenous antibiotic options for more toxic patients pending cultures include ceftriaxone
(1 to 2 g once daily), IV ciprofloxacin (400 mg every 12 hours) or IV levofloxacin (500 to 750
mg IV once daily), piperacillin/tazobactam (3.375 g IV every 6 hours), or carbapenems such as
meropenem or imipenem (500 mg IV every 6 to 8 hours).

• Ceftazidime 1 to 2 g IV every 8 hours, piperacillin/tazobactam, or carbapenems are optimal

choices for Pseudomonas due to this organism’s increasing ciprofloxacin resistance.

• Aminoglycosides (2 mg/kg IV loading dose followed by 1 mg/kg IV every 8 to 12 hours,

adjusted for kidney function) are potentially nephrotoxic, and are used only when there is no
better alternative. Vancomycin 1 g IV every 12 hours, linezolid 600 mg IV or PO every 12

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hours, or daptomycin 4 to 6 mg/kg IV daily for gram-positive cocci (e.g., enterococci,

staphylococci).

• Ampicillin 1 to 2 g IV every 4 to 6 hours for ampicillin-sensitive enterococci with

aminoglycoside for synergy. Urinary obstruction is promptly drained by nephrostomy tube.
Surgical drainage of abscess formation(s).

• Pregnant females with acute pyelonephritis are hospitalized and treated initially with a
second- or third-generation cephalosporin.

Renal Abscesses (Renal Carbuncles)

Cortical abscesses historically required surgical drainage; however, using current antibiotics is
commonly sufficient for cure.

• Semisynthetic penicillin, cephalosporin, fluoroquinolone, or vancomycin, with guidance

from culture and sensitivity results.

1. Parenteral therapy for 10 to 14 days followed by oral therapy for 2 to 4 wk.

2. Fever should resolve in 5 to 6 days and pain within 24 hours.

3. If no clinical response occurs within 48 hours, percutaneous or open drainage

should be considered. More extreme measures are occasionally required, including
enucleation or nephrectomy.

Corticomedullary Abscesses

• Parenteral therapy for at least 48 hours is typically successful.

• May require incision and drainage and possibly nephrectomy.

• If defervescence occurs, IV antibiotic treatment may be switched to complete a 2-wk course

of oral antibiotic therapy.

Perinephric Abscesses

• Serious complication with mortality in the 25% to 50% range.

• Lesions require early recognition, surgical drainage, and parenteral antibiotics (not adequate
alone) to reduce mortality.

• Initial antibiotic therapy should include an aminoglycoside and an antistaphylococcal agent.

1. If Pseudomonas species grow in culture or are suspected, an antipseudomonal beta-

lactam antibiotic should be administered with the aminoglycoside.

2. For enterococcus, an aminoglycoside and ampicillin are recommended.

• Reported with tuberculosis or fungi as rare causes.

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• Nephrectomy may be considered with clinical deterioration despite aggressive therapy.

Calculi-Related Infections
Chronic pyelonephritis may lead to struvite stone formation, which is comprised of magnesium
ammonium phosphate (struvite) and calcium carbonate-apatite. Formation requires infection with a
urease-producing organism, such as Proteus or Klebsiella . Under normal conditions the urine is
undersaturated with ammonium phosphate.

Symptoms directly attributable to struvite stones are uncommon. Most frequently, patients will
present with symptoms of a urinary tract infection, mild flank pain, or hematuria. The stone may
grow rapidly over a period of wks to mos and, if not adequately treated, can develop into a staghorn
or branched calculus filling the entire renal pelvis and calyces.

Medical treatment for struvite stones is often ineffective and only indicated when surgery is not an
option. Mortality is 28% with observation vs. 7.2% with surgical treatment. The most common
surgical intervention is percutaneous nephrolithotomy. Open surgery, once the gold standard, is
rarely used now.

Surgical intervention is generally recommended in patients with newly discovered stones or in

patients with a solitary kidney or two equally functioning kidneys. Nephrectomy is a reasonable
option in patients with a nonfunctional kidney, especially if chronic infection is present.

Renal Papillary Necrosis

• Admission for parenteral antibiotics:

1. Initial therapy should cover E. coli , Enterobacter , Proteus , and Klebsiella species,
pending culture results.

2. For more serious infections, Pseudomonas and Enterococcus should also be

covered.

3. Empiric therapy agent options include the following:

a. Aminoglycosides

b. Cefotaxime

c. Ceftriaxone

d. Ceftazidime

e. Cefepime

f. Piperacillin-tazobactam

g. Imipenem-cilastatin

h. Meropenem

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i. Ciprofloxacin

4. Continue parenteral therapy until fever and clinical symptoms improve.

Xanthogranulomatous pyelonephritis: Rare variant of chronic pyelonephritis with destruction of

renal parenchyma.

• Generally, unilateral

• Usually in individuals with obstructing stones

• CT is the diagnostic modality of choice and can provide staging information

• Can be confused with malignancy

• Treatment is surgical nephrectomy

Chronic Rx

• Repair underlying structural problems especially when kidney function is compromised.

1. Reflux

2. Obstruction

3. Suspect nephrolithiasis

• Avoid urinary catheters.

Disposition

• If pyelonephritis is uncomplicated with no significant GI symptoms, treatment may be

initiated on an outpatient basis with close monitoring of therapeutic response(s) in 48 to 72
hours.

• If pyelonephritis is complicated and symptoms persist for >48 to 72 hours, admission is

recommended for any of the following: Significant GI symptoms that preclude oral therapy,
pregnancy, urinary tract obstruction, suspected renal or perinephric abscess, bacterial sepsis,
diabetes or other immunocompromised states, recurrent or refractory pyelonephritis, or
infection with unusual or antibiotic-resistant microorganisms.

• If sepsis is present, consider intensive care unit hospitalization.

• Acute pyelonephritis may be fatal when complications develop such as emphysematous

pyelonephritis (mortality rate, 20% to 80%), perinephric abscess (mortality rate, 20% to
50%), or sepsis syndrome (>25% overall mortality rate).

• Acute deterioration or nonresponse to conventional therapy may be due to a complication,

resistant organism, or unrecognized comorbidity.

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• Diabetic patients with acute pyelonephritis are prone to bacteremia, longer hospital stays,
and greater mortality. Diabetics should be considered complicated patients.

• Patients >65 yr of age experience greater mortality, septic shock, bedridden status, and
immunosuppression. In males, mortality is also increased with the use of antibiotics in the
previous mo.

Referral

• General surgery or urology for suspected abscess

• Infectious disease for resistant organisms and poor response to routine antibiotic therapy as
outlined

• Urology to correct underlying urologic problems (e.g., reflux and hydronephrosis)

• Nephrology consult for renal dysfunction or nephrolithiasis evaluation

• Critical care medicine if ICU admission is required

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Copyright © 2020 Elsevier, Inc. All rights reserved.

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