Highlights & Basics
- Acute pyelonephritis in adults commonly presents as acute-onset fever, chills, severe back or flank pain, nausea and vomiting, and costovertebral angle tenderness.
- Urinalysis and urine culture confirm the diagnosis of pyelonephritis. Urine cultures, obtained prior to treatment, demonstrate bacteria, most often Escherichia coli.
- The route and choice of empiric antibiotics depend on the severity of illness and the presumed bacterial sensitivities pending culture results.
- Complications most often result from inappropriate (wrong drug or wrong dose) antibiotic use or antibiotic resistance, leading to recurrent or progressive infection.
- Other common causes of complications are inadequate treatment of anatomic abnormalities (e.g., kidney stones or obstruction), preventing bacterial clearance.
Quick Reference
History & Exam
Key Factors
fever
Other Factors
nausea and vomiting
dysuria, frequency, or urgency
flank pain or costovertebral angle tenderness
Diagnostics Tests
1st Tests to Order
urinalysis
Gram stain
urine culture
complete blood count
erythrocyte sedimentation rate
C-reactive protein
procalcitonin
blood culture
Other Tests to consider
renal ultrasound
contrast-enhanced spiral computed tomography
magnetic resonance imaging
Emerging Tests
interleukin
copeptin
Treatment Options
presumptive
high index of suspicion with mild-to-moderate symptoms and uncomplicated disease
empiric oral antibiotic therapy
long-acting parenteral antibiotic
high index of suspicion with severe symptoms or complicated disease or pregnant patients
hospitalization and empiric intravenous antibiotic therapy
Definition
Classifications
Acute pyelonephritis classification, Medical Clinics of North America, 1995
- Age
- Infants
- Older patients (>60 years)
- Anatomic abnormality
- Vesicoureteric reflux
- Polycystic kidney disease
- Horseshoe kidney
- Double ureter
- Ureterocele
- Foreign body
- Renal stone
- Urinary, ureteric, or nephrostomy catheter
- Impaired renal function
- Immunocompromised
- Diabetes mellitus
- Sickle cell disease
- Transplantation
- Malignancy
- Chemotherapy
- Radiotherapy
- Alcohol dependence
- HIV
- Corticosteroid use
- Use of immunosuppressants
- Instrumentation
- Cystoscopy
- Male sex
- Recurrent infection
- Infection foci in prostate
- Anatomic abnormalities
- Obstruction
- Benign prostatic hypertrophy
- Renal stone
- Foreign body
- Bladder neck obstruction
- Posterior ureteral valve
- Neurogenic bladder
- Pregnancy
Vignette
Common Vignette
Other Presentations
Epidemiology
Etiology
Pathophysiology
Images
Cross-section of a kidney with acute suppurative pyelonephritis. The white streaks are purulent exudates throughout the kidney, in both the tubules and the interstitium
External surface of the kidney with multifocal irregular, whitish, raised lesions consisting of purulent exudates
Interstitial infiltrates and edema in acute pyelonephritis. Some glomeruli also show evidence of a second kidney disease, focal glomerulosclerosis
Higher magnification: polymorphonuclear cell infiltrates in and around the renal tubules
Psoas muscle shadow enhanced by retroperitoneal air in emphysematous pyelonephritis
Diagnostic Approach
Physical exam
Laboratory tests
Imaging studies
Risk Factors
History & Exam
Tests
Differential Diagnosis
Chronic pyelonephritis
Differentiating Signs/Symptoms
- Suggested by a relevant history of underlying medical problems, such as anatomic abnormalities that predispose to obstruction (e.g., kidney stones), metabolic factors (e.g., diabetes), or recurrent infections with resistant bacteria that lead to permanent renal damage evident on imaging studies.
Differentiating Tests
- Imaging studies often show small, irregular, scarred kidneys.
Pelvic inflammatory disease
Differentiating Signs/Symptoms
- Determined via a history of sexual intercourse; lower abdominal, pelvic, or low back pain; pain with movements; vaginal discharge; fevers or chills; abdominal or cervical tenderness.
- Pelvic exam may show vaginitis, urethral discharge, or herpetic ulcerations.
- Cervical exam may show cervicitis.
Differentiating Tests
- Cervical cultures can identify causative pathogens (e.g., Neisseria gonorrhoeae, Chlamydia trachomatis).
- Microscopic examination of vaginal discharge demonstrates neutrophils.
Pelvic pain syndrome
Differentiating Signs/Symptoms
- Recurrent symptoms, including dysuria, pain on intercourse, and pelvic pain, occur with negative cultures.
- Symptoms that affect primarily the bladder may be associated with a small bladder and frequent voiding.
Differentiating Tests
- No differentiating tests exist.
Cystitis
Differentiating Signs/Symptoms
- Does not display systemic signs or symptoms (e.g., fevers, chills, nausea, vomiting, and back pain).
- Often associated with dysuria and frequency.
Differentiating Tests
- No differentiating tests exist.
Acute prostatitis
Differentiating Signs/Symptoms
- Can be associated with anal intercourse in men. Symptoms may include dysuria, frequency, and blood in the urine, or may be mild and subacute. May recur in patients who are treated for an adequate duration (up to 3 weeks).
- Physical exam shows a tender, often enlarged prostate.
Differentiating Tests
- Microscopic analysis shows WBCs in urine obtained after prostate massage or by collection of the terminal portion of a urine sample.
Lower lobe pneumonia
Differentiating Signs/Symptoms
- Often complain of cough and pleuritic chest pain. Physical exam may show decreased breath sounds, rales, or rhonchi.
Differentiating Tests
- Chest radiography is useful in making the diagnosis.
Screening
Pregnancy
Treatment Approach
Treatment setting
- Inability to maintain oral hydration or adherence to the medication regimen
- Hypotension
- Vomiting
- Dehydration
- Sepsis
- High WBC count
- Patients with a temperature >102.2ºF (39.0ºC)
- Severely ill patients with marked debility or multiple comorbidities
- Pregnancy
- Uncertainty about the diagnosis.
Empiric antibiotic choices
Mild-to-moderate and uncomplicated pyelonephritis
Severe and complicated pyelonephritis or pregnancy
Recurrent disease
Treatment Options
high index of suspicion with mild-to-moderate symptoms and uncomplicated disease
empiric oral antibiotic therapy
Primary Options
- ciprofloxacin
500 mg orally twice daily
- ciprofloxacin
- ofloxacin
200-300 mg orally twice daily
- ofloxacin
Secondary Options
- levofloxacin
250-500 mg orally once daily
- levofloxacin
Comments
- Antibiotics should be chosen based on local bacterial sensitivity profiles pending results.
- In the setting of fluoroquinolone hypersensitivity or if known fluoroquinolone resistance is >10%, an alternative acceptable choice is trimethoprim/sulfamethoxazole.
- Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[50] The FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[51] [52]
- The risks of not treating an infection far outweigh the risk of antibiotic therapy in patients without pyelonephritis. Most uncomplicated cases are cured without sequelae.
- Treatment course: Infectious Diseases Society of America recommendations affirm that in mild cases, 10 to 14 days of outpatient treatment with oral antibiotics is generally sufficient, and shorter courses of highly active agents (e.g., fluoroquinolones) are also appropriate.[32] More recent guidance from the American College of Physicians also supports the use of short-course antibiotic treatment (e.g., 5 to 7 days with a fluoroquinolone) for both men and nonpregnant women with uncomplicated pyelonephritis.[56]
long-acting parenteral antibiotic
Primary Options
- ceftriaxone
1 g intravenously as a single dose
- ceftriaxone
- gentamicin
3-5 mg/kg intravenously as a single dose
- gentamicin
Comments
- If local bacterial sensitivity profiles are not known, guidelines suggest adding a onetime intravenous dose of a long-acting antimicrobial, such as ceftriaxone or a consolidated 24-hour dose of an aminoglycoside.[32] [45] This is also recommended in areas where fluoroquinolone resistance is >10%.[32] [45]
high index of suspicion with severe symptoms or complicated disease or pregnant patients
hospitalization and empiric intravenous antibiotic therapy
Primary Options
- ciprofloxacin
400 mg intravenously every 12 hours
- ciprofloxacin
- ofloxacin
200-400 mg intravenously every 12 hours
- ofloxacin
- ampicillin
2 g intravenously every 4 hours
and
- gentamicin
3-5 mg/kg/day intravenously
- ampicillin
- gentamicin
3-5 mg/kg/day intravenously
- gentamicin
Secondary Options
- levofloxacin
250-500 mg intravenously once daily
- levofloxacin
Comments
- Indications for hospitalization include inability to maintain oral hydration or adherence to the medication regimen; patients with fever >102.2ºF (39.0ºC), high WBC count, hypotension, vomiting, dehydration, or sepsis; severely ill patients with marked debility or multiple comorbidities; and uncertainty about the diagnosis. Older and immunocompromised patients, who are at risk for more severe disease, are usually hospitalized. Appropriate management of the urologic abnormality or the underlying complicating factor is mandatory.
- Because high drug concentrations in the renal medulla are more strongly correlated with cure than serum or urinary drug levels, agents such as aminoglycosides and fluoroquinolones, with high renal tissue levels, may be preferable to beta-lactam antibiotics.[49] The European Association of Urology suggests use of fluoroquinolones only in limited circumstances (e.g., when resistance in the community is <10% and antibiotics can be given orally) and advises against their use in patients admitted to a urology floor or who have received fluoroquinolones within the last 6 months due to the high risk of resistance.[45]
- Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[50] The FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[51] [52]
- Antimicrobial susceptibility of uropathogens in the community will also guide treatment decisions.
- Gentamicin should only be used in pregnant women when the benefits of treatment outweigh the risks. The risks associated with the use of this drug are mainly nephrotoxicity and ototoxicity. With appropriate dosing and monitoring of serum trough levels, many specialists use this drug in pregnancy as there are data supporting its use.[57] [65] [66] However, there have been case reports of gentamicin associated with fetal toxicity when used in pregnancy, so caution is advised.
- Treatment course is 2 weeks.
mild-to-moderate symptoms with uncomplicated disease
targeted oral antibiotic therapy
Primary Options
- ciprofloxacin
500 mg orally twice daily
- ciprofloxacin
- ofloxacin
200-300 mg orally twice daily
- ofloxacin
Secondary Options
- levofloxacin
250-500 mg orally once daily
- levofloxacin
- amoxicillin/clavulanate
875 mg orally twice daily; or 500 mg orally three times daily
- amoxicillin/clavulanate
Comments
- Antibiotics should be chosen based on results of cultures if taken.
- Most uncomplicated cases are cured without sequelae.
- Fluoroquinolones and cephalosporins are recommended for oral treatment of uncomplicated pyelonephritis.
- Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[50] The FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[51] [52]
- Treatment course: Infectious Diseases Society of America recommendations affirm that in mild cases, 10 to 14 days of outpatient treatment with oral antibiotics is generally sufficient, and shorter courses of highly active agents (e.g., fluoroquinolones) are also appropriate.[32] Trimethoprim/sulfamethoxazole for 14 days is recommended if the pathogen is known to be susceptible.[32] More recent guidance from the American College of Physicians recommends short-course (5 to 7 days) antibiotic treatment with a fluoroquinolone in men or nonpregnant women with uncomplicated pyelonephritis, or 14 days of trimethoprim/sulfamethoxazole, based on antibiotic susceptibility.[56]
severe symptoms or complicated disease or pregnant patients
targeted intravenous antibiotic therapy
Primary Options
- ciprofloxacin
400 mg intravenously every 12 hours
- ciprofloxacin
- ofloxacin
200-400 mg intravenously every 12 hours
- ofloxacin
- ampicillin
2 g intravenously every 4 hours
and
- gentamicin
3-5 mg/kg/day intravenously
- ampicillin
- gentamicin
3-5 mg/kg/day intravenously
- gentamicin
Secondary Options
- levofloxacin
250-500 mg intravenously once daily
- levofloxacin
Comments
- Patients with either severe symptoms (not able to take oral medication, volume depleted, early septic hemodynamic parameters, other laboratory parameters may also be abnormal) or complicated disease, and all pregnant patients, should be admitted and treated with intravenous agents.[57] [67] Choice of antibiotic agent should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results.[32] [45]
- Hospitalized patients should show improvement in 48 to 72 hours; if not, consider repeat cultures and/or imaging studies to evaluate other potential infectious etiologies or anatomic or functional genitourinary pathology interfering with treatment.
- The duration of therapy should be adjusted according to the patient's response to treatment.
- If gram-positive cocci are causative, treat with ampicillin-sulbactam with or without an aminoglycoside.[32]
- With improvement, the patient's regimen can be changed to an oral antimicrobial to which the organism is susceptive to complete the course of therapy.[32]
- Gentamicin should only be used in pregnant women when the benefits of treatment outweigh the risks. The risks associated with the use of this drug are mainly nephrotoxicity and ototoxicity. With appropriate dosing and monitoring of serum trough levels, many specialists use this drug in pregnancy as there are data supporting its use.[57] [65] [66] However, there have been case reports of gentamicin associated with fetal toxicity when used in pregnancy, so caution is advised.
- Treatment course is 2 weeks.
- Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[50] The FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[51] [52]
recurrent disease within 1 to 2 weeks
culture and sensitivity-directed antibiotic therapy
Primary Options
- ciprofloxacin
500 mg orally twice daily
- ciprofloxacin
- ofloxacin
200-300 mg orally twice daily
- ofloxacin
Secondary Options
- levofloxacin
250-500 mg orally once daily
- levofloxacin
- amoxicillin/clavulanate
875 mg orally twice daily; or 500 mg orally three times daily
- amoxicillin/clavulanate
Comments
- Repeat urine culture and antimicrobial susceptibility testing is indicated. If, on repeat culture, the bacterial strain and susceptibility profile is the same, a renal ultrasound or computed tomographic scan should be obtained.
- Retreatment can be with either a longer treatment course of the same antibiotic as used in initial therapy or a different antibiotic treatment based on results of urine culture and sensitivities.
- Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[50] The FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[51] [52]
Emerging Tx
Antioxidant/anti-inflammatory therapies
Vaccine therapy
Meropenem/vaborbactam
Plazomicin
Cefiderocol
Imipenem/cilastatin/relebactam
Prevention
Primary Prevention
- Increase fluid intake to at least 8 glasses per day to maintain bladder hygiene.
- Improve voiding habits by always responding to initial urge to void.
- Void after intercourse to rid urethra of bacteria acquired during sex, and if there is a history of atypical anatomy or recurrent urinary tract infections.
Secondary Prevention
Follow-Up Overview
Prognosis
Uncomplicated infections
Complicated infections
Monitoring
Complications
Citations
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Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52:e103-120.[Abstract][Full Text]
European Association of Urology. Guidelines on urological infections. 2022 [internet publication].[Full Text]
Glaser AP, Schaeffer AJ. Urinary Tract Infection and Bacteriuria in Pregnancy. Urol Clin North Am. 2015 Nov;42(4):547-60.[Abstract][Full Text]
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Key Articles
Referenced Articles
Guidelines
Diagnostic
Summary
Guidelines for use of radiographic testing in the presence of clinical urinary tract infection. Includes appropriateness scores for advanced radiologic testing including computed tomography, magnetic resonance imaging, and antegrade pyelography.Published by
American College of Radiology
Published
2022
Summary
Urine cultures are recommended when acute pyelonephritis is suspected. Consideration should be given to additional diagnostic studies in women who present with atypical symptoms of acute uncomplicated pyelonephritis.Published by
European Association of Urology
Published
2022
Treatment
Summary
Best practice advice from the American College of Physicians on the use of short-course antibiotics in common infections, including uncomplicated acute pyelonephritis in both men and nonpregnant women.Published by
American College of Physicians
Published
2021
Summary
Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. This guideline is currently being updated; projected publication summer 2022.Published by
Infectious Diseases Society of America; European Society for Microbiology and Infectious Disease
Published
2011
Summary
Includes guidance on the management of mild-to-moderate and severe cases of acute pyelonephritis in adults.Published by
European Association of Urology
Published
2022