Acute pyelonephritis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

high index of suspicion with mild-to-moderate symptoms and uncomplicated disease

1st line – empiric oral antibiotic therapy

Back

1st line –

empiric oral antibiotic therapy

Antibiotics should be chosen based on local bacterial sensitivity profiles pending results.

Oral fluoroquinolones and cephalosporins are recommended for empiric treatment of uncomplicated pyelonephritis.[35][54]

In the setting of fluoroquinolone hypersensitivity or if known fluoroquinolone resistance is >10%, an alternative acceptable choice is trimethoprim/sulfamethoxazole.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[57] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

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: In mild cases, 10-14 days of outpatient treatment with oral antibiotics is generally sufficient, and shorter courses of highly active agents (e.g., fluoroquinolones) are also appropriate where fluoroquinolone resistance is <10%.[35][60][61] Guidance from the American College of Physicians also supports the use of short-course antibiotic treatment (e.g., 5-7 days with a fluoroquinolone) for both men and nonpregnant women with uncomplicated pyelonephritis.[59]

Primary options

cefixime: 400 mg orally once daily

ciprofloxacin: 500 mg orally twice daily

ofloxacin: 200-300 mg orally twice daily

Secondary options

levofloxacin: 250-500 mg orally once daily

sulfamethoxazole/trimethoprim: 160 mg orally twice daily

Consider – long-acting parenteral antibiotic

Back

Consider –

long-acting parenteral antibiotic

Treatment recommended for SOME patients in selected patient group

If local bacterial sensitivity profiles are not known, consider adding a onetime intravenous dose of a long-acting antimicrobial, such as ceftriaxone or a consolidated 24-hour dose of an aminoglycoside.[35] This is also recommended in areas where fluoroquinolone resistance is >10%.[35]

Primary options

ceftriaxone: 1 g intravenously as a single dose

gentamicin: 3-5 mg/kg intravenously as a single dose

high index of suspicion with severe symptoms or complicated disease or pregnant patients

1st line – hospitalization and empiric intravenous antibiotic therapy

Back

1st line –

hospitalization and empiric intravenous antibiotic therapy

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; uncertainty about the diagnosis; all pregnant patients. Older and immunocompromised patients, who are at risk for more severe disease, are also usually hospitalized. Appropriate management of the urologic abnormality or the underlying complicating factor is mandatory.

Possible regimens include a fluoroquinolone (e.g., ciprofloxacin, levofloxacin), an extended-spectrum cephalosporin (e.g., ceftriaxone), an aminoglycoside (e.g., gentamicin) with or without ampicillin (if enterococcus is being considered), or an extended-spectrum beta-lactam (e.g., ceftolozane/tazobactam, ceftazidime/avibactam, piperacillin/tazobactam, imipenem/cilastatin, imipenem/cilastatin/relebactam).[10][35][53]

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 as first-line agents to beta-lactam antibiotics.[56] The European Association of Urology (EAU) suggests use of fluoroquinolones only in limited circumstances (e.g., when resistance in the community is <10% and the patient has contraindications for third-generation cephalosporins or an aminoglycoside) 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.[35]

Patients with sepsis or risk of infection with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) organism can be considered for empiric treatment with extended-spectrum beta-lactams. This can further be tailored as susceptibility data becomes available.[11]

Antimicrobial susceptibility of uropathogens in the community will also guide treatment decisions.

In pregnant patients with acute pyelonephritis, the American College of Obstetrics and Gynecology (ACOG) recommends using a broad-spectrum beta-lactam with consideration of the addition of an aminoglycoside (e.g., ampicillin plus gentamicin), or a single-dose cephalosporin (e.g., ceftriaxone). In patients with a penicillin allergy, aztreonam is an appropriate choice.[10] 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.[62][72][73] 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.

Primary options

ceftriaxone: 1 g intravenously every 24 hours

ciprofloxacin: 400 mg intravenously every 12 hours

gentamicin: 5-7 mg/kg intravenously every 24 hours

ampicillin: 1-2 g intravenously every 4-6 hours

and

gentamicin: 5-7 mg/kg intravenously every 24 hours

aztreonam: 1 g intravenously every 8-12 hours

Secondary options

levofloxacin: 750 mg intravenously every 24 hours

ceftolozane/tazobactam: 1.5 g intravenously every 8 hours

imipenem/cilastatin/relebactam: 1.25 g intravenously every 6 hours

piperacillin/tazobactam: 3.375 g intravenously every 6 hours

imipenem/cilastatin: 500 mg intravenously every 6 hours

ceftazidime/avibactam: 2.5 g intravenously every 8 hours

cefiderocol: 2 g intravenously every 8 hours

ACUTE

mild-to-moderate symptoms with uncomplicated disease

1st line – targeted oral antibiotic therapy

Back

1st line –

targeted oral antibiotic therapy

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.

Alternatively, if the organism is known to be susceptible, trimethoprim/sulfamethoxazole or an oral beta-lactam may be used for mild cases.[35][59]

Treatment course: In mild cases, 10-14 days of outpatient treatment with oral antibiotics is generally sufficient, and shorter courses of highly active agents (e.g., fluoroquinolones) are also appropriate where fluoroquinolone resistance is <10%.[35][60][61] Trimethoprim/sulfamethoxazole for 14 days is recommended if the pathogen is known to be susceptible.[35] Guidance from the American College of Physicians recommends short-course (5-7 days) antibiotic treatment with a fluoroquinolone in men or nonpregnant women with uncomplicated pyelonephritis, or 14 days of trimethoprim/sulfamethoxazole, based on antibiotic susceptibility.[59]

Primary options

cefixime: 400 mg orally once daily

ciprofloxacin: 500 mg orally twice daily

ofloxacin: 200-300 mg orally twice daily

Secondary options

levofloxacin: 250-500 mg orally once daily

sulfamethoxazole/trimethoprim: 160 mg orally twice daily

amoxicillin/clavulanate: 875 mg orally twice daily; or 500 mg orally three times daily

severe symptoms or complicated disease or pregnant patients

1st line – hospitalization and targeted intravenous antibiotic therapy

Back

1st line –

hospitalization and targeted intravenous antibiotic therapy

Patients with either severe symptoms (fever >102.2ºF [39.0ºC], not able to take oral medication, volume depleted, early septic hemodynamic parameters, other abnormal laboratory parameters) or complicated disease, and all pregnant patients, should be admitted and treated with intravenous agents.[62][63] Choice of antibiotic agent should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results.[35]

Possible regimens include a fluoroquinolone (e.g. ciprofloxacin, levofloxacin), an extended-spectrum cephalosporin (e.g., ceftriaxone), an aminoglycoside (e.g., gentamicin) with or without ampicillin (if enterococcus is being considered), or an extended-spectrum beta-lactam (e.g., ceftolozane/tazobactam, ceftazidime/avibactam, piperacillin/tazobactam, imipenem/cilastatin, imipenem/cilastatin/relebactam).[10][35][53]

The EAU suggests use of fluoroquinolones only in limited circumstances (e.g., when resistance in the community is <10% and the patient has contraindications for third-generation cephalosporins or an aminoglycoside) 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.[35]

Patients with sepsis or risk of infection with an ESBL-E organism can be considered for treatment with extended-spectrum beta-lactamase inhibitors and further tailored as susceptibility data becomes available.[11]

In pregnant patients with acute pyelonephritis, the ACOG recommends using a broad-spectrum beta-lactam with consideration of the addition of an aminoglycoside (e.g., ampicillin plus gentamicin), or a single-dose cephalosporin (e.g., ceftriaxone). In patients with a penicillin allergy, aztreonam is an appropriate choice.[10] 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.[62][72][73] However, there have been case reports of gentamicin associated with fetal toxicity when used in pregnancy, so caution is advised.

Hospitalized patients should show improvement in 48-72 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.

Treatment course is usually 2 weeks, but the duration of therapy should be adjusted according to the patient's response to treatment.

Transitioning to oral therapy can be considered when susceptibility to an appropriate oral agent is demonstrated, and the patient is clinically improving and hemodynamically stable.[63][53][69]

Primary options

ceftriaxone: 1 g intravenously every 24 hours

ciprofloxacin: 400 mg intravenously every 12 hours

gentamicin: 5-7 mg/kg intravenously every 24 hours

ampicillin: 1-2 g intravenously every 4-6 hours

and

gentamicin: 5-7 mg/kg intravenously every 24 hours

aztreonam: 1 g intravenously every 8-12 hours

Secondary options

levofloxacin: 750 mg intravenously every 24 hours

ceftolozane/tazobactam: 1.5 g intravenously every 8 hours

imipenem/cilastatin/relebactam: 1.25 g intravenously every 6 hours

piperacillin/tazobactam: 3.375 g intravenously every 6 hours

imipenem/cilastatin: 500 mg intravenously every 6 hours

ceftazidime/avibactam: 2.5 g intravenously every 8 hours

cefiderocol: 2 g intravenously every 8 hours

ONGOING

recurrent disease within 1 to 2 weeks

1st line – culture and sensitivity-directed antibiotic therapy

Back

1st line –

culture and sensitivity-directed antibiotic therapy

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.

Primary options

cefixime: 400 mg orally once daily

ciprofloxacin: 500 mg orally twice daily

ofloxacin: 200-300 mg orally twice daily

Secondary options

levofloxacin: 250-500 mg orally once daily

sulfamethoxazole/trimethoprim: 160 mg orally twice daily

amoxicillin/clavulanate: 875 mg orally twice daily; or 500 mg orally three times daily

Use of this content is subject to our disclaimer

Acute pyelonephritis

Treatment algorithm

high index of suspicion with mild-to-moderate symptoms and uncomplicated disease

empiric oral antibiotic therapy

Primary options

Secondary options

long-acting parenteral antibiotic

Primary options

high index of suspicion with severe symptoms or complicated disease or pregnant patients

hospitalization and empiric intravenous antibiotic therapy

Primary options

Secondary options

mild-to-moderate symptoms with uncomplicated disease

targeted oral antibiotic therapy

Primary options

Secondary options

severe symptoms or complicated disease or pregnant patients

hospitalization and targeted intravenous antibiotic therapy

Primary options

Secondary options

recurrent disease within 1 to 2 weeks

culture and sensitivity-directed antibiotic therapy

Primary options

Secondary options