Approach

The main goals of treatment are infection control and symptom reduction. The decision whether to treat the patient empirically, and whether to admit the patient for intravenous antibiotic treatment, should be based on the patient's symptoms and comorbidities.

Treatment setting

Indications for hospitalization include:

  • 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.

Older and immunocompromised patients, who are at risk for more severe disease, are also usually hospitalized.

Empiric antibiotic choices

Treatment should start before the results of blood or urine cultures are received in patients in whom a high suspicion of infection is present to prevent the patient from deteriorating. The empiric choice of antibiotics should be based on severity of disease, history of prior antibiotic use, local bacterial susceptibilities and risk factors for resistance.​[35][52]​​[53]

There is increasing resistance to the oral antibiotics currently recommended for the empiric treatment of uncomplicated pyelonephritis; these include oral fluoroquinolones and cephalosporins.​[35][54][55]​ However, one systematic review looking at the efficacy of cephalosporins for the treatment of uncomplicated acute pyelonephritis from 2010 to 2022 showed that cephalosporins continue to be an effective treatment option and not inferior to fluoroquinolones or trimethoprim/sulfamethoxazole.[54]

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.[56] Prescription of a reduced dosage of gentamicin in patients with a decline in renal function is advisable. Antimicrobial susceptibility of uropathogens in the community will also guide treatment decisions.

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.

Mild-to-moderate and uncomplicated pyelonephritis

These patients are able to take oral medication and are hemodynamically stable, and other laboratory parameters are essentially normal. Treatment is with oral antibiotics. Possible antibiotic regimens include fluoroquinolones, cephalosporins, and sulfonamides.​[35][54][58][59]​​​​​​​ Up to 10-14 days of outpatient treatment with oral antibiotics is generally sufficient in mild cases.​[35]​ Courses of highly active agents (e.g., fluoroquinolones) as short as 5-7 days may be sufficient for mild or moderate cases in areas where fluoroquinolone resistance is <10%.[35][60][61]​​ If local bacterial sensitivity profiles are not known or in areas where fluoroquinolone resistance is >10%, a onetime intravenous dose of a long-acting antimicrobial such as ceftriaxone or a consolidated 24-hour dose of an aminoglycoside, can be considered at the initiation of therapy.​[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, depending on antibiotic susceptibility.[59] Routine post-treatment urine cultures in asymptomatic patients are not required.

Severe and complicated pyelonephritis

Patients with pyelonephritis, and with severe symptoms (fever >102.2°F [39.0°C], not able to take oral medication, volume depleted, early septic hemodynamic parameters, other abnormal laboratory parameters), complicated disease, and/or all pregnant patients, should be admitted and treated with intravenous agents.[10][62][63]​​​​ Older and immunocompromized patients, who are at risk for more severe disease, are also usually hospitalized. Blood and urine cultures should be obtained. The choice of antibiotic regimen should be based on culture results where available and local resistance patterns. Treatment should not be delayed while awaiting culture results but therapy should be adjusted where needed when available.[10]​ 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]​​​​ 

Antimicrobial-resistant (AMR) infections leading to severe and complicated pyelonephritis are increasing. This includes infections caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P aeruginosa).[53][64]​​​​​​ Patients with sepsis or risk of infection with an 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]​ For example, ceftolozane/tazobactam is likely to be effective against ESBL-E, but recent studies suggest preserving it for the treatment of DTR P aeruginosa or polymicrobial infections (e.g., both DTR P aeruginosa and ESBL-E).[53]​ The European Association of Urology suggests use of fluoroquinolones only in limited circumstances (e.g., when resistance in the community is <10% and the patient has a contraindications to a third-generation cephalosporin or 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]​

Historically, treatment consisted of intravenous antibiotics for 6 weeks. Studies later showed that a 2-week course of therapy was often sufficient for bacteriologic cure and improvement of symptoms.[65][66] One randomized noninferiority study showed that stopping effective nonfluoroquinolone antibiotics following clinical improvement at day 7 was noninferior to continued treatment until day 14 in selected patients with acute pyelonephritis requiring hospitalization.[67]​ ​However, other studies and systematic reviews assessing the evidence for shorter versus longer duration antibiotic treatment have revealed conflicting results and high quality trials assessing strategies to shorten antibiotic treatment duration for bacterial infections in secondary care settings should now be a priority.[67][68]​​ 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.[53][63]​​[69]

Further complications seen with severe acute pyelonephritis include obstruction requiring catheterization, sepsis, renal failure, abscess formation, and antibiotic failure. Follow-up urine cultures are recommended several weeks after completion of treatment, in order to document bacteriologic cure.

Pregnancy

Pregnant women found to have asymptomatic bacteriuria on screening should be treated to ensure eradication of the bacteria.[10][35][62]​​[70]​ However, there is some uncertainty regarding the most effective duration of antibiotic treatment. [ Cochrane Clinical Answers logo ] [Evidence C]​ The American College of Obstetricians and Gynecologists (ACOG) recommends a 5 to 7-day course of targeted antibiotics to treat asymptomatic bacteriuria in pregnancy with colony counts of 100,000 CFU/mL or higher.[10]

In pregnant patients with acute pyelonephritis, the ACOG recommends a 14-day course of antibiotic therapy, but with clinical improvement patients can be transitioned from intravenous antibiotics to appropriate oral therapy to complete this. First-line antimicrobial management includes 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). For patients with a penicillin allergy, aztreonam is an appropriate choice.[10]​ Cure rates are high for pregnant women treated with antibiotics; however, recurrent pyelonephritis occurs in up to 25% of pregnant patients before delivery.[10][71] Urine culture should be obtained after completion of antibiotics to ensure no residual infection.[10]

Recurrent disease

Recurrence usually occurs within 1-2 weeks. The most likely cause of recurrence is insufficient duration of initial treatment. Other possibilities include development of antibiotic resistance or selection for another organism. Repeat urine culture and antimicrobial susceptibility testing is indicated. If, on repeat culture, the bacterial strain and susceptibility profile are the same, a complicating factor should be considered.[35] A renal ultrasound or computed tomographic scan should be obtained to assess for any anatomic or functional genitourinary pathology interfering with treatment. Retreatment can be with either a longer treatment course of the same antibiotic as used in initial therapy or a different antibiotic treatment.

Use of this content is subject to our disclaimer