Pyelonephritis Empiric Therapy

Updated: Jan 13, 2022
  • Author: Mony Fraer, MD, MHCDS, FACP, FASN; Chief Editor: Thomas E Herchline, MD  more...
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Patients who are suspected of having pyelonephritis should have a urine culture and susceptibility test performed. [1] Empiric therapy should be adjusted based on the infecting uropathogen. [2, 1]

Empiric therapy regimens described below include the following:

  • Outpatient treatments
  • Inpatient treatments
  • Treatment for pregnant patients

Outpatient Treatment

First-line therapy

Although fluoroquinolones have been the customary choice for first-line empiric therapy, rising rates of resistance and increasing concern about adverse effects from this class of drugs have led to alternative recommendations, such as the following [3] :

  • Cephalexin 500 mg PO 2-3 times a day (up to 1 to 1.5 g 3-4 times a day for severe infections) for 7-10d (for non-pregnant women and men age 16 years and older who are able to take oral antibiotics, and in whom the severity of their condition does not require intravenous antibiotics)
  • Cefuroxime 750 mg to 1.5 g IV 3 times a day (for patients who are vomiting, unable to take oral antibiotics, or severely unwell)

First-line empiric fluoroquinolone therapy is with one of the following:

  • Ciprofloxacin (Cipro) 500 mg PO q12h for 7d
  • Ciprofloxacin extended-release (Cipro XR, Proquin XR) 1000 mg PO q24h for 7d
  • Levofloxacin (Levaquin) 750 mg PO q24h for 5d

If fluoroquinolone resistance in the community is known to be > 10%, then include a single dose of one of the following:

Second-line therapy

Second-line empiric therapy is with trimethoprim/sulfamethoxazole 160/800 mg (Bactrim DS, Septra DS) 1 tablet PO BID for 14d. If trimethoprim is used when the susceptibility is not known, an initial single IV dose of one of the following may also be given:

  • Ceftriaxone 1 g IV
  • Gentamicin 7 mg/kg IV
  • Tobramycin 7 mg/kg IV
  • Amikacin 20 mg/kg IV

Inpatient Treatment

Patients with pyelonephritis who require hospitalization should be treated with one of the IV antimicrobial regimens listed below. The treatment of choice should be based on local resistance data, and the drug regimen should be tailored according to susceptibility results. IV therapy should be given for 24-48 h or until severe symptoms improve. Duration of therapy, inclusive of initial IV therapy,  should be as follows:

  • Ciprofloxacin: 7 d
  • Levofloxacin: 5 d
  • Beta-lactams: 10-14 d.

First-line therapy (fluoroquinolones)

First-line therapy is with one of the following fluoroquinolones:

  • Ciprofloxacin (Cipro) 400 mg IV q12h
  • Levofloxacin (Levaquin) 750 mg IV q24h

Second-line therapy (preferred if patient is critically ill or pregnant)

Extended-spectrum cephalosporins or penicillins:


Monobactam (penicillin allergy):

Third-line therapy (aminoglycosides)

See the list below:

  • Gentamicin 3 mg/kg/day IV/IM in three divided doses or 7 mg/kg/day pulsed dosing or
  • Tobramycin 3 mg/kg/day IV/IM in three divided doses or 7 mg/kg/day pulsed dosing or
  • Amikacin 10 mg/kg/day IV/IM in three divided doses or 20 mg/kg/day pulsed dosing
  • All of the above can be administered with or without ampicillin 500 mg IM/IV q6h

A study of a hospital program promoting aminoglycosides as empiric treatment of pyelonephritis found that first-line use of aminoglycosides was associated with higher rates of in vitro activity and lower overall mortality compared with non-aminoglycoside antibiotics, and with a comparable rate of acute kidney injury. [4]


Treatment During Pregnancy

Inpatient admission is warranted for any pregnant patient with pyelonephritis. Avoid fluoroquinolones and aminoglycosides in pregnant patients.

Antibiotic selection should be based on urine culture sensitivities, if known. Often, therapy must be initiated on an empirical basis, before culture results are available. This requires clinical knowledge of the most common organisms and their practice-specific or hospital-specific sensitivities to medications.

Institution-specific drug resistances should also be considered before a treatment antibiotic is chosen. For instance, with E coli infection alone, resistance to ampicillin can be as high as 28%-39%. Resistance to trimethoprim-sulfamethoxazole has been described as 31%, and resistance to first-generation cephalosporins may be as high as 9-19%.

Therapy should be given for 24-48h or until severe symptoms improve. Duration of therapy should be 10-14d, inclusive of initial IV therapy.

First-line treatment is with one of the extended-spectrum cephalosporins or penicillins listed below:

  • Ampicillin-sulbactam (Unasyn) 1.5 g IV q6h
  • Piperacillin-tazobactam (Zosyn) 3.375 g IV q6h
  • Cefotaxime (Claforan) 1-2 g IV q8h
  • Ceftriaxone (Rocephin) 1 g IV q24h
  • Ceftazidime (Fortaz, Tazicef) 2 g IV q8h