Katelin M. Lisenby, PharmD, BCPS, Dana G. Carroll, PharmD, BCPS, CDE, CGP and Catherine Scarbrough, MD, MSc, FAAFP Reviewed 06/2017

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Subject: Pyelonephritis

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  • Acute pyelonephritis is a syndrome caused by an infection of the renal parenchyma and renal pelvis, often producing localized flank/back pain combined with systemic symptoms, such as fever, chills, and nausea. It has a wide spectrum of presentation, from mild illness to septic shock.

  • Chronic pyelonephritis is the result of progressive inflammation of the renal interstitium and tubules, due to recurrent infection, vesicoureteral reflux, or both.

  • Pyelonephritis is considered uncomplicated if the infection is caused by a typical pathogen in an immunocompetent patient who has normal urinary tract anatomy and renal function.

  • System(s) affected: renal; urologic

  • Synonym: acute upper urinary tract infection (UTI)

Geriatric Considerations

  • May present as altered mental status; absence of fever is common in this age group.

  • Elderly patients with diabetes and pyelonephritis are at higher risk of bacteremia, longer hospitalization, and mortality.

  • The high prevalence of asymptomatic bacteriuria in the elderly makes the use of urine dipstick less reliable for diagnosing UTI in this population 1[A].

Pregnancy Considerations

  • Most common medical complication requiring hospitalization

  • Affects 1-2% of all pregnancies. Morbidity does not differ between trimesters.

  • Urine culture as test of cure 1 to 2 weeks after therapy

Pediatric Considerations

  • UTI is present in ~5% of patients age 2 months to 2 years with fever and no apparent source on history and physical exam.

  • Treatment (oral or IV; inpatient or outpatient) should be based on the clinical situation and patient toxicity.



Community-acquired acute pyelonephritis: 28/10,000/year 


Adult cases: 250,000/year, with 200,000 hospitalizations 


  • Escherichia coli (>80%)

  • Other gram-negative pathogens: Proteus, Klebsiella, Serratia, Clostridium, Pseudomonas, and Enterobacter

  • Enterococcus

  • Staphylococcus: Staphylococcus epidermis, Staphylococcussaprophyticus (number 2 cause in young women), and Staphylococcus aureus

  • Candida


  • Underlying urinary tract abnormalities

  • Indwelling catheter/recent urinary tract instrumentation

  • Nephrolithiasis

  • Immunocompromise, including diabetes

  • Elderly, institutionalized patients (particularly women)

  • Prostatic enlargement

  • Childhood UTI

  • Acute pyelonephritis within the prior year

  • Frequency of recent sexual intercourse; spermicide use; new sex partner within the prior year

  • Stress incontinence in the previous 30 days

  • Pregnancy

  • Hospital-acquired infection

  • Symptoms >7 days at time of presentation


  • Indwelling catheters

  • Renal calculi

  • Benign prostatic hyperplasia



  • In adults

    • ▪ Fever
    • ▪ Flank pain
    • ▪ Nausea ± vomiting
    • ▪ Malaise, anorexia
    • ▪ Myalgia
    • ▪ Dysuria, urinary frequency, urgency
    • ▪ Suprapubic discomfort
    • ▪ Mental status changes (elderly)
  • In infants and children

    • ▪ Fever
    • ▪ Irritability and poor feeding
    • ▪ GI symptoms


  • In adults

    • ▪ Fever: ≥38ºC (100.4ºF)
    • ▪ Costovertebral angle tenderness
    • ▪ Presentation ranges from no physical findings to septic shock.
    • ▪ Mental status changes common in the elderly
    • ▪ A pelvic exam may be necessary in female patients to exclude pelvic inflammatory disease.
  • In infants and children

    • ▪ Sepsis
    • ▪ Fever
    • ▪ Poor skin perfusion
    • ▪ Inadequate weight gain/weight loss
    • ▪ Jaundice to gray skin color


  • Obstructive uropathy

  • Acute bacterial pneumonia (lower lobe)

  • Cholecystitis

  • Acute pancreatitis

  • Appendicitis

  • Perforated viscus; aortic dissection

  • Pelvic inflammatory disease; ectopic pregnancy

  • Kidney stone

  • Diverticulitis


Initial Tests (lab, imaging)

  • Urinalysis: pyuria ± leukocyte casts, hematuria, nitrites (sensitivity 35-85%; specificity 92-100%), and mild proteinuria

  • Urine leukocyte esterase positive (sensitivity 74-96%; specificity 94-98%)

  • Urine Gram stain; urine culture (>100,000 colony-forming units/mL or >100 colony forming units/mL + symptoms) and sensitivities

  • CBC, BUN, Cr, GFR, and pregnancy test (if indicated)

  • C-reactive protein levels have been shown to correlate with prolonged hospitalization and recurrence; serum albumin ≪3.3 g/dL also associated with risk for hospital admission.

  • Imaging not necessary in routine cases

  • Pediatrics: Recent guidelines recommend renal/bladder US (not voiding cystourethrogram), after first UTI.

Follow-Up Tests & Special Considerations

  • Catheterization/suprapubic aspirate should be used to obtain samples from non-toilet-trained children.

  • Catheterization may also be necessary for some geriatric patients.

  • Blood culture(s): indicated if diagnostic uncertainty, immunosuppression, or a suspected hematogenous source

  • Recent antibiotic use may alter lab results.

  • If patient’s condition does not improve within 72 hours, if obstruction/anatomic abnormality suspected, or if certain lab abnormalities are present (urine pH >7, GFR ≪40, 50% decline in renal function), consider:

    • ▪ CT scan of abdomen and pelvis ± contrast
    • ▪ US of kidneys, ureter, bladder
    • ▪ Cystoscopy with ureteral catheterization

Test Interpretation

  • Acute: abscess formation with neutrophil response

  • Chronic: fibrosis with reduction in renal tissue


  • ≤7 days of treatment is equivalent to longer regimens in adults (including those with bacteremia) without urogenital abnormalities 2[A].

  • IV antibiotics are indicated for inpatients who are toxic appearing or unable to tolerate oral antibiotics.


  • Broad-spectrum antibiotics initially, tailor therapy to culture and sensitivity results

  • Analgesics and antipyretics

  • Consider urinary analgesics (e.g., phenazopyridine 200 mg q8h) for dysuria.


  • For empiric oral therapy, a fluoroquinolone is recommended. Should fluoroquinolone resistance exceed 10% or the patient has nausea/vomiting, a single initial IV dose of a long-acting antibiotic such as ceftriaxone 1 g is additionally recommended.

  • For parenteral therapy, fluoroquinolone, aminoglycoside ± ampicillin, an extended-spectrum cephalosporin with or without a β-lactamase inhibitor, an extended-spectrum penicillin with or without an aminoglycoside, or a carbapenem are recommended.

  • Contraindications:

    • ▪ Known drug allergy
    • ▪ Fluoroquinolones are not recommended in children, adolescents, and pregnant women unless other alternatives are not available.
    • Nitrofurantoin does not achieve reliable tissue levels for treatment of pyelonephritis.
  • Precautions

    • ▪ Most antibiotics require adjustments in dosage for patients with renal insufficiency.
    • ▪ Monitor aminoglycoside levels and renal function.
    • ▪ If Enterococcus is suspected based on Gram stain, ampicillin ± gentamicin is a reasonable empiric choice; unless patient is penicillin-allergic, then use vancomycin. If outpatient, add amoxicillin to fluoroquinolone, pending culture results and sensitivity. Do not use a 3rd-generation cephalosporin for suspected/proven enterococcal infections.
    • ▪ >20% E. coli strains are resistant to ampicillin and TMP-SMX in community-acquired infections.

First Line

  • Adults

    • ▪ Oral (initial outpatient treatment)
    • ▪ Trimethoprim-sulfamethoxazole (TMP-SMX) (160/800 mg): 1 tab q12h for 14 days provided uropathogen known to be susceptible ± ceftriaxone 1 g initial IV dose given IV (assuming normal creatinine clearance [CrCl])
    • ▪ Severe illness: IV therapy until afebrile 24 to 48 hours and tolerating oral hydration and medications, then oral agents to complete up to a 2-week course
  • Pediatric

    • ▪ Oral: cefdinir: 14 mg/kg/day for 10 to 14 days; ceftibuten 9 mg/kg/day for 10 to 14 days; cefixime 8 mg/kg/day for 10 to 14 days
    • ▪ IV (general indication for IV therapy is age ≪2 months or clinical concern in other ages)
      • * Ceftriaxone: 75 mg/kg/day (also can be used IM in outpatient setting)
      • * Cefotaxime: 150 mg/kg/day divided in 3 to 4 doses
      • * Ampicillin: 100 mg/kg/day divided in 4 doses + gentamicin 7.5 mg/kg/day divided in 3 doses

Second Line

  • Oral

    • ▪ Oral β-lactams should be used with caution due to inferior efficacy and higher relapse rates; if used, provide an initial IV dose of ceftriaxone or a consolidated 24-hour dose of an aminoglycoside; longer courses of therapy (10 to 14 days) recommended
    • Cefpodoxime (Proxetil): 200 mg q12h
    • ▪ Amoxicillin-clavulanate: 875/125 mg q12h or 500/125 mg q8h
  • IV

    • ▪ Piperacillin-tazobactam: 3.375 g q6-8h
    • ▪ Ticarcillin-clavulanate: 3.1 g q4-6h
    • Meropenem: 500 mg q12h
    • ▪ Ceftolazone-tazobactam: 1.5 g q8h

Pediatric Considerations

  • Treat children ≪2 years of age and children with febrile or recurrent UTI for 10 to 14 days.

  • Initial empiric antibiotic choice should cover E. coli. Add ampicillin if Enterococcus is suspected.

    • ▪ Oral antibiotics (ceftibuten, cefixime, and amoxicillin/clavulanic acid) may be used alone, or
    • ▪ IV antibiotics (single daily dosing if an aminoglycoside is chosen) for 2 to 4 days, followed by oral antibiotics for a total of 10 to 14 days 3[A]
  • Complete outpatient antibiotic course in entirety


  • Acute pyelonephritis unresponsive to therapy

  • Chronic pyelonephritis

  • Abnormal urogenital anatomy


Perinephric abscess may require surgical drainage. 


  • Inpatient therapy for severe illness (e.g., high fevers, severe pain, marked debility, intractable vomiting, inability to tolerate oral intake, possible sepsis), risk factors for complicated pyelonephritis, pregnancy, or extremes of age

  • Outpatient therapy if mild to moderate illness (not pregnant, no nausea/vomiting; fever and pain not severe), uncomplicated, and tolerating oral hydration and medications. Many patients can be treated as outpatients.

  • IV fluids as indicated for dehydration or renal calculi

  • Discharge on oral agent after patient is afebrile 24 to 48 hours to complete up to 2 weeks of therapy.



  • Women: Routine follow-up cultures not recommended unless symptoms recur after 2 weeks; then, urologic evaluation is necessary.

  • Men, children, adolescents, patients with recurrent infections, patients with risk factors: repeat cultures 1 to 2 weeks after completing therapy; urologic evaluation after first episode of pyelonephritis and with recurrences

Patient Monitoring

  • No response within 48 hours (5% of patients): Reevaluate and review cultures, CT scan, or US to review anatomy; adjust therapy as needed; urologic consult. The two most common causes of failure to respond are a resistant organism and nephrolithiasis.

  • Work with parents to monitor response in children.


Encourage fluid intake. 


95% of treated patients respond within 48 hours. 


  • Kidney abscess

  • Metastatic infection: skeletal system, endocardium, eye, meningitis with subsequent seizures

  • Septic shock and death

  • Acute/chronic renal failure


Ninan  S, Walton  C, Barlow  G. Investigation of suspected urinary tract infection in older people. BMJ.  2014;349:g4070.  [View Abstract]
Eliakim-Raz  N, Yahav  D, Paul  M, et al. Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection—7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother.  2013;68(10):2183–2191.  [View Abstract]
Strohmeier  Y, Hodson  EM, Willis  NS, et al. Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev.  2014;(7):CD003772.  [View Abstract]


  • Beetz R, Westenfelder M. Antimicrobial therapy of urinary tract infections in children. Int J Antimicrob Agents.  2011;38(Suppl):42–50.

  • Goel RH, Unnikrishnan R, Remer EM. Acute urinary tract disorders. Radiol Clin N Am.  2015;53(6):1273–1292.

  • 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(5):e103–e120.

  • Noelle L. Urinary tract infections in older adults. Clin Geri Med.  2016;32:532–538.

  • Roberts KB; and the Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics.  2011;128(3):595–610.

  • Takhar SS, Moran GJ. Diagnosis and management of urinary tract infection in the emergency department and outpatient settings. Infect Dis Clin North Am.  2014;28(1):33–48.

  • Wagenlehner FM, Umeh O, Steenbergen J, et al. Ceftolazone-tazobactam compared to levofloxacin in treatment of complicated urinary tract infections, including pyelonephritis: a randomized, double-blind, phase 3 trial (ASPECT-cUTI). Lancet.  2015;385(9981):1949–1956.

  • Wang A, Nizran P, Malone MA, et al. Urinary tract infections. Prim Care.  2013;40(3):687–706.



  • N12 Tubulo-interstitial nephritis, not spcf as acute or chronic

  • N10 Acute tubulo-interstitial nephritis

  • N11.9 Chronic tubulo-interstitial nephritis, unspecified

  • N11.8 Other chronic tubulo-interstitial nephritis

  • N11.1 Chronic obstructive pyelonephritis


  • 590.80 Pyelonephritis, unspecified

  • 590.10 Acute pyelonephritis without lesion of renal medullary necrosis

  • 590.00 Chronic pyelonephritis without lesion of renal medullary necrosis

  • 590.11 Acute pyelonephritis with lesion of renal medullary necrosis

  • 590.01 Chronic pyelonephritis with lesion of renal medullary necrosis


  • 45816000 Pyelonephritis (disorder)

  • 197768004 Acute pyelonephritis without medullary necrosis (disorder)

  • 197760006 Chronic pyelonephritis without medullary necrosis (disorder)

  • 197769007 Acute pyelonephritis with medullary necrosis (disorder)

  • 197761005 Chronic pyelonephritis with medullary necrosis (disorder)


  • Pyelonephritis can present with isolated confusion or mental status changes (no fever) in the elderly.

  • The most common causes of poor response to treatment are antibiotic resistance and coexisting nephrolithiasis.

  • Fluoroquinolones are generally the initial drugs of choice for treating pyelonephritis. Oral β-lactams are less effective, with the exception that parental β-lactams may be preferred in cases of complicated urinary tract infections.