> Table of Contents > PYELONEPHRITIS
PYELONEPHRITIS
Katelin M. Lisenby, PharmD
Dana G. Carroll, PharmD, BCPS, CDE
Catherine Scarbrough, MD
image BASICS
DESCRIPTION
  • 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 in 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.
EPIDEMIOLOGY
Incidence
Community-acquired acute pyelonephritis: 28/10,000/year
Prevalence
Adult cases: 250,000/year, with 200,000 hospitalizations
ETIOLOGY AND PATHOPHYSIOLOGY
  • Escherichia coli (>80%)
  • Other gram-negative pathogens: Proteus, Klebsiella, Serratia, Clostridium, Pseudomonas, and Enterobacter
  • Enterococcus
  • Staphylococcus: Staphylococcus epidermis, Staphylococcus saprophyticus (number 2 cause in young women), and Staphylococcus aureus
  • Candida
RISK FACTORS
  • 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
COMMONLY ASSOCIATED CONDITIONS
  • Indwelling catheters
  • Renal calculi
  • Benign prostatic hyperplasia
image DIAGNOSIS
PHYSICAL EXAM
  • In adults
    • Fever: ≥38°C (100.4°F)
    • 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
DIFFERENTIAL DIAGNOSIS
  • Obstructive uropathy
  • Acute bacterial pneumonia (lower lobe)
  • Cholecystitis
  • Acute pancreatitis
  • Appendicitis
  • Perforated viscus; aortic dissection
  • Pelvic inflammatory disease; ectopic pregnancy
  • Kidney stone
  • Diverticulitis
DIAGNOSTIC TESTS & INTERPRETATION
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 colonyforming 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.
  • In some geriatric patients catheterization may also be necessary.
  • Blood culture(s): indicated in 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 or if obstruction/anatomic abnormality suspected, 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
image TREATMENT
  • 7 days or less of treatment is equivalent to longer treatment regimens in adult patients (including those with bacteremia) without urogenital abnormalities (2)[A].
  • IV antibiotics are indicated for inpatients who are toxic or unable to tolerate oral antibiotics.
GENERAL MEASURES
  • 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.
MEDICATION
  • For empiric oral therapy, a fluoroquinolone is recommended. Should fluoroquinolone resistance exceed 10% or the patient have 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 or 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.
    • P.889

    • 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 third 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)
      • Ciprofloxacin: 500 mg q12h for 7 days
      • Ciprofloxacin XR: 1,000 mg/day for 7 days
      • Levofloxacin: 750 mg/day for 5 days
    • 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])
      • Ciprofloxacin: 400 mg q12h
      • Levofloxacin: 750 mg/day
      • Cefotaxime: 1 g q8-12h up to 2 g q4h
      • Ceftriaxone: 1 to 2 g/day
      • Cefepime: 1 to 2 g q12h
      • Gentamicin: 5 to 7 mg/kg of body weight daily
      • Ampicillin: 2 g q6h ± gentamicin for Enterococcus
    • 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
Adults
  • Oral
    • Oral &bgr;-lactams should be used with caution to treat pyelonephritis 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 and 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
Pediatric Considerations
  • Children <2 years of age and children with febrile or recurrent UTI are usually treated 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
ISSUES FOR REFERRAL
  • Acute pyelonephritis unresponsive to therapy
  • Chronic pyelonephritis
  • Abnormal urogenital anatomy
SURGERY/OTHER PROCEDURES
Perinephric abscess may require surgical drainage.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • 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 Criteria
Discharge on oral agent after patient is afebrile 24 to 48 hours to complete up to 2 weeks of therapy.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • 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.
DIET
Encourage fluid intake.
PROGNOSIS
95% of treated patients respond within 48 hours.
REFERENCES
1. Ninan S, Walton C, Barlow G. Investigation of suspected urinary tract infection in older people. BMJ. 2014;349:g4070.
2. 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.
3. Strohmeier Y, Hodson EM, Willis NS, et al. Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev. 2014;(7):CD003772.
Additional Reading
&NA;
  • Beetz R, Westenfelder M. Antimicrobial therapy of urinary tract infections in children. Int J Antimicrob Agents. 2011;38(Suppl):42-50.
  • Colgan R, Williams M, Johnson JR. Diagnosis and treatment of acute pyelonephritis in women. Am Fam Physician. 2011;84(5):519-526.
  • 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.
  • Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012;366(11):1028-1037.
  • Kang C, Kim K, Lee SH, et al. A risk stratification model of acute pyelonephritis to indicate hospital admission from the ED. Am J Emerg Med. 2013;31(7):1067-1072.
  • Roberts KB. 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.
  • Wang A, Nizran P, Malone MA, et al. Urinary tract infections. Prim Care. 2013;40(3):687-706.
Codes
&NA;
ICD10
  • N12 Tubulo-interstitial nephritis, not spcf as acute or chronic
  • N10 Acute tubulo-interstitial nephritis
  • N11.9 Chronic tubulo-interstitial nephritis, unspecified
Clinical Pearls
&NA;
  • 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 the initial drugs of choice. for treating pyelonephritis. Oral &bgr;-lactams are less effective.