Acute Pyelonephritis

Aka: Acute Pyelonephritis, Pyelonephritis

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II. Definitions

  1. Pyelonephritis
    1. Upper Urinary Tract Infection involving Kidney

III. Epidemiology

  1. Accounts for 200,000 hospitalizations annually in U.S
  2. Highest Incidence in otherwise healthy women ages 15 to 29 years

IV. Causes

  1. Ascending infection via Bladder and ureter (most cases)
  2. Hematogenous spread
    1. Prostatitis or Benign Prostatic Hyperplasia
    2. Serious comorbid chronic illness
    3. Immunocompromised patients
    4. Hematogenous spread of staph. or fungal infection

V. Etiologies

  1. Normal host
    1. Escherichia coli (80-90%)
    2. Klebsiella Pneumoniae (3-6%)
    3. Staphylococcus Saprophyticus (<3%)
    4. Other Gram Negative Bacteria (e.g. Proteus, Enterobacter)
    5. Enterococcus
  2. Elderly
    1. Escherichia coli (60%)
    2. Proteus
    3. Klebsiella
    4. Serratia
    5. Pseudomonas
  3. Urinary Catheter associated infection
    1. Bacteriuria in 50% at 5 days, and 100% at 30 days
    2. Mixed Bacterial Infection
  4. Diabetes Mellitus
    1. Klebsiella
    2. Enterobacter
    3. Clostridium
    4. Candida
  5. Immunosuppression
    1. Aerobic, Gram Negative Rods (non-enteric)
    2. Candida

VI. Risk Factors: Pyelonephritis in women

  1. Frequent sexual intercourse in prior month (3 times weekly)
  2. New sexual partner in the last year
  3. Recent Spermicide use
  4. Family History of Urinary Tract Infections (esp in patient's mother)
  5. Prior Urinary Tract Infections in the last year
  6. Diabetes Mellitus
  7. Stress Incontinence in the last 30 days

VII. Risk Factors: Antibiotic Resistance (Multi-Drug Resistance)

  1. Frequent medical care
  2. Advanced age
  3. Diabetes Mellitus
  4. Recurrent Urinary Tract Infections
  5. Indwelling Urinary Catheter
  6. Urologic Abnormalities
  7. Hospitalization within last 3 months
  8. Travel outside the United States in last 30 days
  9. Recent Antibiotic use within last 3 months
    1. Fluoroquinolones
    2. Cephalosporins
    3. Antipseudomonal Penicillins
  10. History of multi-drug resistant urine isolates
    1. Extended-Spectrum Beta Lactamase Producing Organisms (ESBL Resistance)

VIII. Risk Factors: Complicated Pyelonephritis (with higher risk of complications such as abscess, Antibiotic Resistance)

  1. Age under 1 or over 60 years
  2. Urologic Abnormality
    1. Polycystic Kidney
    2. Vesicoureteral reflux
  3. Urinary Tract Obstruction
    1. Ureterolithiasis
    2. Benign Prostatic Hyperplasia
    3. Urinary tract tumor
  4. Immunocompromised State
    1. Diabetes Mellitus
    2. HIV Infection
    3. Corticosteroids
    4. Sickle Cell Anemia
    5. Organ Transplant
  5. Indwelling Urinary Catheter
  6. Pregnancy
  7. Male gender

IX. Symptoms

  1. Fever
  2. Chills and malaise
  3. Flank Pain
  4. Nausea and Vomiting
  5. Abdominal Pain or Suprapubic Pain
  6. Acute Cystitis symptoms (absent in 20% of cases)
    1. Dysuria
    2. Urinary Frequency
    3. Urinary urgency

X. Signs

  1. Fever
  2. Costovertebral Angle Tenderness
  3. Abdominal tenderness (esp. suprapubic tenderness)
  4. Sepsis signs
    1. Tachycardia
    2. Hypotension

XI. Diagnosis

  1. Fever over 100.4 F
    1. May be absent early in course
    2. Not uniformly present in elderly (only in 80%)
    3. Not uniformly present in catheter-associated UTI
  2. Flank Pain
  3. Urinalysis with bacteriuria or pyuria

XII. Labs

  1. Urinalysis
    1. Leukocyte esterase or nitrite positive
    2. Microscopic Hematuria may be present (contrast with Gross Hematuria in Acute Cystitis)
    3. Microscopic examination may show WBC Casts
    4. Consider urine Gram Stain where available
      1. Gram Positive Cocci suggests Enterococcus or Staphylococcus Saprophyticus
  2. Urine Culture (positive in 90% of Pyelonephritis)
    1. Manditory in all suspected cases of Pyelonephritis (before Antibiotics given)
    2. Diagnosis requires at least 10,000 CFU/mm3
    3. Consider lower threshold in men and in pregnancy
  3. Blood Culture indications (positive in 10-40% cases, obtain in severe infection or hospitalized patients)
    1. Immunocompromised patient
    2. Unclear diagnosis
    3. Hematogenous source suspected
    4. Failure to improve after 48-72 hours
    5. Predominant organism not clear with Urine Culture
      1. Indwelling catheterization
      2. Antibiotic use preceded Urine Culture
  4. Other labs
    1. Urine Pregnancy Test
    2. Basic metabolic panel with Serum Creatinine
    3. Complete Blood Count
    4. Other testing as indicated by differential diagnosis in unclear cases

XIII. Imaging

  1. Indications
    1. Not routinely indicated in uncomplicated Pyelonephritis
    2. Recurrent or refractory infections
    3. Critical Illness (i.e. Sepsis)
    4. New Acute Renal Failure (GFR <40 ml/min)
    5. Suspected Ureteral Stone (infected Ureteral Stone requires emergent intervention)
    6. Known urologic abnormalities
    7. Failed response to Antibiotics after 48 to 72 hours
  2. Modalities
    1. CT Abdomen with contrast (preferred in non-pregnant patients)
    2. Renal Ultrasound (pregnant patients)
    3. Renal MRI (specific indications as directed by local Consultation)

XIV. Differential Diagnosis

  1. Pelvic Inflammatory Disease
  2. Acute Cholecystitis
  3. Appendicitis
  4. Pneumonia

XV. Disposition: Hospitalization indications

  1. Inability to stay hydrated and take medications orally
  2. Failed outpatient management
  3. Pregnancy (some cases may be treated outpatient)
    1. High morbidity and mortality compared with other cohorts (Sepsis occurs in up to 17% of cases)
    2. High risk of recurrence
  4. Severe illness
    1. Sepsis or Toxic appearance
    2. High fever (>103 F)
  5. Severe, intractable flank or Abdominal Pain
  6. Comorbidity, esp. if unstable (relative indications)
    1. Diabetes Mellitus
    2. Underlying urologic or renal disorder
    3. Severe liver disease
    4. Severe heart disease
    5. Debilitated condition
  7. Other (relative indications)
    1. Noncompliance
    2. Uncertain diagnosis
    3. Male gender

XVI. Management: Pregnancy

  1. See Pyelonephritis in Pregnancy

XVII. Management: General Measures

  1. Treat as Sepsis if consistent with presentation
  2. Oral or Intravenous Fluid hydration
  3. Analgesics and antipyretics
    1. NSAIDs
    2. Acetaminophen
  4. Antiemetics
    1. Ondansetron

XVIII. Management: Oral agents for acute uncomplicated non-pregnant cases

  1. Outpatient management with oral Antibiotic indications
    1. Tolerating oral Antibiotics and oral fluids (with or without oral Antiemetics)
    2. No signs of Sepsis
    3. Non-pregnant
    4. No absolute hospitalization indications (see above)
  2. Treatment course
    1. Course 7 days
      1. Uncomplicated Pyelonephritis
      2. Fluoroquinolones course is typically 7 days in all Pyelonephritis cases
        1. Eliakim-Raz (2013) J Antimicrob Chemother 68(10):2183-91 [PubMed]
    2. Course 10-14 days
      1. Complicated Pyelonephritis
        1. Urinary Tract Obstruction
        2. Male gender
        3. Immunosuppression
      2. Beta-Lactams (Augmentin, Cephalosporins) course is typically 10-14 days
      3. Trimethoprim-Sulfamethoxazole course is typically 14 days
  3. Consider a single initial dose of IV Antibiotics if Emesis or community Antibiotic Resistance>10% (see below)
    1. Ceftriaxone 1-2 g IV or
    2. Ertapenem (Invanz) 1 g IV or
    3. Gentamicin 5 mg/kg IV or
    4. Plazomicin (Zemdril) 15 mg/kg
  4. Preferred agents: Fluoroquinolones (if community E. coli resistance rate <10%)
    1. See Fluoroquinolone for associated adverse effects (Informed Consent with patient)
    2. Ciprofloxacin 500 mg orally twice daily for 7 days
    3. Ciprofloxacin XR 1000 mg daily for 7 days
    4. Levofloxacin 750 mg orally daily for 7 days
  5. Preferred agent: Trimethoprim-Sulfamethoxazole
    1. Trimethoprim-Sulfamethoxazole (Bactrim) twice daily for 14 days
  6. Alternative agents (higher resistance rates, accompany with initial dose of a broad spectrum IV Antibiotic)
    1. Amoxicillin-Clavulanate (Augmentin) twice daily for 10-14 days
    2. Cefixime (Suprax) 400 mg orally daily for 10-14 days
    3. Cefpodoxime 200 mg orally twice daily for 10-14 days
    4. Cephalexin (Keflex) 500 mg orally twice daily for 10-14 days
  7. Precautions
    1. Do NOT use Nitrofurantoin or fosfomycin
      1. Inadequate renal penetration to treat Pyelonephritis

XIX. Management: IV agents in non-pregnant patients

  1. Duration of treatment
    1. Convert from IV to oral in first 48-72 hours
  2. Preferred Agents: Patients at LOW risk for Bacterial resistance
    1. Ciprofloxacin 400 mg IV every 12 hours
    2. Levofloxacin (Levaquin) 750 mg IV every 24 hours
    3. Ceftriaxone (Rocephin) 1 to 2 g IV q24 hours
  3. Preferred Agents: Patients at HIGH risk for multi-drug Bacterial resistance
    1. Ertapenem 1 g IV every 24 hours
    2. Meropenem 1 g IV every 8 hours
    3. Piperacillin-Tazobactam (Zosyn) 3.375 to 4.5 g IV every 6 hours
    4. Cefepime 2 g IV every 12 hours
    5. Ceftazidime/Avibactam (Avycaz) 2.5 g every 8 hours
    6. Ceftolozane/Tazobactam 1.5 g IV every 8 hours
    7. Imipenem/Cilastin (Primaxin) 500 mg every 6 hours
    8. Meropenem/Vaborbactam (Vabomere) 2 g every 8 hiurs
    9. Plazomicin (Zemdril) 15 mg/kg IV every 24 hours
  4. Alternative regimens
    1. Gentamicin 5 mg/kg IV every 24 hours

XX. Complications

  1. Perinephric Abscess
    1. May also occur secondary to Staphylococcus Aureus bacteremia
  2. Emphysematous Pyelonephritis
    1. Occurs in older women with Diabetes Mellitus
    2. Infection produces intraparenchymal gas
    3. Associated with papillary necrosis and Renal Failure
  3. Urinary Tract Infection due to obstruction
    1. Associated with Ureterolithiasis, BPH, or tumor
    2. May result in renal abscess and severe infection
    3. Infected Ureteral Stone requires emergent surgical intervention (decompression, e.g. Ureteral Stenting)
  4. Malacoplakia (rare)

XXI. References

  1. (2019) Sanford Guide, accessed on IOS 10/19/2019
  2. Escobar in Marx (2002) Rosen's Emergency Med, p. 1401
  3. Colgan (2011) Am Fam Physician 84(5): 519-26 [PubMed]
  4. Gupta (2011) Clin Infect Dis 52(5):e103-20 +PMID:21292654 [PubMed]
  5. Herness (2020) Am Fam Physician 102(3):173-80 [PubMed]
  6. Hooton (2003) Infect Dis Clin North Am 17(2):303-32 [PubMed]
  7. Ramakrishnan (2005) Am Fam Physician 71(5):933-42 [PubMed]
  8. Roberts (1999) Urol Clin North Am 26:753-63 [PubMed]

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