Pyelonephritis

Acute pyelonephritis is a bacterial infection of the renal pelvis and kidney, most commonly caused by ascending Escherichia coli (>90% in young women), presenting with flank pain, fever, and urinalysis evidence of UTI. [1] Clinical presentations range from mild flank pain with low-grade fever to septic shock, with bacteremia rates varying from <10% to >50% depending on host factors. [1] The estimated annual incidence in the United States is 459,000–1,138,000 cases. [1]

• Onset and progression: Sudden onset of flank pain (unilateral or bilateral), fever, chills, malaise — ask about timing and rapidity of symptom development [1]
• Lower urinary tract symptoms: Dysuria, frequency, urgency, hematuria — present in ~80% but absent in up to 20% of patients [1-2]
• Systemic symptoms: Fever (may be absent early), rigors, nausea, vomiting, anorexia [3-4]
• Prior UTI history: Recent cystitis, prior pyelonephritis episodes, recurrent UTIs
• Recent antibiotic use or hospitalization: Increases risk of resistant organisms [1]
• Recent travel: Particularly to areas endemic for ESBL-producing organisms [1]
• Urologic history: Known stones, structural abnormalities, catheterization, recent urologic procedures [5]
• Pregnancy status: Must be assessed in all women of reproductive age [3]
• Important negatives: Vaginal discharge (suggests alternative diagnosis), diarrhea, cough, genital discharge [6]

• Sepsis signs: Hypotension, tachycardia, tachypnea, altered mental status, lactate elevation [7]
• Inability to tolerate oral intake (persistent vomiting) [1]
• Urine pH ≥7.0 (suggests urease-producing organism, e.g., Proteus; associated with struvite stones) [1]
• New decrease in GFR to ≤40 mL/min (suggestive of obstruction) [1]
• Known or suspected urolithiasis with concurrent infection (obstructed infected system = urologic emergency) [1][8]
• Failure to improve within 48–72 hours of appropriate antibiotics [4][8]
• Abnormalities in multiple CBC cell lines (leukocytosis + thrombocytopenia + anemia) — highly correlated with ICU admission [3]
• Immunocompromised state, diabetes, pregnancy, advanced age — higher risk for complications [9]

• Empiric outpatient oral options:
  • Fluoroquinolones (ciprofloxacin 500 mg BID or levofloxacin 750 mg daily × 5–7 days) — if local resistance <10% [1][10]
  • TMP-SMX (160/800 mg BID × 7–14 days) — if susceptibility known or local resistance <10% [10]
  • Oral 3rd-generation cephalosporins (cefpodoxime) — limited evidence but used in practice [11]
• Supplemental parenteral dose at discharge: Ceftriaxone 1 g IV, gentamicin, amikacin, or ertapenem — recommended when anticipated resistance to the oral agent exceeds 10% [1][11]
• Inpatient parenteral options: Ceftriaxone, fluoroquinolones IV, piperacillin-tazobactam, carbapenems (for ESBL concern), aminoglycosides [8][12]
• Contraindicated/avoid:
  • Nitrofurantoin — does not achieve adequate renal tissue concentrations; only effective in the bladder [1]
  • Oral fosfomycin — same limitation, urine-only concentrations [1]
  • Fluoroquinolones carry FDA black box warnings (tendon rupture, neuropathy, aortic dissection) — weigh risk/benefit [11]
• IV-to-oral transition: The 2025 IDSA guideline suggests transitioning to oral therapy once clinically improving, able to take PO, and an effective oral option is available — even in the setting of gram-negative bacteremia [13]
• Duration: 7 days for fluoroquinolones; 10–14 days for TMP-SMX or beta-lactams [1][10]

• Aggressive hydration is essential — oral if tolerated, IV if not [1]
• No specific dietary triggers for pyelonephritis
• Encourage adequate fluid intake during recovery to maintain urine output
• Cranberry products have limited evidence for prevention of recurrent UTI and no role in acute treatment

• GU: Dysuria, frequency, urgency, hematuria, flank pain, suprapubic pain
• GI: Nausea, vomiting, diarrhea, abdominal pain (may mimic intra-abdominal pathology)
• Constitutional: Fever, chills, rigors, malaise, fatigue
• Respiratory: Dyspnea (consider ARDS in severe cases, especially pregnancy) [3]
• Neurologic: Altered mental status (sepsis indicator) [7]
• OB/GYN: Vaginal discharge (alternative diagnosis), contractions (in pregnancy) [3]

• Collateral: Medication compliance, recent antibiotic courses, recent healthcare exposures, functional status in elderly patients
• Family history: Vesicoureteral reflux (familial predisposition), polycystic kidney disease, recurrent UTIs
• Social context: Ability to take oral medications at home, reliable follow-up, stable home situation — critical for disposition decisions [1]

• Female sex (short urethra, proximity to GI flora) [1]
• Sexual intercourse (strongest behavioral risk factor in young women) [9]
• Recent spermicide use
• Prior UTI or pyelonephritis [9]
• Urinary tract obstruction (stones, BPH, strictures) [5]
• Indwelling urinary catheter or recent instrumentation [5]
• Diabetes mellitus [9]
• Immunosuppression (transplant, HIV, chemotherapy) [9]
• Pregnancy (physiologic hydronephrosis, ureteral dilation) [3]
• Advanced age (higher hospitalization rates) [1]
• Anatomic/congenital urinary tract abnormalities [9]
• Recent antibiotic use or hospitalization (risk for resistant organisms) [1]

• Nephrolithiasis/ureterolithiasis — colicky pain, hematuria, may coexist with infection (pyonephrosis = emergency) [1]
• Renal abscess/perinephric abscess — failure to improve on antibiotics, CT needed [1]
• Acute cholecystitis — right-sided pain, Murphy's sign, may overlap with right-sided pyelonephritis [1]
• Appendicitis — right lower quadrant/flank pain, especially retrocecal appendix [1]
• Pelvic inflammatory disease — lower abdominal pain, cervical motion tenderness, vaginal discharge [1]
• Acute prostatitis (in men) — fever + pyuria without flank pain [1]
• Renal vein thrombosis — flank pain, hematuria, proteinuria [1]
• Paraspinous muscle disorders — musculoskeletal flank pain without systemic signs [1]
• Emphysematous pyelonephritis — diabetic patients, gas on imaging, high mortality [9]
• Lower lobe pneumonia — may present with upper abdominal/flank pain and fever

• Prior UTIs or pyelonephritis episodes (recurrence risk)
• Known urolithiasis or urologic surgery
• Diabetes mellitus (risk for emphysematous pyelonephritis, complicated course)
• Immunocompromising conditions
• Chronic kidney disease (baseline GFR important for comparison)
• Structural urinary tract abnormalities (vesicoureteral reflux, neurogenic bladder)
• Pregnancy history
• Drug allergies — particularly beta-lactams and fluoroquinolones
• Recent antibiotic use (resistance risk) [1]

• Vital signs: Fever (≥38°C), tachycardia, hypotension (sepsis), tachypnea [2-3]
• CVA tenderness — the only physical exam finding that increases the probability of upper tract UTI; nearly pathognomonic when combined with fever and pyuria [2][4]
• Abdominal exam: Flank tenderness, suprapubic tenderness; assess for peritoneal signs (alternative diagnosis)
• Pelvic exam (if indicated): Rule out PID, vaginitis, cervicitis
• Skin: Assess for mottling, delayed capillary refill (sepsis)
• Mental status: Confusion or altered sensorium suggests sepsis [7]
• Absence of flank pain should raise suspicion for an alternative diagnosis [4]

• Urinalysis with microscopy: Pyuria (WBC), bacteriuria, nitrites, leukocyte esterase — dipstick sensitivity ~75%, specificity ~82% for combined LE/nitrite [2]
• Urine culture with susceptibilities: Mandatory in all suspected pyelonephritis — the cardinal confirmatory test; typically ≥10⁴ CFU/mL of a uropathogen [1-2][8]
• Blood cultures: Not needed in uncomplicated cases; obtain if sepsis suspected, immunocompromised, or diagnostic uncertainty [8][14]
• CBC: Leukocytosis expected; multi-cell-line abnormalities predict adverse outcomes [3]
• BMP/CMP: Creatinine (assess for obstruction if GFR ≤40), electrolytes, glucose
• Lactate: If sepsis suspected [7]
• CRP/procalcitonin: Not routinely needed in uncomplicated cases; procalcitonin ≥0.50 ng/mL has ~82% sensitivity for bacteremia in febrile UTI [15]
• Pregnancy test: All women of reproductive age

• Uncomplicated pyelonephritis: Imaging is NOT indicated [4][8]
• Indications for imaging: [1][9]
  • Sepsis or septic shock
  • Known or suspected urolithiasis
  • Urine pH ≥7.0
  • New GFR decrease to ≤40 mL/min
  • Failure to improve within 48–72 hours
  • Complicated patient (diabetes, immunocompromised, recurrent pyelonephritis)
• First-line: CT abdomen/pelvis with IV contrast — detection rate ~84% vs ~40% for ultrasound [9]
• CT findings: Focal/multifocal decreased parenchymal enhancement, renal swelling, perinephric stranding, abscess, gas (emphysematous pyelonephritis) [9]
• Ultrasound: Reasonable first-line in pregnancy and when CT is contraindicated; good for detecting hydronephrosis and stones but poor sensitivity for parenchymal changes [9]
• Non-contrast CT: Adequate if primary concern is urolithiasis [9]

• qSOFA score: ≥2 of altered mentation, SBP ≤100, RR ≥22 — identifies patients at risk for poor outcomes from sepsis [16]
• SOFA score: For ICU-level assessment of organ dysfunction [16]
• Point-of-care ultrasound (POCUS): Assess for hydronephrosis at bedside in the ED
• Bedside bladder scan: Evaluate for urinary retention
• Post-void residual: If obstruction suspected

• Not routinely indicated for uncomplicated pyelonephritis
• Obtain ECG if:
  • Sepsis or hemodynamic instability (to evaluate for sepsis-related cardiac dysfunction)
  • Elderly patients or those with cardiac comorbidities
  • Pre-existing cardiac disease with new tachycardia
• ECG findings in sepsis-associated pyelonephritis: Sinus tachycardia (most common), QT prolongation (54% of sepsis patients), new atrial fibrillation/flutter (associated with poor outcomes, OR 2.19), ST-T wave changes [17]
• QT prolongation is particularly relevant given that fluoroquinolones (commonly used for pyelonephritis) also prolong QT — exercise caution with concurrent QT-prolonging medications [17]

Typical presentation: Young woman with acute onset of fever, unilateral flank pain, CVA tenderness, dysuria/frequency, and pyuria/bacteriuria on UA. [1]

Atypical presentations to recognize

• Absence of lower urinary tract symptoms (~20%) [1]
• Absence of fever early in the course [4]
• Elderly patients may present with altered mental status, generalized weakness, or GI symptoms without classic localizing signs
• Bilateral pyelonephritis (less common, more severe)

Severity stratification: [1]

• Mild: Low-grade fever, minimal nausea, no vomiting, stable vitals → outpatient
• Moderate: Higher fever, vomiting, unable to tolerate PO initially → ED observation/short stay
• Severe: Sepsis, septic shock, hemodynamic instability, obstruction → admission

Complications: Renal/perinephric abscess, emphysematous pyelonephritis, urosepsis, septic shock, ARDS, renal insufficiency, preterm labor (in pregnancy) [1][3]

Initial stabilization

• IV fluid resuscitation if dehydrated or hemodynamically unstable [1]
• Antipyretics/analgesics (acetaminophen, NSAIDs if no renal contraindication)
• Antiemetics (ondansetron) if vomiting

Outpatient management (uncomplicated, tolerating PO, stable): [1][8]

• Fluoroquinolone (ciprofloxacin 500 mg PO BID × 7 days or levofloxacin 750 mg PO daily × 5 days) if local resistance <10%
• TMP-SMX DS PO BID × 14 days (or 7 days if susceptible E. coli) [10]
• Consider single dose of ceftriaxone 1 g IV or IM before discharge if resistance concern >10% [1][11]

Inpatient management (severe illness, unable to tolerate PO, sepsis, pregnancy, obstruction): [1][3][8]

• IV antibiotics: Ceftriaxone 1–2 g IV daily, fluoroquinolone IV, or piperacillin-tazobactam
• If ESBL concern: Carbapenem (ertapenem or meropenem) [12]
• Transition to oral therapy once clinically improving, afebrile, tolerating PO [13]

Source control: Urgent urologic decompression (percutaneous nephrostomy or ureteral stent) if obstructed infected system [1][8]

Pregnancy: Admit all patients; IV ampicillin + gentamicin or ceftriaxone; complete 14 days total therapy [3]

Specialist consultation triggers

• Urology: Obstructing stone with infection, abscess requiring drainage, emphysematous pyelonephritis
• Infectious disease: MDR organisms, ESBL-producing pathogens, treatment failure, immunocompromised host [1]

• Follow-up timing: Primary care or urology within 48–72 hours if discharged from ED; sooner if culture results require antibiotic change [8]
• Expected course: Most patients improve within 48–72 hours of appropriate antibiotics [4][8]
• Return immediately for:
  • Worsening or persistent fever >48–72 hours on antibiotics
  • Inability to keep down oral medications or fluids
  • Worsening flank pain
  • Signs of sepsis: confusion, lightheadedness, rapid heart rate, difficulty breathing
  • Decreased urine output
• No routine follow-up testing needed if clinical course is uneventful [1]
• If no improvement at 48–72 hours: Repeat urine culture, obtain imaging (CT with contrast), and reconsider diagnosis [1][4][8]
• Patient counseling: Complete the full antibiotic course; maintain hydration; avoid nephrotoxic agents (NSAIDs with caution if renal function borderline)

1. Acute Pyelonephritis in Adults. — Johnson JR, Russo TA. The New England Journal of Medicine. 2018.

2. Uncomplicated Urinary Tract Infection. — Hooton TM. The New England Journal of Medicine. 2012.

3. Urinary Tract Infections in Pregnant Individuals. — Committee on Clinical Consensus—Obstetrics Obstetrics and Gynecology. 2023.

4. Diagnosis and Treatment of Acute Pyelonephritis in Women. — Colgan R, Williams M, Johnson JR. American Family Physician. 2011.

5. Clinical Practice Guideline by Infectious Diseases Society of America (IDSA): 2025 Guideline on Management and Treatment of Complicated Urinary Tract Infections: Introduction and Methods. — Barbara W. Trautner, Nicolás W. Cortés-Penfield, Kalpana Gupta, et al Infectious Diseases Society of America. 2025.

6. Ann Arbor Guide to Triaging Adults With Suspected Urinary Tract Infection for In-Person and Telehealth Settings. — Meddings J, Chrouser K, Fowler KE, et al. JAMA Network Open. 2026.

7. Sepsis and Septic Shock. — Meyer NJ, Prescott HC. The New England Journal of Medicine. 2024.

8. Acute Pyelonephritis in Adults: Rapid Evidence Review. — Herness J, Buttolph A, Hammer NC. American Family Physician. 2020.

9. ACR Appropriateness Criteria® Acute Pyelonephritis: 2022 Update. — Expert Panel on Urological Imaging, Smith AD, Nikolaidis P, et al. Journal of the American College of Radiology : JACR. 2022.

10. Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians. — Lee RA, Centor RM, Humphrey LL, et al. Annals of Internal Medicine. 2021.

11. Clinical Practice Guideline by Infectious Diseases Society of America (IDSA): 2025 Guideline on Management and Treatment of Complicated Urinary Tract Infections: Selection of Antibiotic Therapy for Complicated UTI. — Barbara W. Trautner, Nicolás W. Cortés-Penfield, Kalpana Gupta, et al Infectious Diseases Society of America. 2025.

12. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. — Tamma PD, Heil EL, Justo JA, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.

13. Clinical Practice Guideline by Infectious Diseases Society of America (IDSA): 2025 Guideline on Management and Treatment of Complicated Urinary Tract Infections: Timing of Intravenous to Oral Antibiotics Transition for Complicated UTI. — Barbara W. Trautner, Nicolás W. Cortés-Penfield, Kalpana Gupta, et al Infectious Diseases Society of America. 2025.

14. Early Care of Adults With Suspected Sepsis in The Emergency Department and Out-of-Hospital Environment: A Consensus-Based Task Force Report. — Yealy DM, Mohr NM, Shapiro NI, et al. Annals of Emergency Medicine. 2021.

15. A Reference Standard for Urinary Tract Infection Research: A Multidisciplinary Delphi Consensus Study. — Bilsen MP, Conroy SP, Schneeberger C, et al. The Lancet. Infectious Diseases. 2024.

16. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. — Evans L, Rhodes A, Alhazzani W, et al. Critical Care Medicine. 2021.

17. Association of Electrocardiogram Abnormalities With Clinical Outcomes in Emergency Department Sepsis Patients. — Kotruchin P, Chuehongthong M, Tangpaisarn T, et al. The Western Journal of Emergency Medicine. 2026.