emDOCs Podcast – Episode 143: Infected Ureterolithiasis

How do we define infected ureterolithiasis?

• There is no universally accepted criteria or definition, but generally may define this as positive urine culture (UC) with >100,000 colony-forming units of a single uropathogen in a patient with a ureteral stone. 
• Since the urine culture is unavailable in the ED, we must rely on the urinalysis and clinical findings. 

Does having a stone increase the risk of UTI?

• Stones and UTIs are risk factors for each other.
• Higher urinary pH and bacterial colonization precipitate and worsen new and existing stones.
• Bacteria can create an alkaline environment, which, in turn, worsens stone formation.
• Biofilm formation on preexisting stones increases infection risks. 

How common are infected stones?

• The lifetime risk of a ureteral stone is 15%. 
• Infections occur in up to ⅓  of patients with a stone.
• Risk of infected stones goes up for:
  • Females
  • Stones >5mm
  • Multiple stones
  • Staghorn calculi

Likelihood of developing severe illness:

• 20-50% of patients with an infected stone can progress to sepsis/septic shock.
• Rates of bacteremia, AKI, hospital length of stay, and mortality are all significantly higher in patients with UTI AND obstruction.
• Up to 30% of patients with urinary obstruction will have an AKI, and mortality is 8-27% in patients with ureteral stone infection AND sepsis or septic shock. 
• One study found a 27% mortality rate in patients with septic shock and urinary obstruction, with a mortality rate of 11% if there was no obstruction. See this Shift Pearls.

Clinical features associated with infected stones:

• Signs and symptoms of infected urolithiasis often overlap with those of pyelonephritis and uncomplicated urolithiasis.
• Elevated temperature (>37.9° C) is the strongest sign associated with infected urolithiasis (likelihood ratio [LR]+ 15; OR 3.1 (95% CI 1.8-13.6).
• Others more strongly associated with infected urolithiasis: 
  • Reported fever (relative risk [RR] 6.6, 95% CI 3.1-13, LR+ 5)
  • Dysuria (RR 4.4, 95% CI 1.8-11, LR+ 2) 
  • Chills (RR 3.0, 95% CI 1.3-6.7, LR +3) 
  • Urinary frequency (RR 2.5, 95% CI 1.1-5.5, LR+ 2)
  • Malodorous urine (RR 2.7, 95% CI 0.5-8.4, LR+ 3)
• Urinary urgency, hesitancy, hematuria, nausea, and vomiting are not associated with a significantly higher risk of infected urolithiasis.

Interpretation of the UA:

• Urine leukocyte esterase (LE): 
  • Sensitivity and specificity 86%; LR+ 6 and LR- 0.2. 
  • Large LE:  Specificity and LR+ increase to 98% and 24.
• Pyuria cutoffs: 
  • >5 WBCs/hpf → sensitivity 86%, specificity 79%, LR+ 4, LR- 0.2 
  • >10 WBCs/hpf → specificity 87%, LR+ 6, LR- 0.2
  • >15 WBCs/hpf → specificity 91%, LR+ 8, LR- 0.3
  • >20 WBCs/hpf → specificity 93%, LR+ 9, LR-  0.3
• Nitrites: 
  • Sensitivity 43%, specificity 99%, LR+ 36, LR- 0.6
• Other:
  • The presence of bacteria suggests infection.
  • Squamous cells suggest contamination (repeat the UA).
• Bottom line: WBC > 5/hpf and positive LE are markers for infection. Positive nitrites = infection.

Usefulness of lab studies:

• Labs are not a reliable method for determining infection.
• WBC > 10K and CRP > 3.5 mg/L may be associated with higher rates of infection, though not reliably. 
• A creatinine level can assist in determining if an AKI is present but is unreliable in diagnosing infection.

The role of imaging:

• Ultrasound
  • If a patient has a UTI and looks septic, consider US imaging to evaluate for hydronephrosis.
  • Sensitivity>70% for hydronephrosis, LR+ 3. 
  • Sensitivity for renal infection is 56%, but if pyonephrosis or pus with urinary obstruction is present, then LR+ 30.
• CT with or without IV contrast is the recommended imaging modality.
  • American College of Radiology Appropriateness Criteria suggests that CT imaging (with and/or without IV contrast) in patients with suspected renal infection and a history of stone or obstruction is appropriate.
  • CT with IV contrast has several advantages: high sensitivity for stones > 3 mm; may diagnose other conditions or abscesses; can determine the severity of obstruction; helps with operative planning.

Management:

• Treatment revolves around resuscitation, antibiotics, and urology consultation. 
• Most common organisms associated with infected urolithiasis:
  • E. coli, Klebsiella
  • Enterococcus species
  • Proteus 
  • Pseudomonas
    • Risk factors for Pseudomonas:
      • Indwelling catheter or nephrostomy tube
      • Immunosuppression
      • Recurrent UTIs
      • Dementia
• Antibiotics
  • Target gram-negative rods and urease-producing organisms 
  • Evaluate prior UCs if they are available to help guide therapy. 
  • Ceftriaxone is an excellent first-line agent. 
  • Broaden coverage for high-risk patients or those who are septic-appearing.
    • Options:  piperacillin-tazobactam, cefepime, or carbapenem (meropenem).
    • Consider adding linezolid or vancomycin if patients are ill-appearing or have risk factors for MRSA. 

Urology interventions:

• Patients who are critically ill with an infected stone and obstruction need urgent decompression due to the risk of AKI and mortality with the obstruction.
• The American Urological Association strongly recommends urgent collecting system drainage with a stent or nephrostomy tube in those with infected stones and obstruction.
• Timely decompression (within 1-2 days) improves survival by 10-30%. The sicker the patient, the earlier decompression should be.
• Decompression includes shockwave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, and placement of ureteral stent and nephrostomy tube.

Disposition:

• There is no consensus admission criteria.
• Disposition decisions should be made with a urology specialist.
• Reasons to consider admission:
  • Significant stone burden (i.e., >10-15 mm or multiple stones)
  • Solitary kidney
  • Intractable symptoms (nausea, vomiting, pain)
  • Urinary extravasation
  • Severe renal function impairment
  • Ill-appearing or signs of clinical instability (sepsis or septic shock)
  • Significant comorbidities such as advanced age or immunosuppression 
  • Complete obstruction or hydronephrosis
  • Inability to follow up and/or inability to take PO antibiotics 
• Discharge may be possible with shared decision-making and urology consultation/follow-up for the following:
  • Smaller and non-obstructing stones
  • Well-appearing, afebrile, without significant comorbid conditions
  • Able to take oral antibiotics and follow up with urology
  • Use antibiotics for complicated UTIs based on local sensitivities: 
    • Fluoroquinolones (i.e., ciprofloxacin, levofloxacin) 
    • Later-generation cephalosporins (i.e., cefpodoxime)
    • Amoxicillin-clavulanate

Summary:

• Infected ureterolithiasis can be a urologic emergency; patients may rapidly decompensate with septic shock.
• The strongest predicting feature of an infected stone is fever. 
• 20-50% of patients with an infected stone can progress to sepsis or septic shock.
• Urinalysis interpretation: WBC > 5/hpf and positive LE are markers for infection; positive nitrites ARE an infection.
• CT with IV contrast in suspected infected urolithiasis has the advantage of being able to diagnose other conditions or abscesses.
• Criteria for discharge with oral antibiotics: smaller/non-obstructing infected stones; well-appearing, afebrile, without significant comorbid conditions; able to take oral antibiotics and follow up with urology.

Reference:

1. Yoo MJ, Pelletier J, Koyfman A, Long B. High risk and low prevalence diseases: Infected urolithiasis. Am J Emerg Med. 2024;75:137-142. PMID: 37950981 
2. Reyner K, Heffner AC, Karvetski CH. Urinary obstruction is an important complicating factor in patients with septic shock due to urinary infection. Am J Emerg Med. 2016;34(4):694-696. PMID: 26905806