What is the recommended treatment for a patient suspected of having a urinary tract infection caused by a urease splitting organism?

Treatment of Urinary Tract Infections Caused by Urease-Splitting Organisms

The primary treatment for UTIs caused by urease-splitting organisms requires complete surgical stone removal combined with culture-directed antibiotic therapy, as these infections are classified as complicated UTIs and the bacteria reside within the stone matrix itself, making medical therapy alone insufficient. 1

Understanding Urease-Splitting Organisms and Their Clinical Significance

Urease-splitting organisms—primarily Proteus mirabilis, but also including certain strains of Klebsiella, Pseudomonas, Staphylococcus, Ureaplasma urealyticum, and Corynebacterium urealyticum—produce the enzyme urease that hydrolyzes urea into ammonia and carbon dioxide. 1, 2, 3 This biochemical process creates an alkaline urinary environment (elevated pH) and high ammonia concentrations that promote crystallization of magnesium ammonium phosphate (struvite) and calcium carbonate apatite, leading to rapid formation of large, branched "infection stones." 1, 4

The presence of urea-splitting bacteria on culture is a documented risk factor for complicated UTI and should prompt evaluation for underlying anatomical abnormalities or stone disease. 1

Immediate Management Approach

Obtain Cultures Before Treatment

• Urine culture and susceptibility testing is mandatory before initiating empirical therapy, as all UTIs associated with urease-splitting organisms are complicated UTIs by definition. 1
• Blood cultures should be obtained if upper tract infection or systemic symptoms are present. 5
• Stone fragments, when available, should be cultured as bacteria reside within the stone itself and may differ from urine cultures. 1

Empirical Antibiotic Selection

• For systemically ill patients requiring hospitalization, initiate combination intravenous therapy with either amoxicillin plus an aminoglycoside, second-generation cephalosporin plus an aminoglycoside, or third-generation cephalosporin as monotherapy. 5
• Fluoroquinolones (ciprofloxacin or levofloxacin) can be used for stable patients, but only if local fluoroquinolone resistance is <10% and the patient has not used fluoroquinolones in the last 6 months. 6, 7
• Treatment duration should be 14 days minimum when infection stones or prostatitis cannot be excluded. 6

Definitive Management: Stone Removal is Essential

Complete surgical removal of all stone material is the therapeutic goal and is necessary to eradicate the causative organisms, as bacteria embedded within the stone matrix cannot be eliminated by antibiotics alone. 1, 4

Surgical Options (in order of preference)

• Percutaneous nephrolithotomy (PNL) monotherapy is the primary modality for staghorn calculi. 1
• Combinations of PNL and extracorporeal shock wave lithotripsy (ESWL) for complex stones. 1
• ESWL monotherapy for smaller stones. 1
• Open surgery (anatrophic nephrolithotomy) is reserved for selected cases where less invasive methods are not feasible. 1, 3

Critical Caveat About Residual Fragments

Residual stone fragments after initial treatment will harbor bacteria and serve as a nidus for recurrent infection and stone growth—complete stone clearance must be achieved. 1 The majority of studies indicate that residual fragments grow and perpetuate infection, though some suggest small fragments may be sterilized with aggressive medical management. 1

Post-Operative Medical Management

Treatment of Residual Fragments

• Chemolysis via ureteral catheter or nephrostomy can be attempted for small residual fragments. 3
• Potassium citrate administration increases the nucleation pH (pHn) more than urinary pH, reducing struvite crystallization risk. 1, 3
• Urease inhibitors (acetohydroxamic acid) may prevent stone growth but have significant toxicity limiting their use. 1, 3

Prevention of Recurrence

• Frequent monitoring for recurrent UTI and stone recurrence is essential, with aggressive treatment of any new infections. 2, 4
• Long-term antibiotic prophylaxis should be approached judiciously due to resistance concerns, but may be necessary in patients with persistent risk factors. 1, 3
• Urinary acidification has been proposed but is difficult to achieve in the presence of urease-producing bacteria. 3

Common Pitfalls to Avoid

• Do not rely on antibiotics alone without addressing stone burden—the bacteria within stones cannot be eradicated medically. 1
• Do not assume urine culture predicts stone culture—bacteria within stones differ from urine in 51% of infection stones and 67% of metabolic stones. 8
• Avoid empiric fluoroquinolones in patients with recent fluoroquinolone exposure or in areas with >10% resistance. 6, 5
• Do not treat asymptomatic bacteriuria in the absence of stones or symptoms. 5
• Be aware that Ureaplasma urealyticum and Corynebacterium urealyticum are urease-producers not isolated by conventional cultures and require specific testing. 3

Long-Term Outcomes

Untreated staghorn calculi from urease-splitting organisms will destroy the kidney and/or cause life-threatening sepsis over time, making aggressive intervention mandatory. 1 The goal is preservation of renal function, prevention of sepsis, and elimination of the infectious nidus through complete stone removal combined with appropriate antimicrobial therapy.