Complicated UTIs with urolithiasis

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Ludong Qiao (Department of Urology, Tongren Hospital of Peking University, Beijing, China)

Executive summary


1. Although it is not sufficient toexclude the presence of urinary tractinfection (UTI) midstream urine (MSU) culture should be obtained before any treatment is planned.(GR: A)

2. Incase of an UTI with systemic symptoms (fever, but also chills and low temperature) blood culture must be performed. (GR: A)

3. Image studies including US and CT must be highly recommended for diagnosis and evaluation of cUTI associated with urolithiasis.(GR: A)


1. For sepsis with obstructing stones, the collecting system should be urgently decompressed, using percutaneous drainage or ureteral stenting.(GR: A)

2. Definitive treatment of the stone should be delayed until sepsis is resolved. (GR: A)

3. Collect urine for antibiogram test following decompression.(GR: A)

4. Start antibiotics immediately thereafter (+ intensive care if necessary). (GR: A)

5. Re-evaluate antibiotic regimen following antibiogram findings.(GR: A)

6. Recommendations for therapeutic measures of infection stones

7. Surgical removal of the stone material as complete as possible (GR: A)

8. Short-term antibiotic course (GR: B)

9. Long-term antibiotic course (GR: B)

10. Urinary acidification: ammonium chloride, 1 g, 2 or 3 times daily (GR: B)

11. Urinary acidification: methionine, 200-500 mg, 1-3 times daily (GR: B)

12. Urease inhibition (GR: A)


Urolithiasis may be a cause as well as a result of UTI. Stone obstruction leads to urinary stasis, which enables bacteria to adhere to the urothelium and multiply,thus causing UTI. Primary UTI caused byurea-splitting organisms may lead to struvite stone formation, causing obstruction,stasis and further infection. This is the clinical consequences of the “vicious cycle”: stones → obstruction → stasis → infection → stones. Obstructive pyelonephritis is also one of the life-threatening cUTI, and prompt diagnosis and treatment including medical as well as surgical interventions to rescue the patients. Complicated UTIs with urolithiasis are discussed in the chapter.


An electronic literature search was performed on PubMed from 2004 through 2014, limited to studies in the English language, using the key words “Urolithiasis” OR “urinary calculi” AND “urinary tract infection”. Abstracts were reviewed, relevant articles were studied in full-length version, and further references were obtained from these articles. In total, 103 abstracts were reviewed, 86 articles were studied in detail, and 47 were included as references in this part.


Stones with infection: stones complicated by UTIs, which are metabolic stones that passively trap bacteria from coexistent UTIs and may consist of calcium or non-calcium.

Infection stones: stones that occur following UTIs caused by urease-producing gram-negative organisms, which pathogenesis play a key role in stone formation. Infection stones contain the following minerals: struvite and/or carbonate apatite and/or ammonium urate.

Staghorn calculi are those stones that fill the major part of therenal collecting system. Typically, they occupy the renal pelvis andbranch into most of the calyces, mimicking the horns of a deer orstag.


The incidence of infected urolithiasis has increased in recent years.The rates of associated sepsis increased from 6.9% to 8.5%, and severe sepsis increased from 1.7% to 3.2%; mortality rates at 0.25–0.20%. The rising prevalence has been linked to increasing rates of obesity, diabetes, and metabolic syndrome. Women were twice likely to have infected urolithiasis (LE: 3)[1]. To the complete kidney staghorn calculi, 56% of them weremetabolic and 44% were infection stones (LE: 3)[2]. Staghorn calculi or high stone burden, infection, and ureteral obstruction are the top three causes of loss for function in one kidney (LE: 1a)[3]. Urinary tract obstruction due to urolithiasis is also the main cause of emphysematous pyelonephritis (LE: 3)[4] and xanthogranulomatous pyelonephritis (LE: 3)[5].


Stones with infection

There are about 8%- 24%of patients presenting with acute nephrolithiasis having UTI in the emergency department (LE: 3)[6][7]and 12.5%of patients emergency drainage because of the SIRS from urosepsis.The risk factors for emergency drainage arepatient’s performance status, ageand sex (LE: 3). For these patients, Escherichia coliis the most frequenturopathogen, others including Proteus mirabilis, Klebsiella, and Enterococcus. Some of them aremultiple uropathogens infection. Candida albicans can also be isolated from urine of these patients (LE: 3,1b)[8][9].

Infection stones

The occurrence of infection stones has decreased over the past 20 years as a result of the significantly improved diagnosis and treatment of UTIs. (LE: 3)[10]The incidence varies according to geographical location, gender, and age of the patient.In industrialized countries, the relative proportion of occurrence in women ranged from 3.2 to 10.1%. (LE: 3)[11] In developing countries, major differences in the incidence of infection stones were observed according to continent and region, from 42.9% in Sub-Saharan Africa to 13% in South America and 2.7% in Asia Minor. (LE: 3)[12]

Infection stones are not associated with metabolic abnormalities intrinsic to the patient, but are a result from bacterial metabolism(LE: 1a)[13]. Formation of infection stones depends on urea-hydrolization in the presence of urease by urease-producing bacteria. (Table 1) (LE: 1a)[14][15][16][17]

Urolithiasis Table 1.png

Clinical features

Clinical presentation of infected urolithiasis can vary from the dysuria, urgency, frequency, flank pain, costovertebral angle tenderness, suprapubic pain and fever to severe obstructive acute pyelonephritis with imminent urosepsis. Nearly an half of patients with flank pain are caused by a ureteral stone (LE: 3)[18].

Risk factors for development of infection stones are urinary tract obstructions, catheter, neurogenic bladder voiding disruptions, pouches, as well as distal renal tubular acidosis and medullary sponge kidney (LE: 1a)[19][20].

Diagnostic criteria (testing procedures)

Symptoms (physical examination):

Fever,heart rate, respiratory rate, blood pressure, CVA pain, any abnormal situation of urinary system.

Laboratory tests (radiological investigation, others)

Blood analysis for leucocyte, Serum creatinine, CRP, PCT.


Pyuria has only a moderate accuracy in identifying UTI. Fever, a greater degree of pyuria and female sex increases the likelihood of infection. (LE: 3)[6].

Urine pH measurements: Infection stones contain struvite and/or carbonate apatite and/or ammonium urate typically providing evidence for urease-producing bacteria, which increase ammonia ions and develop alkaline urine. Carbonate apatite starts to crystallise at a urine pH Level of 6.8. Struvite only precipitates at pH > 7.2 (LE: 1a)[15][16][17][19].

Urine culture is needed. Significant bacteriuria is defined by counts of > 104 cfu/mL, in the mid stream urine (MSU) or straight catheter urine sample (LE: 1a)[21][22]. Positive bladder urine culture does not always correlate with stone and renalpelvic cultures, including in patients with sterile positive bladder urine culture.To the patients with obstructing ureteral stone or infected stones,midstream urine culture and sensitivity test is a poor predictor of infection (LE: 3)[23].

Blood culture: Incase of an UTI with systemic symptoms (fever, but also chills and low temperature), blood culture must be performed. Two sets allow for the differentiation between true bacteremia and contamination.

A single physical examination or laboratory finding cannot predict UTI in urolithiasis patients with complete reliability. The presence of pyruria, fever, and leukocytosis significantly increase the odds of a positive urine culture (LE: 3)[24].

Imaging might be considered in men, diabetic persons and patients with history of relapsing UTI , urolithiasis structural and urological abnormality, patients with symptoms of urolithiasis the, febrile UTI, urine pH≥7.0, and/or renal insufficiency (estimated glomerular filtration rate, ≤40 mL/min/1.73 m3)[25][26][27](LE: 1a) (LE: 3) (LE: 3). Ultrasound, plain abdominal film, urographyand abdominal and pelvic CT scans are the most common imaging tools. MR urography is an attractiv ealternative to CT urography because ionizing radiation is not used.However, the sensitivities for detecting urolithiasis and small urothelial carcinoma(largely due to the inferior spatial resolution relative to CT) are presumably lower for MR urography (LE: 1a)[28].


Stones with infection

Decompression Infection in the obstructed urinary tract caused by urolithiasis poses an imminent threat to the patient and may induce significant morbidity including sepsis, pyonephrosis (suppurative destruction of renal parenchyma), and even death (LE: 3)[29]. The treatment of infected and obstructive urolithiasis involves prompt decompression of the renal collecting system.For decompression of the renal collecting system, retrograde ureteral catheterization (RUC) and percutaneous nephrostomy (PCN) are equally effective (LE: 1b)[30]. Neither modality demonstrated superiority in promoting a more rapid recovery after drainage. The decision of which mode of drainage to use may be based on logistical factors, surgeon preference and stone characteristics (LE: 3)[9]. RUC has certain failure rate (LE: 1b)[31]. PCN avoids general anesthesia, aswell as instrumentation of the infected urinary tract, and it is classically considered as a safer method of drainage in critically ill patients (LE: 3)[32]. Training background, favorable physician reimbursement, the timing of the intervention and patient-specific factors such as prostatic enlargement or altered lower urinary tract anatomy are the significant drivers in this decision-making process (LE: 3,4)[33][34]

Antibiotic treatment

The antimicrobial treatment options for empirical therapy of stones with infection are listed in Table 2[35].

Urolithiasis Table 2.png

The most common gram positive UTI pathogen in most countries of Asia is Enterococcus spp. Effective antibiotic options are listed in Table 3.[36]

Urolithiasis Table 3.png

Infection Stones

There are three points of treatment to achieve possible therapy (LE: 1a)[16].

1) Removal of all stones and stone analysis are the first step of infection stone treatment with endoscopic equipment and shockwave lithotripsy.

2) Antibiotic therapy Antibiotic therapy is advised in patients affected by infection stones prior to and/or after treatment. Antibiotic therapy significantly reduces the bacterial load, decreasing the risk of sepsis, antibiotics prevent recurrence or re-growth of stones after treatment. Urine specimens for bacteriological cultures should be routinely collected at each follow-up visit. In case of recurring UTI antibiotic therapy based on results of sensitivity testing should be carried out[19]. Different schedules of targeted antibiotic therapy are shown in Table 4 [37][38][39][40](LE: 3).

Urolithiasis Table 4.png

3) Prevention of recurrence

All infection-stone formers are deemed at high risk of recurrence.Some methods can be used to prevent the recurrence of infection stone:

Lifestyle or dietary modification:

Increase fluid intake: at least 2 L per day. Chronic low fluid intake/low urine output is associated with the occurrence of UTI, and ensuring a high urine output with increased fluid intake has been shown to prevent recurrent urolithiasis (LE: 2a)[41].

Urease inhibitors

Aceto-hydroxamic acid (AHA) causes a complete non-reversible and non-competitive inhibition of the enzyme urease (LE: 1b)[42].

Dissolution therapy

Chemolysis with hemiacidrin may be a secondary treatment for infection stones and the success rates in stone dissolution is 68-80%,which are described in the literatures (LE: 3)[43][44].

Urinary acidification

Methionine, 200-500 mg, 1-3 times daily or ammonium chloride, 1 g, 2 or 3 times daily can be used (LE: 3)[45][46].

Urinary alkalinization

Oral intake of citrate can be used in order to prevent struvite crystal formation and aggregation by increasing urinary citrate Levels, although there has been a reluctance in relation to the potential increase in urinary pH (LE: 1b)[47].


UTI: Urinary Tract Infection, MSU: Midstream Urine, SIRS: Systemic Inflammatory Response Syndrome, CVA: Costovertebral Angle, CRP: C-Reactive Protein, PCT: Procalcitonin, CT: Computer Tomography, MR: Magnetic Resonance, RUC: Retrograde Ureteral Catheterization, PCN: Percutaneous Nephrostomy, PCNL: Percutaneous Nephrolithotomy, ESWL: Extracorporeal Shock Wave Lithotripsy , AHA: Aceto-Hydroxamic Acid


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