Steve Dong, MD
Leonard G. Gomella, MD, FACS
BASICS
DESCRIPTION
• Complicated urinary tract infection (UTI) occurs in adults with functional or structural abnormalities of the genitourinary system who develop an infection. Associated abnormalities can include:
– Structurally abnormal urinary tract (eg, BPH, kidney stones)
– Functionally abnormal urinary tract (eg, neurogenic bladder, vesicoureteric reflux)
– Impaired host defense (eg, immunosuppression/diabetes)
– Increased bacterial virulence, multidrug-resistant organism
– Children and pregnant women
– Hospital-acquired infection (1)
• Patients with complicated UTI are more likely to harbor multiresistant pathogens, and whose infections are more difficult to eradicate (2).
EPIDEMIOLOGY
Incidence
• UTI accounts for 7 million physician visits annually and 100,000 hospital admissions.
• Complicated UTI is a wide spectrum; its incidence depends on age, sex, host, and environmental factors.
Prevalence
• For men, the lifetime prevalence of UTI is 14 per 100. Compared to women which is 53 per 100.
• The prevalence of asymptomatic bacteriuria, which makes host at risk for symptomatic episodes of complicated UTI
– Patients with indwelling catheter: Approaches 100% based on timing.
– Elderly nursing home residents: 50%
– Patients with neurogenic bladder managed by clean intermittent catheterization: 30–40% (Table 1).
RISK FACTORS
• Male gender
• Elderly
• Hospital associated infection
• Pregnancy
• Diseases: Diabetes mellitus; history of recent UTI; diseases that cause immunosuppression or require treatment with immunosuppressive agents such as steroids
• Recent antimicrobial use
• Indwelling urinary catheter
• Recent urologic intervention
• Urinary tract obstruction (eg, kidney stones, benign prostatic hypertrophy [BPH], urethral stricture disease)
• Spinal cord injury with neurogenic bladder
• Azotemia caused by intrinsic renal disease
Genetics
• Six genes in humans have found to be associated with host response to infection predispose them to UTI
– HSPA1B, CXCR1 & 2, TLR2, TLR4, TGF-β1
PATHOPHYSIOLOGY
• Primary UTI occurs via 1 of 3 routes (1):
– Ascending by inoculation of urethra/urethral catheter with bowel flora: Most common
– Hematogenous seeding of kidney
– Lymphatic spread
• Structural, functional, or metabolic abnormalities allow infection of more uncommon pathogens, and increase the rate of therapy failure
• Escherichia coli, accounts for only approximately half of infections with complicated UTI, compared to uncomplicated (75–95%)
• A broader range of organisms can seen in complicated UTI, include Proteus mirabilis and Klebsiella pneumoniae as well as Pseudomonas, Serratia, Providencia, enterococci, staphylococci, and fungi (3)
ASSOCIATED CONDITIONS
• Diabetes mellitus (10%)
• Renal failure
• Multiple sclerosis
• Spinal cord injury
GENERAL PREVENTION
• Proper infection control practice in health care facilities to avoid contact transfer of resistant organisms between patients.
• Avoid over-treatment of asymptomatic bacteruria
• For patients with spinal cord injury, maintain a low bladder pressure to prevent reflux, ascending infections, and progression to renal failure. Monitoring of bladder pressure and function can be done with urodynamics testing
• Prevention of complicated UTI with long-term prophylaxis in at risk adult population is not recommended due to the emergence of resistant organisms (4)
DIAGNOSIS
HISTORY
• Assess for any of risk factors listed above.
Clinical presentation may or may not be associated with clinical symptoms (eg, dysuria, urgency, flank pain, fever)
• Clinical presentation may vary from severe obstructive pyelonephritis with imminent urosepsis to catheter associated UTI, which disappears once the catheter is removed.
• Patients with spinal cord injuries can present with bladder, leg spasms, or autonomic dysreflexia.
• Patients with multiple sclerosis may present with fatigue or worsening neurologic function.
• Fever without localizing findings is a common presentation of UTI in patients with chronic indwelling catheters.
PHYSICAL EXAM
• Check vital signs to assess severity of infection, presence of systemic disease.
• Assess for suprapubic pain, flank pain, urethral discharge rectal exam for tenderness
• Evaluate for anatomical abnormalities, such as the presence of a nephrostomy tube, or an ileal conduit
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis
– Pyuria is almost always present
– Unless the collecting system is obstructed
– White cell casts suggest a renal origin
• Urine culture is positive for a UTI with the following:
– ≥105 cfu/mL in mid-stream sample
– ≥104 cfu/mL in a straight catheter urine sample
Imaging
• Is recommended in patients suspected of complicated infection, especially in those not responding to therapy for 48–72 h, in patients with rapid recurrent infection and found to have bacteria susceptible to antimicrobial used (ie, persistence), when obstruction suspected, as well as history of kidney stones or has symptoms of renal colic
• Renal Ultrasound
– For patients who could not be exposed to radiation
– Cheap and readily available
– Best to evaluate for hydronephrosis
– Lack details and sensitivities of other imaging modalities
• Computed tomography (CT) urogram
– The study of choice
– Most sensitive in detecting abnormalities and able to delineate the extent of disease. Has 3 phases
No contrast—evaluate for renal or ureteral calculi, gas-forming infections, hemorrhage
Contrast—detect areas lacking perfusion due to infection induced ischemia
Delayed phase—detect for any filling defects such as fungus ball
• Magnetic resonance imaging (MRI)
– Has no advantage over CT except in patients who wants to avoid contrast and radiation (3)
Diagnostic Procedures/Surgery
• Urologic evaluation is often necessary in the setting of a complex UTI
• Urinary obstruction associated with UTI must be relived emergently. e.g. placing a ureteral stent or nephrostomy tube for a obstructing ureteral calculus, or placing a Foley catheter for urethral stricture.
• Cystoscopy allows direct visualization of bladder to assess for foreign body, ectopic ureters, diverticula, stones, or other abnormalities that could be a nidus for infection
• Post-void residual (PVR): Should be considered in men with baseline voiding symptoms; high residual with stasis increases risk of infection
• Localization studies: Selective cultures from each kidney via ureteral catheterization and prostatic cultures are helpful in identifying source of bacterial persistence.
Pathologic Findings
• In acute pyelonephritis—polynuclear leukocytes are seen throughout renal tubules, may form casts that can be seen in an urinalysis
• In chronic pyelonephritis, both lymphocytes and plasma cells are the predominant cells.
DIFFERENTIAL DIAGNOSIS
• For cystitis: Interstitial cystitis vs. urethritis
• For pyelonephritis:
– Pancreatitis vs. appendicitis vs. diverticulitis vs. acute focal/multifocal nephritis
– Urolithiasis
TREATMENT
GENERAL MEASURES
If severe infection or toxicity is present, CT should be obtained to rule out obstructive pyelonephritis; if found, decompression is critical.
MEDICATION
First Line
• Common oral antimicrobials:
– Fluoroquinolones: More expensive (levofloxacin > ciprofloxacin), cover staphylococci and most gram-negatives including Pseudomonas
– Trimethoprim-sulfamethoxazole: Resistance is often seen, therefore not recommended for empiric therapy (3)
• Commonly parenteral antimicrobials:
– For those who have hemodynamic instability, or cannot tolerate oral therapy, or for patients with suspected resistant organisms
– Gentamicin: Can cover Staphylococci, most gram-negatives including Pseudomonas; augments ampicillin for coverage in pyelonephritis
– Cephalosporin
– Carbapenem
– Aminopenicillin PLUS a β-lactam inhibitor. Aminopenicillin by itself (eg, ampicillin) is not recommended for empiric therapy (3)
• For complicated pyelonephritis (1,5)
– Renal/perirenal abscess is suspected if indolent/recurrent fever >72 h and/or persistently positive culture despite antimicrobial treatment; CT when suspect; if small renal abscess, then antimicrobial treatment; if large (>3 cm) renal abscess or perinephric abscess, then percutaneous drainage
– Inpatient therapy is recommended:
IV fluoroquinolone or ampicillin + gentamicin or 3rd-generation cephalosporin (3)
Duration without bacteremia: 2–3 days IV then 10–14 days PO antimicrobial
Duration with bacteremia: 7 days IV, then 10–14 days appropriate PO antimicrobial
Second Line
• Colistin: Reserved for extended-spectrum β-lactamase (ESBL)-producing bacteria that are resistant to gentamycin and carbapenems.
• Tigecycline: Has activity against ESBL-bacteria, but is unstable in urinary tract.
SURGERY/OTHER PROCEDURES
As needed for cause of complicated UTI, such as stone, foreign body, or enlarged prostate
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
Cranberry juice and products have not been shown to reduce the risk of complicated UTI.
ONGOING CARE
PROGNOSIS
When appropriate antimicrobial therapy is chosen, complicating factors are identified and treated, and close follow-up is achieved with documentation of clearance of infection, a good prognosis is expected.
COMPLICATIONS
• More likely to occur in patients with comorbidities
• Acute complicated pyelonephritis can progress to emphysematous pyelonephritis, renal abscess, perinephric abscess, or papillary necrosis.
• Infections can spread to cause bone and joint infection, or endocarditis
• Renal failure in patients with spinal cord injury with recurrent sepsis
FOLLOW-UP
Patient Monitoring
Repeat urine cultures must be obtained because patients with complicated UTI are more at risk for recurrent infection
REFERENCES
1. Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell-Walsh Urology, 10th ed. Philadelphia, PA: Saunders; 2012.
2. Neal DE. Complicated Urinary Tract Infections. Urol Clin N Am. 2008;35:13–22.
3. Hooton TM, Calderwood SB, Bloom A. Acute Complicated cystitis and pyelonephritis. UptoDate.com. Accessed January 2014.
4. Nicolle LE; AMMI Canada Guidelines Committee. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol. 2005:16(6):349–360.
5. Pallett A, Hand K. Complicated urinary tract infections: Practical solutions for the treatment of multiresistant Gram-negative bacteria. J Antimicrob Chemother. 2010;65(Suppl ):iii25–33.
See Also (Topic, Algorithm, Media)
• Pyelonephritis
• Urethritis, Acute Male
• Urinary Tract Infection (UTI), Adult Female
• Urinary Tract Infection (UTI), Adult Male
• Urinary Tract Infection (UTI), Complicated, Adult Image 
• Urinary Tract Infection (UTI), Complicated, Pediatric
CODES
ICD9
• 592.0 Calculus of kidney
• 599.0 Urinary tract infection, site not specified
• 600.01 Hypertrophy (benign) of prostate with urinary obstruction and other lower urinary tract symptoms (LUTS)
ICD10
• N20.0 Calculus of kidney
• N39.0 Urinary tract infection, site not specified
• N40.1 Enlarged prostate with lower urinary tract symptoms
CLINICAL/SURGICAL PEARLS
• Complicated UTI can have a wide range of atypical presentations, eg, MS patients with neurologic decompensation, spinal cord injury patients with spams or autonomic dysreflexia, or nursing home patient who has indwelling Foley with fever should be suspected of UTI.
• CT should be considered the imaging of choice, and with a low threshold with any history of stone, flank pain, or pyelonephritis not improving or persistent positive culture.
• Presence of obstruction on imaging requires urgent decompression.