Urinary Tract Infections: Diagnosis and Treatment

• Urinary Tract Infections (UTI) are common bacterial infections in ambulatory care
• Up to 60% of women experience symptomatic UTIs in their lifetime
• 10% of women have UTIs each year
• Etiologic agents of UTI, pathogenesis, clinical manifestations, diagnostic methods, and treatment options are key to consider
• Understanding the clinical differences of UTI in special populations such as those with Diabetes Mellitus, Pregnancy, and transplant patients is imporant

Terminology

• Significant Bacteriuria: 10^5 cfu/ml, which equals ≥100,000 colonies/mL
• Asymptomatic Bacteriuria: ≥100,000 colonies, but without symptoms
• Cystitis is an infection of the bladder, whereas urethritis is an infection of the urethra
• Acute Pyelonephritis: A sudden and severe kidney infection
• Complicated UTI: UTIs associated with factors that increase the risk of treatment failure
• Uncomplicated UTI: Acute cystitis or pyelonephritis in healthy non-pregnant women
• Intrarenal and Perinephric Abscess indicate collections of pus within or around the kidney

Recurrent UTI

• Reinfection: Recurrent infection with a different organism
• Relapsed Infection: Recurrence with the same organism, typically within 2 weeks of treatment

Risk Factors

• Risks include:
  • Previous UTI
  • GU procedure
  • Foreign body like Foley Catheter
  • Calculi
  • Neurogenic Bladder
  • Renal Transplant

Pathogenesis

• Ascending Route (95%): Occurs through colonization
• Hematogenous Route (<5%): Occurs through the bloodstream
• Lymphatic Route: Very rare

Uropathogens

• Acute Uncomplicated Cystitis is commonly caused by E. coli (70-90%)
• Other possible pathogens include S. saprophyticus (15%)
• Acute Uncomplicated Pyelonephritis is also primarily caused by E. coli (90%)
• Other possible pathogens include Klebsiella (4%), and Proteus (4%)

Other Organisms

• Corynebacterium urealyticum can lead to struvite stones
• Adenoviruses (particularly type 11) can result in hemorrhagic cystitis, more common in pediatric allogenic hematopoietic stem cell transplant recipients
• Acinetobacter species, ESBL, and other MDRO species may pose risk
• Candida spp a fungi often occur in patients with indwelling catheters

Uropathogenic E.coli (UPEC)

• An important virulence factor is cell wall antigens (O antigens), including: 01, 02, 04, 06, 07, 08, 075, 0150, and 018ab
• K antigens: K1, K2, K5, K12, K13, K51 work to protect against macrophages
• Adhesins: P fimbriae, Type1 fimbriae, S fimbriae, and Adhesins are key
• Motility: H-antigen = Flagella
• Siderophore aerobactin captures Fe2+ from tissue for the bacteria to survive

Host Defense Mechanisms

• Urine helps fight infection through several mechanisms
  • Acidic pH makes it intolerable for pathogens (pH=~5.5)
  • High urine osmolality
  • Urinary inhibitors of bacterial adherence
  • Competitive inhibitors of attachment to uroepithelial cells
  • Mechanical flushing from urine flow
• Mucosal immunity also assists
  • Urothelial secretion of cytokines and chemokines
  • Mucopolysaccharide lining, which increases difficulty of bacterial penetration
  • Mucosal IgA
  • In men, prostatic secretions contain bactericidal zinc and the urethra is longer

Genetic Factors

• Genetic factors that increase the risk of UTI are:
  • Primarily for women
  • P blood group (P1)
  • ABH blood group (B and AB nonsecretors)
  • Rh-
  • Lewis recessive phenotype
  • Nonsecretor phenotype

Immunocompromised Patients

• Those most affected by UTIs are:
  • Renal transplant patients
  • Those with AIDS
  • Individuals with certain malignancies (GIT)
  • Those with Diabetes Mellitus
  • The elderly

Risk factors for recurrent UTI in young women:

• Genetic Susceptibility: ABO/secretor status, P blood group, HLA type, being Black (?)
• Behavioral Susceptibility: Use of spermicides, specific voiding practices, and estrogen deficiency in postmenopausal women
• Facilitated by: Behavioral factors such as sexual intercourse
• Other risk factors: Sexual intercourse, a new sexual partner, first UTI before age 15, spermicide use, and maternal history of UTI

Renal Transplants

• UTI is the single most common bacterial infection for renal transplant patients
• 50% of patients develop it in the early post-op period
• 60% of Gram-Negative Rod (GNR) bacteremia stems from UTI
• Early period post-transplant (3-6 Months) are marked by high incidence of pyelonephritis, bacteremia, and relapse
• Therapy is not recommended for Asymptomatic bacteriuria

Factors related to UTI in AIDS patients

• Unprotected, insertive anal intercourse
• Lack of circumcision
• Overt AIDS with CD4 < 200
• Advanced AIDS with protein-calorie malnutrition

Clinical Manifestations of UTI

• Neonates and children < 2 years present non-specifically while elderly patients are asymptomatic
• Lower urinary tract infection/cystitis:
  • No fever
  • Suprapubic pain
  • Dysuria
  • Frequency
  • Urgency
• Upper urinary tract infection/pyelonephritis:
  • Fever & chills
  • Flank pain radiating to the groin
  • Lower UTI symptoms
  • Nausea/Vomiting
  • CVA tenderness

Diagnosis

• Microscopic exam of urine indicates a clean-catch midstream urine specimen
• Dipstick leukocyte esterase has high sensitivity and specificity for detecting pyuria
• Microscopic or gross hematuria may be present (hemorrhagic cystitis)
• Pyuria is evident (at least 10 leukocytes/mm3).
• Presence of RBC in urine can be indicative of Calculi, Tumors, Vasculitis, GN, AND Renal TB.
• A WBC cast indicates pyelonephritis
• Urine culture can quantify bacteria, indicative of > 10^5 bacteria / ml

• 10^5 bacteria / ml is quantified as 100,000 colonies/mL

• Adequate collection methods involve:
  • Midstream clean catch
  • Catheterization
  • Suprapubic aspiration
• UTI is the most common source of GNR bacteremia

Treatment

• Uncomplicated Cystitis
  • Nitrofurantoin for 5 days
  • TMP/SMX for 3 days
• Pyelonephritis First Line treatment:
  • Fluoroquinolone or Ceftriaxone
  • TMP/SMX
• Fluoroquinolone:
  • Not used in pregnant women
  • IV antibiotics

Risk Factors for Multi-Drug Resistant Gram-Negative UTIs:

• Previous MDRO urinary isolate
• In-patient stay at a healthcare facility
• Use of a fluoroquinolone, trimethoprim-sulfamethoxazole, or broad-spectrum beta-lactam
• Travel to areas with high rates of multidrug-resistant organisms

Prevention includes:

• Post-Menopausal women: intravaginal estrogen
• Avoiding spermicides
• Mear despues de chingar

Asymptomatic Bacteriuria:

• Treat pregnant females
• Treat Traumatic Urologic procedure: Transurethral prostatectomy, percutaneous lithotomy, etc.

UTI can complicate Pregnancy

• Asymptomatic bacteriuria: 5-10%; If untreated, 20-30% can develop into Pyelonephritis
• Recurrent asymptomatic bacteriuria needs to be treated
• Cystitis: is seen in 0.3-1.3% or pregnant mothers
• Pyelonephritis: is seen in 1-2% or pregnant mothers
• Dilatation of ureters and renal pelvis is seen
• Decreased ureteral peristalsis may result
• Glucose and aminoaciduria can result
• Reduced bladder tone is present

Complications of UTI in Pregnancy include:

• Respiratory insufficiency
• Sepsis syndrome
• Renal dysfunction
• Anemia (Hemolysis)
• Preterm birth and low birth weight results

Clinical Presentations of UTI in Diabetics:

• Increase in rate of Acute pyelonephritis
• Fivefold higher rate than non-diabetics
• Bilateral involvement
• 15-20% positive blood cultures
• More common in women
• Complicated UTI that can result in:
  • Renal cortical abscess
  • Xanthogranulomatous pyelonephritis
  • Emphysematous cystitis: pneumaturia
  • Perinephric abscess
  • Fungal infection
  • Resistant organism

Xanthogranulomatous Pyelonephritis

• Diffuse parenchymal destruction is seen
• Predisposing factors :obstruction
• Patients show (staghorn calculi) and infections
• Those at risk are patients with E.coli and Proteus spp
• Adults > 40 years
• Common in Males > females
• Affects one side in a Unilateral manner
• Diagnosis involves: Ct scan or biopsy
• Treatment involves : nephrectomy

Key Points

• UPEC virulence factors increase the risk of UTI
• Structural, genetic, and behavioral factors increase the risk of UTI
• Treat Asymptomatic Bacteriuria: Pregnancy and GU procedures
• Tx cystitis should be short term
• Pyelo should be treated for 14 days
• Intravaginal estrogen therapy is helpful for Post-menopausal females