UTI: Diagnosis, Treatment, and Prevention

• Urinary tract infections (UTIs) are common bacterial infections, especially in ambulatory care within the U.S.
• Symptomatic UTIs affect up to 60% of women during their lifetime, and 10% of women each year.

Terminology

• Significant Bacteriuria is 10^5 cfu/ml ≥100,000 colonies/mL
• Asymptomatic Bacteriuria is ≥100,000 colonies but without symptoms
• Cystitis is inflammation of the bladder.
• Urethritis is inflammation of the urethra.

Recurrent UTI Classifications

• A reinfection involves a different organism.
  • It is the most common cause of recurrent infection.
  • Occurs more than 2 weeks after the original infection.
  • It should be treated with the same first-line agent.
• A relapsed infection involves the same organism.
  • Recurrence happens within 2 weeks of treating the original infection.
  • A culture guides antibiotic selection.
  • It is treated for 7-10 days.

Complicated Cystitis Definition

• Defined by one of these factors: pregnancy, male sex, recent antibiotic exposure, healthcare-acquired infection, urinary catheter, immunosuppression (including diabetes mellitus (DM)), chronic kidney disease (CKD), neurogenic bladder, or urinary obstruction

Pathogenesis Routes

• Ascending route (95%): Colonization
• Hematogenous route (<5%)
• Lymphatic route

Risk Factors

• All ages: Previous UTI, GU procedure, Foley Catheter, Calculi
  • Females: Neurogenic bladder & Renal transplant
  • Males: Lack of circumcision
• Adults
  • Females: Sexual intercourse, pregnancy, DM
  • Males: Insetive rectal intercourse
• Older Age
  • Both: Functional or mental impairment
  • Females: Menopause & bladder prolapse
  • Males: BPH

Uropathogens

• Acute uncomplicated cystitis: E. coli (70-90%), S. saprophyticus accounts for 15%
• Acute uncomplicated pyelonephritis: E. coli accounts for 90%

Other Organisms

• Corynebacterium urealyticum, formerly Corynebacterium group D2, is a nosocomial pathogen.
  • It's a GPR urea-splitting, and slow-growing bacillus that leads to struvite stones.
• Adenoviruses (particularly type 11) causes hemorrhagic cystitis in pediatric allogenic hematopoietic stem cell transplant recipients.
• MDRO is bacteria such as Acinetobacter species and ESBL.
• Anaerobic organisms are rare.
• Fungi, like Candida spp., occur in patients with indwelling catheters who are receiving antimicrobial therapy.
• Staphylococcus saprophyticus tends to cause infection in young, sexually active females, and is coagulase-negative.

Uropathogenic E. coli (UPEC) Virulence Factors

• Cell wall antigens (O antigens): 01, 02, 04, 06, 07, 08, 075, 0150, 018ab
• K antigens: K1, K2, K5, K12, K13, K51 (protects them from macrophages)
• Adhesins: P fimbriae, Type1 fimbriae, S fimbriae, Adhesins, etc.
• Motility: H-antigen = Flagella
• Resistance to serum bactericidal activity
• Production of alpha hemolysins
• Siderophore aerobactin: Captures iron from tissue for bacteria's survival
• Cytotoxic necrotizing factor type 1

Urinary Tract Host Defense Mechanisms

• Urine provides defense by:
  • Acidic pH intolerant to pathogens pH=5.5
  • High urine osmolality
  • Urinary inhibitors of bacterial adherence
  • Competitive inhibitors of attachment to uroepithelial cells
  • Mechanical flushing of urine flow
• Mucosal immunity defenses:
  • Urothelial secretion of cytokines and chemokines
  • Mucopolysaccharide lining, which increases difficulty of bacterial penetration
  • Mucosal IgA
  • Prostatic secretions containing bactericidal zinc contributes to a longer urethra length in men

Genetic Factors Increasing UTI Risk

• Mainly for women: P blood group (P1), ABH blood group (B and AB nonsecretors), Rh-, Lewis recessive phenotype, and Nonsecretor phenotype.

Immunocompromised patients most affected by UTIs:

• Including renal transplant recipients, AIDS patients, individuals with GIT malignancies, those with DM, and the elderly

Risk factors for recurrent UTI in young women:

• Sexual intercourse (the more frequent the more likely), a new sexual partner, age at first UTI < 15, any spermicide use, and maternal history of UTI.

Renal Transplants and UTIs

• UTIs are the single most common bacterial infection in renal transplant patients.
• 50% of patients will develop UTIs in the early post-op period.
• 60% of GNR bacteremia comes from UTIs.
  • GNR = Gram (-)
• High incidence of pyelonephritis, bacteremia, and relapse rate during early period post-transplant (3-6 months)
• Therapy is not recommended for asymptomatic bacteriuria.

Factors contributing to UTI occurrence in AIDS patients:

• Unprotected, insertive anal intercourse; lack of circumcision; overt AIDS with CD4 < 200; and advanced AIDS with protein-calorie malnutrition.

Malignancy and UTI

• Wasting from protein calorie malnutrition
• GUT/GIT malignancies include a higher incidence and wider spectrum of organisms.
  • Fistulous tracts, e.g., colovesical fistula and anaerobes

Clinical Manifestations of UTI

• Neonates and children < 2 years exhibit nonspecific symptoms.
• Elderly patients might be asymptomatic.
• Lower urinary tract infection/cystitis: symptoms include:
  • No fever
  • Suprapubic pain, dysuria, Frequency, and Urgency
• Upper urinary tract infection/pyelonephritis:
  • Fever & chills
  • Flank pain radiating to the groin
  • LUTI symptoms
  • Nausea/Vomiting, and CVA tenderness

Diagnosis of UTI

• Microscopic examination of urine: clean-catch midstream urine specimen
• Pyuria: At least 10 leukocytes/mm3 of midstream urine
• Dipstick leukocyte esterase: high sensitivity and specificity for detecting pyuria
• Microscopic or gross hematuria (hemorrhagic cystitis)
• Note, pyuria does not always mean UTI. RBC in the urine is associated with calculi, tumor, vasculitis, glomerulonephritis, and renal TB.
• WBC cast indicates pyelonephritis. Sterile pyuria has WBC in the urine, but no growth on culture and is associated with TB, Chlamydia, and Fungal infections.
• Urine culture: quantification of bacteria: > 10^5 bacteria/ml
• Adequate methods for urine collection include:
  • Midstream clean catch, catheterization, and suprapubic aspiration
• UTI is the most common source of GNR bacteremia.
• Bacteremia occurs in 60% of elderly males with pyelonephritis

Diagnosis With Radiology

• Non-contrast CT scan
• B-mode ultrasonography
• Plain abdominal XR

UTI Treatment

• Uncomplicated Cystitis:
  • Nitrofurantoin for 5 days
  • TMP/SMX for 3 days
  • Cefaclor for 5 days
  • Cefpodoxime for 3 days
  • Cephalexin for 7 days
  • Cefdinir for 5 days
• Patients will present only with a complaint of painful urination/burning sensation.
• Pyelonephritis First Line:
  • Fluoroquinolone or Ceftriaxone
  • TMP/SMX
• Avoid fluoroquinolones in pregnancy.
• Treat pyelonephritis for 10-14 days.

Risk factors for multidrug-resistant gram-negative urinary tract infections include:

• A previous MDRO urinary isolate, in-patient stay at a health care facility, use of a fluoroquinolone or trimethoprim-sulfamethoxazole, or broad-spectrum beta-lactam, and travel to parts of the world with high rates of multidrug-resistant organisms like India, Mexico, Israel, and Spain

Prevention of UTI

• Post-Menopausal women: intravaginal estrogen.
• Avoid spermicides
• Post-coital voiding
• It is uncertain if cranberry juice (>4L), Probiotics and Lactobacillus acidophilus, and Chronic Abx have an effect.

Who should be treated in Asymptomatic Bacteriuria?

• Pregnant females and traumatic urologic procedure patients like Transurethral prostatectomy and percutaneous lithotomy patients

UTI Complicating Pregnancy

• Asymptomatic bacteriuria occurs in 5-10 % of pregnancies.
  • 20-30% of untreated cases develop into pyelonephritis.
• Recurrent asymptomatic bacteriuria, cystitis (0.3-1.3%), and pyelonephritis (1-2%).
• Progesterone decreases the muscular tone of the bladder.

Pathogenesis of UTI during Pregnancy includes:

• Dilatation of ureters and renal pelvis
• Decreased ureteral peristalsis
• Pregnancy-induced glucosuria and aminoaciduria
• Reduced bladder tone is caused by progesterone

Complications in Pregnancy from a UTI include:

• Respiratory insufficiency, sepsis syndrome, renal dysfunction, anemia (hemolysis), and preterm birth with low birth weight

Clinical Presentations of UTI in Diabetics

• Fivefold higher rate of acute pyelonephritis compared to non-diabetics.
• Bilateral involvement.
• Positive blood cultures in 15-20% of cases. It's more common in women.
• Complicated UTIs
  • Renal cortical abscess
  • Xanthogranulomatous pyelonephritis
  • Emphysematous cystitis: pneumaturia
  • Perinephric abscess
  • Fungal infection
  • Resistant organism

Xanthogranulomatous Pyelonephritis

• It leads to diffuse parenchymal destruction and caused by obstruction
• (staghorn calculi) and infections
• It is primarily caused by E. coli and Proteus spp.
• Common in Adults > 40 years & Males > females
• Typically Unilateral, diagnose with CT scan or biopsy, and treated with nephrectomy

Xanthogranulomatous Pyelonephritis - Microscopic description

• Foamy macrophages with lipid-laden content.
• Plasma cells and lymphocytes are present.
• Should be distinguished and may be miss-diagnosed as renal cell carcinoma

Key points

• UPEC virulence factors increased risk of UTI
• Structural , genetic and behavioral factors increased risk of UTI
• Tx ASB during Pregnancy and GU procedures
• Tx cystitis short term vs Pyelo 14 d
• Intravaginal estrogen for Post-menopausal females