Microbiology of Urinary Tract Infections

Urinary Tract Infections in Adults

• Urinary infections can be categorized as either acute uncomplicated cystitis or acute complicated UTI.

• Acute simple cystitis is presumed confined to the bladder, with no signs or symptoms suggesting upper tract or systemic infection.

• Acute complicated UTI presents with signs/symptoms indicating infection beyond the bladder, including fever (>99.9°F/37.7°C), chills, rigors, significant fatigue/malaise, flank pain, costovertebral angle tenderness, or pelvic/perineal pain in men.

• Special populations warrant unique management considerations, including pregnant women and renal transplant recipients.

UTI Definitions

• Lower UTI: Cystitis, urethritis, prostatitis.

• Upper UTI: Pyelonephritis, intra-renal abscess, perinephric abscess (usually late complications of pyelonephritis).

• Uncomplicated UTI: Infection in a structurally and neurologically normal urinary tract. Simple cystitis lasting 1-5 days.

• Complicated UTI: Infection in a urinary tract with functional or structural abnormalities (e.g., indwelling catheters, renal calculi). Includes cystitis of long duration or hemorrhagic cystitis.

Asymptomatic Bacteriuria

• Isolation of a specified quantitative count of bacteria in a properly collected urine specimen from an individual without urinary tract infection (UTI) symptoms.

• A count of ≥10⁵ colony-forming units (CFU)/mL indicates asymptomatic bacteriuria.

Indications for Screening/Treating UTIs

• Pregnancy
• Patients undergoing urologic interventions
• Renal transplant recipients
• Patients with neurological or structural abnormalities of the urinary tract
• Older patients
• Patients with Diabetes Mellitus

Clinical Symptoms and Presentation

• Cystitis: Dysuria, urinary urgency/frequency, bladder fullness/discomfort. Hemorrhagic cystitis (bloody urine) can occur in up to 10% of otherwise healthy women.

• Pyelonephritis (upper UTI): Fever, sweating, nausea, vomiting, flank pain, dysuria, and signs/symptoms of dehydration and hypotension. A history of vaginal discharge may suggest vaginitis, cervicitis, or pelvic inflammatory disease as a possible cause for dysuria.

Diagnosis of UTI

• Urinalysis (UA): Microscopic examination for WBCs, RBCs, and bacteria.

• Urine dipstick test: Rapid screening test for leukocyte esterase and nitrite, although nitrites are only positive in ~25% of cases.

• Urine culture: Indicated for pyelonephritis, children, pregnant women, and patients with urinary tract abnormalities.

Indications for Evaluating the Urinary Tract

• Children: Ultrasound, intravenous pyelogram (IVP), or computed tomography (CT) scan.
• Bacteremic pyelonephritis not responding to therapy: Ultrasound, IVP, or CT scan.
• Nephrolithiasis or neurogenic bladder: Ultrasound, CT, or IVP with post-voiding films.
• Men with 1st or 2nd infection: Careful prostate examination, ultrasound, or IVP with post-voiding films.

Differential Diagnosis

• Vaginitis
• Pelvic inflammatory disease
• Painful bladder syndrome (Interstitial cystitis)

Microbial Species

• Escherichia coli
• Enterobacteriaceae (e.g., Klebsiella spp., Proteus spp)
• Pseudomonas
• Enterococci
• Staphylococci (methicillin-sensitive Staphylococcus aureus [MSSA] and methicillin-resistant S. aureus [MRSA])
• Candida spp

Pathogenesis of UTI

• Hematogenous Route: Bacteria enter the bloodstream and travel to the kidneys.
• Ascending Route: Bacteria enter the urinary tract via the urethra and ascend to the bladder and/or kidneys. This begins with colonization of the vaginal introitus and urethra before reaching the bladder.

Factors Predisposing to UTI in Women

• Short urethra
• Sexual intercourse without post-coital voiding
• Use of diaphragms or spermicides
• Estrogen deficiency

Host Factors Predisposing to UTI

• Extra-renal obstruction (posterior urethral valves, urethral strictures)
• Renal calculi
• Incomplete bladder emptying
• Neurogenic bladder
• Immunocompromised individuals (e.g., diabetes, transplant recipients)

Virulence

• Ability of microorganisms to overcome body defenses.
• Factors include the number of infecting microorganisms, their route of entry, and the host's immune response.

Virulence Factors

• Adhesion
• Invasion
• Resistance of host immunity
• Secretion of toxins
• Competition for iron and nutrients

Antibacterial Host Defenses

• Urine flow and micturition
• Urine osmolality and pH
• Inflammatory response (PMNs, cytokines)
• Inhibitors of bacterial adherence (e.g., bladder mucopolysaccharide, secretory immunoglobulin A)

UTI: Upper Tract Disease

• Symptoms: Fever (>38°C), nausea, vomiting, costovertebral pain, urinary frequency, urgency, dysuria.
• Evaluation: Urine culture, potentially blood cultures, imaging if no improvement. Microbiology (e.g., E. coli, Citrobacter, Pseudomonas aeruginosa, Enterococci, Staphylococcus spp).
• Treatment: Intravenous antibiotics for 10-14 days (or longer for perinephric abscess).

Treatment: General Principles

• Quantitative cultures may be unnecessary for typical uncomplicated cystitis.
• Culture urine in cases of upper UTI, complicated UTI, or treatment failure.
• Susceptibility testing needed for all recurrent or complicated infections; perhaps not uncomplicated cases.
• Identify/correct predisposing factors (obstruction, calculi, diabetes).

Recurrent UTI

• Risk factors: P1 blood group positive, post-menopausal status, diabetes, recent antimicrobial use, behavioral risks (spermicide use, new partner), first UTI before age 15.

Prevention Strategies

• Alternative contraception methods.
• Postcoital voiding and increased fluid intake.
• Cranberry juice (for sexually active women with history of UTIs).
• Antibiotic prophylaxis (>2 symptomatic UTIs within 6 months or >3 over 12 months).
• Postcoital vs. continuous prophylaxis vs. self-treatment.

Empiric Antimicrobials

• Choice of antimicrobial agents to reach high concentrations in urine and vaginal secretions to inhibit E. coli (the primary pathogen in cystitis).
• Short course (3 days) for uncomplicated infections.
• Longer duration (10-14 days) for complicated infections (e.g., pyelonephritis).

Empiric Therapy - Acute Simple Cystitis

• Trimethoprim (with/without sulfamethoxazole)
• Nitrofurantoin
• Fosfomycin
• Ciprofloxacin

Empiric Therapy - Acute Simple Cystitis - Beta-lactams

• Amoxicillin-clavulanate (500 mg twice daily)
• Cefpodoxime (100 mg twice daily) or (300 mg twice daily)
• Cefadroxil (250 to 500 mg every six hours)

Empiric Therapy - Acute Complicated Urinary Tract Infection

• Ceftriaxone (1 gram IV once daily)
• Piperacillin-tazobactam (3.375 grams IV every six hours).
• Fluoroquinolones (e.g., ciprofloxacin or levofloxacin), Imipenem (500 mg IV every 6 hours), Meropenem (1 gram IV every 6-8 hours), or Doripenem (500 mg IV every 8 hours).
• Vancomycin (for MRSA)

Bacterial Virulence Factors-I

• Enhanced adherence to uroepithelial cells (Type 1 & P fimbriae).
• P fimbriae bind to galactose disaccharide on uroepithelial cells and P blood group antigens (D-galactose).
• Phase variation (Type 1 down-regulated; Type P upregulated during upper tract infections).

Bacterial Virulence Factors-II

• Flagella-enhanced motility
• Production of hemolysins.
• Production of aerobactin (iron acquisition in the iron-poor urinary tract).