Urinary Tract Infections

Objectives

1. Differentiate between asymptomatic bacteriuria, uncomplicated cystitis and pyelonephritis.

2. Apply the results of laboratory tests and clinical signs and symptoms to aid in the diagnosis of urinary tract infections.

3. Design empiric and definitive pharmacotherapy plans (drug, dose, route, frequency and duration) for the management of complicated and uncomplicated urinary tract infections.

4. Describe adverse effects and monitoring parameters for drug regimens used to treat urinary tract infections.

Define asymptomatic bacteriuria

1. Lack of urinary symptoms

2. Presence of at least 1 species of bacteria in the urine (≥10^5 CFUs/mL)

3. With or without pyuria (white blood cells in urine) (20 WBC/mm³

When Routine Screening is NOT Recommended in Asymptomatic Bacteriuria → what patients?

1. Non-pregnant women

2. Patients with diabetes

3. Older adults in the community

4. Long-term care facility patients

5. Spinal cord injury patients

6. Indwelling catheter patients

When Routine Screening IS Recommended

1. Pregnant women

2. Patients undergoing urologic procedures

3. Kidney transplant patients

Define acute uncomplicated cystitis

1. Infection confined to the bladder in afebrile men and women

2. Absence of flank pain, fever or tenderness

3. Pyuria (>10 WBC/mm³)

4. Culture positive for uropathogens >1,000 CFU/mL (not required for diagnosis)

Signs, symptoms and lab values of UTI

• Dysuria, increased frequency/urgency

• 25 WBC/mm³

• Blood, nitrite and leukocyte esterase on urinalysis

• No fever, chills, or flank pain

Describe the results of a UA based on:

• Bacteria

• WBC

• Leukocyte esterase

• Nitrite

What are empiric therapy selection factors to look out for?

Patient factor: allergies, age, renal function

Medication factor: efficacy, safety, tolerability

Local resistance patterns of E.coli (empiric therapy; urine culture and susceptibility tests not usually performed)

Trimethoprim/Sulfamethoxazole (Bactrim)

• Dose

• Duration

• First line?

• When to not use?

1. One double-strength tablet (160 mg/800 mg) PO BID

2. 3 days

3. First line due to high cure rate and short therapy course

4. Do not use when

   • Sulfa allergy

   • High rates of resistance in community (20%)

   • Patient had recent treatment of Bactrim within last 3 months

Nitrofurantoin (Macrobid)

• Dose

• Duration

• First line?

• When to not use?

1. 100 mg PO BID (of the monohydrate/macrocrystal formulation)

2. 5 days

3. First-line due to high cure rate and low baseline resistance, especially when resistance to trimethoprim/ sulfamethoxazole is high

4. Do not use in patients with:

   • CrCl < 40 mL/min

   • Pyelonephritis

Fosfomycin

• Dose

• Duration

• First line?

• Disadvantages

1. 3 grams orally (powder packet)

2. One dose

3. First-line due to high cure rate and single dose therapy, especially if resistance to TMP/SMX in community is high

4. Disadvantages:

   • Expensive.

   • Ideally should not be used for pyelonephritis (limited systemic absorption)

Oral Beta-lactam Antibiotics

• Agents

• Duration

• First line?

• When should avoid?

1. Different agents include:

   • Amoxicillin/clavulanic acid

   • Cefpodoxime

   • Cefixime

2. Duration depends on agent → 3-7 days

3. Not first-line for treatment of uncomplicated cystitis → more collateral damage

4. In general you should avoid unless other agents cannot be used

Fluoroquinolones (Ciprofloxacin and Levofloxacin)

• Dose

• Duration

• Cure rate?

• ADRs

1. Dose

   • Ciprofloxacin: 250 mg PO twice daily or 500 mg PO once daily

   • Levofloxacin: 250 mg PO daily

2. 3 days

3. High cure rate but also high rates of resistance

4. ADRs

   • C. difficile infection

   • Prolonged QT interval

   • Tendon rupture (esp. in older adults)

   • Peripheral neuropathy.

   • Renally dosed

5. Avoid use unless other agents are not appropriate (ADRs)

Describe the safety monitoring for

• Bactrim

• Macrobid

• Fosfomycin

• Fluoroquinolones

• B-lactams

How do we tell the difference between uncomplicated cystitis and pyelonephritis?

Any nausea/vomiting, fever, chills, flank pain, or signs of hydronephrosis on imaging?

No → Cystitis: Treat with empiric antibiotics

Yes → Pyelonephritis: Obtain urine culture, start empiric antibiotics and target based on culture results

Describe the Four-Step Approach to Choosing Empiric Antibiotics for Complicated UTI

1. Severity of illness (sepsis or no sepsis)

2. Risk factors for resistance

3. Patient-specific considerations

4. The antibiogram (if patient is septic)

Pyelonephritis Treatment Principles

1. Urine culture and susceptibility testing should be performed

2. When local resistance patterns are not known, an initial intravenous dose of a long-acting, broad-spectrum parenteral antimicrobial is recommended

3. Empiric therapy should be de-escalated based on the results of the urine culture

Define sepsis

1. Life-threatening organ dysfunction (inhospital mortality >10%)

2. Caused by dysregulated host response to infection

3. Identified by SOFA score increase of 2 or more points

IV treatment of patients with Pyelonephritis and Sepsis → Preferred choices

IV treatment of patients with Pyelonephritis and Sepsis → Alternative choices

Describe the dosing for:

• Cefepime

• Ceftriaxone

• Meropenem

• Piperacillin- tazobactam

• Cefepime → 1-2g every 8-12 hours

• Ceftriaxone → 1-2g daily

• Meropenem → 1g every 8 hours

• Piperacillin- tazobactam → 4.5g every 8 hours

Treatment of Patients with Pyelonephritis without Sepsis

If using IV route:

• Same as previous tables for sepsis

• Except Carbapenems move to “alternative” therapy table

If using oral route

• Fluoroquinolones

• Trimethoprim-Sulfamethoxazole

• Amoxicillin-Clavulanate

• Oral cephalosporins

Duration of Treatment for Pyelonephritis

• Fluroquinolones: 5 to 7 days

• Non-fluoroquinolones: 7 days

Reasons to Switch from IV to PO Antibiotics

• Reduce need for IV access (cost + convenience)

• Lower risk of complications from IV administration

• Decrease volume of fluid and amount of sodium given to patient

What are the next steps if patient is clinically improving?

• Assess for oral options

• Switch to oral agent

• Treat for 7 days total