Infectious Disease: Antibiotic Selection & Stewardship

Antibiotic Selection & Stewardship

Master antibiotic selection and stewardship with free flashcards and spaced repetition practice. This lesson covers empiric therapy principles, culture-directed treatment, antimicrobial spectrum considerations, and stewardship strategies—essential concepts for NAPLEX success and clinical practice.

Welcome to Antibiotic Selection & Stewardship 💊

Choosing the right antibiotic at the right time can mean the difference between successful treatment and therapeutic failure. As a pharmacist, you'll be at the forefront of optimizing antimicrobial therapy, preventing resistance, and ensuring patient safety. This lesson will equip you with the clinical reasoning skills needed to excel on the NAPLEX and in practice.

Core Concepts 🎯

1. The Foundation: Pharmacist's Role in Antibiotic Therapy

Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials to improve patient outcomes, reduce microbial resistance, and decrease unnecessary costs. Pharmacists play a crucial role in:

• Dose optimization based on pharmacokinetic/pharmacodynamic (PK/PD) principles
• Culture review and antibiotic de-escalation
• Allergy assessment and cross-reactivity evaluation
• Monitoring for efficacy and adverse effects
• Education of patients and healthcare providers

💡 Key Point: The goal is NOT to restrict antibiotics unnecessarily, but to ensure the RIGHT drug, dose, duration, and route for EACH patient.

2. Empiric vs. Definitive Therapy 🔬

🧠 Mnemonic - "BED" for Empiric Therapy Selection:

• Bug (most likely pathogen)
• Environment (hospital vs. community, local resistance)
• Drug factors (penetration, PK/PD, allergy)

3. Spectrum of Activity: The Right Width 📊

Antibiotic spectrum refers to the range of bacteria an agent can effectively treat:

┌─────────────────────────────────────────────────────────┐
│           SPECTRUM OF ACTIVITY                          │
├─────────────────────────────────────────────────────────┤
│                                                         │
│  NARROW ──────────────────────────→ BROAD             │
│                                                         │
│  Penicillin G    Cefazolin    Ceftriaxone    Meropenem│
│  (Strep only)    (MSSA+)      (many G+/G-)   (most)   │
│                                                         │
│  ✓ Less resistance pressure                            │
│  ✓ Preserves microbiome                                │
│  ✓ Lower cost (usually)                                │
│                                                         │
└─────────────────────────────────────────────────────────┘

Key Principle: Start BROAD empirically (cover likely threats), then NARROW based on cultures (de-escalation).

⚠️ Common Mistake: Staying on broad-spectrum agents (like piperacillin-tazobactam or meropenem) when cultures show a susceptible organism that could be treated with a narrower agent.

4. Critical Patient Factors 🏥

Before selecting ANY antibiotic, assess:

A. Renal Function 🫘

• Many antibiotics require dose adjustment for CrCl < 50 mL/min
• High-risk agents: aminoglycosides, vancomycin, fluoroquinolones
• Use Cockcroft-Gault equation for dosing (NAPLEX standard)

B. Hepatic Function 🫀

• Affects metabolism of: macrolides, clindamycin, ceftriaxone, fluoroquinolones
• Watch for: prolonged half-life, increased toxicity risk

C. Allergy History ⚠️

💡 Pro Tip: A childhood "rash" to amoxicillin is often viral exanthem, NOT true allergy. Consider penicillin skin testing or graded challenge if beta-lactam is clearly superior option.

D. Site of Infection 📍

• CNS: Need CSF penetration (ceftriaxone, meropenem, vancomycin)
• Bone: Prolonged therapy, good penetration (fluoroquinolones, clindamycin, linezolid)
• Urine: Many antibiotics concentrate in urine (nitrofurantoin only for cystitis)
• Lung: Consider tissue penetration (fluoroquinolones excellent, aminoglycosides poor)

E. Pregnancy/Lactation 🤰

• Safe: Penicillins, cephalosporins, azithromycin
• Avoid: Fluoroquinolones (cartilage), tetracyclines (teeth/bones), aminoglycosides (ototoxicity)

5. PK/PD Optimization: Maximizing Efficacy 📈

Three main patterns determine dosing strategies:

🧠 Memory Device - "Concentration Killers": Aminoglycosides, Fluoroquinolones, Daptomycin = "AFD" = need high peaks to kill bacteria effectively.

6. Culture Interpretation & De-escalation 🔬

┌────────────────────────────────────────────────┐
│      CULTURE-DIRECTED THERAPY WORKFLOW         │
└────────────────────────────────────────────────┘

    📦 Obtain Cultures BEFORE Antibiotics
           |
           ↓
    💊 Start Empiric Broad-Spectrum
           |
           ↓
    ⏰ Wait 24-72 hours for results
           |
      ┌────┴────┐
      ↓         ↓
   ❌ Negative  ✅ Positive + Susceptibilities
      |         |
      |         ↓
      |    🎯 DE-ESCALATE to Narrow Agent
      |         |
      |         ↓
      |    📊 Assess Clinical Response (48-72h)
      |         |
      ↓         ↓
   🔄 Re-evaluate diagnosis
   Consider:
   • Non-bacterial cause
   • Inadequate culture technique
   • Fastidious organism
   • Antibiotic already given

De-escalation Example:

• Day 1: Sepsis, unknown source → Start vancomycin + piperacillin-tazobactam
• Day 3: Blood cultures grow MSSA, sensitive to oxacillin → Switch to cefazolin (narrower, equally effective, lower cost)

💡 Critical Point: De-escalation is NOT a sign of initial error—it's SMART stewardship that balances empiric coverage with pathogen-directed therapy.

7. Common Resistance Patterns 🦠

Understanding resistance mechanisms helps predict therapy:

🧠 Mnemonic - "MRSA VRE ESBL CRE" = "Most Resistant Superbugs Are Very Resistant, Extremely Scary, Broadly Lethal, Carbapenem-Resistant Enemies"

8. Duration of Therapy ⏱️

Shorter is often better (reduces resistance, adverse effects, cost):

💡 Stewardship Pearl: Use procalcitonin levels to guide duration in pneumonia and sepsis (decreasing levels suggest bacterial clearance).

9. Stewardship Strategies in Action 🛡️

Core Stewardship Interventions:

A. Prospective Audit with Feedback

• Review antibiotic prescriptions 24-48 hours after initiation
• Provide recommendations for optimization
• Most effective intervention for reducing inappropriate use

B. Formulary Restriction with Preauthorization

• Restrict broad-spectrum or last-line agents
• Require infectious disease or stewardship approval
• Example: Carbapenems, daptomycin, newer agents

C. Automatic Stop Orders

• Limit empiric therapy to 48-72 hours
• Force reassessment with culture data
• Prevents unnecessarily prolonged therapy

D. IV-to-PO Conversion

• Switch when patient afebrile, hemodynamically stable, tolerating PO
• High bioavailability agents: fluoroquinolones, linezolid, metronidazole, fluconazole
• Reduces cost, line complications, hospital stay

E. Dose Optimization Programs

• Vancomycin AUC monitoring (target 400-600 for serious infections)
• Extended-infusion beta-lactams (piperacillin-tazobactam over 4 hours)
• Aminoglycoside once-daily dosing

🔔 Did You Know? Implementing antimicrobial stewardship programs reduces C. difficile infections by 30-50% by decreasing unnecessary antibiotic exposure!

10. Special Populations & Considerations 👥

Immunocompromised Patients 🛡️

• Neutropenic fever: Immediate empiric therapy (cefepime or meropenem ± vancomycin)
• Consider fungal coverage if fever persists > 4-7 days
• Prophylaxis in high-risk patients (transplant, chemotherapy)

Critically Ill/Septic Patients 🚨

• Time is crucial: Antibiotics within 1 hour of sepsis recognition
• Use broad-spectrum agents empirically
• Source control essential (drainage, debridement)
• Higher doses may be needed due to increased volume of distribution

Pediatric Patients 👶

• Weight-based dosing (mg/kg)
• Avoid: fluoroquinolones (< 18 years), tetracyclines (< 8 years)
• Consider age-specific pathogens (Group B Strep in neonates)

Geriatric Patients 👴

• Renal function decline (use CrCl, not just SCr)
• Polypharmacy concerns (drug interactions)
• Higher risk of C. difficile, adverse effects
• May need longer courses due to comorbidities

Clinical Examples 📝

Example 1: Community-Acquired Pneumonia (CAP)

Case: 68-year-old female presents with fever, productive cough, and chest pain. CXR shows right lower lobe infiltrate. No recent hospitalization. No antibiotic use in past 3 months. CrCl 55 mL/min.

Reasoning:

1. Most likely pathogens: S. pneumoniae, H. influenzae, atypicals (Mycoplasma, Chlamydophila)
2. Setting: Outpatient → community pathogens, low resistance risk
3. Patient factors: Age > 65, chronic disease risk
4. Guideline recommendation: Respiratory fluoroquinolone OR beta-lactam + macrolide

Appropriate Empiric Choices:

• Option 1: Amoxicillin-clavulanate 875/125 mg PO BID + azithromycin 500 mg PO daily × 3 days, then amox-clav alone to complete 5-7 days
• Option 2: Levofloxacin 750 mg PO daily × 5 days

Rationale: Covers typical and atypical pathogens. Beta-lactam + macrolide preferred in some guidelines to reduce fluoroquinolone use (stewardship). Levofloxacin offers convenience (once daily, single agent) but reserve for patients who can't tolerate combination therapy.

Monitoring: Clinical improvement expected in 48-72 hours. If worsening, consider hospitalization and IV therapy.

Example 2: Complicated UTI with ESBL E. coli

Case: 55-year-old diabetic male with fever, flank pain, nausea. Recent hospitalization 1 month ago. Urine culture grows E. coli resistant to ceftriaxone and ciprofloxacin, susceptible to meropenem and nitrofurantoin.

Reasoning:

1. Organism: ESBL E. coli (likely given resistance pattern)
2. Infection type: Pyelonephritis (upper tract, systemic symptoms)
3. Nitrofurantoin limitation: Only achieves therapeutic levels in bladder, NOT kidneys
4. Need: Systemic agent with good renal penetration

Initial Management:

• Empiric (if susceptibilities pending): Meropenem 1 g IV q8h (if ESBL suspected based on history)
• Definitive (with susceptibilities): Ertapenem 1 g IV daily × 5-7 days

Stewardship Considerations:

• Ertapenem preferred over meropenem (no pseudomonal activity = narrower spectrum)
• Once daily dosing → potential for outpatient parenteral therapy (OPAT)
• Transition to PO not feasible here due to resistance to all oral options except potentially TMP-SMX (if susceptible—must check)

Key Point: ⚠️ Nitrofurantrofurantoin is ONLY for uncomplicated cystitis (bladder infections), NEVER for pyelonephritis or systemic infections!

Example 3: MRSA Bacteremia

Case: 45-year-old with IV drug use history admitted with fever and chills. Blood cultures × 2 sets positive for MSSA (initially reported as Gram-positive cocci in clusters, then confirmed MRSA by mistake in this scenario—let's correct: MSSA, susceptible to oxacillin). TEE negative for endocarditis.

Reasoning:

1. Organism: Methicillin-susceptible S. aureus (MSSA)
2. Source: Likely injection drug use
3. Complication screening: TEE to rule out endocarditis (required for all S. aureus bacteremia)
4. Duration: Minimum 14 days from first negative blood culture

Antibiotic Selection:

• Initial empiric: Vancomycin 15-20 mg/kg IV q8-12h (until susceptibilities known)
• Definitive: DE-ESCALATE to cefazolin 2 g IV q8h × 14 days

Why cefazolin over vancomycin for MSSA?

• Superior efficacy: Cefazolin has better bactericidal activity against MSSA
• Lower mortality: Studies show improved outcomes vs. vancomycin for MSSA
• Stewardship: Narrower spectrum, preserves vancomycin for true MRSA

Monitoring:

• Repeat blood cultures after 2-4 days (should be negative)
• Monitor for metastatic infections (vertebral osteomyelitis, septic arthritis)
• If persistently positive cultures → search for undrained source, consider longer therapy

💡 High-Yield NAPLEX Fact: For MSSA bacteremia, beta-lactams (nafcillin, oxacillin, cefazolin) are PREFERRED over vancomycin!

Example 4: Antibiotic Allergy Assessment

Case: 72-year-old with severe sepsis from intra-abdominal infection. Patient reports "penicillin allergy—got hives as a child." Requires immediate broad-spectrum therapy.

Decision-Making Process:

Recommendation:

• Use cefepime or meropenem (distant structural similarity to penicillin)
• Have resuscitation equipment available during first dose
• Monitor closely for 1 hour after administration
• Consider allergy consultation for future testing if beta-lactams will be needed long-term

Alternative if high risk or patient refuses: Aztreonam (for Gram-negatives) + vancomycin/metronidazole (for Gram-positives/anaerobes)

Common Mistakes ⚠️

Mistake 1: "Double-Covering" Without Indication

❌ Error: Using two agents with overlapping coverage (e.g., ceftriaxone + cefepime)

✅ Correct Approach: Use combination therapy ONLY when:

• Empiric coverage of multiple organism classes needed (e.g., Gram-positive AND Gram-negative AND anaerobes)
• Synergy documented (e.g., beta-lactam + aminoglycoside for Enterococcus endocarditis)
• Preventing resistance (e.g., dual therapy for Pseudomonas in severe infections)

Why it matters: Increases cost, toxicity risk, resistance pressure without benefit

Mistake 2: Ignoring Renal Function for Dose Adjustments

❌ Error: Giving standard-dose vancomycin 1 g IV q12h to patient with CrCl 25 mL/min

✅ Correct Approach:

• Calculate CrCl using Cockcroft-Gault
• Adjust dose AND/OR frequency based on package insert or clinical guidelines
• For vancomycin: Use AUC-based dosing (requires pharmacokinetic consultation) or traditional trough monitoring
• Example adjustment: Vancomycin 1 g IV q24-48h depending on levels

Why it matters: Prevents nephrotoxicity, ototoxicity, and other dose-related adverse effects

Mistake 3: Using Oral Antibiotics for Serious Infections Initially

❌ Error: Starting oral levofloxacin for patient with septic shock from pneumonia

✅ Correct Approach:

• Serious infections (sepsis, meningitis, endocarditis, severe pneumonia) require IV therapy initially
• Switch to PO when:
  • Hemodynamically stable
  • Afebrile for 24-48 hours
  • Tolerating oral intake
  • High bioavailability agent available

Why it matters: IV ensures reliable drug delivery and adequate serum levels in critically ill patients with potential absorption issues

Mistake 4: Continuing Empiric Broad-Spectrum Therapy After Cultures

❌ Error: Keeping patient on vancomycin + pip-tazo when cultures show E. coli susceptible to ceftriaxone

✅ Correct Approach:

• Review cultures daily
• De-escalate within 48-72 hours of positive culture
• Switch to ceftriaxone 1-2 g IV daily (narrower, equally effective)

Why it matters: Reduces C. difficile risk, resistance development, drug costs, and adverse effects

Mistake 5: Treating Colonization or Contamination

❌ Error: Starting antibiotics for single blood culture with coagulase-negative Staph in asymptomatic patient

✅ Correct Approach:

• Distinguish infection from colonization/contamination:
  • Coagulase-negative Staph: Usually contaminant unless from prosthetic device or multiple positive cultures
  • Bacteriuria without symptoms (asymptomatic bacteriuria): Do NOT treat (except pregnancy or pre-urologic procedure)
  • Positive sputum culture in patient without pneumonia symptoms: Likely colonization

Why it matters: Unnecessary antibiotics expose patients to risks without benefits and promote resistance

Mistake 6: Missing Drug Interactions

❌ Error: Prescribing ciprofloxacin to patient on warfarin without monitoring plan

✅ Correct Approach:

• Screen for interactions before prescribing:
  • Fluoroquinolones ↑ warfarin effect (increased INR/bleeding risk)
  • Rifampin ↓ many drugs (warfarin, oral contraceptives, antiretrovirals)
  • Azithromycin/fluoroquinolones: QT prolongation (avoid with other QT-prolonging drugs)
  • Linezolid: MAOI activity (avoid with SSRIs, tyramine-rich foods)

Why it matters: Prevents serious adverse events and therapeutic failures

Key Takeaways 🎯

1. Start broad, narrow down: Empiric therapy should cover likely pathogens based on infection site and patient factors; de-escalate to targeted therapy once cultures available.

2. Patient-specific factors are critical: Always assess renal function, allergies, site of infection, and resistance risk factors before selecting an antibiotic.

3. PK/PD principles optimize outcomes: Concentration-dependent agents (aminoglycosides) need high peaks; time-dependent agents (beta-lactams) need extended time above MIC.

4. Stewardship is everyone's responsibility: Prospective audit, IV-to-PO conversion, and de-escalation reduce resistance and improve patient outcomes.

5. Culture review is mandatory: Check susceptibilities daily and narrow therapy accordingly—staying on broad-spectrum agents when narrower options exist is poor stewardship.

6. Allergy assessment prevents unnecessary alternatives: Most "penicillin allergies" are not true Type I reactions; careful assessment may allow beta-lactam use.

7. Duration matters: Shorter courses (5-7 days) are often adequate for common infections; prolonged therapy (4-6 weeks) reserved for endocarditis, osteomyelitis, or specific pathogens.

8. Don't treat colonization: Asymptomatic bacteriuria, single contaminated blood cultures, and respiratory colonization do not require antibiotics.

9. MRSA vs. MSSA: For MSSA bacteremia, beta-lactams (cefazolin) are SUPERIOR to vancomycin.

10. Time-sensitive infections: Sepsis, neutropenic fever, and meningitis require antibiotics within 1 hour of recognition.

📋 Quick Reference Card

📚 Further Study

1. CDC Antibiotic Stewardship Resources: https://www.cdc.gov/antibiotic-use/stewardship-report/index.html - Comprehensive guidelines and implementation toolkits

2. IDSA Guidelines on Antimicrobial Stewardship: https://www.idsociety.org/practice-guideline/amr-guidance/ - Evidence-based recommendations for specific infections

3. Sanford Guide to Antimicrobial Therapy: https://www.sanfordguide.com/ - Gold standard reference for antibiotic selection (subscription required, but available in most institutions)

Congratulations! 🎉 You've completed this comprehensive lesson on antibiotic selection and stewardship. Master these concepts with spaced repetition, and you'll be well-prepared for NAPLEX questions and real-world clinical practice. Remember: the right drug, right dose, right duration, right patient—every time!