Infectious Disease Pharmacotherapy Essentials

Master infectious disease pharmacotherapy with free flashcards and evidence-based clinical decision-making practice. This lesson covers antibiotic selection by pathogen, resistance mechanisms, empiric therapy protocols, and renal dosing adjustments—essential skills for the NAPLEX and clinical pharmacy practice. 🦠

Welcome to Infectious Disease Pharmacotherapy

Infectious disease pharmacotherapy represents one of the most dynamic areas tested on the NAPLEX. Unlike cardiovascular medications where therapy is often chronic and predictable, antimicrobial selection requires rapid clinical decision-making based on infection site, likely pathogens, local resistance patterns, and patient-specific factors. The NAPLEX emphasizes application over memorization—you'll need to select appropriate empiric therapy, adjust for renal function, recognize drug interactions, and counsel patients on adherence and adverse effects.

This lesson builds on basic pharmacology by focusing on clinical scenarios you'll encounter in practice and on the exam. We'll explore the top antimicrobials by class, their spectra of activity, and most importantly, when NOT to use them. 💊

Core Concepts in Antimicrobial Therapy

The Empiric Therapy Framework 🎯

Empiric therapy means starting treatment before culture results return (usually 48-72 hours). Your selection depends on:

Antibiotic Classes by Mechanism 🔬

Cell Wall Synthesis Inhibitors (bactericidal)

• Beta-lactams: Penicillins, cephalosporins, carbapenems, monobactams
• Vancomycin: Glycopeptide for Gram-positive including MRSA
• Key concept: Time-dependent killing (maximize time above MIC)

Protein Synthesis Inhibitors (mostly bacteriostatic)

• Tetracyclines (doxycycline): Broad spectrum, avoid in pregnancy
• Macrolides (azithromycin): Atypical coverage, QT prolongation risk
• Aminoglycosides (gentamicin): Gram-negative, concentration-dependent killing
• Linezolid: MRSA alternative, watch for serotonin syndrome

DNA/RNA Synthesis Inhibitors

• Fluoroquinolones (levofloxacin, ciprofloxacin): Broad spectrum, tendon rupture/QT risk
• Metronidazole: Anaerobes and C. difficile

Folate Synthesis Inhibitors

• Trimethoprim-sulfamethoxazole (TMP-SMX): UTIs, MRSA, PCP prophylaxis

Understanding Antimicrobial Spectrum 🌈

SPECTRUM OF ACTIVITY: Common Antibiotics

                    Gram +    Gram -    Atypical   Anaerobes
                    -------   -------   --------   ---------
Penicillin G        ████      ░░░░      ░░░░       ░░░░
Amoxicillin         ████      ██░░      ░░░░       ░░░░
Amox-Clav           ████      ████      ░░░░       ████
Cefazolin (1st gen) ████      ██░░      ░░░░       ░░░░
Ceftriaxone (3rd)   ████      ████      ░░░░       ░░░░
Cefepime (4th)      ████      ████      ░░░░       ░░░░
Azithromycin        ██░░      ░░░░      ████       ░░░░
Levofloxacin        ████      ████      ████       ░░░░
Vancomycin          ████      ░░░░      ░░░░       ░░░░
Metronidazole       ░░░░      ░░░░      ░░░░       ████

████ = Excellent   ██░░ = Limited   ░░░░ = None

💡 NAPLEX Tip: The exam loves testing spectrum gaps. Know that vancomycin has ZERO Gram-negative activity and that standard penicillin won't cover MRSA.

Beta-Lactam Allergy: The 10% Rule ⚠️

Approximately 10% of patients report penicillin allergy, but only 1-2% have true IgE-mediated reactions. The NAPLEX will test your ability to distinguish:

Reaction Type	Symptoms	Can Use Other Beta-Lactams?
Type I (IgE)	Anaphylaxis, angioedema, bronchospasm within 1 hour	❌ Avoid all beta-lactams (10% cross-reactivity)
Delayed	Maculopapular rash after days	✅ May use cephalosporins (different side chain)
Non-allergic	GI upset, "didn't agree with me"	✅ Can use any beta-lactam

🧠 Mnemonic for Anaphylaxis Alternatives: "VALF" - Vancomycin, Aztreonam, Levofloxacin, Fluoroquinolones

Community-Acquired Pneumonia (CAP) Protocol 🫁

CAP is a NAPLEX favorite because it integrates pathogen knowledge, guideline adherence, and severity assessment.

Outpatient CAP (otherwise healthy)

• First-line: Amoxicillin 1g TID × 5-7 days
• Alternative: Doxycycline 100mg BID or azithromycin 500mg × 5 days
• With comorbidities: Amoxicillin-clavulanate + macrolide OR respiratory fluoroquinolone (levofloxacin 750mg daily)

Inpatient CAP (non-ICU)

• Beta-lactam (ceftriaxone 1-2g daily) + macrolide (azithromycin 500mg daily)
• OR respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily)

Severe CAP (ICU)

• Beta-lactam + macrolide OR beta-lactam + fluoroquinolone
• Add vancomycin or linezolid if MRSA risk factors present

CAP PATHOGEN DECISION TREE

        Community-Acquired Pneumonia
                  |
        ┌─────────┴──────────┐
        ↓                    ↓
   Outpatient            Inpatient
        |                    |
   ┌────┴────┐         ┌─────┴──────┐
   ↓         ↓         ↓            ↓
Healthy  Comorbid   Non-ICU       ICU
   |         |         |            |
   ↓         ↓         ↓            ↓
 Amox    Amox-Clav  CTX+Azith   CTX+Azith
  or       +         or          +
Doxyc   Macrolide   Levoflox   Vanc (if MRSA)

💡 Why add a macrolide? Covers atypical pathogens (Mycoplasma, Chlamydophila, Legionella) that beta-lactams miss.

Urinary Tract Infections: Uncomplicated vs. Complicated 🚽

Uncomplicated Cystitis (healthy women)

• First-line: Nitrofurantoin 100mg BID × 5 days OR TMP-SMX DS BID × 3 days
• Alternatives: Fosfomycin 3g × 1 dose
• ⚠️ Avoid fluoroquinolones (FDA black box warnings, save for complicated infections)

Complicated UTI or Pyelonephritis

• Outpatient: Ciprofloxacin 500mg BID × 7 days OR levofloxacin 750mg daily × 5 days
• Inpatient: Ceftriaxone 1g daily (step down to oral based on culture)

Asymptomatic Bacteriuria

• Do NOT treat except in pregnancy or before urologic procedures
• NAPLEX loves testing this—unnecessary antibiotics promote resistance!

Drug	Advantages	Disadvantages	Key Point
Nitrofurantoin	Low resistance, preserves gut flora	CrCl <30: ineffective, pulmonary fibrosis with long-term use	Only for cystitis, not pyelonephritis
TMP-SMX	Inexpensive, effective	High resistance in some areas (>20%), hyperkalemia risk	Check local antibiogram
Fosfomycin	Single dose, excellent adherence	Lower efficacy than 5-day courses	Good for adherence concerns
Ciprofloxacin	Excellent Gram-negative coverage	FDA warnings: tendon rupture, neuropathy, aortic dissection	Reserve for complicated UTI

Renal Dosing Adjustments: The Critical Skill 💧

Many antimicrobials require dose adjustment for renal impairment. The NAPLEX will test calculations and clinical judgment.

Creatinine Clearance (CrCl) Calculation - Cockcroft-Gault

Male:   CrCl = [(140 - age) × IBW] / (SCr × 72)

Female: CrCl = [(140 - age) × IBW × 0.85] / (SCr × 72)

Where:
  age = years
  IBW = Ideal Body Weight (kg)
  SCr = Serum Creatinine (mg/dL)

Common Renal Dosing Adjustments

Drug	CrCl >50	CrCl 30-50	CrCl 10-30	CrCl <10
Levofloxacin	750mg daily	750mg × 1, then 500mg q48h	750mg × 1, then 500mg q48h	500mg × 1, then 250mg q48h
Ceftriaxone	No adjustment	No adjustment	No adjustment (hepatic excretion)	No adjustment
Vancomycin	15-20mg/kg q12h	Increase interval or decrease dose	Dose by levels	Dose by levels
Acyclovir	800mg 5×/day	800mg TID	800mg BID	800mg daily

💡 NAPLEX Pearl: Ceftriaxone is unique among cephalosporins—it's eliminated hepatically AND renally, so no dose adjustment needed even in severe renal impairment.

Skin and Soft Tissue Infections (SSTIs) 🩹

SSTIs range from simple cellulitis to life-threatening necrotizing fasciitis. The key is distinguishing purulent vs. non-purulent.

Non-Purulent Cellulitis (no abscess)

• Likely pathogen: Streptococcus pyogenes (Group A Strep)
• Treatment: Cephalexin 500mg QID × 5-7 days OR dicloxacillin 500mg QID
• Penicillin allergy: Clindamycin 300-450mg TID

Purulent SSTI (abscess, furuncle)

• Likely pathogen: S. aureus including MRSA
• Treatment: Incision & drainage + TMP-SMX DS BID × 5-7 days OR doxycycline 100mg BID
• Alternative: Clindamycin 300-450mg TID (watch for inducible resistance)

Severe/Complicated SSTI

• IV vancomycin 15-20mg/kg q12h (target trough 15-20 mcg/mL)
• Alternative: Daptomycin 4-6mg/kg daily (NOT for pneumonia—inactivated by surfactant)
• Linezolid 600mg BID (expensive, risk of myelosuppression and serotonin syndrome)

SSTI TREATMENT ALGORITHM

           Skin Infection
                 |
        ┌────────┴─────────┐
        ↓                  ↓
   Purulent          Non-purulent
   (abscess)         (cellulitis)
        |                  |
   I&D + oral         Oral beta-lactam
        |                  |
   ┌────┴────┐            ↓
   ↓         ↓        Cephalexin
Mild      Severe      or
  |         |      Dicloxacillin
  ↓         ↓
TMP-SMX  Vancomycin
  or       IV
Doxyc

⚠️ Common NAPLEX Trap: Don't use daptomycin for pneumonia! It binds to pulmonary surfactant and becomes inactive.

Clostridioides difficile Infection (CDI) 💩

CDI results from antibiotic-induced disruption of gut flora. The 2021 IDSA guidelines changed first-line therapy.

Initial Episode (non-severe)

• First-line: Fidaxomicin 200mg BID × 10 days (expensive but lower recurrence)
• Alternative: Vancomycin 125mg PO QID × 10 days
• ⚠️ Metronidazole NO LONGER first-line (inferior cure rates)

Initial Episode (severe) - WBC >15,000 OR SCr ≥1.5× baseline

• Vancomycin 125mg PO QID × 10 days
• Fulminant: Vancomycin 500mg PO QID + metronidazole 500mg IV q8h

First Recurrence

• Vancomycin taper/pulse regimen OR fidaxomicin 200mg BID × 10 days

Second Recurrence

• Fecal microbiota transplant (FMT) - 90% cure rate!
• Bezlotoxumab (monoclonal antibody) as adjunct to reduce recurrence

🧠 Mnemonic for CDI Risk Factors: "CAFE" - Clindamycin/cephalosporins, Age >65, Fluoroquinolones, Exposure to healthcare

Antiviral Therapy: Focus on Common Infections 🦠

Influenza

• Oseltamivir (Tamiflu) 75mg BID × 5 days
• Must start within 48 hours of symptom onset for benefit
• Reduces duration by ~1 day, prevents complications in high-risk patients
• Dose adjustment: CrCl 10-30: 30mg BID; CrCl <10: 30mg daily

Herpes Simplex (HSV)

• Genital HSV (first episode): Acyclovir 400mg TID × 7-10 days OR valacyclovir 1g BID × 7-10 days
• Genital HSV (recurrence): Valacyclovir 500mg BID × 3 days
• Suppressive therapy: Valacyclovir 500-1000mg daily (reduces transmission by 50%)
• Herpes labialis: Acyclovir cream 5× daily OR valacyclovir 2g BID × 1 day

Herpes Zoster (Shingles)

• Valacyclovir 1g TID × 7 days OR acyclovir 800mg 5×/day × 7 days
• Start within 72 hours of rash onset
• Consider higher doses in immunocompromised patients

💡 Valacyclovir vs. Acyclovir: Valacyclovir is a prodrug with better bioavailability (54% vs. 10-20%), allowing less frequent dosing and better adherence.

Antifungal Therapy Essentials 🍄

Oral Candidiasis (Thrush)

• First-line: Nystatin suspension 400,000-600,000 units (swish & swallow) QID × 7-14 days
• Fluconazole-refractory: Itraconazole solution 200mg daily OR posaconazole 400mg BID × 3 days, then 400mg daily

Vulvovaginal Candidiasis (VVC)

• Uncomplicated: Fluconazole 150mg PO × 1 dose OR topical azole (miconazole, clotrimazole) × 1-7 days
• Complicated/Recurrent: Fluconazole 150mg on days 1, 4, 7 then weekly × 6 months

Invasive Candidiasis

• Echinocandin preferred: Caspofungin 70mg load, then 50mg daily OR micafungin 100mg daily
• Alternative: Fluconazole 800mg load, then 400mg daily (if susceptible)

Drug Interactions with Azoles ⚠️

Azoles (fluconazole, itraconazole, voriconazole, posaconazole) are potent CYP3A4 inhibitors:

Interacting Drug	Effect	Management
Warfarin	↑ INR, bleeding risk	Monitor INR closely, may need 20-30% warfarin dose reduction
Statins	↑ myopathy/rhabdomyolysis risk	Avoid simvastatin/lovastatin; use atorvastatin with dose limit
Tacrolimus	↑ levels, nephrotoxicity	Reduce tacrolimus dose by 50-70%, monitor levels
Benzodiazepines	↑ sedation	Avoid triazolam/midazolam; use lorazepam instead
Phenytoin	↑ phenytoin levels; ↓ azole levels	Bidirectional interaction, monitor both

Clinical Examples

Example 1: Pneumonia with Renal Impairment 🫁

Case: A 72-year-old man presents to the ED with productive cough, fever (38.9°C), and hypoxemia. Chest X-ray shows right lower lobe infiltrate. He has a history of hypertension and CKD stage 3 (baseline SCr 1.8 mg/dL). Weight 80 kg, no drug allergies.

Clinical Decision-Making Process:

Step	Assessment	Decision
1	Severity assessment	Inpatient CAP (non-ICU) based on oxygen requirement
2	Empiric regimen selection	Beta-lactam + macrolide OR fluoroquinolone
3	Calculate CrCl	CrCl = [(140-72) × 80] / (1.8 × 72) = 42 mL/min
4	Renal adjustment needed?	Yes for levofloxacin (CrCl 30-50 range)
5	Final recommendation	Ceftriaxone 1g IV daily + azithromycin 500mg IV daily

Rationale:

• Ceftriaxone: No renal adjustment needed (dual excretion)
• Azithromycin: No renal adjustment needed (hepatic excretion)
• Alternative would be levofloxacin 750mg × 1, then 500mg q48h (adjusted for CrCl 42)
• Duration: Minimum 5 days, until clinically stable (afebrile 48-72h, able to eat, normal mentation)

💡 NAPLEX Application: The exam might present this case and ask: "Which regimen requires NO dose adjustment?" The answer would be ceftriaxone + azithromycin.

Example 2: MRSA SSTI with Drug Interaction 🩹

Case: A 45-year-old woman presents with a large, fluctuant abscess on her thigh. I&D performed with purulent drainage. She takes sertraline 100mg daily for depression. Past cultures have grown MRSA. She requests oral therapy as she travels frequently for work.

Medication Options Analysis:

Drug	Pros	Cons	Recommendation
TMP-SMX DS BID	Excellent MRSA coverage, BID dosing	None in this case	✅ Best choice
Doxycycline 100mg BID	Good coverage, BID dosing	Photosensitivity warning	✅ Acceptable alternative
Linezolid 600mg BID	Excellent MRSA coverage	⚠️ Risk of serotonin syndrome with sertraline!	❌ Avoid
Clindamycin 300mg TID	Good coverage if susceptible	Need D-test for inducible resistance	⚠️ Only if D-test negative

Decision: Prescribe TMP-SMX DS 1 tab BID × 7 days

Critical counseling points:

• Take with full glass of water to prevent crystalluria
• Stay hydrated (2-3 liters daily)
• Watch for rash (Stevens-Johnson syndrome risk, though rare)
• Monitor for hyperkalemia if on ACE inhibitors or ARBs
• Finish entire course even if abscess improves quickly

⚠️ NAPLEX Focus: Linezolid + SSRI/SNRI = serotonin syndrome risk! This is a high-yield drug interaction. Symptoms include agitation, confusion, tremor, hyperthermia, and muscle rigidity.

Example 3: UTI in Pregnancy 🤰

Case: A 28-year-old woman at 14 weeks gestation presents with dysuria, frequency, and urgency. Urinalysis shows WBC 50-100, nitrite positive, bacteria present. No fever or flank pain. Allergies: Sulfa drugs (hives as a child).

Pregnancy Considerations for UTI Therapy:

Drug	Pregnancy Category/Safety	Use in This Case?
Nitrofurantoin	Avoid at term (risk of hemolytic anemia in newborn), OK in 2nd trimester	✅ Best option
TMP-SMX	Avoid 1st trimester (neural tube defects) & at term (kernicterus)	❌ Sulfa allergy + 2nd trimester concerns
Amoxicillin-clavulanate	Safe throughout pregnancy	✅ Good option
Cephalexin	Safe throughout pregnancy	✅ Good option
Fluoroquinolones	❌ Avoid - cartilage damage in fetus	❌ Contraindicated
Tetracyclines	❌ Avoid - teeth staining, bone effects	❌ Contraindicated

Decision: Nitrofurantoin monohydrate 100mg BID × 5 days OR Cephalexin 500mg QID × 5 days

Additional management:

• Follow-up urine culture in 1-2 weeks to document cure
• Consider suppressive therapy (nitrofurantoin 50-100mg daily) for remainder of pregnancy if recurrent UTIs
• Asymptomatic bacteriuria MUST be treated in pregnancy (unlike non-pregnant patients) due to pyelonephritis risk

💡 NAPLEX Pearl: Pregnancy is one of the few situations where you MUST treat asymptomatic bacteriuria. Untreated bacteriuria leads to pyelonephritis in 20-30% of pregnant women.

Example 4: Antibiotic Stewardship Decision 🎯

Case: A 35-year-old man presents to urgent care with 3 days of nasal congestion, facial pressure, and clear nasal discharge. No fever. He requests "a Z-pack" because "it always helps my sinus infections."

Stewardship Analysis:

VIRAL RHINOSINUSITIS vs BACTERIAL SINUSITIS

        Symptoms < 10 days?
               |
        ┌──────┴──────┐
        ↓             ↓
      YES            NO
        |              |
   Likely VIRAL   Consider
        |          bacterial
        ↓              |
   No antibiotics  Still wait?
        |              |
        ↓         ┌────┴────┐
   Supportive     ↓         ↓
      care      Mild    Severe
        |         |         |
        ↓         ↓         ↓
   - Saline   Wait 7   Antibiotics
   - Decongest  more    if no
   - NSAIDs     days   improvement

Decision: No antibiotics indicated

Counseling: "Your symptoms suggest a viral sinus infection, which antibiotics won't help. Viral infections typically last 7-10 days. I recommend:

• Saline nasal irrigation 2-3 times daily (most effective!)
• Pseudoephedrine 30-60mg every 4-6 hours for congestion (check BP first)
• Ibuprofen 400mg every 6 hours as needed for pain
• Return if symptoms worsen after initial improvement, persist beyond 10 days, or you develop fever >38.3°C"

When to treat acute bacterial sinusitis:

1. Severe symptoms (fever ≥39°C + purulent discharge ≥3 days)
2. Worsening after initial improvement ("double sickening")
3. Persistent symptoms ≥10 days without improvement

If antibiotics indicated: Amoxicillin-clavulanate 875/125mg BID × 5-7 days (covers S. pneumoniae including resistant strains and H. influenzae)

⚠️ NAPLEX Stewardship Question: The exam might show this case and ask which action is most appropriate. The answer is symptomatic treatment without antibiotics + counseling on when to return.

Common Mistakes to Avoid ⚠️

1. Using IV vancomycin for C. difficile infection ❌ Wrong: IV vancomycin doesn't reach colonic lumen in therapeutic concentrations ✅ Right: ORAL vancomycin or fidaxomicin (need drug in GI tract where C. diff lives)

2. Prescribing nitrofurantoin for pyelonephritis ❌ Wrong: Nitrofurantoin doesn't achieve adequate tissue levels in kidney ✅ Right: Use nitrofurantoin ONLY for cystitis (bladder infection); choose fluoroquinolone or ceftriaxone for pyelonephritis

3. Forgetting to adjust aminoglycoside dosing based on weight AND renal function ❌ Wrong: Using standard dose without calculating based on actual body weight ✅ Right: Gentamicin loading dose = 5-7mg/kg (use ABW for obese patients), then adjust interval based on CrCl and levels

4. Missing the QT prolongation risk with azithromycin + other QT-prolonging drugs ❌ Wrong: Prescribing Z-pack to patient on amiodarone without considering interaction ✅ Right: Choose alternative antibiotic (doxycycline) or monitor ECG if macrolide essential

5. Treating viral pharyngitis with antibiotics ❌ Wrong: "Strep throat" = antibiotics for everyone with sore throat ✅ Right: Use Centor criteria; only treat if ≥3 criteria OR positive rapid strep test

6. Using ceftriaxone in neonates receiving calcium-containing IV solutions ❌ Wrong: Can cause fatal precipitation in lungs and kidneys ✅ Right: Use alternative cephalosporin (cefotaxime) in neonates, especially if on IV calcium

7. Forgetting about double coverage for Pseudomonas in severe infections ❌ Wrong: Single antipseudomonal agent for pneumonia in ICU patient with bronchiectasis ✅ Right: Use two agents with different mechanisms (e.g., cefepime + tobramycin) until sensitivities known

8. Inadequate duration of therapy for endocarditis or osteomyelitis ❌ Wrong: Treating with standard 7-10 day course ✅ Right: Endocarditis = 4-6 weeks IV, osteomyelitis = minimum 4-6 weeks (often longer)

Key Takeaways 📚

NAPLEX Question Strategies:

• Application over recall: Expect cases requiring you to SELECT therapy, not just define drugs
• Calculate before answering: Many questions require CrCl calculation for dosing
• Read carefully for contraindications: Allergy history, pregnancy status, organ dysfunction
• Consider the whole patient: Concurrent medications, comorbidities, adherence factors

📚 Further Study

Evidence-Based Guidelines:

• IDSA Clinical Practice Guidelines: https://www.idsociety.org/practice-guideline/practice-guidelines/
• CDC Antibiotic Prescribing and Use: https://www.cdc.gov/antibiotic-use/
• Sanford Guide to Antimicrobial Therapy (subscription): https://www.sanfordguide.com/

Practice Resources:

• NAPLEX Competency Statements (focus on Area 1): https://nabp.pharmacy/programs/naplex/
• Johns Hopkins Antibiotic Guide: https://www.hopkinsguides.com/hopkins/index/Johns_Hopkins_ABX_Guide

Master infectious disease pharmacotherapy by practicing case-based questions, calculating renal doses until it becomes automatic, and understanding the "why" behind empiric therapy choices. The NAPLEX rewards clinical reasoning—think like a pharmacist, not just a student! 💊🎓