dr huang

INFECTIOUS DISEASES THERAPEUTIC CONCEPTS SPRING 2025

  • Instructor Information:

    • Vanthida Huang, PharmD, BSPHM, FCCP

    • Professor of Pharmacy Practice/Biomedical Sciences/Veterinary Medicine

    • Director of Infectious Diseases Translational Research Fellowship

    • Date of Lecture: March 10-15, 2025

    • Copyright © Huang & Midwestern University, 2025. All rights reserved.

Reading Materials

  • Required Texts:

    • Dipiro JT et al., Pharmacotherapy: Pathophysiologic Approach. Chapter e126 “Laboratory Tests to Direct Antimicrobial Pharmacotherapy”, 12e, 2023. (AccessPharmacy)

    • Dipiro JT et al., Pharmacotherapy: Pathophysiologic Approach. Chapter 127 “Antimicrobial Regimen Selection”, 12e, 2023. (AccessPharmacy)

  • Recommended Texts:

    • Mandell, Douglas, & Bennett’s Principles and Practice of Infectious Diseases, 9th ed., 2020. (Ebook via MWU Library)

    • Chapter 16

    • Chapter 17

    • Kuper KM et al., "Antimicrobial susceptibility testing: A primer for Clinicians.” Pharmacotherapy 2009;29(11):1326-1343.

    • Wenzler E et al., "Antimicrobial Susceptibility Testing: An Updated for Clinicians in the era of Antimicrobial resistance.” Pharmacotherapy 2003;43(4):264-278.

Learning Objectives

  1. Describe the effects of infection on the body systems.

  2. Describe the approach for working up a patient with an infection.

  3. Describe host factors that must be considered when selecting an empiric antimicrobial regimen.

  4. Select empiric antimicrobial therapy based on:

    • Pharmacokinetic properties

    • Tissue penetration

    • Resistance

  5. List factors that contribute to antimicrobial failure.

  6. Understand the process of pathogen identification and culturing.

  7. Discuss various susceptibility methods and their role.

  8. For each class of antimicrobial:

    • Recognize drug names (generic & brand) in each class.

    • Know the spectrum which the antimicrobial is active or inactive.

    • List common adverse effects, serious warnings, monitoring parameters, precautions, and drug interactions.

The Infectious Diseases (ID) Workup

  1. Is there an infection present?

  2. Testing for microorganisms.

  3. Considerations for antimicrobial therapy.

  4. Follow-up & monitoring.

  5. Streamlining therapy.

  6. Discontinuation.

Approach to ID Therapy Selection

  • Steps for Selection of Antimicrobials:

    1. Confirm the presence of infection.

    2. Identification of the pathogen.

    3. Selection of presumptive therapy considering every infected site.

    4. Monitor therapeutic response.

Patient Case Study: RG

  • Patient Profile:

    • 63-year-old, 70 kg male.

    • Status: Intensive care unit (ICU) patient.

    • Medical History: Emergency resection of large bowel; mechanically ventilated.

  • Clinical Presentation (Day 20 Post-Op):

    • Sudden confusion.

    • Blood pressure: 70/30 mmHg.

    • Heart rate: 130 bpm.

    • Cold extremities; circumoral pallor.

    • Temperature: 40°C (axillary).

    • Respiratory rate: 24 breaths/min.

    • Copious yellow-green secretions from the endotracheal tube.

  • Physical Examination:

    • Sinus tachycardia; no rubs or murmurs; rhonchi with decreased breath sounds.

    • Distended abdomen; new abdominal pain; absent bowel sounds; guaiac positive stool.

    • Urine output: 10 mL/hour over the past 2 hours.

    • Erythema around the central venous catheter.

  • Diagnostic Tests:

    • Radiograph: Bilateral lower lobe infiltrates.

    • Urinalysis: >50 WBC/HPF, few casts, specific gravity 1.015.

    • Pending cultures: blood, tracheal aspirate, urine.

    • Notable lab values include:

    • Na=131 mEq/L (135-147)

    • K=4.1 mEq/L (3.5-5.0)

    • Cl=110 mEq/L (95-105)

    • CO2=16 mEq/L

    • BUN=58 mg/dL (8-18)

    • SCr=3.8 mg/dL (0.6-1.2) [increase from 0.9 mg/dL at admission]

    • Glucose=320 mg/dL (70-110)

    • Serum albumin=2.1 g/L (4-6)

    • Hgb=10.3 g/dL

    • Hct=33% (39-49%)

    • WBC=15,600/mm³ (with bands present)

    • Platelets=40,000/mm³ (130,000-400,000)

    • PT=18 seconds (10-12)

    • ESR=65 mm/hour (0-20)

    • Procalcitonin=1 µg/L (<0.25 µg/L)

Establishing the Presence of an Infection

  • Fever:

    • Hallmark of infectious diseases.

    • Can also indicate non-infectious disease states (e.g., drug-induced fever).

  • Local Signs:

    • Signs can be visually assessed if infection is superficial.

    • Symptoms refer to the affected organ systems.

  • White Blood Cell (WBC) Count:

    • Elevated in response to infections but also non-infectious states such as rheumatoid arthritis (RA), leukemia, or due to drugs (e.g., corticosteroids).

    • Types:

    • Granulocytes

      • PMN (polymorphonuclear) leukocytes: Neutrophils, Bands (immature) = left shift, Basophils, Eosinophils.

    • Agranulocytes: Lymphocytes, Monocytes.

  • Other Tests Used for Establishing Infections:

    • Erythrocyte sedimentation rate (ESR)

    • C-reactive protein (CRP)

    • Cytokines

    • Procalcitonin (PCT)

Clinical Microbiology and Culture

  • Determining Likely Pathogens:

    • Differentiating colonization vs. infection.

    • Classification of infectious organisms.

    • Identification methods for pathogens:

    • Appropriate culture obtaining and transport methods.

    • Methods to detect organisms and perform susceptibility testing.

    • Direct examination methods (e.g., Gram staining).

  • Gram Stain Interpretation:

    • Positive and negative classifications for cocci and bacilli.

    • Examples:

      • Positive Cocci: Staphylococci, Streptococci.

      • Negative Bacilli: Escherichia coli, Klebsiella spp., Pseudomonas spp.

Patient Case Continued

  • RG's Tracheal Aspirate:

    • Gram stain shows gram-negative bacilli.

    • Culture Results:

    • Serratia marcescens grown from culture: Initial treatment initiated with imipenem and gentamicin while waiting for susceptibility results.

  • Concern: Determining whether the isolate (Serratia) represents a true bacterial infection vs. colonization or contamination.

Antimicrobial Susceptibility Testing

  • Qualitative Testing Methods:

    • Disk Diffusion.

  • Quantitative Testing Methods:

    • Minimum Inhibitory Concentration (MIC), Broth Microdilution, Etest, and Automation Systems.

  • Microbial Classification:

    • Consideration for actions of quantifying measurements for various pathogens: testing zones, interpreting results, and comparing against standard breakpoints.

Conclusion and Therapeutic Guidelines

  • Empiric Antimicrobial Therapy Principles:

    • Consider factors such as severity and acuity of disease, host factors, drug factors, combination therapy, and monitoring therapeutic responses.

  • Common Clinical Practice Applications:

    • Knowledge of common clinical laboratory tests and understanding discrepancies in resistance issues vs. lab testing errors.

    • Goals of therapy include achieving effective treatment with reduced resistance potential while managing patient-specific factors.