Learning goals
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Understand five mechanisms of antibiotic action
-
Differentiate empiric vs. directed therapy
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Recognize bacterial resistance mechanisms
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Apply PK/PD principles: bacteriostatic vs. bactericidal, time vs. concentration dependence
Mechanisms of action
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Cell Wall Synthesis Inhibition: Penicillins, Cephalosporins, Carbapenems, Vancomycin.
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Protein Synthesis Inhibition: Aminoglycosides (30S), Macrolides, Clindamycin, Tetracyclines (50S).
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Cell Membrane Disruption: Daptomycin, Polymyxins.
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Nucleic Acid Synthesis Inhibition: Fluoroquinolones, Rifampin.
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Antimetabolite Activity: TMP-SMX (folate synthesis).
Mechanisms of antibiotic action
|
Mechanism |
Antibiotic classes / Examples |
|---|---|
|
Cell Wall Synthesis Inhibition |
Penicillins, Cephalosporins, Carbapenems, Vancomycin |
|
Protein Synthesis Inhibition |
Aminoglycosides (30S), Macrolides, Clindamycin, Tetracyclines (50S) |
|
Cell Membrane Disruption |
Daptomycin, Polymyxins |
|
Nucleic Acid Synthesis Inhibition |
Fluoroquinolones, Rifampin |
|
Antimetabolite Activity |
TMP-SMX (folate synthesis) |
Types of antimicrobial therapy applications
|
Type |
Description |
Example |
|---|---|---|
|
Empiric |
Treatment initiated before the pathogen is identified |
Vancomycin + Cefepime for sepsis |
|
Definitive |
Treatment based on culture and sensitivity results |
Directed therapy after lab identification |
|
Primary Prophylaxis |
Prevention of infection in high-risk patients |
TMP-SMX in HIV |
|
Secondary Prophylaxis |
Prevention of recurrent infection |
Penicillin for rheumatic fever |
|
Preemptive |
Treatment given based on lab evidence before symptoms develop |
Early antiviral therapy |
|
Suppression |
Long-term therapy for incurable infections |
Chronic antibiotics in select cases |
Mechanisms of resistance
|
Mechanism |
Details |
|---|---|
|
Decreased Accumulation |
↓ Porins, ↑ Efflux pumps |
|
Target Modification |
PBP2a in MRSA, altered DNA gyrase |
|
Enzymatic Inactivation |
β-lactamases, aminoglycoside-modifying enzymes |
Susceptibility testing
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MIC: Minimum Inhibitory Concentration.
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MBC: Minimum Bactericidal Concentration.
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Interpretation: Susceptible (S), Intermediate (I), Resistant (R).
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Do NOT compare MICs across drugs.
Pharmacodynamic parameters and dosing strategies
|
Parameter |
Description |
Example Drugs |
Dosing Strategy |
|---|---|---|---|
|
Cmax/MIC |
Concentration-Dependent |
Aminoglycosides |
High peak doses, less frequent administration |
|
T>MIC |
Time-Dependent |
β-lactams |
Frequent dosing or continuous infusion to maintain drug levels above MIC |
|
AUC/MIC |
Time + Concentration-Dependent |
Vancomycin |
Individualized dosing based on drug exposure (AUC) and infection severity |
Bacteriostatic vs. bactericidal
-
Bacteriostatic: Inhibits growth (e.g., Tetracyclines, Macrolides).
-
Bactericidal: Kills bacteria (e.g., Penicillins, Fluoroquinolones).
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MBC/MIC Ratio: >4 = static, ≤4 = cidal.
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Bacteriostatic and bactericidal agents are equivalent for the treatment of most infectious diseases in immunocompetent hosts
Adverse effects
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All antibiotics: Adverse effects related to changes to microbes in and on host (normal flora).
-
Class toxicities (e.g., hypersensitivities to sulfa).
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Drug-specific toxicities (e.g., rifampin = red-orange body fluids).
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Idiosyncratic reactions: Rare, unpredictable, but often life-threatening/severe.
Mnemonics
-
Time kills slowly; concentration kills fast.
Learning goals
- Describe the five basic mechanisms of action of antimicrobials against bacterial cells (inhibition of cell wall synthesis, inhibition of protein synthesis, alteration of cell membranes, inhibition of nucleic acid synthesis, and antimetabolite activity)
- Define empiric versus directed antimicrobial therapy and describe the basic principles behind selecting an empiric antimicrobial regimen
- Discuss the pharmacokinetic (static versus cidal) and pharmacodynamic (time-dependent versus concentration-dependent) principles of antimicrobial therapy
- Describe three main mechanisms by which bacteria resist the activity of antimicrobials
Required pre-class materials
Study materials
These materials are not required; they are supplementary to large group session. They are intended as a curated guide to content focused on the learning objectives. There are both textbook and video resources for this session for students to use per their preference. For each reference, I have designated the learning goal addressed with a and number.
Click the book icons below to go to the library resources listed.
- General Considerations
- 1 Spectrum of Action
- Table 23-1: Characteristics of Antibacterial Drugs. This table is a useful introduction to basic spectrum of activity for prototypical antibiotics in major classes. There are much more detailed spectrum charts for use in clinical practice (e.g., Sanford Guide) that list activity of individual agents against individual pathogens. But this is a good place to start.
- 3 4 Susceptibility and Resistance
- 4 Bacterial resistance to antimicrobials
Put a pin in it
Recommendations for learning about antibiotics as you progress through the 4-year curriculum
Sketchy Medical Pharm: Sketchy can be a useful tool to help memorize the factoids. The Sketchy videos include a lot of indications/clinical uses of these agents, which is not part of this session’s objectives. And you may not have yet learned about many of the clinical entities mentioned in the videos.
If you’re planning on using Sketchy, my advice would be to incorporate Sketchy antimicrobial videos after completing the bulk of the systems-based infectious disease content (~FMS 511).
Best clinical references to use for choosing an antibiotic for a given patient including most up-to-date recommendations in antimicrobial stewardship.
-
- The Sanford Guide to Antimicrobials (pocket book, app, and web-based available): The “gold standard” includes references to key studies and extended pharmacology.
- Hopkins Abx: Clinically oriented and user friendly, some limited free versions available that will serve vast majority of need for basic antimicrobial use.