In Depth Notes on Antimicrobial Agents

Chapter 14: Antimicrobial Agents

Objectives Overview

  • Define Terms
    • Antimicrobial agents: substances that kill or inhibit microbial growth.
    • Antibiotic: a type of antimicrobial agent specifically used against bacteria.
  • Testing Susceptibility
    • Describe methods for bacterial susceptibility testing to determine effective antibiotics.
  • Antimicrobial Combinations
    • Explore possible outcomes when combining multiple antimicrobials.

Key Groups of Antimicrobial Agents

  • Penicillins
    • Different classes: Natural, Penicillinase-resistant, Aminopenicillins, Carboxypenicillins, Ureidopenicillins.
  • Cephalosporins
    • Categorized into five generations, each with its spectrum of activity.
  • Macrolides/Azalides/Ketolides
    • Recognize the similarities and differences in their use.
  • Fluoroquinolones
    • Similarities and clinical use.
  • Antimycobacterials
    • Listing and their specific use cases.
  • Azole Antifungals
    • Compare different azoles on the spectrum of antifungal activity.

Principles of Antimicrobial Therapy

  • Gram Staining
    • Differentiates bacteria into Gram-positive (purple) and Gram-negative (pink) based on cell wall structure.
  • Other Staining Methods
    • Acid-fast stains and ELISAs for pathogen identification.

Identification of Pathogen

  • Specimen Collection: Blood, urine, sputum, cerebrospinal fluid, pleural fluid, synovial fluid, peritoneal fluid, stool.
  • Results typically in 24 hours via:
    • Kirby-Bauer Disk Diffusion: Measures susceptibility with antibiotic-impregnated disks.
    • E-test: Determines minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC).

Factors Affecting Antimicrobial Therapy

  • Host Factors: Includes immune competence, age, organ function (liver/kidney), pH, and pregnancy.
  • Pharmacodynamics: Study of drug effectiveness based on concentration and bacterial response.
    • Discuss concepts like time-kill studies, concentration-dependent effects, and post-antibiotic effect (PAE).

Antimicrobial Combinations

  • Used to cover broader spectrums and identify polymicrobial infections.
  • Understanding synergy vs antagonism in drug combinations.

Monitoring Therapy Response

  • Evaluation of clinical signs (fever, labs, cultures) and adverse effects can indicate treatment success or failure.

Classes of Antibiotics

Beta-Lactams

  • Penicillins: Inhibit cell wall synthesis, bactericidal, examples (Natural, Penicillinase-resistant).
  • Cephalosporins: Similar action, varying effectiveness against Gram-positive and negative bacteria across generations.
  • Carbapenems: Broad spectrum and used against multi-drug resistant infections; similar action to beta-lactams.
  • Monobactams: Effective against aerobic Gram-negative bacteria; low adverse reaction incidence.

Other Antibiotics

  • Aminoglycosides: Inhibit protein synthesis, often used for severe Gram-negative infections; nephrotoxic and ototoxic effects.
  • Tetracyclines: Inhibit protein synthesis; broad spectrum but can damage bone growth and calcium absorption.
  • Macrolides and Ketolides: Bacteriostatic, used in respiratory tract infections and chlamydia.
  • Quinolones: Bactericidal for DNA synthesis; relatively safe but can have gastrointestinal side effects.
  • Chloroamphenicol: Broad spectrum but serious side effects like bone marrow suppression.
  • Vancomycin: Bactericidal against Gram-positive organisms; used mainly for MRSA with nephrotoxic potential.

Adverse Reactions

  • Common reactions range from gastrointestinal disturbances, hypersensitivity, to severe effects like oxidative damage (from tetracyclines) and bone marrow suppression (in antibiotics such as chloramphenicol).

Antimycobacterials

  • INH: Inhibits cell wall synthesis; hepatotoxicity potential.
  • Rifampin: Interrupts RNA polymerase function; bodily fluid discoloration.
  • Ethambutol: Risk of optic neuropathy; bacteriostatic action.

Antifungals

  • Polyenes (Amphotericin B): Mechanism includes cell membrane permeability; severe infusion-related reactions.
  • Azoles: Reduction in ergosterol production; used mainly for candidiasis.
  • Echinocandins: Inhibit fungal cell wall synthesis; mild side effects.

Antivirals

  • Acyclovir: Treatment for herpes viruses; risk of nephrotoxicity.
  • Oseltamivir/Zanamivir: For influenza A/B; mild side effects.

Biologics and Monoclonal Antibodies

  • Utilized for various conditions with the potential to target infectious diseases; examples include Raxibacumab for anthrax.

Clinical Considerations

  • Thorough assessment of antibiotic therapy including efficacy indicators before, during, and after treatment is crucial to limit misuse and resistance development.