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.