Antimicrobial Treatment

Principles of Antimicrobial Therapy

Antimicrobial therapy revolutionized medicine in the 1940s, significantly reducing the incidence of infectious diseases. However, complete eradication of infectious diseases remains unattainable, and the threat of a post-antibiotic era looms due to rising drug resistance.

• Main Goal: Destroy the infective agent without harming host cells.

• Ideal Drug Characteristics:

  • Toxic to microbes, nontoxic to host

  • Microbicidal (kills microbes) rather than microbistatic (inhibits growth)

  • Soluble and potent in body fluids

  • Remains active long enough, not broken down or excreted prematurely

  • Does not promote resistance

  • Assists host defenses

  • Delivered to infection site

  • Does not cause allergies or secondary infections

Terminology of Antimicrobials

Origins of Antimicrobial Drugs

Most antibiotics are metabolic products of bacteria and fungi, produced to inhibit competitors in their environment.

• Bacterial sources: Streptomyces, Bacillus

• Fungal sources: Penicillium, Cephalosporium

Pre-Therapy Considerations

Before starting antimicrobial therapy, three factors must be considered:

• Identity of the microorganism

• Susceptibility (sensitivity) to drugs

• Patient's overall medical condition

Identifying the Agent

• Identification should occur before drug administration

• Direct examination of body fluids, sputum, or stool is rapid

• Therapy may begin based on immediate findings and epidemiological data

Testing for Drug Susceptibility

Susceptibility testing is essential for certain pathogens and when initial treatment fails for fungal or protozoal infections.

• Key organisms: Staphylococcus spp., Neisseria gonorrhoeae, Enterococcus faecalis, aerobic gram-negative bacilli

Kirby-Bauer Technique

This is a standardized method for testing antimicrobial susceptibility using agar plates and antibiotic discs.

• Measure the zone of inhibition around each disc

• Compare to standards for each drug

Tube Dilution Test

This quantitative method determines the minimum inhibitory concentration (MIC) of a drug.

• Serial dilutions of drug in broth

• Inoculate with microbe, incubate, and examine for growth

MIC: The lowest concentration of drug that inhibits visible growth.

Therapeutic Index (TI)

The therapeutic index is the ratio of the toxic dose to the minimum effective dose:

• Smaller TI = higher risk of toxicity

• Higher TI = safer drug

Before Prescribing an Antibiotic

• Consider preexisting conditions, allergies, liver/kidney disease

• Special precautions for infants, elderly, pregnant women

• Drug interactions and synergistic effects

Mechanisms and Spectrum of Antimicrobial Action

Selective Toxicity

Selective toxicity refers to the ability of a drug to target microbial cells without harming host cells. Drugs targeting unique microbial structures (e.g., peptidoglycan cell wall) are most selectively toxic.

Major Targets of Antimicrobial Agents

• Cell wall synthesis

• Nucleic acid (DNA/RNA) synthesis

• Protein synthesis (ribosome)

• Cytoplasmic membrane structure/function

• Folic acid synthesis

Drugs That Target the Cell Wall

• Penicillins: Penicillin G/V, ampicillin, carbenicillin, amoxicillin, nafcillin, cloxacillin, clavulanic acid

• Cephalosporins: Cefazolin, cefaclor, cephalexin, cefotaxime, ceftriaxone, cefepime, ceftaroline

• Carbapenems: Doripenem, imipenem, aztreonam

• Miscellaneous: Bacitracin, isoniazid, vancomycin, fosfomycin tromethamine

Drugs That Target Protein Synthesis

• Aminoglycosides: Streptomycin

• Tetracyclines: Tetracycline, tigecycline

• Macrolides: Erythromycin, clarithromycin, azithromycin

• Miscellaneous: Clindamycin, quinupristin + dalfopristin (Synercid), linezolid

Drugs That Target Folic Acid Synthesis

• Sulfamethoxazole

• Silver sulfadiazine

• Trimethoprim

Drugs That Target DNA or RNA

• Fluoroquinolones: Ciprofloxacin, ofloxacin, levofloxacin

• Miscellaneous: Rifampin

Drugs That Target Cytoplasmic or Cell Membranes

• Polymyxin B

• Daptomycin

Spectrum of Activity

• Broad-spectrum: Effective against multiple groups (e.g., tetracyclines)

• Narrow-spectrum: Target specific groups (e.g., polymyxin)

• Penicillins: Originally narrow-spectrum, now improved for broader use

Clinical Considerations and Resistance

Response to Treatment

• In vitro results may not match in vivo outcomes

• Drug diffusion, resistance, mixed infections, and patient compliance affect success

Concept Checks

• Safest antibiotic: Drug B (TI: 12) is safer than Drug A (TI: 1.2), despite a smaller zone of inhibition.

• Least toxic mode of action: Antibiotic C (acts on peptidoglycan cell wall) is least toxic to human cells.

Summary Table: Mechanisms of Action

Additional info:

• Selective toxicity is highest for drugs targeting structures unique to microbes (e.g., peptidoglycan).

• Therapeutic index is a critical safety measure in drug selection.

• Susceptibility testing guides effective therapy and helps prevent resistance.