Chapter 10: Controlling Microbial Growth in the Body: Antimicrobial Drugs – Study Guide

Controlling Microbial Growth in the Body: Antimicrobial Drugs

Relationship Between Chemotherapeutic and Antimicrobial Agents

Chemotherapeutic agents are chemicals used to treat diseases, while antimicrobial agents are a subset specifically used to treat infections caused by microorganisms.

• Chemotherapeutic agents: Any chemical used in the treatment, relief, or prophylaxis of a disease.

• Antimicrobial agents: Chemotherapeutic agents that target microbes (bacteria, fungi, viruses, protozoa).

• Example: Penicillin is both a chemotherapeutic and an antimicrobial agent.

Types of Antimicrobial Drugs

• Antibiotics: Substances produced naturally by microorganisms that inhibit or kill other microbes.

• Synthetic drugs: Antimicrobial compounds synthesized entirely in the laboratory.

• Semisynthetic drugs: Natural antibiotics that have been chemically modified to enhance their properties.

• Example: Amoxicillin is a semisynthetic derivative of penicillin.

History and Timeline of Antibiotics

The discovery and development of antibiotics revolutionized medicine. Key milestones include:

• 1928: Alexander Fleming discovers penicillin from Penicillium mold.

• 1940s: Howard Florey and Ernst Chain develop penicillin for clinical use.

• 1944: Selman Waksman discovers streptomycin, the first antibiotic effective against tuberculosis.

• Subsequent decades: Discovery of tetracyclines, chloramphenicol, and other classes.

Selective Toxicity

Selective toxicity refers to the ability of a drug to target microbial cells without harming host cells.

• Essential for effective antimicrobial therapy.

• Targets unique features of prokaryotes (e.g., peptidoglycan cell wall), eukaryotes (e.g., ergosterol in fungi), or viral processes (e.g., reverse transcriptase).

• Example: Penicillins inhibit cell wall synthesis, which is absent in human cells.

Mechanisms of Antimicrobial Drugs

Antimicrobial drugs act through several mechanisms:

• Inhibition of cell wall synthesis (e.g., beta-lactams like penicillin)

• Inhibition of protein synthesis (e.g., tetracyclines, aminoglycosides)

• Disruption of cytoplasmic membrane (e.g., polymyxins, antifungals)

• Inhibition of nucleic acid synthesis (e.g., quinolones, rifampin)

• Antimetabolite activity (e.g., sulfonamides)

Gram-positive vs. Gram-negative:

• Drugs targeting cell wall synthesis (e.g., penicillins) are generally more effective against Gram-positive bacteria due to their thick peptidoglycan layer.

• Drugs that disrupt the outer membrane or inhibit protein synthesis may be more effective against Gram-negative bacteria.

Qualities of an Ideal Antimicrobial Agent

• Selective toxicity

• Non-allergenic and non-toxic to host

• Soluble in body fluids and stable

• Long shelf-life

• Microbicidal rather than microbistatic

• Unlikely to foster resistance

Evaluating Antimicrobial Drugs

Effectiveness is measured by laboratory tests such as:

• Minimum Inhibitory Concentration (MIC): Lowest concentration that inhibits visible growth.

• Minimum Bactericidal Concentration (MBC): Lowest concentration that kills 99.9% of the bacteria.

Example Table: Broth Dilution Test Results

Antibiotic Concentration (µg)	Growth	Growth in Subculture
200	-	-
100	-	-
50	-	+
25	+	+

• Interpretation: MBC is the lowest concentration with no growth in subculture (100 µg).

Tests for Efficacy of Antimicrobial Agents

• Kirby-Bauer Disk Diffusion Test: Measures zone of inhibition around antibiotic disks on agar plates.

• Broth Dilution Test: Determines MIC and MBC by exposing bacteria to serial dilutions of drug.

• E-test (Epsilometer test): Uses a strip with a gradient of antibiotic concentration to determine MIC.

Routes of Administration

• Oral: Easiest, but absorption may be variable.

• Intramuscular (IM): Delivers drug via injection into muscle; allows for slower, sustained release.

• Intravenous (IV): Directly into bloodstream; rapid and complete delivery.

• Topical: Applied to skin or mucous membranes; used for superficial infections.

• Limitations: Some drugs cannot be given orally due to poor absorption or degradation in the GI tract.

Side Effects of Antimicrobial Drugs

• Toxicity: Damage to organs (e.g., nephrotoxicity, ototoxicity).

• Allergic reactions: Hypersensitivity responses, such as anaphylaxis.

• Disruption of normal microbiota: Can lead to secondary infections (e.g., Clostridioides difficile colitis).

Normal Microbiota vs. Transient Microbiota

• Normal microbiota: Microorganisms that colonize the body permanently without causing disease under normal conditions.

• Transient microbiota: Microbes that are present temporarily and do not persist in the body.

Development of Antimicrobial Resistance

Resistance arises through genetic changes that enable microbes to withstand drug effects.

• Mechanisms: Mutation, acquisition of resistance genes via horizontal gene transfer (conjugation, transformation, transduction).

• Example: MRSA (Methicillin-resistant Staphylococcus aureus).

Mechanisms of Resistance

• Enzymatic destruction or inactivation of drug (e.g., beta-lactamases)

• Alteration of drug target site

• Decreased permeability or increased efflux of drug

• Bypass of metabolic pathway inhibited by drug

Multiple Resistance vs. Cross Resistance

• Multiple resistance: Microbe is resistant to several unrelated drugs.

• Cross resistance: Resistance to one drug confers resistance to similar drugs (often within the same class).

Retarding Resistance

• Use high concentrations of drug for appropriate duration.

• Use combination therapy (multiple drugs with different mechanisms).

• Limit use of antimicrobials to necessary cases.

• Promote patient compliance with prescribed regimens.