Principles of Antimicrobial Therapy

Definition and Goals

Antimicrobial therapy is a cornerstone of modern microbiology and medicine, aiming to eliminate infectious agents while minimizing harm to the host. The central concept is selective toxicity, where drugs target microbial cells without damaging host tissues.

• Antimicrobial chemotherapy: The use of drugs to destroy infectious agents without harming the host's cells.

• Selective toxicity: The ability of a drug to kill or inhibit microbial cells while sparing host cells.

Types and Sources of Antimicrobial Drugs

Natural, Semisynthetic, and Synthetic Antibiotics

Antimicrobial drugs can be produced naturally by microorganisms, modified from natural compounds, or synthesized entirely in the laboratory.

• Antibiotics: Microbially produced antimicrobial agents, typically derived from bacteria and fungi.

• Less than 1% of known antibiotics are clinically useful; many are modified to enhance efficacy (semisynthetic).

• Semisynthetic antibiotics: Artificially modified natural antibiotics to improve their spectrum, efficacy, or reduce side effects. They retain a "natural core."

• Synthetic antibiotics: Entirely man-made in the laboratory.

Microbial Producers of Antibiotics

Many antibiotics are derived from specific genera of bacteria and fungi. These organisms produce compounds that inhibit the growth of competing microbes.

• Bacterial producers: Streptomyces and Bacillus

• Fungal producers: Penicillium and Cephalosporium

• Zones of inhibition on agar plates indicate colonies producing antibiotics.

Table: Selected Microbial Sources of Antibiotics

Spectrum of Antimicrobial Drugs

Broad vs. Narrow Spectrum

The spectrum of an antimicrobial drug refers to the range of microbes it affects. This property is crucial for selecting appropriate therapy.

• Broad spectrum: Effective against a wide variety of microbial types, including both Gram-positive and Gram-negative bacteria (e.g., tetracyclines).

• Narrow spectrum: Effective against a limited group of microbes, such as drugs targeting mainly Gram-positive bacteria (e.g., bacitracin).

• Medium spectrum: Effective against some Gram-positive and Gram-negative bacteria.

Example: Bacitracin is effective for Gram-positive bacteria, while polymyxin targets Gram-negative bacteria.

Mechanisms of Action of Antimicrobial Drugs

Major Targets in Bacterial Cells

Antimicrobial drugs act by interfering with essential microbial processes. The main targets include:

• Cell wall synthesis: Penicillins and cephalosporins block peptidoglycan synthesis, causing cell lysis.

• Cell membrane function: Polymyxins disrupt phospholipids, causing leakage (especially in Gram-negative bacteria).

• Nucleic acid synthesis: Quinolones inhibit DNA gyrase, blocking DNA replication.

• Protein synthesis: Aminoglycosides (e.g., streptomycin, gentamicin) bind to the 30S ribosomal subunit, causing misreading of mRNA; tetracyclines block tRNA attachment; macrolides (e.g., erythromycin) bind to the 50S subunit.

• Metabolic pathways: Sulfonamides inhibit folic acid synthesis, which is essential for nucleic acid production in bacteria.

Key Terms and Examples

• Beta-lactam antibiotics: Interfere with cell wall synthesis; includes penicillins and cephalosporins. Characterized by the beta-lactam ring structure.

• Semisynthetic penicillins: Ampicillin and amoxicillin have broader spectra, effective against Gram-negative infections.

• Penicillinase-resistant penicillins: Methicillin, nafcillin, cloxacillin; designed to resist bacterial enzymes that degrade penicillin.

Summary Table: Mechanisms and Examples of Antimicrobial Drugs

Additional info:

• Antimicrobial drugs are selected based on their spectrum, mechanism of action, and the susceptibility of the pathogen.

• Drug resistance is a growing concern, often resulting from genetic mutations or acquisition of resistance genes.