Antimicrobial Strategies and Therapies

Antimicrobial Strategies

• Methods to inhibit or destroy microorganisms
• Types: Antibiotics (e.g., β-lactams), antifungals (e.g., amphotericin B), antivirals (e.g., oseltamivir), Phage Therapy, antimicrobial peptides (AMPs), and alternative therapies (vaccines, antisense oligonucleotides, probiotics).

Antimicrobial Peptides (AMPs)

• 10-60 amino acids long
• Interact negatively-charged cell membranes
• Form transmembrane water-permeable pores
• Inhibit protein, DNA, and RNA synthesis

Phage Therapy

• Naturally occurring or genetically modified to increase sensitivity to specific bacteria
• Infect and lyse bacteria
• Bacteria and phages have co-evolved
• Can be used in conjunction with antibiotics
• Specific (won't harm other cells)
• Fewer side effects than antibiotics

Antisense Oligonucleotides

• Short, chemically modified, single-stranded molecules
• Complementary to mRNA target
• Target pathogen essential genes (replication, resistance, virulence)
• Possible to augment host immune response
• Cause RNA cleavage or blockage

Antibiotics

• Mnemonic, antibiotic class, examples, and coverage for different groups of antibiotics
• MOA (mechanism of action) for each class of antibiotics, e.g., inhibit protein synthesis (30S or 50S), cell wall synthesis, folate synthesis, or DNA replication
• Uses for each class of antibiotics, e.g., bacteremia, skin, urinary, respiratory infections

Mechanisms of Antibiotics (Cell Wall Inhibitors)

• β-lactams: Block peptidoglycan cross-linking by inhibiting penicillin-binding proteins (PBPs).
• Bactericidal.
• β-lactam moiety mimics D-Ala-D-Ala moiety, binds to transpeptidase that links peptidoglycan molecule.
• Examples: Penicillins (e.g., amoxicillin), Cephalosporins (e.g., cefepime), Carbapenems (e.g., meropenem), Monobactams (e.g., aztreonam), β-lactamase inhibitors (e.g., clavulanic acid).

Mechanisms of Antibiotics (Other Inhibitors)

• Glycopeptides: Block peptidoglycan synthesis.
• Macrolides: Bind the 50S ribosome.
• Aminoglycosides: Bind the 30S ribosome.
• Other inhibitors: Fluoroquinolones, Nitroimidazoles, Trimethoprim

Resistance Mechanisms

• β-lactam resistance includes enzymatic production (β-lactamases), efflux pumps, and target modification
• Vancomycin resistance involves D-Ala-D-Ala to D-Ala-D-Ser modification to prevent vancomycin binding

Key Antibiotics Overview

• β-lactams, Vancomycin, Macrolides, Aminoglycosides, and Fluoroquinolones

Laboratory Methods

• Gram stain, acid-fast stains, fungal stains, parasite microscopy, virus detection and culture methods.
• Methods for identifying bacteria, mycobacteria, fungi, and viruses, as well as culture methods.

Opportunistic Infections

• Defined by infections occurring in individuals with weakened immune systems.
• Contributing factors include congenital defects, acquired conditions (cancer, diabetes, HIV/AIDS), immunosuppressive therapies, malnutrition, age-related decline, and foreign bodies.

Emerging/Re-emerging Infectious Diseases (EIDs/RIDs)

• Definitions: Emerging Infectious Diseases (EIDs): Newly appearing or rapidly increasing diseases Re-emerging Infectious Diseases (RIDs): Previously controlled diseases increasing.
• Categories: Newly emerging, re-emerging, deliberately emerging
• Anthropogenic factors: Ecological changes, human demographics/behaviors, healthcare advances, travel/trade, and climate change
• Microbial factors: Microbial evolution and drug resistance

Vaccines

• Purpose: Expose immune system to pathogens/components without causing disease
• Types: Live attenuated, inactivated, subunit/conjugate, viral vectored, nucleic acid
• Ideal characteristics: Safety, effectiveness, cost-effectiveness
• Outcomes: Disease eradication, disease reduction, and herd immunity
• Challenges: HIV vaccine development and COVID-19 vaccines
• Side effects: Mild and severe (rare)
• Contraindications

Drug Discovery

• Early drug discoveries relied on trial and error using natural products.
• Modern process includes target identification, hit identification, hits to leads, lead optimization, and preclinical/clinical trials.
• Emerging strategies in drug discovery include rational drug design, phenotypic screening, and drug repurposing.

Specific Infections

• HIV/AIDS, Candidiasis, Pneumocystis jiroveci pneumonia (PCP), and toxoplasmosis.
• Specific causes, forms, pathogenesis, diagnosis, treatment, for each condition are addressed.