Microbial Resistance and Drug Susceptibility Quiz

Introduction to Chemotherapy

• Chemotherapy involves using drugs to eliminate pathogenic organisms or cancerous cells.
• The principle behind chemotherapy is selective toxicity, targeting a crucial function in invading organisms (or cancer cells) that differs from the host's.

Objectives

• Understand the mechanisms of selective toxicity in chemotherapeutic drugs.
• Describe the modes of action of various chemotherapeutic drugs.
• Detail the side effects associated with these drugs, including resistance mechanisms.

Overview

• Chemotherapy aims to eradicate pathogenic organisms or cancerous cells, treating infectious illnesses and cancer.
• Selective toxicity is essential for chemotherapy; drugs must inhibit a critical function specific to the disease-causing agent without harming the host.

The Chemotherapeutic Drugs

• Antimicrobial drugs (antibacterial, antifungal, and antiviral agents).
• Antiparasitic drugs.
• Antineoplastic and immunopharmacology drugs.

History

• Early use of antibiotics involved treating skin infections.
• Louis Pasteur and Paul Vuillemin identified the concept of antibiosis, where one organism inhibits another.
• Alexander Fleming discovered penicillin while observing a bacterial culture inhibited by a Penicillium mold.

Synthetic Drugs

• Historical use of mercury compounds for syphilis treatment.
• Paul Ehrlich's work on arsphenamine (Salvarsan) initiated chemotherapy.
• Sulfonamides (derived from Prontosil) were the first effective systemic antibacterial agents.

Part One: Antimicrobial Drugs

• Antibiotics categorized as antibacterial agents, antifungal agents, and antiviral agents
• Antiparasitic drugs in additional sections
• Antineoplastics and immunopharmacology drugs also covered.

Classification of Antimicrobial Drugs

• Cell wall synthesis inhibitors.
• Protein synthesis inhibitors.
• Metabolic and nucleic acid inhibitors.
• Cell membrane inhibitors.

Antimicrobial Activity of Chemotherapeutic Drugs

• Bactericidal or bacteriostatic effects.
• Spectrum of action against pathogens.
• Concentration and time dependencies affecting effectiveness.

Effect: Bactericidal or Bacteriostatic.

• Bactericidal drugs kill pathogens rapidly.
• Bacteriostatic drugs inhibit pathogen growth but do not kill them.
• This principle also applies to antifungal drugs.

In vitro effects of bactericidal and bacteriostatic drugs.

Bactericidal or Bacteriostatic Drugs

• Bactericidal drugs work by disrupting essential microbial functions.
• Bacteriostatic drugs inhibit essential metabolic reactions.

Bactericidal or Bacteriostatic Drugs

• Reversible and irreversible protein synthesis inhibitors.
• Some antibiotics can be either bactericidal or bacteriostatic depending on concentration and pathogen.

Antimicrobial Spectrum

• Narrow-spectrum drugs are used against only specific bacteria.
• Broad-spectrum drugs affect a wider range of bacteria.

Concentration- and Time-Dependent Effects

• Minimal inhibitory concentration (MIC) determines bacterial susceptibility.
• Concentration-dependent killing rate (CDKR) measures rate of death of pathogens.
• Post-antibiotic effect (PAE) considers persistence of drug's effectiveness after drug removal.

Some aminoglycosides and some fluoroquinolones.

• Some aminoglycosides exhibit CDKR against Gram-negative bacteria.
• Penicillins and other β-lactam antibiotics generally do not exhibit CDKR.

Bacterial Resistance

• Innate (pre-existing) vs acquired drug resistance
• Innate resistance may arise from genetic structure
• Spontaneous mutations, plasmids (transferable resistance), and transformation / transduction can also cause resistance.

Primary Mechanisms of Microbial Resistance

• Drug inactivation by enzymes produced by the microbe.
• Reduced accumulation of drugs due to impaired uptake or increased efflux.
• Reduced affinity of the drug target for its macromolecule.

Mechanism of Microbial Resistance

• Examples detailed for inactivation, accumulation, affinity reduction

Some transport proteins.

• Some microbial resistance arises from transport mechanisms similar to the P-glycoprotein in humans which removes drugs from intracellular compartments (like cancer cells).

Host Factors

• Pregnancy, allergies, immune status, kidney and liver function, and presence of indwelling medical devices must be considered.

Antimicrobial Activity

• Testing for microbial susceptibility/resistance using broth dilution, disk diffusion (Kirby-Bauer), and E-test methods
• Essential to diagnose and treat infections correctly.

The Selection of Antimicrobial Drugs

• Factors to consider include the causative organism, patient's situation, and other characteristics of the infection / organism

Prophylactic Therapy

• Preventive measures such as sterilization of equipment, disinfection, and antibiotic administration can help prevent infections.

Prevention of Infection During Surgical Procedures

• Examples of infections and preferred drugs for prevention
• Pathogens involved

Prevention of Disease Transmission

• Infections and their preferred drugs for prevention
• Example: Prevention of herpes simplex, HIV, or influenza

Summary of Important Points

• Overview of antibiotics and antimicrobial actions.
• Mechanisms of bacterial action
• Determining sensitivity
• Resistance mechanisms

Acquired Microbial Resistance.

• Resistance can arise from mutations and transfer of genes (R factors) through conjugation, transformation, or transduction.
• Mechanisms include drug inactivation, reduced uptake, or altered targets.
• Key factors for selecting drugs, such as considering patient characteristics, the pathogen, type of infection, and drug pharmacokinetics.

Combination Drug Therapy

• Combination therapy can help address various forms of infection and limit development of drug resistance through synergy.
• Different outcomes for treatment depending on whether pathogens are mixed or not.

Relationship between two drugs and their combined effect

• Antagonistic
• Additive
• Synergistic
• Indifferent

Bactericidal drugs

• Effective against rapidly dividing bacteria
• Reduced effect if bacterial growth slowed by bacteriostatic drugs

If two bactericidal drugs that target different microbial functions are given in combination

• Effects can be additive or synergistic.

Combination therapy

• May help prevent resistance in cases such as tuberculosis.
• Synergistic interactions help limit bacterial growth.

Prophylactic therapy

• Preventing infections through measures such as instrument sterilization and preventative antibiotics
• Key factors for selection are based on risks such as the type of procedure, organism, and patient factors.

Adverse Effects Profile.

• Potential drug risks must be weighed against benefits especially when dealing with minor infections.
• Fluoroquinolones are reasonably safe compared to aminoglycosides.