24. Intro to Chemotherapy

What are bacteria and how are they classified by shape?

Bacteria are single-celled organisms classified by shape into:

• Cocci: Spherical

• Bacilli: Rod-shaped

• Spirilla: Spiral-shaped

What are the two major classifications of bacteria based on cell wall composition?

• Gram-positive: Thick peptidoglycan layer, stains purple

• Gram-negative: Thin peptidoglycan + outer membrane, stains pink

How can bacteria be classified by nutrition and respiration?

• Nutrition: Autotrophic (make own food) vs. Heterotrophic (require organic nutrients)

• Respiration: Aerobic (require O₂) vs. Anaerobic (grow without O₂)

Give examples of Gram-positive and Gram-negative bacteria.

• Gram-positive: All Staphylococci, all Streptococci, some Listeria species

• Gram-negative: Salmonella, Pseudomonas, Enterococci, E. coli

What are viruses?

Smallest pathogens, consisting of a protein structure that contains RNA or DNA

How do viruses replicate?

Only inside of a cell host.

What can viruses infect?

All types of life forms: animals, plants, microorganisms

What are fungi and give common examples of fungal infections?

Fungi are uni- or multicellular plant-like organisms; examples:

• Candidiasis (yeast infection)

• Athlete’s foot

• Ringworm

Which pathogens are the largest and give examples?

Parasitic worms (helminths): largest pathogens; examples:

• Pinworms

• Tapeworms

What are prions and what disease do they cause?

Prions are self-replicating, protein-based infectious agents; cause Creutzfeldt-Jakob disease (neurodegenerative).

What are the characteristics of an ideal antimicrobirals?

• Toxic to microbe but not host cells

• Great PK and PD: potent and doesn’t break down easily

• Cidal, not static

• Can get to site of infection

• Doesn’t develope resistance

• Doesn’t cause allergies

• Reasonably priced

What is the primary goal of chemotherapeutic drugs?

To disrupt essential cell processes or structures in pathogens (bacteria, fungi, protozoa) and even abnormal host cells (cancer), or inhibit viral replication.

What three factors must be considered before selecting a chemotherapeutic drug?

• Nature of the microorganism causing infection

• Degree of susceptibility of the microorganism to drugs

• Overall medical condition of the patient

What is the main mechanism of an antibiotic?

Most antibiotics interfere with functions of enzymes required to synthesize or assemble macromolecules or destroy structures already formed in cell. 

What is the main difference between bacteriostatic and bactericidal drugs?

• Bacteriostatic: Inhibit bacterial growth (metabolic reactions) but do not kill; rely on host immunity.

• Bactericidal: Kill bacteria by causing lethal changes in metabolism or essential activities; useful when host defenses are weak.

When are bactericidal drugs preferred over bacteriostatic drugs?

When host defenses cannot control the pathogen

Can a drug be both bacteriostatic and bactericidal?

Yes, depending on their concentration and the bacterial species against which they are used.

What does “spectrum of activity” mean for antimicrobials?

It refers to the range of organisms an antimicrobial can control, which can be narrow or broad.

What are the advantages and disadvantages of narrow-spectrum antimicrobials?

• Advantage: Targets the pathogen only → less disruption of normal flora

• Disadvantage: Requires identification of the pathogen before use

What are the advantages and disadvantages of broad-spectrum antimicrobials?

• Advantage: Effective against a wide range of organisms

• Disadvantage: Disrupts normal flora, increasing risk of superinfection and resistance

What are some issues with antimicrobial drugs?

• Allergic reactions

• Toxic effects to human

• Suppression of normal flora

• Antimicrobial resistance 

What is the role of chromosomal determinants in bacterial resistance?

Mutations in bacterial genes during division can alter drug targets or metabolic pathways, reducing antibiotic effectiveness.

How does gene amplification contribute to resistance?

Antibiotic exposure can increase copies of resistance genes, leading to overproduction of drug-destroying enzymes or efflux pumps.

What are extrachromosomal determinants of resistance and why are they clinically important?

Plasmids replicate independently in the cytoplasm and often carry resistance genes; most clinically significant resistance is plasmid-mediated.

How do bacteria inactivate antimicrobial drugs?

By producing drug-inactivating enzymes that cleave or modify the drug molecule

What is the mechanism of resistance involving alteration of target molecules?

Structural changes in the drug’s binding site, prevent antibiotic binding, rendering the drug ineffective.

How do bacteria reduce drug entry or increase drug elimination?

• Decreased uptake: Altered transport proteins block drug entry.

• Increased elimination: Efflux pumps actively expel the drug from the cell.

What is the metabolic mechanism of resistance?

Bacteria use an alternate metabolic pathway to bypass the one blocked by the drug, maintaining essential functions.

Why are enterococci clinically significant in antimicrobial resistance?

Enterococci are intrinsically resistant to many common antimicrobials, making infections difficult to treat.

What is VRE and why is it important?

Vancomycin-Resistant Enterococcus (VRE) refers to strains of enterococci that have acquired resistance to vancomycin 

Why is Staphylococcus aureus clinically significant in antimicrobial resistance?

It is a common cause of nosocomial infections and has developed resistance to many antibiotics, including penicillin.

What does MRSA stand for and what does it indicate?

Methicillin Resistant Staphylococcus aureus

What is VISA?

Vancomycin-Intermediate Staphylococcus aureus

What is the Kirby-Bauer disc diffusion method used for?

It is a qualitative test to determine bacterial susceptibility to antimicrobial drugs.

How is the Kirby-Bauer test performed?

• Discs containing specific concentrations of antibiotics are placed on an agar plate inoculated with bacteria.

• After incubation, a clear zone of inhibition around the disc indicates susceptibility.

What does the size of the zone of inhibition indicate?

Larger zone = greater susceptibility; smaller or no zone = resistance.

What is MIC?

Minimum Inhibitory concentration. It is a quantitative test that determines lowest drug conc needed to prevent growth of specific organism.