Antimicrobials and Vaccines

What does spectrum of activity mean in the context of antibiotics?

It refers to the range of bacteria an antibiotic can target.

When would a broad-spectrum antibiotic be favored?

Broad-spectrum antibiotics are favored in life-threatening infections when the causative agent is unknown.

Why is a narrow spectrum favored in most cases?

Narrow-spectrum antibiotics target the pathogen specifically and cause less disruption to the microbiome.

Under what circumstances would a bactericidal versus a bacteriostatic antibiotic be a consideration?

Bactericidal is preferred for life-threatening infections or immunocompromised patients; bacteriostatic is for mild infections where the immune system can help eliminate bacteria.

What does 'selective toxicity' mean in the context of antibiotics?

It means the antibiotic targets bacterial processes/structures without harming the host.

What is a measure of 'selective toxicity'?

The therapeutic index, which is the ratio of the toxic dose to the therapeutic dose.

What is a 'therapeutic window,' and how do we determine it?

It is the range between the lowest therapeutic dose and the toxic dose, determined through clinical testing.

Why would the half-life of a medication be an important consideration for someone on kidney dialysis?

Kidney function affects drug excretion; long half-life drugs can accumulate and cause toxicity.

What structure do the most common cell wall inhibitors have in common?

The β-lactam ring.

The first generations of cell wall inhibitors had what spectrum of activity, and what were they effective against?

Narrow spectrum; effective against Gram-positive bacteria.

What was the very first inhibitor of cell wall synthesis discovered?

Penicillin.

Is the therapeutic window for most cell wall inhibitors large or small?

Large.

What is the exception to the large therapeutic window for cell wall inhibitors?

Glycopeptides like vancomycin have a narrow therapeutic window.

Why are inhibitors of protein synthesis so unpredictable in terms of toxicity?

They can affect mitochondrial ribosomes, which are similar to bacterial ribosomes (70S).

What is the safest inhibitor of protein synthesis?

Macrolides.

What is the most dangerous inhibitor of protein synthesis?

Aminoglycosides due to their toxicity (e.g., kidney and ear damage).

Which inhibitor of protein synthesis has the broadest spectrum of activity?

Tetracyclines.

Why are inhibitors of nucleic acid synthesis so diverse?

They target various steps in DNA and RNA metabolism, like replication and transcription.

Why are most antimetabolites bacteriostatic?

They competitively inhibit metabolic pathways, halting growth without killing bacteria.

Why are most cell membrane inhibitors only used topically?

They are toxic to human cells because they damage cell membranes indiscriminately.

State and explain the 4 mechanisms of antibiotic resistance.

1. Antibiotic-inactivating enzymes,

2. Alteration in target molecule

3. Decreased uptake of medication

4. Increased elimination of medication.

What are the 2 mechanisms by which bacteria can attain antibiotic resistance?

1. Spontaneous mutations,

2. Horizontal gene transfer via plasmids.

Why is a B cell response the favored response for a vaccine?

B cells produce antibodies, providing long-term immunity and memory responses.

How many lives per year are vaccines estimated to save?

2-3 million lives annually.

How many still die due to preventable vaccine-preventable diseases?

About 1.5-2 million annually.

What are the chances of a severe reaction to vaccines?

Less than 1 in 1,000,000.

What are the chances of dying from measles?

6 in 1,000 pediatric cases are fatal.

What is the concept behind an attenuated vaccine?

It uses weakened live pathogens that replicate poorly but stimulate immunity.

What are the advantages of an attenuated vaccine?

Strong, long-lasting immunity.

What are the disadvantages of an attenuated vaccine?

Risk of reversion to virulence and issues in immunocompromised patients.

What is the concept behind an inactivated vaccine?

Inactivated pathogens that cannot replicate.

What are the three possible types of inactivated vaccines?

Whole virus, bacterial toxins (toxoids), purified subunits.

Which inactivated vaccine can be used directly postnatally?

Hepatitis B vaccine.

What are the advantages of an inactivated vaccine?

No risk of infection.

What are the disadvantages of an inactivated vaccine?

Weaker immune response compared to live vaccines.

What is the concept behind a recombinant vaccine?

It uses genetic engineering to produce antigens.

What is the only recombinant virus vaccine currently in use?

Hepatitis B vaccine.

What is the concept behind an RNA vaccine?

It provides genetic instructions to produce an antigen that triggers an immune response.

Why is an RNA vaccine unlikely to become a common form of vaccine for longstanding diseases?

RNA vaccines may not provide long-term immunity and require further development.