Antibiotics

What is the difference between disinfectants and antiseptics?

Disinfectants are used on inanimate objects; antiseptics can be applied to living tissues.

What defines an antibiotic?

Antimicrobial agents produced by bacteria or fungi that humans use therapeutically.

Why are antibiotics essential in medicine beyond treating infections?

They make chemotherapy, organ transplants, invasive surgeries, and premature infant care possible.

What are the two major problems associated with antibiotics today?

Decreased pharmaceutical interest in new antibiotics and inevitable bacterial resistance.

List common examples of antibiotic misuse that promote resistance.

Empiric/blind use, broad-spectrum overuse, pediatric use for viral infections, patients not completing courses, antibiotics in animal feed.

What does MIC stand for?

Minimum inhibitory concentration.

What does the MIC represent?

The lowest antibiotic concentration that inhibits visible bacterial growth.

What are the major bacterial targets of antibiotics?

Cell wall synthesis, protein synthesis, DNA/RNA synthesis, folate synthesis, and cell membrane alteration.

Why can antibiotics target bacteria but not human cells?

The targets are absent or structurally different in eukaryotes.

What structure is shared by all β-lactam antibiotics?

The β-lactam ring

How do β-lactams kill bacteria?

They bind Penicillin binding proteins (transpeptidases), blocking cross-linking → weak cell wall → lysis.

How does β-lactamase confer resistance?

It cleaves the β-lactam ring, destroying the antibiotic

What bacterial gene encodes the alternative PBP (PBP2a)?

mec

How does PBP2a promote methicillin resistance?

It does not bind methicillin or other β-lactams

What is vancomycin's mechanism of action?

It binds D-Ala–D-Ala on peptidoglycan precursors, blocking transpeptidation

How do van genes cause resistance?

They replace D-Ala–D-Ala with D-Ala–D-Lac, preventing vancomycin binding

What type of bacteria is vancomycin mainly used against?

Gram-positive bacteria

What does antibiotic use actively select for?

Antibiotic-resistant bacteria

What is horizontal gene transfer?

Acquisition of new resistance genes from another organism, often via plasmids

Why are plasmid-encoded genes a major concern?

They spread resistance rapidly → "superbugs."

List five bacterial strategies for antibiotic resistance.

1. Prevent antibiotic entry (e.g., Gram-negative outer membrane)

2. Modify/destroy antibiotic (β-lactamase)

3. Efflux pumps

4. Alter target (PBP changes, ribosomal modifications)

5. Bypass inhibited pathways (use environmental folate)

What is an example of a carbapenemase that threatens many Gram negatives?

NDM-1 (New Delhi metallo-β-lactamase-1)

What condition is most strongly associated with prior antibiotic use?

Pseudomembranous colitis

How do antibiotics enable C. difficile infection?

They disrupt normal microbiota, allowing C. diff spores to germinate and overgrow

Is C. difficile invasive?

No; disease results from exotoxins, not invasion

What type of toxins does C. difficile produce?

A-B toxins (large clostridial cytotoxins)

What does the “A” domain of C. diff A-B toxins do?

Carries enzymatic activity that disrupts regulatory proteins → cytoskeletal changes, cell death, inflammation

What is the primary route of C. difficile transmission?

Fecal–oral transmission via endospores

What is a key diagnostic tool for pseudomembranous colitis?

Endoscopy showing characteristic lesions

What is a common treatment for C. difficile infection?

Oral vancomycin or IV metronidazole; sometimes fecal microbiota transplantation