Cell wall synthesis inhibitors

What are antimicrobial drugs?

Drugs used to treat infections caused by microorganisms

What is another name for antimicrobial drugs?

Chemotherapeutic agents

What does “selective toxicity” mean?

The drug harms bacteria more than the human host

What is bactericidal vs bacteriostatic?

• Bactericidal = kills bacteria

• Bacteriostatic = stops bacterial growth

What is broad-spectrum vs narrow-spectrum?

• Broad = works on many bacteria

• Narrow = works on specific bacteria

What do cell wall synthesis inhibitors do?

They block peptidoglycan formation → weaken cell wall → bacteria burst (lysis)

Why do these drugs mainly affect bacteria and not humans?

Humans don’t have a cell wall

When are these drugs most effective?

On rapidly growing bacteria

What is the main mechanism of β-lactam antibiotics (like penicillins)?

They inhibit transpeptidase → prevent cross-linking of peptidoglycan

What are penicillin-binding proteins (PBPs)?

Enzymes that help build the bacterial cell wall

What happens when PBPs are inhibited?

Weak cell wall → cell lysis

What role do autolysins play?

They break down the cell wall → bacteria die faster when synthesis is blocked

Who discovered penicillin?

Alexander Fleming

What is the basic structure of penicillin?

β-lactam ring + thiazolidine ring

What organisms do natural penicillins treat?

Gram (+), some Gram (-), anaerobes, spirochetes

Examples of natural penicillins

Penicillin G, Penicillin V

What are antistaphylococcal penicillins used for?

-Penicillinase-producing staph

-Examples:

• Methicillin

• Nafcillin

• Oxacillin

What are extended-spectrum penicillins?

-Broader coverage including Gram (-)

-Examples:

• Ampicillin

• Amoxicillin

What are antipseudomonal penicillins?

-Target Pseudomonas infections

-Examples:

• Piperacillin

• Ticarcillin

How do bacteria resist penicillin?

• β-lactamase enzymes (break drug)

• Altered PBPs

• Decreased permeability

• Efflux pumps

What do β-lactamase inhibitors do?

-Block β-lactamase → protect antibiotic

-Examples:

• Clavulanic acid

• Sulbactam

What is the most common side effect of penicillin?

Allergy (rash → anaphylaxis)

Other side effects of penicillin?

• Diarrhea

• Nephritis

• Neurotoxicity

• Electrolyte issues

How are cephalosporins related to penicillins?

Similar structure (β-lactam), but more resistant to β-lactamase

What happens as generations increase?

• ↑ Gram (-) coverage

• ↑ resistance

• ↓ Gram (+) coverage

Describe the first generation

-Strong Gram (+)

-Example:

• Cefazolin

Describe the third generation

-Strong Gram (-), crosses BBB

-Example:

• Ceftriaxone

Describe the fourth generation

-Broad + resistant

-Example:

• Cefepime

Key side effects of cephalosporins

• Allergy (cross with penicillin)

• Bleeding

• Disulfiram-like reaction with alcohol

What are carbapenems?

-Broad-spectrum, powerful β-lactams

-Example:

• Imipenem (given with cilastatin)

Why does carbapenems are give with cilastatin?

Prevents drug breakdown → reduces toxicity

What do carbapenems cover?

Gram (+), Gram (-), anaerobes, Pseudomonas

What is the main monobactam?

Aztreonam

What does monobactam cover?

Gram (-) only

Is monobactam safe in penicillin allergy?

Yes (minimal cross-reactivity)

How does vancomycin work?

Binds D-Ala-D-Ala → blocks cell wall synthesis

What bacteria does vancomycin treat?

Gram (+), including MRSA

How is vancomycin given?

• IV → systemic infections

• Oral → C. difficile

Major side effects of vancomycin

• Nephrotoxicity

• Ototoxicity

• “Red man syndrome” (fast infusion)

How does bacitracin work?

Blocks transport of cell wall components

Why is bacitracin only topical?

Nephrotoxic

What is fosfomycin used for?

UTIs (especially in women)

Is fosfomycin safe in pregnancy?

Yes

What is cycloserine used for?

Resistant tuberculosis

Major side effect of cycloserine

CNS toxicity

How does daptomycin work?

Disrupts membrane → depolarization → cell death

What is daptomycin used for?

Resistant Gram (+) infections (like VRE)

Which drugs are bactericidal?

Most cell wall inhibitors (penicillins, cephalosporins, vancomycin)

Which bacteria are NOT affected by bactericidals?

• Mycobacteria

• Fungi

• Viruses

What infection is strongly associated with antibiotic use?

Clostridium difficile colitis

Memory Tricks

• β-lactams = “Break the wall” → cell dies

• Vancomycin = “VANquishes Gram +”

• 3rd gen cephalosporins → think “brain” (cross BBB)

• Red man = fast vancomycin infusion