Antimicrobial Pharmacology I

What are the four major bacterial targets of antibiotics?

1. Cell wall

2. Cell membrane

3. Protein synthesis (ribosomes)

4. Nucleic acid metabolism

What does bacteriostatic mean?

Inhibits bacterial growth without directly killing the bacteria

What does bactericidal mean?

Kills bacteria

What does bacteriolytic mean?

Kills bacteria by causing cell lysis

What is Minimum Inhibitory Concentration (MIC)?

Lowest concentration preventing visible bacterial growth

What is Minimum Bactericidal Concentration (MBC)?

Lowest concentration that kills bacteria under the test conditions

Which is routinely measured more often: MIC or MBC?

MIC

What is the difference between concentration-dependent and time-dependent killing?

- Concentration-dependent: higher concentrations increase killing

- Time-dependent: duration above MIC matters

Which antibiotic classes show concentration-dependent killing?

Aminoglycosides and Quinolones

Which major antibiotic class shows time-dependent killing?

Beta-lactams

What pharmacodynamic exposure index is associated with vancomycin?

AUC/MIC

Which antibiotic classes are generally bactericidal because they inhibit the cell wall?

Beta-lactams and glycopeptides

Which antibiotics are bacteriostatic?

- Chloramphenicol

- Clindamycin

- Macrolides

- Sulfonamides

- Tetracyclines

- Trimethoprim

Which antibiotics are bactericidal?

- Aminoglycosides

- Bacitracin

- Beta-lactams

- Fluoroquinolones

- Daptomycin

- Fosfomycin

- Glycopeptides/lipoglycopeptides

- Metronidazole

Which two antibiotics can be bacteriostatic OR bactericidal depending on conditions?

- Linezolid

- Nitrofurantoin

Which combination is listed as bactericidal despite its individual components being bacteriostatic?

Trimethoprim-sulfamethoxazole

Why can bacteriostatic antibiotics still cure infection?

They stop bacterial growth so host immunity can clear the organism

What are the major general mechanisms of antibiotic resistance?

- Drug inactivation

- Altered target

- Reduced drug entry

- Efflux

What do bacterial efflux pumps do?

Pump antibiotic out, lowering concentration at its target

What happens when bacteria alter an antibiotic's binding target?

The drug binds less effectively.

How can bacteria enzymatically inactivate beta-lactam antibiotics?

Beta-lactamases hydrolyze the beta-lactam ring

What is horizontal gene transfer in antimicrobial resistance?

Transfer of resistance genes between bacteria

What is the major structural material in the bacterial cell wall?

Peptidoglycan

What does the bacterial cell wall protect against?

Loss of structural integrity and osmotic lysis

Which sugars alternate in the peptidoglycan backbone?

N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)

Which peptidoglycan sugar has the peptide side chain attached?

NAM

What dipeptide terminates the peptidoglycan precursor?

D-Ala-D-Ala

What enzyme forms peptide cross-links in the cell wall?

Transpeptidase (penicillin-binding protein; PBP)

What does PBP remove during transpeptidation?

The terminal D-alanine

Why is peptidoglycan cross-linking important?

It makes the cell wall strong and rigid.

What enzyme elongates the NAG-NAM glycan chain?

Transglycosylase (glycosyltransferase).

What color do Gram-positive bacteria stain?

Purple/violet

What color do Gram-negative bacteria stain?

Pink/red

How do Gram-positive and Gram-negative cell envelopes differ?

- Gram-positive: thick peptidoglycan

- Gram-negative: thin peptidoglycan plus outer membrane

Why does the Gram-negative outer membrane matter for antibiotics?

It can restrict antibiotic entry

What four antibiotic classes are beta-lactams?

- Penicillins

- Cephalosporins

- Carbapenems

- Monobactams

What is the direct target of beta-lactam antibiotics?

Penicillin-binding proteins (PBPs), including transpeptidases.

How do beta-lactams kill bacteria?

Inhibit PBP-mediated cross-linking, weakening the cell wall

Are beta-lactams time-dependent or concentration-dependent bactericidal drugs?

Time-dependent bactericidal

What is the most emphasized beta-lactam resistance mechanism?

Beta-lactamase production

Besides beta-lactamase, what three mechanisms cause beta-lactam resistance?

Altered PBPs, impaired penetration, efflux pumps

What is the difference between PBP and beta-lactamase?

- PBP builds cell wall cross-links

- Beta-lactamase destroys susceptible beta-lactam drugs

What are the natural penicillins?

Penicillin G and Penicillin V

What are the antistaphylococcal penicillins?

Oxacillin, Dicloxacillin, Nafcillin

Which penicillin subgroup is resistant to staphylococcal penicillinase?

Antistaphylococcal penicillins

What are the Aminopenicillins?

Ampicillin and Amoxicillin

Which penicillin is classified as a ureidopenicillin?

Piperacillin

Which penicillin subgroups are listed as beta-lactamase sensitive?

- Natural penicillins

- Aminopenicillins

- Piperacillin

Is Amoxicillin beta-lactamase resistant?

No

Which penicillin subgroup is particularly associated with MSSA treatment?

Antistaphylococcal Penicillins

What is the major adverse-effect category of penicillins?

Hypersensitivity/allergic reactions

What manifestations can occur with penicillin hypersensitivity?

Rash, fever, bronchospasm, serum sickness, anaphylaxis

What is the Jarisch-Herxheimer reaction associated with?

An inflammatory reaction after treating syphilis with antibiotics such as penicillin

What neurologic adverse effect can occur with high penicillin exposure in renal failure?

Seizures

What are the first-generation cephalosporins?

Cefadroxil, Cefazolin, Cephalexin

What are the second-generation cephalosporins?

Cefaclor, Cefprozil, Cefuroxime

What are the third-generation cephalosporins?

Cefdinir, Cefpodoxime, Ceftriaxone

Which cephalosporin is fourth generation?

Cefepime

Which cephalosporin is fifth generation?

Ceftaroline

What general Gram-negative coverage trend occurs across cephalosporin generations?

Later generations generally have increased Gram-negative coverage

What is the MOA of cephalosporins?

Inhibit PBPs and bacterial cell wall cross-linking

What are the two cephamycins?

Cefoxitin and Cefotetan

Which cephalosporin generation includes cephamycins?

Second generation

What distinguishing coverage do cephamycins have?

Anaerobic activity

Which fifth-generation cephalosporin has MRSA activity?

Ceftaroline

What altered PBP does ceftaroline bind to cover MRSA?

PBP2a

What is ceftaroline fosamil?

The prodrug of ceftaroline

Which cephalosporin is a siderophore antibiotic?

Cefiderocol

How does cefiderocol gain entry into Gram-negative bacteria?

Uses iron transport pathways after binding iron (Trojan horse mechanism)

What type of pathogens is cefiderocol notable for covering?

Certain multidrug-resistant Gram-negative bacteria

What structural feature most strongly predicts penicillin-cephalosporin allergic cross-reactivity?

Similarity of the R1 side chain

Which antibiotic is the monobactam?

Aztreonam

What organisms does aztreonam cover?

Aerobic Gram-negative bacteria

What cephalosporin is a key allergy cross-reactivity exception for aztreonam?

Ceftazidime (shared/similar side chain).

What are the carbapenems?

Imipenem, Meropenem, Ertapenem.

How broad is carbapenem coverage in general?

Broad Gram-positive and Gram-negative activity (agent-specific exceptions)

What is the route of administration for Carbapenems?

IV

What important neurologic adverse effect is associated with carbapenems?

Seizures

Why is imipenem administered with cilastatin?

Cilastatin prevents renal dehydropeptidase I from degrading imipenem

What enzyme is inhibited by cilastatin?

Renal dehydropeptidase I

Is cilastatin a bacterial beta-lactamase inhibitor?

No, it inhibits a human renal enzyme

What do beta-lactamase inhibitors do?

Protect susceptible beta-lactam antibiotics from bacterial beta-lactamase hydrolysis

What are the first-generation beta-lactamase inhibitors?

Clavulanate, Sulbactam, Tazobactam

What are the second-generation beta-lactamase inhibitors?

Avibactam, Durlobactam, telebactam, Vaborbactam

Which beta-lactamase inhibitor generation has a beta-lactam ring?

First generation

What inhibitor is paired with Amoxicillin?

Clavulanate

What inhibitor is paired with Ampicillin?

Sulbactam

What inhibitor is paired with Piperacillin?

Tazobactam

What inhibitor is paired with Meropenem?

Vaborbactam

What antibiotic class does vancomycin belong to?

Glycopeptides

What is vancomycin's Gram-stain spectrum?

Gram-positive bacteria

Why is vancomycin generally given IV for systemic infections?

It is poorly absorbed orally

What is vancomycin's direct binding target?

D-Ala-D-Ala on peptidoglycan precursors

How does vancomycin affect bacterial cell wall synthesis?

Interferes with glycan-chain elongation and peptide cross-linking

How does vancomycin's direct target differ from beta-lactams?

Vancomycin binds D-Ala-D-Ala; beta-lactams bind PBPs

Which enzyme-mediated cell wall process is disrupted by vancomycin binding?

Transglycosylase-mediated NAG-NAM polymerization

Is vancomycin bacteriostatic or bactericidal?

Bactericidal

To which alternate termini can bacteria switch to reduce vancomycin binding?

D-Ala-D-Lac or D-Ala-D-Ser

How do excess D-Ala-D-Ala sites produce vancomycin resistance?

They sequester the drug at decoy sites in the thickened cell wall

What toxicities are associated with vancomycin?

Nephrotoxicity and rare ototoxicity