Antibiotic Toolkit

Question 1

What are the mechanisms of antibiotic actions?

Answer 1

1. Concentration-dependant killing
   - Aminoglycosides
   - Quinolones

Important to not underdose - higher concentration kills more rapidly

2. Time-dependant killing
   - Beta-lactams

Important to not skip doses - no increased killing with increased concentration

Question 2

What are the 4 classes of beta-lactams?

Answer 2

Penicillin
Cephalosporins
Clavulanic acid (beta-lactamase inhibitor)
Carbapenem H

Question 3

What is the mechanism of action of Beta-lactams, and how is it excreted?

Answer 3

Time-dependant bactericidal killing
Inhibits formation of peptidoglycan cross-links -> hinders cell wall synthesis

Eliminated by renal tubular secretion
Adverse effects: hypersensitivity and CNS toxicity

Question 4

How is resistance against beta-lactams mediated?

Answer 4

By beta-lactamases: (cannot be overcome by higher doses)
- Gram negatives
- Anaerobes
- Staphylococci
By penicillin-binding proteins: (overcome by higher doses)
- S.pneumoniae

Question 5

What do penicillins act against?

Answer 5

Gram positives and spirochaetes
- Streptococci
- Syphilis
- Enterococci
- Listeria
- Actinomyces

Question 6

What do aminopenicillins act against?

Answer 6

Ampicillin (IV)
Amoxicillin (oral)

Cover the same organisms as penicillin + Haemophilus :
- Streptococci (especially S.pneumoniae)
- Syphilis
- Enterococci
- Listeria
- Actinomyces
- Haemophilus

Question 7

What does cloxacillin act against?

Answer 7

Cloxacillin (IV)
Flucloxacillin (oral)

Resists beta-lactamases
Only for Gram-positves

Question 8

What are the beta-lactamase inhibitors?

Answer 8

Irreversible inhibitors:
- Clavulanate
- Tazobactam

Combine with beta-lactams:
- Amoxicillin-clavulunate
- Piperacillin-tazobactam H

Question 9

What do the cephalosporins act against?

Answer 9

1st gen
- Cefazolin (surgical prophylaxis)
- Cephalexin
- Strep and Staph

2nd gen
- Cefuroxime
- plus Haemophilus and CAP GN

3rd gen
- Ceftriaxone (Good CSF penetration -meningitis, gonorrhe, typhoid)
- Ceftazidime H
- plus typhoid, spirochaetes

4th gen
- Cefepime H

Question 10

What do carbapenems act against?

Answer 10

Broad spectrum covering most H acquired GP, GN and anaerobes

Question 11

What is the commonest adverse reaction to beta-lactams?

Answer 11

Maculopapular rash amoxicillin (>72hrs)

Anaphylaxis <1hr and angiooedema/urticaria/bronchospasm <72hrs - Type 1 hypersensitivity -IgE mediated

Question 12

What do beta lactams cross react with?

Answer 12

Cephalosporins

3rd gen cephalosporins <5%, so can be used if penicillin allergy if hypersensitivity was not IgE mediated

If IgE mediated, then avoid entire class (incl carbapenems)

Question 13

What is the mechanism of action of the glycopeptides, and when are they used?

Answer 13

Time dependant killing - act on cell wall

Vancomycin - given IVI - covers GP (especially cloxacillin-resistant Staph)

Slow IVI required -> red man syndrome
Nephrotoxic

Question 14

What is the mechanism of action of the aminoglycosides?

Answer 14

Concentration-dependant killing - bactericidal inhibitors of protein synthesis

Given parenterally - poor tissue penetration

Can have synergy with beta-lactams

Question 15

What is the main aminoglycoside, and what is it used for?

Answer 15

Gentamicin
Serious community- required infections
- pyelonephritis
- synergy with beta-lactams in polymicrobial infections

Amikacin H

Question 16

What is the adverse reaction of aminoglycosides?

Answer 16

**Ototoxicity **
- High tone deafness initially
- Vestibular
- Irreversible

Nephrotoxicity
- Tubular toxin - avoid in elderly/CKD
- Reversible

Question 17

What is the mechanism of action of the quinolones?

Answer 17

Concentration-dependant killing
Targets DNA gyrase and topoisomerase IV

Question 18

What are the different quinolones, and what are they used for?

Answer 18

Fluroquinolones

First gen - poorly absorbed - GN aerobes

Second gen - well absorbed - GN aerobes (+ Pseudomonas)
- Ciprofloxacin
- Bacterial dysentery
- Pyelonephritis
- Prostatitis

Third gen - well absorbed - GP (especially Strep), GN (excl pseudomonas)
- Moxifloxacin
- MDR TB
- RTI (only if severe beta lactam allergy)

Question 19

What are the adverse reactions to quinolones?

Answer 19

Rashes
CNS toxicity (headache, dizziness, excitation, seizures)
Tendinitis

Limit use in children

Question 20

What is the mechanism of action of the macrolides, and what do they act against?

Answer 20

Bacteriostatic - Inhibit protein synthesis (50s ribosome)

GP (S.pneumoniae resistance)

Question 21

What are the different macrolides, and what adverse events can occur?

Answer 21

Erythromycin
Clarithromycin (Inhibits CYP450 metabolism)
Azithromycin (Inhibits CYP450 metabolism)

GIT toxicity- nausea, vomiting, diarrhoea

Act against:
- Atypical pneumonia - Legionella, Mycoplasma, Chlamydophila
- H.pylori - clarithromycin/azithromycin
- Chlamydia ureteritis/cervicitis - azithromycin
- Pertussis
- Chancroid
- M.avium in AIDS - clarithromycin/azithromycin

Question 22

What is the mechanism of action for the tetracyclines, and what are the adverse events?

Answer 22

Bacteriostatic - inhibit protein synthesis (30s ribosome)

Good absorption (especially doxycycline) - resistance by efflux/enzymatic breakdown

Toxicity - nausea, vomiting, photosensitivity, teeth discolouration

Question 23

What are the tetracyclines used for?

Answer 23

Rickettsia
Brucellosis
Acne
Falciparum malaria prophylaxis
Chlamydia STI (ureteritis/PID) - superceded by azithromycin

Question 24

What is Co-trimoxazole made of? What is the mechanism of action? What are the adverse events?

Answer 24

Sulfamethoxazole (sulphonamide) + trimethoprim

Blocks bacterial folate pathway, prevents nucleic acid synthesis

Main adverse event:
- Sulphonamide hypersensitivity (Steven-Johnsons syndrome/Toxic Epidermal Necrolysis)
- Maculopapular rash (in HIV)

Question 25

When is Co-trimoxazole used?

Answer 25

In HIV
- Pneumocystis jirovecii pneumonia
- Toxoplasmosis
- Cystoisospora belli diarrhoea
- Primary prophylaxis

Question 26

What is the mechanism of action of metronidazole?

Answer 26

Toxic to DNA (forms nitro radical with anaerobic metabolism)

Adverse:
- Metallic taste
- Disulfuram-like effect (avoid alcohol)
- Neurotoxic and neutropenia in long term

Question 27

What is metronidazole used for?

Answer 27

Anaerobes:
- Cocci
- GN bacilli
- GP spore-forming bacilli

Entamoeba histolytica
Trichomonas vaginalis
Giardia lamblia