Antibiotic Toolkit Flashcards
What are the mechanisms of antibiotic actions?
-
Concentration-dependant killing
- Aminoglycosides
- Quinolones
Important to not underdose - higher concentration kills more rapidly
-
Time-dependant killing
- Beta-lactams
Important to not skip doses - no increased killing with increased concentration
What are the 4 classes of beta-lactams?
Penicillin
Cephalosporins
Clavulanic acid (beta-lactamase inhibitor)
Carbapenem H
What is the mechanism of action of Beta-lactams, and how is it excreted?
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
How is resistance against beta-lactams mediated?
By beta-lactamases: (cannot be overcome by higher doses)
- Gram negatives
- Anaerobes
- Staphylococci
By penicillin-binding proteins: (overcome by higher doses)
- S.pneumoniae
What do penicillins act against?
Gram positives and spirochaetes
- Streptococci
- Syphilis
- Enterococci
- Listeria
- Actinomyces
What do aminopenicillins act against?
Ampicillin (IV)
Amoxicillin (oral)
Cover the same organisms as penicillin + Haemophilus :
- Streptococci (especially S.pneumoniae)
- Syphilis
- Enterococci
- Listeria
- Actinomyces
- Haemophilus
What does cloxacillin act against?
Cloxacillin (IV)
Flucloxacillin (oral)
Resists beta-lactamases
Only for Gram-positves
What are the beta-lactamase inhibitors?
Irreversible inhibitors:
- Clavulanate
- Tazobactam
Combine with beta-lactams:
- Amoxicillin-clavulunate
- Piperacillin-tazobactam H
What do the cephalosporins act against?
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
What do carbapenems act against?
Broad spectrum covering most H acquired GP, GN and anaerobes
What is the commonest adverse reaction to beta-lactams?
Maculopapular rash amoxicillin (>72hrs)
Anaphylaxis <1hr and angiooedema/urticaria/bronchospasm <72hrs - Type 1 hypersensitivity -IgE mediated
What do beta lactams cross react with?
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)
What is the mechanism of action of the glycopeptides, and when are they used?
Time dependant killing - act on cell wall
Vancomycin - given IVI - covers GP (especially cloxacillin-resistant Staph)
Slow IVI required -> red man syndrome
Nephrotoxic
What is the mechanism of action of the aminoglycosides?
Concentration-dependant killing - bactericidal inhibitors of protein synthesis
Given parenterally - poor tissue penetration
Can have synergy with beta-lactams
What is the main aminoglycoside, and what is it used for?
Gentamicin
Serious community- required infections
- pyelonephritis
- synergy with beta-lactams in polymicrobial infections
Amikacin H
What is the adverse reaction of aminoglycosides?
**Ototoxicity **
- High tone deafness initially
- Vestibular
- Irreversible
Nephrotoxicity
- Tubular toxin - avoid in elderly/CKD
- Reversible
What is the mechanism of action of the quinolones?
Concentration-dependant killing
Targets DNA gyrase and topoisomerase IV
What are the different quinolones, and what are they used for?
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)
What are the adverse reactions to quinolones?
Rashes
CNS toxicity (headache, dizziness, excitation, seizures)
Tendinitis
Limit use in children
What is the mechanism of action of the macrolides, and what do they act against?
Bacteriostatic - Inhibit protein synthesis (50s ribosome)
GP (S.pneumoniae resistance)
What are the different macrolides, and what adverse events can occur?
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
What is the mechanism of action for the tetracyclines, and what are the adverse events?
Bacteriostatic - inhibit protein synthesis (30s ribosome)
Good absorption (especially doxycycline) - resistance by efflux/enzymatic breakdown
Toxicity - nausea, vomiting, photosensitivity, teeth discolouration
What are the tetracyclines used for?
Rickettsia
Brucellosis
Acne
Falciparum malaria prophylaxis
Chlamydia STI (ureteritis/PID) - superceded by azithromycin
What is Co-trimoxazole made of? What is the mechanism of action? What are the adverse events?
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)
