Q21

What classes of antibiotics are used in the treatment of Staphylococcal infections?

  • Beta-lactamase negative staph
  • Penicillin
  • 1S Generation Cephalosporins
  • Beta-lactamase positive staph
  • Beta-lactamase resistant penicillins — Methicillin / Naficillin,
  • Isoxazoly1 Penicillins (dicloxacillin, flucloxacillin etc)
  • l’ Generation Cephalosporin
  • Beta-lactamase inhibitor with penicillin combination —
  • clavulinic acid, suibactam, tazobactam
  • Vancomycin
  • Aminogycosides
  • Macrolides

Pass: 3 classes

What is the mechanism of resistance in Methicillin Resistant Staph Aureus?

Beta-lactam antibiotics normally bind to PBP’s (Penicillin Binding Proteins) causing inhibition of transpeptidation, thus blocking cell wall synthesis and lead to cell wall death MRSA produce PBP’s that have a low affinity for binding beta-lactam antibiotics and hence render then ineffective May be overcome if used in high enough concentrations, but not clinically achievable

Pass: Must demonstrate understanding of PBP’s binding to pass

What are the adverse effects of Vancomycin?

Local phlebitis
Chills & fever
Flushing due to histamine release (Red Man)
Ototoxicity / nephrotoxicity if administered with aminoglycoside

Pass: Must get 1 to pass


Q22

Describe the mechanism of action of acyclovir.

Converted to monophosphate by virus-specific thymidine kinase (infected cell specific)

Converted to di- and tri- phosphates by host cell enzymes

Inhibits viral DNA synthesis by irreversible binding to viral DNA polymerase, and chain termination

Pass: virus-infected cell specificity and inhibition of viral DNA synthesis (without detail)

What are the indications for acyclovir?

Oral: initial or recurrent genital HSV2 infection

Varicella-Zoster — within 24 h of varicella and 72 h or zoster (higher doses required)

IV: HSV encephalitis, neonatal HSV, serious HSV or VZV


Pass: Use in HSV or VZV, plus encephalitis.


Q23

What are the clinical manifestations of penicillin allergy?

Anaphylaxis

Fever

Skin (Maculopapular rash, Urticarial skin rash , Exfoliative dermatitis)

Serum sickness

Steven Johnson Syndrome

Pass: 2 of 4

NOTES: Serum sickness, nephritis,pseudomembranous colitis

What other side effects of penicillin treatment do you know of?


Renal failure, seizures at high doses, GI disturbance, Candidal infections, Hepatitis (fluclox/oxacillin),

Pass: 3 of 5

 


Q24

Describe the mechanism of antimicrobial activity of azithromycin.

Inhibition of protein synthesis at 50S ribosomal RNA. Pharmacokinetics : good tissue penetration, and long tissue half-lives allowing once daily dosing.

How does azithromycin differ from other antibiotics in its class?

Doesn’t activate cytochrome P450
Very active against Chlamydia
Pass: 1 of 3

NOTES: Macrolide antibiotic. Acts by blocking amino-acyl translocations and formation of initiation complexes. Inhibitory or bacteriocidal activity

 


Q25

Describe the mechanism of antimicrobial activity of the sulphonamides.

Reversibly block folic acid synthesis thus inhibiting growth.

NOTES: Structural analogs of PABA that competitively inhibit dihydropteroate synthetase.
Usually bacteriostatic

Why is trimethoprim commonly administered in combination with sulfamethoxazole?


Antibacterial synergism. Block sequential steps in folic acid dependent purine synthesis

NOTES: The combination is frequently bacteriocidal


Q26

How do you classify cephalosporins?

1 to 4 based on spectrum of activity

Could you expand on that in terms of their spectrum of activity?

Increasing gram negative cover from 1 to 4, less gram positive 1 to 3, 4 a bit of both


Q27

What is the mechanism of action of quinolones?

Inhibits bacterial synthesis of DNA

Describe the antibacterial spectrum of the Quinolones.

Mixed, broad spectrum, newer increasingly broad

What are the possible adverse effects of the quinolones in children?

Cartilage type effect


Q28

Describe the mechanism of action of penicillins.

Inhibition of cell wall synthesis. Interfere with transpeptidation. Covalently binding to PBP. Important in the cross linkage. Bacteriocidal,. Only kills growing cells.
How does resistance to penicillins occur?
a.            Inactivation by beta lactamases

b.            Modification of target PBPs (Pneumo/entrococci)

c.             Impaired penetration of drug to PBP; impact on porin channels. Gram negatives

d.            Efflux pump (gram neg)

Pass: At least 2 including beta-lactamases

In general, what is the anti-microbial spectrum of penicillin G?
Prompt: Could you be specific?

Streptococci, meningococci, enterococci, some pneumococci, treponema pallidum, clostridia, non-betalactamase producing staphylococci


Pass: At least 3 bacteria


Q29

Describe the mechanism of action of trimethoprim.

Inhibition of DNA synthesis. Selective inhibition of bacterial dihydofolic acid reductase which is required from the step dihydrofolic acid to tetrahydrofolic acid. Much less efficient at inhibiting mammalian enzyme.
Can you explain why trimethoprim and sulphonamides when used together are synergistic?
Inhibition of sequential steps in same pathway. Sulphonamides inhibit dihydropteroate synthetase (PABA to DHFA), the step before that at which trimethoprim acts.

How does resistance to trimethoprim occur?

  • Reduced cell permeability
  • Increased production of enzyme DHF reductase
  • Alteration in the enzyme with reduced binding of drug


Pass: Any 1 of 3

 


Q30

List some anti-influenza agents.

Zanamivir, Oseltamivir, Amantadine, Rimantadine

1 to pass

What is the mechanism of action of zanamivir (relenza) and oseltamivir (tamiflu)?

Neuraminidase (a glycoprotein) inhibitors: disrupt viral replication and release

Active against both influenza A and B;

Pass: Some concept

What are the indications for their use?

Approved for treatment of uncomplicated influenza; 5 day course of therapy within 36 — 48 hrs of symptom onset shortens severity and duration of illness; may decrease incidence of respiratory complications

1 to pass

What is the relevance of these agents to emergency medicine practice?
PROMPT: what about during the recent flu pandemic?

May be of use to higher risk groups eg indigenous, pregnant women, older people and immunocompromised, however primary prevention by vaccination is preferred. Used preferably at early phase of pandemic to limit spread and numbers infected, and limit severity of disease in those infected.


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