22B09: Exam Report

List any five classes of antibiotics with anti-staphylococcal activity and provide one example of each class. Outline the mechanism of action and side effects of the five drugs

82% of candidates passed this question.

In general, the question was well answered. Better answers provided examples of antibiotics from different categories of mechanism of action and were able to describe specific side effects relevant or unique to that antibiotic.

Mechanisms of action that were generic in terms of site of action attracted fewer marks. Some examples of antibiotics that candidates provided were not anti-staphylococcal antibiotics (eg; Benzyl Penicillin, Clavulanic acid).

The examiners commented that the use of a tabular format as an answer template resulted in answers scoring marks in most time efficient manner.

Frequent omissions or commissions resulting in lost marks noted by the examiners were as follows; many papers showed a lack of detail regarding the precise mechanism of action of penicillins particularly around inhibition of transpeptidases whilst the use of non-specific side effects such as nausea vomiting and diarrhoea did not attract marks.

T2i / 22B09: List any five classes of antibiotics with anti-staphylococcal activity and provide one example of each class. Outline the mechanism of action and side effects of the five drugs

Penicillin

Glycopeptide

Lincosamides

Cephalosporins

Oxazolidinones

Example

Penicillin

Flucloxacillin

Glycopeptide

Vancomycin

Lincosamides

Clindamycin

Cephalosporins

Cephazolin

Oxazolidinones

Linezolid

MoA

Penicillin

  • Beta lactam ring mimics D-Ala-D-Ala (substrate required for cell wall synthesis)
  • Penicillin binding protein (a transpeptidase) binds instead to the beta-lactam nucleus and is inhibited
  • Subsequent failure of transpeptidation → unable to form peptidoglycans which are essential to structure of bacterial cell wall
  • Eventually, bacterial lysis occurs due to ongoing autolytic enzymes (autolysins, hydrolases) whilst cell wall assembly is inhibited

Glycopeptide

  • Binds D-Ala-D-Ala sequence of cell wall precursors NAM (N-acetylmuramic acid) and NAG N-acetylglucosamine → prohibit binding of the cell wall linking enzyme → interrupting peptidoglycan synthesis
  • Bactericidal against most bacteria, bacteriostatic against C Difficile

Lincosamides

  • Mimics the 3′-ends of types of tRNA, acting as a structural analog
  • Binds to the 23S RNA of the 50S ribosomal subunit → impedes both the assembly of the ribosome and the translation process → inhibits bacterial protein synthesis

Cephalosporins

  • Binds to penicillin binding protein on bacterial cell wall → inhibits transpeptidation → failure to form peptidoglycans which are integral to bacterial cell wall → bactericidal
  • Also thought to play contribute to activation of bacterical cell autolysins → cell lysis

Oxazolidinones

  • Binds to P site of 50S ribosomal subunit → prevents formation of ribosomal-fMet-tRNA complex that initiates protein synthesis
  • Thus inhibits protein synthesis

AE

Penicillin

  • Hypersensitivity
  • Cholestasis/jaundice
  • Pseudomembranous colitis
  • Nephritis
  • Drug fever

Glycopeptide

  • Red man syndrome, idiopathic reaction due to mass histamine release
  • Ototoxicity that is related to peak dose
  • Nephrotoxicity
  • Drug fever
  • Thrombophlebitis
  • DRESS syndrome

Lincosamides

  • Pseudomembranous colitis (most common antibiotic)
  • Urticaria, erythema multiforme, DRESS
  • Jaundice
  • Neuromuscular blockade in overdose, polyarthritis (rare)

Cephalosporins

  • Interstitial nephritis
  • Neutropenia, eosinophilia, both thrombocytopenia and thrombocytosis, impaired platelet aggregation
  • Pruritis and urticaroa

Oxazolidinones

  • Myelosuppression (anaemia, leukopenia, pancytopenia, thrombocytopenia)
  • Peripheral neuropathy
  • Optic neuritis
  • Lactic acidosis in long term treatment
  • Weak inhibitor of MAO (may precipitate serotonin syndrome/hypertensive crisis)

Author: Andrew Wang