16B23: Exam Report

Compare and contrast the mechanism of action, spectrum of activity and adverse effects of benzyl penicillin and fluconazole.

8% of candidates passed this question.

To pass this question each of the three components needed to be compared and contrasted for both agents. A tabulated answer helped in this regard but was not essential. Some answers included information that could not gain marks, as it was not directly relevant to the question asked (e.g. presentation and dose).

In spectrum of activity, as well as what important organisms the agents were effective against, marks were also given for the important organisms that they were not effective against (e.g. MRSA and beta-lactamase producing organisms for penicillin G; and aspergillus for fluconazole).

In general, of the two agents, fluconazole was the least well answered. For example, a common omission either in mechanism of action or in adverse effects was that fluconazole inhibits microsomal P450 enzymes.

Some candidates confused fluoroquinalone with fluconazole.

T2i / 16B23: Compare and contrast the mechanism of action, spectrum of activity and adverse effects of benzyl penicillin and fluconazole

Drug

Benzyl Penicillin

Fluconazole

Class

Benzyl Penicillin

Natural

Penicillin (b-lactam)

Fluconazole

Azole

MoA

Benzyl Penicillin

  1. B lactam ring mimics shape of D-Ala-D-Ala sequence that is the substrate for cell wall transpeptidases

This is the final step in bac cell wall synthesis that allows cross linking

By pretending to be D-Ala-D-Ala, it binds transpeptidases -> inhibits enzyme activity → bac without cell wall → die

  1. Exerts bacterial autolytic effect

Inhibits certain penicillin binding proteins (PBP) related to the activation of autolysis →promotes bac lysis & cell death

Fluconazole

Inhibits the fungal cytP450 enzyme that syntheses ergosterol

Inhibits cell memb formation

Leakage -> cell death

Spectrum

Benzyl Penicillin

Covers

G+

Streptococcal

pneumonia

Listeria

Doesnt

MRSA

G- Bacilli

Atypicals

Fluconazole

Covers

C albicans

Cryptococcus

Covers

C gilbrata

C Krusei (Kompletely resistant)

AE

Benzyl Penicillin

Nephritis

Seizures

High Na+, Low K+

Pseudomembranous colitis

C diff

Anaphylaxis

Fluconazole

Hepatic toxicity – watch LFTs; hepatic failure, hepatitis, abnormal LFTs

GI – nausea, vomiting, diarrhea, abdm pain

CVS – pallor angioedema

CNS – headache, dizziness

Haem: thrombocytopenia, leukopenia

Derm – skin rashes, alopecia