T2i / 18B10 / 16A22: Compare and contrast the pharmacology of vancomycin and flucloxacillin

18B10: Exam Report

Compare and contrast the pharmacology of vancomycin and flucloxacillin.

49% of candidates passed this question.

Most candidates structured their answers well. Expected information included: the class of antibiotic of each agent, their respective pharmaceutics, pharmacodynamics, pharmacokinetics, indications and adverse effects. Better answers provided pharmacodynamic and pharmacokinetic information relevant to each drug rather than generic statements. Good answers also included the common resistance mechanisms for both agents.

16A22: Exam Report

Compare and contrast the mechanism of action (25% of marks), antimicrobial profile (25% of marks), pharmacokinetics (25% of marks) and adverse effects (25% of marks) of Flucloxacillin and Vancomycin.

83% of candidates passed this question.

The structure required to score well was provide by the questions asked. Marks were lost by not mentioning that flucloxacillin is a beta lactam that it does not cover MRSA and that vancomycin covers enterococcus. Better answers could identify that vancomycin is slower at killing sensitive staph than flucloxacillin. Adverse effects were specifically asked for in the question so omitting facts such as associated nausea/vomiting/diarrhoea/anaphylaxis etc. cost some candidates marks. If 25% of marks are allocated to side effects then it is expected more than one adverse effect would be mentioned. Some candidates had incorrect facts – Enterococcus is not a gram negative organism.

T2i / 18B10 / 16A22: Compare and contrast the pharmacology of vancomycin and flucloxacillin

Drugs

Vancomycin

Flucloxacillin

Class

Vancomycin

Glycopeptide

Flucloxacillin

Penicillin; Anti-Staphylococcal

Dose

Vancomycin

30mg/kg (load) + 1.5mg bd (normal renal fn)

Flucloxacillin

250mg qid

Mechanism

Vancomycin

Cell Wall Inhibitor

Flucloxacillin

Cell Wall Inhibitor

MoA

Vancomycin

Binds D-Ala-D-Ala sequence on bacterial cell wall

Interrupts peptidoglycan synthesis → Bactericidal

Flucloxacillin

  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

Time v Concentration

Vancomycin

Time:  time spent above minimal inhibitory dose is what determined efficacy

Flucloxacillin

Time Dependent -> time spent above minimal inhibitory concentration determines efficacy

Post Dose Effect

Vancomycin

2hrs.

Ability to continue bactericidal effects post dose is small

Flucloxacillin

Short 2hrs – bactericidal

Spectrum

Vancomycin

Covers

G+

C diff

C perforinges

Doesn't Cover

G-

VRE

VRSA

ESBL

Flucloxacillin

Covers

G+

Staph aureus

Doesnt

G-

MRSA

Strept

faecalis

Indications

Vancomycin

Suspected/proven MRSA

C diff

Penicillin allergy

Flucloxacillin

Skin and soft tissue infections

Respiratory tract infections

PK

Vancomycin

A

Poor. Only po for C diff

D

PPB 50%.  Vd 2L/kg

M

None

E

Renally excreted unchaged. ∴needs dose adjustment in renal failure

Flucloxacillin

A

80% OBA

D

95% PPB

M

Minimally metabolized by liver

E

Renally excreted

A/E

Vancomycin

Red man syndrome: mass histamine release

Ototoxicity: related to peak dose

Drug fever

Flucloxacillin

Cholestatic

Jaundice

Pseudomembranous colitis

Nephritis

Fever

Resistance

Vancomycin

Bacteria mutate to D-Ala-D-lactate

∴no binding site for Vanc

Flucloxacillin

b-lactamase producing bacteria

Monitoring

Vancomycin

Target 15-20mg/dL

Monitor trough level & renal fn

Flucloxacillin

LFTs Renal fn