19B20: Exam Report

Compare the pharmacology of piperacillin-tazobactam and ciprofloxacin.

58% of candidates passed this question.

This question was most effectively answered using a tabular format. Only a minority of candidates demonstrated a comprehensive knowledge of these level 1 drugs and very few candidates compared the two in areas which lent themselves to comparison. The spectrum of activity generally lacked detail. Few candidates mentioned that piperacillin-tazobactam had superior gram-positive cover, both have extensive gram-negative cover including Pseudomonas. Piperacillin-tazobactam is effective against anaerobes; whilst ciprofloxacin has some atypical cover against Mycoplasma.

The mechanism of action was generally well described for piperacillin; many candidates incorrectly stated the mechanism of action for ciprofloxacin, confusing the drug with a macrolide. Better answers included time- dependant and concentration-dependent killing. The concept of half-life was frequently confused with the dosing interval.

Minimal marks were awarded for “allergy” and “gastrointestinal side-effects”. Better candidates mentioned Liver function derangement, neutropenia, interstitial nephritis for piperacillin and tendonitis for ciprofloxacin.

T2i / 19B20: Compare the pharmacology of piperacillin-tazobactam and ciprofloxacin

Drugs

Tazocin

Ciprofloxacin

Comments

Class

Tazocin

Antipseudomonal

Beta-lactamase inhibitor

Mechanism: the beta lactamse inhibitor (tozobactam) uses itself as a substrate for the bacteria’s b lactamase, which leaves the piperacillin’s b-lactam ring free to bind to the penicillin binding proteins

Ciprofloxacin

Quinolone

Comments

Dose

Tazocin

4.5g  tds

Ciprofloxacin

500-700mg q12-24h

Comments

Mechanism

Tazocin

Cell Wall Inhibitor

Ciprofloxacin

Bacteristatic & Bactericidal

Comments

MoA

Tazocin

  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

Ciprofloxacin

Inhibits DNA gyrase enzymes

Promotes breakage of DNA

Commets

Time v Concentration

Tazocin

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

Ciprofloxacin

Combination concentration and time dependent killing

Comments

Post Dose Effect

Tazocin

Short 2hrs – bactericidal

Ciprofloxacin

Commets

Indication

Tazocin

V Broad Spectrum

Hospital acquired infections

Ciprofloxacin

UTI

Resp tract

Intra-abdm

Anthrax

Comments

Spectrum

Commets

Both have extensive G- cover

Cipro has some atypical cover

Tazocin has superior G+ cover

Tazocin

Covers

Staph auereus (methicillin susceptible)

Coag –ve Staph

Strep pneumonia

H influenza

Moraxella

Neisseria Meningitides

Neisseria gonnorrhoeae

E Coli

Pseudomonas aeruningosa

Doesnt

MRSA

VRE

Atypicals

Ciprofloxacin

Covers

G-

Enterobacter

H influenza

Haemophilus

N g & m

Atypicals –

Legionella

Excellent TB coverage

Doesnt

Almost no G+ cover

Commets

Both have extensive G- cover

Cipro has some atypical cover

Tazocin has superior G+ cover

PK

Tazocin

A

IV only

D

PPB 20%

Vd 0.2L/kg

M

Minor hepatic metabolism

E

Renally excreted

Needs dose adjusted in renal impairment

Ciprofloxacin

A

70% OBA.  Delayed by food

D

20% PPB

 

M

4 metabolites, probably hepatic

E

Renal excretion of metabolites

 

Comments

Tazocin can only be administered IV

Cipro has good OBA

Both have similar PPB

Cipro is hepatically metabolised whereas Tazocin is renally cleared

AE

Tazocin

High Na+ load

Interacts w Vecuronium – prolongs neuromuscular blockade

Ciprofloxacin

CNS – headache, insomnia, dizziness, hallucinations

Renal – interstitial nephritis

CVS – QTC prolongation, TdP, arrhythmias

MSK – joint pain

Skin – toxic epidermal necrolysis

Drug Interaction – with warfarin, increases PT

Monitoring

Tazocin

UEC

Renal fn

LFTs

Ciprofloxacin

Renal fn

Comments

Both require monitoring of organ fn

Cipro will need monitoring of ECG & reconciliation of medications for drug interactions