antibiotics

Question 1

PKPD target for time-dependent bacterial killing (beta-lactams)

Answer 1

Normal: 40-70% of dosing interval > MIC
Critically ill OR Sites of poor penetration: 50-100% of dosing interval > 4-5x of MIC

Question 2

If patient CrCl < 30ml/min, PO ciprofloxacin dose recommended is 250mg q12h or 500mgq24h, which one to choose?

Answer 2

500mg q24h (ciprofloxacin is a concentration-dependent killing drug: 500mg q24h gives a higher peak and hence better kill)

Question 3

What drug can be used with a time-dependent killing antibiotic to block excretion (hence optimise T%>MIC)

Answer 3

Probenecid

Question 4

Rate and extent of killing in concentration-, time- and exposure- dependent kill is related to _______, _______ and ________ respectively

Answer 4

Antibiotic concentration; Amount of time antibiotic concentration is above MIC of organism; Overall drug exposure (AUC vs MIC)

Question 5

IV Vancomycin 500mg q12h vs Vancomycin 1g q24h: Which will give higher AUC in the same patient?

Answer 5

Same AUC (Same patient –> same clearance –> both drugs give same 24h AUC)

Question 6

What to optimise in dosing strategy for concentration-, time- and exposure-dependent kill respectively

Answer 6

Concentration - Peak/Cmax:MIC ratio
Time - T%>MIC
Exposure - AUC:MIC ratio

Question 7

Amoxicillin is a _____ of penicillin. It is formed by adding _____ group to penicillin, which improves coverage against ________ bacteria and confers _______ enabling PO route.

Answer 7

semisynthetic derivative; amino; gram-negative; acid resistance

Question 8

Which antibiotics have poor/no oral bioavailability?

Answer 8

Ceftriaxone (no PO bioavailability), Meropenem (no PO bioavailability), Gentamicin (F <1%)

Question 9

Which antibiotic’s bioavailability is affected by food?

Answer 9

Doxycycline
(Oral F=95% but reduced by 20% with high fat meal/milk)