PHM203 PK Vancomycin And Aminoglycosides:
Questions And Answers
Antibiotic Killing Properties Right Ans - Concentration Dependent Killing:
-Rate and extent of killing dependent on the ratio that can be achieved
between peak drug conc. and MIC of infecting pathogen (eg. aminoglycosides
and fluoroquinolone)
Time Dependent Killing:
-Rate and extent of killing independent of increases in conc. of antibiotic,
determined by the length of time that unbound drug remain above MIC (eg.
vancomycin, beta lactams, macrolides)
AUC/MIC ratio: eg. fluoroquinolone, vancomycin, tigecycline
First Order PK Right Ans - -fraction/proportion/percentage of total
amount of drug removed per unit of time remains constant (Ke)
-half life remains constant
-peak and trough conc will be directly proportional to dose (increasing dose,
keeps interval constant but increases both peak and trough and WIDER
fluctuation between peak and trough conc)
-decreasing the interval, while keeping dose constant also increases peak and
trough but the fluctuation between peak and trough is SMALLER
Steady state Right Ans - Rate of drug going in = Rate of drug going out
-no further accumulation, so maximum and minimum conc remain constant
with each subsequent dose
-don't have to be at steady state to determine half life or Vd
Cockcroft Gault nomogram Right Ans - Derived a relationship between age
and 24 hour creatinine excretion/kg in 249 MALE pt between 18-92 years old
Formula includes age sex and body weight (not IBW)
Drawback: derived from only males, did not correct for excess fat or fluid, CrCl
can vary from day to day by 10-20% (don't dose adjust for no reason!)
MALE
, (140-age)(weight)(1.2)/serum creatinine (micromol/L)
OR
(140-age)(weight)/(72)(serum creatinine (mg/dL)
FEMALE = MALE X 0.85
Pt >30% IBW = obese (use adjusted body weight = IBW + 0.4 (actual - IBW))
Vancomycin PK Right Ans - Average distribution of 30min - 1h
Start with 2 or 3 compartment model and when vancomycin level for TDM are
obtained after the distribution phase is complete, one compartment model can
be used for dosing
Distribution: bone (15%), heart valve, lung tissue, epithelial lining fluid (20-
50%), CNS (meninges)
Protein binding: 50%
Vd: 0.6L/kg (TBW = about 60% body weight)
-range (0.4-1.7 L/kg)
Metabolism: negligible
Elimination: >90% renal, normal renal function then half life is 6h (4-12h)
Factors affecting activity (tissue distribution, inoculum size and protein
binding)
AE - red man syndrome (manage with extending the infusion duration to 2
hours or more and consider pretreatment with hydroxyzine 50mg PO prior to
each dose or diphenhydramine 25-50mg for NPO patient), ototoxicity,
nephrotoxicity (<10% risk during monotherapy when trough conc are
<=15mg/L, 10-20% in 15-20mg/L)
-increase risk in duration >14days, dose >4g/day, trough conc >20mg/L and
concomitant nephrotoxic agent (NSAID, aminoglycoside, ampho B, cisplatin,
diuretic, radiocontrast dye)
-no recommendation regarding minimizing nephrotoxicity by keeping dose
<4g and the role of either individualized PK or CI vancomycin to enable this
Questions And Answers
Antibiotic Killing Properties Right Ans - Concentration Dependent Killing:
-Rate and extent of killing dependent on the ratio that can be achieved
between peak drug conc. and MIC of infecting pathogen (eg. aminoglycosides
and fluoroquinolone)
Time Dependent Killing:
-Rate and extent of killing independent of increases in conc. of antibiotic,
determined by the length of time that unbound drug remain above MIC (eg.
vancomycin, beta lactams, macrolides)
AUC/MIC ratio: eg. fluoroquinolone, vancomycin, tigecycline
First Order PK Right Ans - -fraction/proportion/percentage of total
amount of drug removed per unit of time remains constant (Ke)
-half life remains constant
-peak and trough conc will be directly proportional to dose (increasing dose,
keeps interval constant but increases both peak and trough and WIDER
fluctuation between peak and trough conc)
-decreasing the interval, while keeping dose constant also increases peak and
trough but the fluctuation between peak and trough is SMALLER
Steady state Right Ans - Rate of drug going in = Rate of drug going out
-no further accumulation, so maximum and minimum conc remain constant
with each subsequent dose
-don't have to be at steady state to determine half life or Vd
Cockcroft Gault nomogram Right Ans - Derived a relationship between age
and 24 hour creatinine excretion/kg in 249 MALE pt between 18-92 years old
Formula includes age sex and body weight (not IBW)
Drawback: derived from only males, did not correct for excess fat or fluid, CrCl
can vary from day to day by 10-20% (don't dose adjust for no reason!)
MALE
, (140-age)(weight)(1.2)/serum creatinine (micromol/L)
OR
(140-age)(weight)/(72)(serum creatinine (mg/dL)
FEMALE = MALE X 0.85
Pt >30% IBW = obese (use adjusted body weight = IBW + 0.4 (actual - IBW))
Vancomycin PK Right Ans - Average distribution of 30min - 1h
Start with 2 or 3 compartment model and when vancomycin level for TDM are
obtained after the distribution phase is complete, one compartment model can
be used for dosing
Distribution: bone (15%), heart valve, lung tissue, epithelial lining fluid (20-
50%), CNS (meninges)
Protein binding: 50%
Vd: 0.6L/kg (TBW = about 60% body weight)
-range (0.4-1.7 L/kg)
Metabolism: negligible
Elimination: >90% renal, normal renal function then half life is 6h (4-12h)
Factors affecting activity (tissue distribution, inoculum size and protein
binding)
AE - red man syndrome (manage with extending the infusion duration to 2
hours or more and consider pretreatment with hydroxyzine 50mg PO prior to
each dose or diphenhydramine 25-50mg for NPO patient), ototoxicity,
nephrotoxicity (<10% risk during monotherapy when trough conc are
<=15mg/L, 10-20% in 15-20mg/L)
-increase risk in duration >14days, dose >4g/day, trough conc >20mg/L and
concomitant nephrotoxic agent (NSAID, aminoglycoside, ampho B, cisplatin,
diuretic, radiocontrast dye)
-no recommendation regarding minimizing nephrotoxicity by keeping dose
<4g and the role of either individualized PK or CI vancomycin to enable this
