Pediatric Dosing of Pediatric Dosing of Aminoglycosides and Aminoglycosides and Vancomycin Based on Vancomycin Based on

Pharmacokinetic ConceptsPharmacokinetic Concepts

Marie Varela, Pharm.D., BCPSMarie Varela, Pharm.D., BCPS

Sherene Samu, Pharm.DSherene Samu, Pharm.D..

11

ObjectivesObjectives

Describe basic pharmacokinetic parameters for Describe basic pharmacokinetic parameters for vancomycin and aminoglycosides in pediatric patientsvancomycin and aminoglycosides in pediatric patients

Outline dosing strategies for Outline dosing strategies for aminoglycosidesaminoglycosides based based on pharmacokinetic principleson pharmacokinetic principles

Outline dosing strategies for Outline dosing strategies for vancomycinvancomycin based on based on pharmacokinetic principlespharmacokinetic principles

Select a monitoring plan for vancomycin and Select a monitoring plan for vancomycin and aminoglycosides in pediatric patientsaminoglycosides in pediatric patients

Select an adjusted dosing regimen based on serum Select an adjusted dosing regimen based on serum concentrations for vancomycin and aminoglycosides in concentrations for vancomycin and aminoglycosides in pediatric patientspediatric patients

22

PharmacokineticsPharmacokinetics

DefinitionDefinition: : The study of the time course of a drug and its The study of the time course of a drug and its

metabolites in the body metabolites in the body The study of the ADME of a drug and its The study of the ADME of a drug and its

metabolites in the bodymetabolites in the body AbsorptionAbsorption DistributionDistribution MetabolismMetabolism ExcretionExcretion

Varies greatly with age groups (pediatrics, Varies greatly with age groups (pediatrics, geriatrics)geriatrics)

33

Volume of DistributionVolume of Distribution

44

ExcretionExcretion

Because of the PK and PD characteristics Because of the PK and PD characteristics of vancomycin and aminoglycosides, the of vancomycin and aminoglycosides, the clearance of these drugs is closely clearance of these drugs is closely correlated to creatinine clearancecorrelated to creatinine clearance

55

Estimation of Creatinine ClearanceEstimation of Creatinine Clearance

Schwartz EstimateSchwartz EstimateEstimates creatinine clearance Estimates creatinine clearance from serum creatinine, the from serum creatinine, the patient's height, and a patient's height, and a proportionality constant proportionality constant

CrCl = (k * Ht) / CrCrCl = (k * Ht) / Cr

(Caution: formula tends to (Caution: formula tends to overestimate the actual overestimate the actual creatinine clearance and creatinine clearance and should be used with caution.)should be used with caution.)

http://www-users.med.cornell.eduhttp://www-users.med.cornell.edu

HtHt height in height in centimeterscentimeters

CrCr serum creatinineserum creatinine

KK Constant:Constant:

(see below)(see below)

Infant (LBW < 1 Infant (LBW < 1 year)year)

0.330.33

Infant (Term < 1 Infant (Term < 1 year)year)

0.450.45

Child or Adolescent Child or Adolescent GirlGirl

0.550.55

Adolescent BoyAdolescent Boy 0.700.7066

Elimination Half-life (tElimination Half-life (t½)½)

Associated with first-order kinetics (serum Associated with first-order kinetics (serum concentration diminishes logarithmically concentration diminishes logarithmically over time)over time)

Time it takes for plasma concentration to Time it takes for plasma concentration to reach half of a previous concentrationreach half of a previous concentration

Affected by metabolism and excretionAffected by metabolism and excretion Most drugs follow first-order kinetics Most drugs follow first-order kinetics

(including aminoglycosides and vanco)(including aminoglycosides and vanco)

77

Steady StateSteady State

Equilibrium reached: Equilibrium reached:

Rate of drug in=Rate of drug outRate of drug in=Rate of drug out

Time to reach steady state is a function of tTime to reach steady state is a function of t½½

tt½½ % of Steady State Achieved% of Steady State Achieved

11 50%50%

22 75%75%

33 87.5%87.5%

44 93.75%93.75%

55 100%100%88

Graph of Multiple DosingGraph of Multiple Dosing

Q6h dosingQ6h dosing

t½ t½ = = 6 hours6 hours

99

Pharmacodynamic Concepts Affecting Pharmacodynamic Concepts Affecting Dosing and Monitoring of Dosing and Monitoring of

Aminoglycosides and VancomycinAminoglycosides and Vancomycin

Organism (Gram + vs. Gram -)Organism (Gram + vs. Gram -) MIC of organismMIC of organism Site of infectionSite of infection Dose-response relationships of AbxDose-response relationships of Abx

Concentration vs. time dependent bactericidal Concentration vs. time dependent bactericidal activityactivity

PAE PAE

1010

Concentration Dependent Concentration Dependent AminoglycosidesAminoglycosides

CONCENTRATION dependent killingCONCENTRATION dependent killing Maximize INTENSITY of exposureMaximize INTENSITY of exposure As concentration at site As concentration at site ↑, antimicrobial action ↑↑, antimicrobial action ↑

More pronounced responses to dosage More pronounced responses to dosage adjustmentsadjustments

1111

Gentamicin/TobramycinGentamicin/TobramycinInitial Dosing PediatricsInitial Dosing Pediatrics

1212

Conventional Dosing Extended Interval Dosing

2-2.5 mg/kg/dose q8h 4.5-7.5 mg/kg/dose q24h

CF: 3.3 mg/kg/dose q8h CF: 10-12 mg/kg/dose q24h

Gram + synergy: 1 mg/kg/dose q8h N/A

Lexicomp 1978-2013

Gentamicin/TobramycinGentamicin/TobramycinInitial Neonatal Dosing SBUHInitial Neonatal Dosing SBUH

PMA PMA (weeks)(weeks)

Postnatal (days)Postnatal (days) DoseDose

(mg/kg)(mg/kg)

Interval Interval (hours)(hours)

≤ ≤ 2929 0 to 70 to 7

8 to 288 to 28

> 28> 28

55

44

44

4848

3636

2424

30 to 3430 to 34 0 to 70 to 7

> 7> 7

4.54.5

44

3636

2424

≥ ≥ 3535 ALLALL 44 2424

Reference: NeofaxReference: Neofax

1313

Gentamicin/TobramycinGentamicin/Tobramycin Expected Half-Life Expected Half-Life

(Population Statistics)(Population Statistics)Age Age tt½½

Neonates < 1wkNeonates < 1wk 3 to 11.5 hrs3 to 11.5 hrs

Neonates 1wk-1moNeonates 1wk-1mo 3 to 6 hrs3 to 6 hrs

InfantsInfants 4 4 ±± 1 hrs 1 hrs

ChildrenChildren 2 2 ±± 1 hrs 1 hrs

AdolescentsAdolescents 1.5 1.5 ±± 1 hrs 1 hrs

AdultsAdults Normal Renal Function: 2 to 3 hrNormal Renal Function: 2 to 3 hr

Functionally Anephric: 30 to 60 hrFunctionally Anephric: 30 to 60 hr

Clearance approximately equal to CrCl (≈ 5% metabolized) 1414

Aminoglycosides Target GoalsAminoglycosides Target Goals Tobramycin/Gentamicin Tobramycin/Gentamicin Target Serum ConcentrationsTarget Serum Concentrations

ParameterParameter Serum Serum ConcentrationConcentration ConditionCondition

PeakPeak

4-5 mcg/mL4-5 mcg/mL•UTIUTI

•Gram (+) synergyGram (+) synergy

6-8 mcg/mL6-8 mcg/mL•Pneumonia (within 24 Pneumonia (within 24 to 48 hours)to 48 hours)

TroughTrough <2 mcg/mL to minimize toxicities<2 mcg/mL to minimize toxicities

1515

Time Dependent Time Dependent

VancomycinVancomycin TIME dependent killingTIME dependent killing

Maximize DURATION of exposureMaximize DURATION of exposure

More pronounced responses to interval More pronounced responses to interval adjustmentsadjustments

1616

VancomycinVancomycinInitial Dosing PediatricsInitial Dosing Pediatrics

10-15 mg/kg/dose q6-8 hours10-15 mg/kg/dose q6-8 hours Renal impairmentRenal impairment

GFR 30-50: 10 mg/kg/dose q12hGFR 30-50: 10 mg/kg/dose q12h GFR 10-29: 10 mg/kg/dose q18-24 hoursGFR 10-29: 10 mg/kg/dose q18-24 hours GFR < 10: 10 mg/kg/dose; re-dose based on GFR < 10: 10 mg/kg/dose; re-dose based on

serum concentrationsserum concentrations

1717

Lexicomp 1978-2013

IV VancomycinIV Vancomycin Initial Neonatal Dosing SBUH Initial Neonatal Dosing SBUH

PMA PMA (weeks)(weeks)

Postnatal (days)Postnatal (days) IntervalInterval

≤ ≤ 2929 0 to 140 to 14

> 14> 14

1818

1212

30 to 3630 to 36 0 to 140 to 14

> 14> 14

1212

88

37 to 4437 to 44 0 to 70 to 7

> 7> 7

1212

88

> 44> 44 AllAll 66

Dose: 10 to 15 mg/kg/dose*Dose: 10 to 15 mg/kg/dose*

(*(*This dosing strategy targets a trough of 5-15, therefore 15 mg/kg/dose is preferred. ))

Reference: NeofaxReference: Neofax

VancomycinVancomycin Expected Half-Life Expected Half-Life

(Population Statistics)(Population Statistics)

AgeAge tt1/21/2

NeonatesNeonates 6 to 10 hrs6 to 10 hrs

InfantsInfants 3 to 4 hrs3 to 4 hrs

ChildrenChildren 2.2 to 3 hrs2.2 to 3 hrs

AdultsAdults Normal renal function: 5-11 hrNormal renal function: 5-11 hr

End stage renal: 5 to 7 daysEnd stage renal: 5 to 7 days

Clearance approximately equal to CrCl (≈ 5% metabolized)1919

IV VancomycinIV Vancomycin Target Serum ConcentrationsTarget Serum Concentrations

Trough Trough GoalGoal ConditionCondition

10-15 mcg/mL10-15 mcg/mL •GeneralGeneral

15-20 mcg/mL15-20 mcg/mL •PeritonitisPeritonitis

•OsteomyelitisOsteomyelitis

•MRSA pneumoniaMRSA pneumonia

•CNS infectionsCNS infections

2020Maintain trough in therapeutic range; peak inconsequential

IV VancomycinIV Vancomycin

Dosing StrategiesDosing Strategies Due to pharmacodynamic characteristics, Due to pharmacodynamic characteristics,

optimal give more frequentlyoptimal give more frequently Want trough to remain in therapeutic range; Want trough to remain in therapeutic range;

peak inconsequentialpeak inconsequential For renal impairment, reduce frequenciesFor renal impairment, reduce frequencies

2121

Why Monitor?Why Monitor?

Constant changes in Vd and clearanceConstant changes in Vd and clearance Optimize therapeutic effectsOptimize therapeutic effects Minimize toxicityMinimize toxicity

2222

When to Monitor?When to Monitor? At presumed steady state At presumed steady state

Upon initiation of therapyUpon initiation of therapy After a dosage/frequency adjustmentAfter a dosage/frequency adjustment Upon significant change in weight, fluid status, renal Upon significant change in weight, fluid status, renal

functionfunction After addition of a medication that may affect renal After addition of a medication that may affect renal

function (i.e. Ibuprofen)function (i.e. Ibuprofen) Every week after achieving therapeutic serum Every week after achieving therapeutic serum

concentrationsconcentrations For vancomycin doses of > 15 mg/kg/dose q6h or > 3 g For vancomycin doses of > 15 mg/kg/dose q6h or > 3 g

per day, recheck first therapeutic trough in 2-3 days. per day, recheck first therapeutic trough in 2-3 days. (Then follow above monitoring strategy thereafter.)(Then follow above monitoring strategy thereafter.)

2323

Time to DrawTime to Draw

Peak (aminoglycosides only) Peak (aminoglycosides only) 30 minutes after dose completely infused30 minutes after dose completely infused

Trough (all drugs)Trough (all drugs)30 minutes before the next dose is due 30 minutes before the next dose is due

2424

How to Interpret Lab ResultsHow to Interpret Lab Results

Questions to ask yourselfQuestions to ask yourself Was the initial dosing appropriate? (considering renal Was the initial dosing appropriate? (considering renal

function etc.)function etc.) Was the trough drawn at presumed steady state?Was the trough drawn at presumed steady state? For unexpected high concentrations, was it possible For unexpected high concentrations, was it possible

the trough was drawn after the start of the infusion or the trough was drawn after the start of the infusion or from a line that may not have been flushed?from a line that may not have been flushed?

Was it actually drawn at the time documented in the Was it actually drawn at the time documented in the system? system?

Should the level be redrawn?Should the level be redrawn?

2525

Gentamicin Conventional Dosage Gentamicin Conventional Dosage Adjustment GuidelinesAdjustment Guidelines

2626

If Peak is High(>10

mcg/mL)

Trough is High

Proportional DECREASE in DOSE to bring peak to desired number. Check to see how this change affects trough.

If trough is still high (above range) with this dosage decrease, DECREASE the FREQUENCY.

Trough is in rangeProportional DECREASE in DOSE to bring peak to desired number.

Trough is low (<0.5 mcg/mL)

Proportional DECREASE in DOSE to bring peak to desired number and INCREASE the dosing frequency.

If Peak is Low

(less than target)

Trough is High

Proportional INCREASE in DOSE to bring peak to desired number. Must also DECREASE the dosing frequency

Trough is in Range

Proportional INCREASE in DOSE to bring peak to desired number. Check to see how this change affects the trough.

If the change will cause the trough to be high (above range), also DECREASE the FREQUENCY.

Trough is low

Proportional INCREASE in DOSE to bring peak to desired number. Check to see how this change affects trough.

If the change will cause the trough to be high (above range), also DECREASE the FREQUENCY.

Gentamicin Dosage Gentamicin Dosage Adjustment GuidelinesAdjustment Guidelines

2727

•If peak is in desired range and trough is high, DECREASE THE FREQUENCY.

•After rechecking serum concentrations, may be necessary to increase dose with next adjustment.

•If peak is in desired range and trough is low, most likely no adjustment is necessary.

Vancomycin Dosage Vancomycin Dosage Adjustment GuidelinesAdjustment Guidelines

2828

If trough comes back

HIGH

If trough is in toxic range, hold and draw random serum concentrations until below 15 mcg/mL.

May calculate patient half-life using formula if there are 2 concentrations after a dose and one value is at least twice the other.

When concentration is below 15 mcg/mL, recalculate dose and restart.

If half-life is greater than dosing interval, increase dosing interval to greater than or equal to one half-life

If trough comes back

LOW

If trough is less than half of target, increase the frequency. If the frequency is already Q6H, increase the dose to 15 mg/kg. If trough is still low, increase the dose in small increments (i.e. 2 mg/kg per dose)

If trough is more than half of target, increase the dose based on a linear relationship; calculate as a proportional ratio to trough. Maximum increase of 50% at one time.

Note: Q6h hours in the maximum frequency

Common MythCommon Myth

Adjust the dose by 10%Adjust the dose by 10% Is this an appropriate recommendation?Is this an appropriate recommendation? In what situation, if ever, would this apply?In what situation, if ever, would this apply?

2929

Calculating Actual Half-LifeCalculating Actual Half-Lifeto choose best dosage intervalto choose best dosage interval

K = ln K = ln C1C1

C2C2

ΔΔ Time Time

tt½½ = 0.693/K = 0.693/K

K=elimination rate constant

Δ Time = hours

•Can be done from random levels if spaced far enough apart

(one number at least twice the other)

•Can be done from peak and trough if at steady state3030

CommunicationCommunication

VerbalVerbal Progress notesProgress notes Sign outsSign outs

3131

Case 1Case 1

Reason for visitReason for visit Chronic CSF leakChronic CSF leak Comes to ER with symptoms of bending Comes to ER with symptoms of bending

down, having rhinorrheadown, having rhinorrhea

Started on vancomycinStarted on vancomycin Trough goal = Trough goal = 15-20 mcg/mL15-20 mcg/mL

3232

Case 1Case 1

Date Dosing Schedule Dose Received Time

2/3/10 1 g x1 STAT 1 g 1629

2/4/101.5 g Q12H 1.5 g 0400

1 g Q12H 1 g 1520

2/5 /10

VANCOMYCIN TROUGH 10.1 mcg/mL

0330

1 g Q12H1 g 0400

1 g 1530

3333

Case 1Case 1

Pharmacy recommendation on Pharmacy recommendation on 2/5/102/5/10 Draw a level on 2/6/10 AMDraw a level on 2/6/10 AM If level ≤ 10 mcg/mL, give 1 g Q8HIf level ≤ 10 mcg/mL, give 1 g Q8H If level 11-12 mcg/mL, give 1.5 g Q12HIf level 11-12 mcg/mL, give 1.5 g Q12H If 13-15 mcg/mL, give 1.2 g Q12hIf 13-15 mcg/mL, give 1.2 g Q12h

3434

Case 1Case 1

Date Dosing Schedule Dose Received Time

2/6/10

VANCOMYCIN TROUGH 11 mcg/mL 0300

1 g Q12H 1 g 0330

1.5 g Q12H 1.5 g 1530

2/7/10 1.5 g Q12H1.5 g 0330

1.5 g 1530

2/8/10VANCOMYCIN TROUGH

17.5 mcg/mL 0300

3535

Case 2Case 2

Reason for admissionReason for admission LethargyLethargy Mental status changesMental status changes FeverFever

Started on gentamicin Started on gentamicin R/O sepsis (gram negative coverage)R/O sepsis (gram negative coverage)

3636

Case 2Case 2

Target Serum ConcentrationsTarget Serum Concentrations Peak: 6-10 mcg/mLPeak: 6-10 mcg/mL Trough: < 2 mcg/mLTrough: < 2 mcg/mL

Gentamicin Dose: 2.5 mg per kg q8h Gentamicin Dose: 2.5 mg per kg q8h

3737

Case 2Case 2

Date Dosing Schedule Dose Received Time

1/27/10 43 mg Q8H 43 mg 22:00

1/28/10 43 mg Q8H 43 mg 06:00

43 mg Q8H 43 mg 14:00

1/28/10 Gentamicin Peak 5.2 mcg/mL 15:00

Gentamicin Trough 1.3 mcg/mL 21:30

1/28/10 43 mg Q8H 43 mg 22:00

3838

Case 2Case 2

Dosage AdjustmentDosage Adjustment Want peak 6 or greaterWant peak 6 or greater

If 43 mg yields peak of 5.2, what dose If 43 mg yields peak of 5.2, what dose would bring it to 6?would bring it to 6?

Use linear proportion as long as interval is Use linear proportion as long as interval is unchangedunchanged

3939

Case 2Case 2

Dosage Adjustment ContinuedDosage Adjustment Continued What effect would that have on trough (if What effect would that have on trough (if

dose was increased to 49 mg q8h)?dose was increased to 49 mg q8h)? If 43 mg yields a trough of 1.3 mcg/mL, 49 If 43 mg yields a trough of 1.3 mcg/mL, 49

mg would bring it to what trough? mg would bring it to what trough?

4040

Case 2Case 2

What if trough calculated to greater than 2?What if trough calculated to greater than 2? Answer: increase the intervalAnswer: increase the interval

MonitoringMonitoring After dosage change, repeat peak and trough After dosage change, repeat peak and trough

around 3around 3rdrd dose of the new regimen dose of the new regimen

4141

Case StudyCase Study

Term neonateTerm neonate DOB: 1/25/12DOB: 1/25/12 Diagnosis: chorioamnionitisDiagnosis: chorioamnionitis Weight 3.65 kgWeight 3.65 kg Start antibiotics: ampicillin Start antibiotics: ampicillin

gentamicingentamicin

4242

Case 3 ( 1) GentamicinCase 3 ( 1) Gentamicin

4343

Gentamicin ordered: 14.6 mg q 24 hours

Dosed at 4 mg per kg

Questions:Questions:

Was this dosed properly?Was this dosed properly? What criteria are used to determine if this What criteria are used to determine if this

was dosed properly?was dosed properly? What level(s) will be drawn to properly What level(s) will be drawn to properly

monitor this drug?monitor this drug? What serum concentrations are we What serum concentrations are we

targeting?targeting?

4444

Gentamicin DosingGentamicin Dosing

4545

PMA (weeks)Postnatal

(days)Dose

(mg/kg)Interval (hours)

≤ 29 0 to 7

8 to 28

> 28

5

4

4

48

36

24

30 to 34 0 to 7

> 7

4.5

4

36

24

≥ 35 ALL 4 24

PMA is the equivalent to Gestational Age plus Postnatal Age

Case 3 (2) GentamicinCase 3 (2) Gentamicin

4646

Question:Question:

What time should the peak be drawn?What time should the peak be drawn? What time should the trough be drawn?What time should the trough be drawn?

4747

Case 3 (3) Gentamicin Case 3 (3) Gentamicin

4848

Case 3 (4) Gentamicin Case 3 (4) Gentamicin

4949

Question:Question:

What is your evaluation of this peak?What is your evaluation of this peak? How do we proceed from here?How do we proceed from here?

5050

5151

Date Dosage Regimen

AdminTime

Time of Blood Draw

Peak, Trough or Random

Result SerumCreat

Comments

1/25/12 Gent 14.6 mg q24

9:00 No serum creatinine. Wt= 3.65 kg 4 mg/kg

1/26/12 “ 8:081/27/12 “ 8:08 9:00

(11:09)Peak 33.7

Mcg/mLIf you “believe” these numbers, t ½ =1.88

12:39(12:55)

Random 9.3Mcg/mL

Expected t ½ in neonate=3-6 hours

Aminoglycoside Pharmacokinetic

Monitoring

Drug: Gentamicin

Case 3 (5) Gentamicin Case 3 (5) Gentamicin

5252

5353

Date Dosage Regimen

AdminTime

Time of Blood Draw

Peak, Trough or Random

Result SerumCreat

Comments

1/25/12 Gent 14.6 mg q24

9:00 No serum creatinine. Wt= 3.65 kg 4 mg/kg

1/26/12 “ 8:081/27/12 “ 8:08 9:00

(11:09)Peak 33.7

Mcg/mLIf you “believe” these numbers, t ½ =1.88

12:39(12:55)

Random 9.3Mcg/mL

Expected t ½ in neonate=3-6 hours

1/28/12 8:15 Trough 1.6Mcg/mL

Aminoglycoside Pharmacokinetic

Monitoring

Drug: Gentamicin

Question:Question:

Next step?Next step? Give a dose (4 mg/kg dose) now (9AM) and Give a dose (4 mg/kg dose) now (9AM) and

draw a peak 30 minutes after it is infuseddraw a peak 30 minutes after it is infused

5454

Case 3 (6) Case 3 (6)

5555

EvaluationEvaluation

Check initial dosing for correctnessCheck initial dosing for correctness Evaluate the credibility of the laboratory valuesEvaluate the credibility of the laboratory values Identify possible reasons for serum Identify possible reasons for serum

concentration to be different than what is concentration to be different than what is expectedexpected

Confirm that all doses were given as scheduledConfirm that all doses were given as scheduled Confirm that blood was drawn at the correct timeConfirm that blood was drawn at the correct time Repeat lab work if necessaryRepeat lab work if necessary Make adjustments based on pharmacokinetic Make adjustments based on pharmacokinetic

relationshipsrelationships5656

Case 4 (1) VancomycinCase 4 (1) Vancomycin

5757

Dosed at 10 mg/kg per dose every 8 hours.

Premature infant is 3 weeks old when vancomycin is

added..

Case 4 (2) VancomycinCase 4 (2) Vancomycin

5858

Case 4 (3) VancomycinCase 4 (3) Vancomycin

5959

4th dose

Case 4 (4) VancomycinCase 4 (4) Vancomycin

6060

What is the next step?What is the next step?

Evaluate the initial dosing strategyEvaluate the initial dosing strategy Evaluate the lab resultEvaluate the lab result Target trough?Target trough? Adjust dose or change the frequency?Adjust dose or change the frequency?

6161

SummarySummary

Basic knowledge of pharmacokinetics will Basic knowledge of pharmacokinetics will optimize prescribing by insuring:optimize prescribing by insuring:

Maximal therapeutic benefitsMaximal therapeutic benefitsMinimal adverse effectsMinimal adverse effectsCost effectivenessCost effectivenessDecreased blood samplingDecreased blood sampling

6262

CE Question #1CE Question #1

A patient is on vancomycin every 8 hours A patient is on vancomycin every 8 hours and his half life is 6 hours. What is the and his half life is 6 hours. What is the earliest you would expect him to be at earliest you would expect him to be at steady state?steady state?a)a) 12 hours12 hours

b)b) 6 hours6 hours

c)c) 18 hours18 hours

d)d) 24 hours24 hours

6363

CE Question #2CE Question #2

A patient is on gentamicin being treated A patient is on gentamicin being treated for a gram negative pneumonia. What is for a gram negative pneumonia. What is the target serum concentrations?the target serum concentrations?a)a) Peak 4; Trough <2Peak 4; Trough <2

b)b) Peak 15; Trough <2Peak 15; Trough <2

c)c) Peak 7; Trough <2Peak 7; Trough <2

d)d) Peak 5; Trough <2Peak 5; Trough <2

6464

CE Question #3CE Question #3

A 4 year old female child with normal renal A 4 year old female child with normal renal function (function (Wt = 18 kg; Ht = 40 inchWt = 18 kg; Ht = 40 inch) is ) is admitted for presumed meningitis. What admitted for presumed meningitis. What would be the appropriate starting dose of would be the appropriate starting dose of vancomycin?vancomycin?a)a) 1g q12h1g q12h

b)b) 15 mg/kg/dose q6h15 mg/kg/dose q6h

c)c) 5 mg/kg/dose q8h5 mg/kg/dose q8h

d)d) 750mg q6h750mg q6h6565

CE Question #4CE Question #4

There is a 10 kg patient that is on vancomycin 150mg There is a 10 kg patient that is on vancomycin 150mg q8h being treated for cellulitis. The trough comes back q8h being treated for cellulitis. The trough comes back at 5 at presumed steady state with all doses given at the at 5 at presumed steady state with all doses given at the appropriate times. The resident calls down to the appropriate times. The resident calls down to the pharmacy and asks you for a dosage adjustment. What pharmacy and asks you for a dosage adjustment. What would be an appropriate recommendation?would be an appropriate recommendation?a)a) Increase the dose by 10%Increase the dose by 10%

b)b) Change the frequency to q6h at the same doseChange the frequency to q6h at the same dose

c)c) Increase the dose to 170mg at the same q8h frequencyIncrease the dose to 170mg at the same q8h frequency

d)d) Switch to linezolid because you don’t know how to adjust Switch to linezolid because you don’t know how to adjust vancomycinvancomycin

6666

Questions?Questions?

6767

ReferencesReferences1.1. Harriet Lane Handbook.Harriet Lane Handbook. 17 17thth ed. Robertson, J and Shilkofski, N Editors. ed. Robertson, J and Shilkofski, N Editors.

Philadelphia: Mosby, Inc., 2005.Philadelphia: Mosby, Inc., 2005.

2.2. Shargel L, Yu ABC. Applied Shargel L, Yu ABC. Applied Biopharmaceutics and PharmacokineticsBiopharmaceutics and Pharmacokinetics. 3. 3rdrd ed. ed. Appleton & Lange, 1993.Appleton & Lange, 1993.

3.3. Thomson MICROMEDEX. 1974 - 2008 MICROMEDEX(R) Thomson HealthcareThomson MICROMEDEX. 1974 - 2008 MICROMEDEX(R) Thomson Healthcare

4.4. Winter ME. Winter ME. Basic Clinical PharmacokineticsBasic Clinical Pharmacokinetics. 4th ed. Baltimore: Lippincott . 4th ed. Baltimore: Lippincott Williams & Wilkins, 2004.Williams & Wilkins, 2004.

5. http://www-users.med.cornell.edu

6. www.merck.com. Merck Manual on-line. Merck Manual on-line

7.7. Young, TE and Mangum, B. Young, TE and Mangum, B. NeofaxNeofax. 18. 18thth ed. Acorn Publishing, Raleigh, 2005. ed. Acorn Publishing, Raleigh, 2005.

8.8. Taketomo, Hoddong and Kraus. Taketomo, Hoddong and Kraus. Pediatric Dosage HandbookPediatric Dosage Handbook. Lexi-comp. 2003-. Lexi-comp. 2003-2004.2004.

6868