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9/21/2010
1
Evaluation of Vancomycin Evaluation of Vancomycin
Dosing for Complicated Dosing for Complicated
Infections in Pediatric Infections in Pediatric
Patients Patients
Spencer H. Durham, Pharm.D., BCPS Spencer H. Durham, Pharm.D., BCPS
Marroyln L. Simmons, Pharm.D., BCPS Marroyln L. Simmons, Pharm.D., BCPS
Sacred Heart Children’s Hospital Sacred Heart Children’s Hospital
Pensacola, FL Pensacola, FL
Pediatric Dosing Pediatric Dosing
Lexi Lexi--Comp’s Pediatric Dosage Comp’s Pediatric Dosage
Handbook Handbook
–– Infants and Children: 40 mg/kg/day Infants and Children: 40 mg/kg/day Infants and Children: 40 mg/kg/day Infants and Children: 40 mg/kg/day
divided every 6 divided every 6- -8 hours 8 hours
–– Non Non--obese oncology patients: 60 obese oncology patients: 60
mg/kg/day divided every 6 hours mg/kg/day divided every 6 hours
–– CNS infections: 60 mg/kg/day divided CNS infections: 60 mg/kg/day divided
every 6 hours every 6 hours
Pediatric Dosing Pediatric Dosing
Other references, such as Micromedex Other references, such as Micromedex
and Harriet Lane, have comparable and Harriet Lane, have comparable
dosing dosing
Recommended dosing originated from Recommended dosing originated from
one study in 1959 and a later study in one study in 1959 and a later study in
1980 1980
Both studies were small, with around Both studies were small, with around
50 patients each 50 patients each
9/21/2010
2
Vancomycin Monitoring Vancomycin Monitoring
Traditional Recommendations: Traditional Recommendations:
–– Peak: 20 Peak: 20- -40 40
–– Trough: 5 Trough: 5--15 15 Trough: 5 Trough: 5 15 15
–– Peak concentration obtained 1 hour after Peak concentration obtained 1 hour after
a 1 hour infusion, at the 3 a 1 hour infusion, at the 3
rd rd
dose dose
–– Trough concentrations checked 30 Trough concentrations checked 30
minutes prior to the 3 minutes prior to the 3
rd rd
dose dose
New Vancomycin New Vancomycin
Guidelines Guidelines
New guidelines for vancomycin New guidelines for vancomycin
monitoring published in 2009 monitoring published in 2009
–– American Society of Health American Society of Health--Systems Systems American Society of Health American Society of Health Systems Systems
Pharmacists Pharmacists
–– Infectious Disease Society of America Infectious Disease Society of America
–– Society of Infectious Disease Pharmacists Society of Infectious Disease Pharmacists
Specific to adult patients Specific to adult patients
New Vancomycin New Vancomycin
Guidelines Guidelines
Peaks should not be monitored Peaks should not be monitored
–– Do not correlate well to either efficacy or toxicity Do not correlate well to either efficacy or toxicity
MICs should be obtained whenever possible MICs should be obtained whenever possible
An AUC/MIC ratio of >400 is the best An AUC/MIC ratio of >400 is the best
predictor of clinical efficacy predictor of clinical efficacy
Trough concentrations should be monitored Trough concentrations should be monitored
instead of the AUC instead of the AUC
9/21/2010
3
New Vancomycin New Vancomycin
Guidelines Guidelines
Troughs should be obtained at steady Troughs should be obtained at steady- -
state, usually just prior to the 4 state, usually just prior to the 4
th th
dose dose
Only monitor troughs if: Only monitor troughs if: y g y g
–– Prolonged therapy expected (>3 Prolonged therapy expected (>3- -5 days) 5 days)
–– Aggressive dosing is needed Aggressive dosing is needed
–– Patients are receiving other nephrotoxic Patients are receiving other nephrotoxic
agents agents
–– Renal dysfunction present Renal dysfunction present
New Vancomycin New Vancomycin
Guidelines Guidelines
All troughs should be kept >10 mg/L All troughs should be kept >10 mg/L
–– Recommended mainly to prevent Recommended mainly to prevent
bacterial resistance bacterial resistance
Troughs of 15 Troughs of 15- -20 are recommended in 20 are recommended in
certain clinical situations certain clinical situations
–– Pathogens with MIC ≥1 mg/L Pathogens with MIC ≥1 mg/L
–– Complicated infections (bacteremia, Complicated infections (bacteremia,
endocarditis, osteomyelitis, meningitis, endocarditis, osteomyelitis, meningitis,
pneumonia) pneumonia)
Pediatric v. Adult Pediatric v. Adult
Factors similar between both groups: Factors similar between both groups:
–– MOA (concentration MOA (concentration- -independent in both groups) independent in both groups)
–– Development of resistance (troughs should be Development of resistance (troughs should be
k t 10) k t 10) kept ≥10) kept ≥10)
–– MIC of infecting pathogen MIC of infecting pathogen
–– Antibiotic penetration Antibiotic penetration
It is reasonable to follow the same It is reasonable to follow the same
recommendations in pediatrics as in adults recommendations in pediatrics as in adults
9/21/2010
4
Pediatric Data Pediatric Data
Some pediatric studies show a dose of 60 Some pediatric studies show a dose of 60
mg/kg/day is more likely to achieve mg/kg/day is more likely to achieve
therapeutic troughs than 40 mg/kg/day therapeutic troughs than 40 mg/kg/day
However, therapeutic troughs were defined, However, therapeutic troughs were defined,
generally, as 5 generally, as 5- -15 15
Currently, no study has addressed pediatric Currently, no study has addressed pediatric
dosing required to obtain troughs of 15 dosing required to obtain troughs of 15- -20 20
Methods Methods
A retrospective chart review was conducted A retrospective chart review was conducted
between July 1, 2009 between July 1, 2009 - - April 30, 2010 April 30, 2010
Inclusion Criteria Inclusion Criteria: all patients receiving : all patients receiving
vancomycin therapy for complicated vancomycin therapy for complicated
infections infections
Exclusion Criteria Exclusion Criteria: :
–– Renal dysfunction Renal dysfunction
–– Receiving vancomycin prior to admission Receiving vancomycin prior to admission
Results Results
73 patients identified, 70 included 73 patients identified, 70 included
–– 2 patients excluded due to renal dysfunction 2 patients excluded due to renal dysfunction
–– 1 patient excluded due to home vancomycin use 1 patient excluded due to home vancomycin use
Patients <50 kg were initiated on 15 Patients <50 kg were initiated on 15
mg/kg/dose every 6 hours mg/kg/dose every 6 hours
Patients >50 kg were initiated on a standard Patients >50 kg were initiated on a standard
dose of 1 gram every 8 hours dose of 1 gram every 8 hours
9/21/2010
5
Results Results
Troughs obtained on 43 patients (61%) Troughs obtained on 43 patients (61%)
–– 36 patients receiving 15 mg/kg/dose every 6 36 patients receiving 15 mg/kg/dose every 6
hours hours
6 ti t i i 1 8 h 6 ti t i i 1 8 h –– 6 patients receiving 1 gram every 8 hours 6 patients receiving 1 gram every 8 hours
–– 1 patient receiving 1 gram every 6 hours 1 patient receiving 1 gram every 6 hours
Troughs were obtained at the 5 Troughs were obtained at the 5
th th
dose or dose or
later later
In 27 patients, vancomycin therapy was In 27 patients, vancomycin therapy was
discontinued prior to obtaining a trough discontinued prior to obtaining a trough
Results Results
3 patients (7%) had an initial trough 15 3 patients (7%) had an initial trough 15- -20 20
–– 2 patients receiving 15 mg/kg/dose every 6 2 patients receiving 15 mg/kg/dose every 6
hours hours
1 ti t i i 1 6 h 1 ti t i i 1 6 h –– 1 patient receiving 1 gram every 6 hours 1 patient receiving 1 gram every 6 hours
38 patients (88%) had troughs <15 38 patients (88%) had troughs <15
2 patients (4%) had troughs >20 2 patients (4%) had troughs >20
–– 1 patient receiving 15 mg/kg/dose every 6 hours 1 patient receiving 15 mg/kg/dose every 6 hours
–– 1 patient receiving 1 gram every 8 hours 1 patient receiving 1 gram every 8 hours
Results Results
18/43 patients had repeat vancomycin 18/43 patients had repeat vancomycin
troughs obtained troughs obtained
Only 5 of the repeat troughs were 15 Only 5 of the repeat troughs were 15- - y p g y p g
20 20
Average dose to obtain a therapeutic Average dose to obtain a therapeutic
trough: trough:
–– 21.15 mg/kg every 6 hours 21.15 mg/kg every 6 hours
Range 18.75 to 23 mg/kg/dose every 6 hours Range 18.75 to 23 mg/kg/dose every 6 hours
9/21/2010
6
Conclusions Conclusions
Vancomycin doses of ~85 mg/kg/day Vancomycin doses of ~85 mg/kg/day
divided every 6 hours are more likely to divided every 6 hours are more likely to
achieve troughs of 15 achieve troughs of 15- -20 than 60 20 than 60
mg/kg/day divided every 6 hours mg/kg/day divided every 6 hours mg/kg/day divided every 6 hours mg/kg/day divided every 6 hours
Further studies should be performed to Further studies should be performed to
adequately assess optimal dosing to achieve adequately assess optimal dosing to achieve
troughs of 15 troughs of 15- -20 in pediatric patients 20 in pediatric patients
New guidelines for the monitoring of New guidelines for the monitoring of
vancomycin in pediatric patients is strongly vancomycin in pediatric patients is strongly
needed needed
References References
1. 1. Benner KW, Worthington MA, Kimberlin DW, Hill K, Buckley K, Benner KW, Worthington MA, Kimberlin DW, Hill K, Buckley K,
Tofil NM. Correlation of vancomycin dosing to serum Tofil NM. Correlation of vancomycin dosing to serum
concentrations in pediatric patients: a retrospective database concentrations in pediatric patients: a retrospective database
review. J Pediatr Pharmacol Ther. 2009;14(2):86 review. J Pediatr Pharmacol Ther. 2009;14(2):86- -93. 93.
2. 2. Dehority W. Use of vancomycin in pediatrics. Pediatr Infect Dis J. Dehority W. Use of vancomycin in pediatrics. Pediatr Infect Dis J.
2010;27(5):462 2010;27(5):462- -464. 464.
3. 3. Frymoyer A, Hersh AL, Benet LZ, Guglielmo BJ. Current Frymoyer A, Hersh AL, Benet LZ, Guglielmo BJ. Current
recommended dosing of vancomycin for children with invasive recommended dosing of vancomycin for children with invasive
methicillin methicillin- -resistant resistant Staphylococcus aureus Staphylococcus aureus infections is infections is
inadequate. Pediatr Infect Dis J. 2009;28(5):398 inadequate. Pediatr Infect Dis J. 2009;28(5):398- -402. 402.
4. 4. Frymoyer A, Hersh AL, Coralic Z, Benet LZ, Guglielmo BJ. Frymoyer A, Hersh AL, Coralic Z, Benet LZ, Guglielmo BJ.
Prediction of vancomycin pharmacodynamics in children with Prediction of vancomycin pharmacodynamics in children with
invasive methicillin invasive methicillin- -resistant resistant Staphylococcus aureus Staphylococcus aureus infections: a infections: a
monte carlo simulation. Clin Therapeutics. 2010;32(3):534 monte carlo simulation. Clin Therapeutics. 2010;32(3):534- -542. 542.
5. 5. Glover ML, Cole E, Wolfsdorf. Vancomycin dosage requirements Glover ML, Cole E, Wolfsdorf. Vancomycin dosage requirements
among pediatric intensive care unit patients with normal renal among pediatric intensive care unit patients with normal renal
function. J Crit Care. 2000;15(1):1 function. J Crit Care. 2000;15(1):1- -4. 4.
References References
6. 6. Jimenez Jimenez- -Truque N, Thomsen I, Saye E, Creech CB. Should Truque N, Thomsen I, Saye E, Creech CB. Should
higher vancomycin trough levels be targeted for invasive higher vancomycin trough levels be targeted for invasive
community community- -acquired methicillin acquired methicillin- -resistant resistant Staphylococcus Staphylococcus
aureus aureus infections in children? Pediatr Infect Dis J. infections in children? Pediatr Infect Dis J.
2010;29(4):368 2010;29(4):368--370 370 2010;29(4):368 2010;29(4):368--370. 370.
7. 7. Piro CC, Crossno CL, Collier A, Ho R, Koyama T, Frangoul H. Piro CC, Crossno CL, Collier A, Ho R, Koyama T, Frangoul H.
Initial vancomycin dosing in pediatric oncology and stem Initial vancomycin dosing in pediatric oncology and stem
cell transplant atients. J Pediatr Hematol Oncol. cell transplant atients. J Pediatr Hematol Oncol.
2009;31(1):3 2009;31(1):3- -7. 7.
8. 8. Robertson J, Shilkofski N. The Harriet Lane Handbook. 17 Robertson J, Shilkofski N. The Harriet Lane Handbook. 17
th th
ed. Philadelphia: Elsevier Mosby;2005:996. ed. Philadelphia: Elsevier Mosby;2005:996.
9. 9. Taketomo CK, Hodding JH, Kraus DM, eds. Lexi Taketomo CK, Hodding JH, Kraus DM, eds. Lexi- -Comp’s Comp’s
Pediatric Dosage Handbook. 14 Pediatric Dosage Handbook. 14
th th
ed. Hudson: Lexi ed. Hudson: Lexi--
Comp;2007:1597. Comp;2007:1597.

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