Vancomycin vs Newer Agents for Gram-positive Infections Debate George D. Rodriguez, Pharm.D. Clinical Pharmacist, The Dr James J Rahal Jr Division of Infectious Diseases Antimicrobial Stewardship Program Manager New York-Presbyterian Queens Assistant Clinical Professor, Pharmacy Sciences Columbia University School of Nursing [email protected]@GeorgeR_IDpharm Bruce M. Jones, Pharm.D., BCPS Infectious Disease Clinical Pharmacy Specialist St. Joseph's/Candler Health System, Inc. Clinical Adjunct Assistant Professor University of Georgia College of Pharmacy 5353 Reynolds Street Savannah, GA 31405 [email protected]@Bruce_M_Jones
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Vancomycin vs Newer Agents for Gram-positive Infections Debate · Vancomycin • Derived from Streptomyces orientalis (1952) • Glycopeptide, binds to D-alanyl-D-alanine precursor
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Vancomycin vs Newer
Agents for Gram-positive
Infections Debate
George D. Rodriguez, Pharm.D.Clinical Pharmacist, The Dr James J Rahal Jr Division of Infectious DiseasesAntimicrobial Stewardship Program ManagerNew York-Presbyterian QueensAssistant Clinical Professor, Pharmacy SciencesColumbia University School of [email protected]@GeorgeR_IDpharm
Bruce M. Jones, Pharm.D., BCPSInfectious Disease Clinical Pharmacy SpecialistSt. Joseph's/Candler Health System, Inc.Clinical Adjunct Assistant ProfessorUniversity of Georgia College of Pharmacy5353 Reynolds StreetSavannah, GA [email protected]@Bruce_M_Jones
Holmes N. AAC 2013; 57(4): 1654-63.Brown J. AAC 2012; 56(2): 634-8.Gawronski KM. Clinical Therapeutics 2013; 35(6): 772-9.Moise-Broder PA et al. Clin Pharmacokinet 2004; 43 (13): 925-42.
Elbarbry F. Eur J Drug Metab Pharmacokinet 2017. 1-10.Lin H. Critical Care 2016; 20: 205-12.Pai MP. Advanced Drug Delivery Reviews 2014; 77: 50-7.Lodise T. CID 2014; 59(5): 666-75
Velazquez A. Clin Microbiol Infect 2013;19:1169-72.Bing G. JAC 2013;68:4-11.
Long-Term Safety and Expanded
Clinical Outcomes Data
“… I will not make age an issue of this campaign clinical debate. I am not going to exploit, for political time purposes, my opponent’s the youth and inexperience of the new gram positive agents.”
• Black Box Warning▫ Nephrotoxicity, especially with preexisting disease▫ Increased mortality for CrCl < 50 ml/min▫ Use in pregnancy only if potential benefit outweighs
risk • Precautions
▫ QTc prolongation, Red-man like syndrome, cross-sensitivity with vancomycin
• Monitor ▫ CBC for improvement▫ SCr at baseline and q48-72h after initiation▫ Pregnancy test
• Can we just overcome this by giving more drug more often to hit goal troughs of 15-20 mg/L?
Deresinski S. Clin Infect Dis. 2007; 44:1543-8.
Weight-based Dosing
I said Super size them fries!
https://www.funnyjunk.com/funny_pictures/563245
Weight-based Dosing
• Loading Doses? 20mg/kg? 25-30mg/kg?
• How have you standardized maintenance doses?
• Infusion reactions
Rybak et al. Am J Health Syst Pharm. 2009; 66: 82-98.
Therapeutic Drug Monitoring
• Narrow Therapeutic Index
▫ Most patients targeted at 15-20 mg/L
⚫ Improves penetration
⚫ Increases chance of hitting AUC:MIC of 400
⚫ Improves clinical outcomes
• Nephrotoxicity
▫ Conflicting data on monotherapy
▫ More and more data with combination of piperacillin/tazobactam
Rybak et al. Am J Health Syst Pharm. 2009; 66: 82-98.
Resistance
• 13/16 peer-reviewed publications on MRSA with a higher MIC to vancomycin treated with vancomycin showed worse clinical outcomes
• Attributed to non-optimal AUC/MIC
• A 5 year study from 2000-2004 with 6,002 isolates showed S. aureus isolates with MIC of 1 to be significantly higher (70.4% vs 19.9%)
• This same study also showed a trend of higher rates of isolates with MIC > 2
1. Holland TL and Fowler VG. J Infect Dis. 2011; 204:329-331
2. Wang et al. J. Clin. Microbiol. 2006; 3883-3886.
Issues With Automated TestingInter-facility MRSA Research of
Average Vancomycin MIC
0.90
1.24 1.24
Vitek 2 Microscan Etest
N=99 Vitek 2 Microscan Etest
Mode MIC 1 1 1.5
MIC = 2 N=1 N=24 N=5
• Within our city-wide stewardship program we evaluated VancomycinMICs at two health systems
• Vitek 2 testing showed consistently lower MICs than both Microscan and Etest
• Higher rates of MIC = 2 on Microscan
Questions???
George D. Rodriguez, Pharm.D.Clinical Pharmacist, The Dr James J Rahal Jr Division of Infectious DiseasesAntimicrobial Stewardship Program ManagerNewYork-Presbyterian QueensAssistant Clinical Professor, Pharmacy SciencesColumbia University School of [email protected]@GeorgeR_IDpharm
Bruce M. Jones, Pharm.D., BCPSInfectious Disease Clinical Pharmacy SpecialistSt. Joseph's/Candler Health System, Inc.Clinical Adjunct Assistant ProfessorUniversity of Georgia College of Pharmacy5353 Reynolds StreetSavannah, GA [email protected]@Bruce_M_Jones