1. Background  Obesity is defined as a body mass index (BMI) ≥30 kg/m 2  33 states have a prevalence of obesity 25% or greater  Evidence illustrates that obese and morbidly obese patients with infection have worse outcomes 2 Percent of Population with BMI≥30 Physiological Differences in Obesity  As body mass increases, blood volume can be approximately twice the volume of ideal body weight 3,4,5  Increased size of internal organs, including the kidneys 3,5  As body mass increases the amount of protein available to bind drugs increases 5 Vancomycin Pharmacokinetics in Obesity  V d of vancomycin variably increases in obese patients 3,4,5  Bauer, et al. showed a better correlation of V d and CrCl with actual body weight (ABW) in comparison to IBW 6  In comparison to non-obese patients, the half life of vancomycin in the obese decreased from 7.2 hr to 3.3 hr 5,7  Based on conventional non-obese dosing, Hall, et al. found that 1 gram twice a day provided 99% of non-obese patients with a successful 10 mg/kg dose in comparison to only 27% of obese patients being successful 8  Sub-therapeutic vancomycin levels less than 10 mcg.ml may contribute to increasing intermediate and resistant strains causing MIC creep to occur, ultimately leading to increased failure rates 9 Objectives Primary Objective:  To prospectively evaluate obese patient kinetics with the goal of describing optimal dosing strategies in this population Secondary Objective:  Evaluate the utility of obtaining peak and trough vancomycin serum concentrations Primary endpoints:  The number of patients achieving therapeutic vancomycin levels per indication Secondary endpoints:  Compare obese population kinetics to patient specific kinetics, evaluation of dose (mg/kg) needed to achieve goal level, comparison of each BMI class, number of patients achieving an AUC/MIC ratio of > 400, clearance of cultures, resolution of WBC count, resolution of fever, and length of stay. Study Protocol  Clinical pharmacists will monitor and assess vancomycin therapy  Pharmacokinetic (PK) pharmacy consult will be offered using ABW and patient’s current estimated renal function  Vancomycin PK consult will include:  Recommendations for initial dosing  Recommended times for peaks and troughs  Adjusted dosing strategies if necessary based on patient- specific PK calculations and measured serum levels References 1.Centers for Disease Control and Prevention Website. Atlanta: Department of Health and Human Services (Accessed on 2010 August 31) http://www.cdc.gov/obesity/data/trends.html#Statehttp://www.cdc.gov/obesity/data/trends.html#State 2.Falaga ME, Athanasoulia AP, Peppas G, Karageorgopoulos DE. Effect of body mass index on the outcome of infections: a systematic review. Obesity Reviews. 2009; 10: 280-289. 3.Blouin R, Bauer L, Miller D, Record K, Griffen W. Antimicrobial Agents and Chemotherapy. April, 1982; 21(4): p. 575 – 580. 4.Bearden D, Rodvold K. Dosage Adjustments for Antibacterials in Obese Patients. Clinical Pharmacology. May 2000; 38(5): p. 415-426. 5.Pai M, Bearden D. Antimicrobial Dosing Considerations in Obese Adult Patients. Pharmacotherapy. 2007; 27(8): p.1081-1091. 6.Bauer L, Black D, Lill J. Vancomycin Dosing in Morbidly Obese Patients. European Journal of Clinical Pharmacology. 1998; 54: p.621- 625. 7.Capitano B, Frye RF, Matzke GR. Vancomycin. In: Clinical Pharmacokinetics. 4th edition. Bethesda: ASHP; 2008. p. 329-340. 8.Hall R, Payne K, Bain A, Rahman A, Nguyen S, et al. Multicenter Evaluation of Vancomycin Dosing – Emphasis on Obesity. American Journal of Medicine. June 2008; 121(6): 515–518. 9.Rybak M, Lomaestro B, Rotschafer J, Moellering R, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Disease Society of America, and the Society of Infectious Diseases Pharmacists. AJHP. 2009; 66:82-98. Disclosure Panel Authors of this presentation have the following to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation: None of the Authors of this presentatnion have anything to disclose Methods  This is a single center, prospective, observational study with a completed retrospective cohort for comparison Vancomycin dosing in the obese population: Comparing outcomes of a prospective pharmacokinetic monitoring program in a community hospital Brittany J. Autry, Pharm.D. 1,2 C. Adrian Bodet MD 1, Rakhi Karwa Pharm.D., BCPS 2, Allison M. Chung, Pharm.D., BCPS 2, Charles E. DuRant, Pharm.D. 1, Bradley M. Wright, Pharm.D., BCPS 2 Mobile Infirmary Medical Center 1 / Auburn University Harrison School of Pharmacy 2 Preliminary Results Patient Demographics Primary Endpoint Retrospective Results & Conclusions  Fifty-five percent of patients had a recorded trough <10 mcg/ml  Only 44.9% and 62.5% of patients achieved a desired trough of ≥10 mcg/ml before and after dose adjustments, respectively  Nineteen patients had a documented indication for a serum trough concentration of 15-20 mcg/ml, but only 2 of these patients achieved that goal  Seventy percent of patients received an initial dose of 1g every 12 hours  None of the patients received the recommended dose of ≥15 mg/kg/dose  The obese population could benefit from dose adjustments based on patient specific pharmacokinetics calculated from steady state peak and trough vancomycin serum concentration levels Prospective Preliminary Conclusions  More patients have achieved goal trough levels compared to outcomes observed in the retrospective study  Obtaining peak levels and calculating patient specific kinetics in this population has been efficacious  More data is needed to achieve the objectives of this study N=13Mean (Range) Age (yrs)56.8 (32-82) Weight (kg)112.4 (89.2-152.1) BMI (kg/m 2 )39.6 (30-61.3) Est. CrCl (ml/min) 75.7 (24-159) IndicationGoal Trough (mcg/ml) % Achieved Empiric10-15100 (1/1) Cellulitis/ abscess 10-1577 (7/9) Spinal meningitis 15-20100 (1/1) Pneumonia15-20100 (1/1) UTI10-15100 (1/1) Trough mcg/ml Initial Dosing Regimen Initial and Adjusted Troughs Did the patient receive Vancomycin? Did the patient have BMI>30mg/kg 2 or weigh at least 110kg? Was the patient on surgical service or pregnant? Exclude patient Was the patient receiving dialysis? Did the patient achieve steady state level by termination of study? = Exclude patient Patient Included NO YES List of patients receiving vancomycin printed daily. Did the patient have BMI ≥30mg/kg 2 or weight >110 kg w/o height Was the patient on surgical service or pregnant? Exclude patient Was the patient receiving dialysis? Did the patient consent to be included in the study? Exclude patient Patient Included NO YES 8%