A-3559. Relationship Between Vancomycin (V) Area Under the Concentration-Time Curve (AUC0-24hr) and Nephrotoxicity (N)
Session: Slide Session: Human Pharmacodynamics of Effect and Toxicity
Monday, October 27, 2008: 12:00 AM
Room: Constitution B (Grand Hyatt)
Background: Data suggest that higher V doses increase N. No study has examined the con-time profile of V in pts to solidify the linkage between V exposure & N. This study examined relationship between V AUC0-24h & incidence of N in infected pts. Methods: Study period: 1/05-1/06. Inclusion criteria: 1) ≥ 18 yrs, 2) non-neutropenic, 3) V for > 48 h, 4) ≥ 1 V level, 5) baseline Scr <2 mg/dL, 6) non-cystic fibrosis pts, 7) no IV contrast dye within 7 d, & 8) no vasopressors at start of V. Demographics, co-morbidities, and tx data were collected. N was defined as an increase in Scr of 0.5mg/dl or 50%, whichever was greater, post V initiation. V PK parameters were estimated by the MAP Bayesian procedure in ADAPT II. After the Bayesian step, the estimated V SCL was use to calculate AUC0-24h (mg*h/L) for each pt. Logistic regression (LR) was used to establish the relationship between V AUC0-24h and N. CART was used to identify the range of V AUCs associated with an increased probability of N. Results: 182 pts met the study criteria. After the Bayesian step, the estimated mean (SD) values for CLslope and CLintercept were: 0.03 (0.02) L*min/h*ml and 0.34 (0.22) L/hr, respectively. In LR, a significant relationship (p = 0.02) between V AUC0-24h and N was observed (figure). In CART, AUC0-24hr > 2260 was associated with N incidence 53.4%. Conclusions: A significant relationship between V AUC and N was observed.
George Drusano, MD, Ordway Research Inst, Albany, NY, Nimish Patel, PharmD, Albany College of Pharmacy and Health Sciences, Albany, NY, Thomas Lodise, PharmD, Albany College of Pharmacy, Albany, NY and  T. P. Lodise,
Cubist Role(s): Consultant, Grant Investigator, Speaker's Bureau, Consultant, Grant Investigator, Speaker's Bureau, Consultant, Grant Investigator, Speaker's Bureau, Consultant, Grant Investigator, Speaker's Bureau, Received: Research Grant, Speaker Honorarium, Consulting Fee.
Pfizer Role(s): Grant Investigator, Speaker's Bureau, Grant Investigator, Speaker's Bureau, Grant Investigator, Speaker's Bureau, Grant Investigator, Speaker's Bureau, Received: Research Grant, Speaker Honorarium, Consulting Fee.
Astra-Zeneca Role(s): Speaker's Bureau, Speaker's Bureau, Speaker's Bureau, Speaker's Bureau, Received: Speaker Honorarium.
Ortho-McNeil Role(s): Consultant, Consultant, Consultant, Consultant, Received: Consulting Fee.
Taganta Role(s): Consultant, Consultant, Consultant, Consultant, Received: Consulting Fee.

Nimish Patel completed a Doctor of Pharmacy degree at the Albany College of Pharmacy in 2006. Dr. Patel completed a specialty pharmacy residency in HIV pharmacotherapy in a joint-affiliated position between the University of Toronto/University Health Network - Toronto General Hospital Immunodeficiency Clinic and McGill University Health Center - L’Institut Thoracique de Montreal. Dr. Patel returned the Albany College of Pharmacy in 2007 to pursue fellowship training in infectious diseases outcomes research. Concurrent to his fellowship training, Dr. Patel is pursuing a Masters of Science in Epidemiology at the State University of New York at Albany - School of Public Health. Dr. Patel’s current research focus examines the predictors and outcomes of multi-drug resistant microbial infections, pharmacoepidemiologic outcomes of novel anti-microbial agents and advanced antimicrobial pharmacokinetic modeling.

Nimish Patel completed a Doctor of Pharmacy degree at the Albany College of Pharmacy in 2006. Dr. Patel completed a specialty pharmacy residency in HIV pharmacotherapy in a joint-affiliated position between the University of Toronto/University Health Network - Toronto General Hospital Immunodeficiency Clinic and McGill University Health Center - LíInstitut Thoracique de Montreal. Dr. Patel returned the Albany College of Pharmacy in 2007 to pursue fellowship training in infectious diseases outcomes research. Concurrent to his fellowship training, Dr. Patel is pursuing a Masters of Science in Epidemiology at the State University of New York at Albany - School of Public Health. Dr. Patelís current research focus examines the predictors and outcomes of multi-drug resistant microbial infections, pharmacoepidemiologic outcomes of novel anti-microbial agents and advanced antimicrobial pharmacokinetic modeling.

Dr. Thomas Lodise is an Associate Professor at Albany College of Pharmacy, Albany, New York. Dr. Lodise, a 1999 Summa Cum Laude Doctor of Pharmacy graduate of Temple University School of Pharmacy, joined the faculty at Albany College of Pharmacy in August 2002. Prior to Albany College of Pharmacy, he completed the APhA-ASHP accredited Pharmacy Practice Residency at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania in 2000 and the Infectious Diseases Pharmacotherapy and Outcomes Fellowship at Wayne State University, Detroit, Michigan in 2002.
Integrating his dual interests in research and patient care, his current research focuses on the epidemiology and outcomes of bacterial infections, and his work explores the antibiotic exposure-response relationship among patients. His specific objectives are threefold: develop patient care strategies and antibiotic regimens that improve outcomes, reduce the likelihood of toxicity, and minimize the emergence of antibiotic resistance.
Dr. Lodise is currently implementing epidemiologic and outcomes research proposals at both the Albany Medical Center and Stratton VA Medical Center. He also collaborates extensively with the Ordway Research Institute. He has received funding from both pharmaceutical industry and competitive grant sources for many of his proposals. To date, he has published over 30 peer-reviewed articles in reputable scientific journals, including Clinical Infectious Diseases, Antimicrobial Agents and Chemotherapy, Chest and Journal of Antimicrobial Chemotherapy.
His clinical practice site is the Stratton VA Medical Center, where he coordinates the antibiotic monitoring service. He is a member of the antibiotic subcommittee at the Albany Medical Center Hospital and is a Visiting Professor at Ordway Research Institute. He is also enrolled in the Ph.D. program in Epidemiology at the State University of New York School of Public Health, Albany, New York.
On a national level, Dr. Lodise is a member of the Society of Infectious Diseases Pharmacists (SIDP), the American Association of Colleges of Pharmacy (AACP) and American College of Clinical Pharmacist (ACCP). On the state level, he is president for the New York ACCP chapter. He also serves as a reviewer for numerous medical and pharmacy journals.