Evaluation of Vancomycin Continuous Infusion in Trauma Patients

Transcription

1 OBJECTIVES Evaluation of Vancomycin Continuous Infusion in Trauma Patients Brittany D. Bissell, Pharm.D. PGY-2 Critical Care Pharmacy Resident Jackson Memorial Hospital Miami, Florida Evaluate the potential disadvantages of intermittent infusion dosing of vancomycin Describe the continuous infusion vancomycin dosing protocol at Jackson Health System (JHS) Summarize post-implementation outcomes of the continuous infusion protocol BACKGROUND INTERMITTENT INFUSION (II) DOSING CHALLENGES Vancomycin is a first-line antibiotic for gram positive infections in the ICU Trough collection Underestimation of AUC Difficulty of dose adjustments Efficacy is determined by ratio of area under the curve to minimum inhibitory concentration of the target organism (AUC 24 :MIC) Guidelines recommend intermittent infusions of mg/kg every 8-12 hours Trough concentrations drawn 30 minutes prior to intermittent steady state doses 45% of institutions achieve trough collection prior to 4 th dose 50-60% of troughs underestimate the AUC Exposure to low concentrations associated with resistance Target goal trough of mg/l for most infections to target AUC 24 :MIC >40 41% of trough levels performed too early More aggressive dosing increases nephrotoxic risk Am J Health Syst Pharm. 2009;66:82 98 Pharmacotherapy. 2013;33: Am J Clin Pathol. 2012;137: Antimicrob Agents Chemother. 2014;58: VANCOMYCIN BY CONTINUOUS INFUSION (CI) BACKGROUND Increased target attainment Simplified level collection and administration Decreased adverse outcomes Definitive benefit of either dosing regimen not confirmed Recent review of 14 clinical trials found no significant improvement in clinical outcomes Decreased mortality with CI in the treatment of MRSA ventilator-assisted pneumonia Faster, more consistent target levels 50% decrease in blood samples required Lower relative risk of kidney injury In March 2013, the JHS Trauma Intensive Care Unit converted its vancomycin dosing standards Continuous infusion nomogram permitted for select patients CrCl >50mL/min Weight >50 kg Central line access Decreased variability in AUC 24 16% decrease in renal replacement therapy Prior to this nomogram, all vancomycin was dosed utilizing intermittent infusions Antimicrob Agents Chemother. 2003;47: Antimicrob Agents Chemother. 2001;45: J Crit Care. 2013;28:9 13. J Antimicrob Chemother. 2012;67: Ann Pharmacother., 2013;47: Crit Care Med. 2005;33:

2 STUDY PURPOSE METHODS To evaluate time to attainment of goal vancomycin levels, patient outcomes, and adverse events with initiation of the vancomycin continuous infusion protocol versus intermittent bolus dosing (II) Single-center retrospective chart review Trauma ICU patients receiving vancomycin Minimum duration of 48 hours July 2011 to July 2015 Study Groups Pre-Protocol (July 1 st 2011-June 30 th 2013) Post-Protocol (July 1 st 2013-June 30 th 2015) METHODS Hypothesis Continuous infusion vancomycin will achieve therapeutic goal targets of vancomycin more quickly Primary outcome Time to target level in patients receiving vancomycin Secondary outcomes Nephrotoxicity* Subtherapeutic levels Supratherapeutic levels Required dose adjustments Therapy failure Duration of therapy Average daily drug exposure Total blood samples required Intermittent dosing Incidence of MSSA/MRSA CONTINUOUS INFUSION NOMOGRAM Infusion start Rounded to nearest 250 mg 48 hour level Goal mg/l Dose adjustment Repeat level < 10 mg/l Bolus 1 gram double infusion dose 20 mg/kg bolus mg/l Bolus 1 gram increase infusion 50% mg/kg/day mg/kg/day infusion infusion mg/l Hold 6 hours decrease infusion 33% hours after dose change >35 mg/l Hold 12 hours decrease infusion 50% *Increase in SCr 0.3 mg/dl within 48 hours or 50% from baseline or urine output <0.5 ml/kg/hour for over 6 hours CONTINUOUS INFUSION PEARLS PATIENT DEMOGRAPHICS Level drawn with any 20-30% decrease in GFR or creatinine rise times baseline Rate of 21 ml/hour mandated for ease of administration No changes in drip volume permitted Central line administration preferred Peripheral line maximum concentration 5 mg/ml Maximum dose 6 grams/500 ml Male gender, n (%) 65 (86.7) 55 (73.3) 0.07 ISS, mean (SD) 37(14) 26 (14) <0.001 Age (year), mean (SD) 43 (16) 52 (18) Weight (kg), mean (SD) 87 (26) 87 (20) 0.91 BMI (kg/m 2 ), median (IQR) 27.2 ( ) 27.5 ( ) 0.38 Creatinine (mg/dl), median (IQR) 0.7 ( ) 0.81 ( ) <0.001 CrCl (ml/min), mean (SD) 174 (77) 118 (51) <0.001 ADD (mg), median (IQR) 2500 ( ) 2000 ( ) 0.14 ADD (mg/kg), median (IQR) 30 (25-32) 27.2 (20-34) 0.39 Concomitant Therapy Vasoactive agent, n (%) 11 (14.7) 20 (26.7) 0.11 Antibiotics, n (%) 74 (98.7) 73 (97.3) 1 2

3 PATIENT DEMOGRAPHICS Indication Pneumonia, n (%) 34 (45.3) 14 (18.7) Meningitis, n (%) 2 (2.7) 0 (0) 0.50 Empiric, n (%) 32 (42.7) 49 (65.3) 0.01 Bacteremia, n (%) 2 (2.7) 7 (9.3) 0.17 SSTI, n (%) 5 (6.7) 4 (5.3) 1 Abdominal, n (%) 0 (0) 1 (1.3) 1 Culture Results MRSA, n (%) 12 (16) 20 (26.7) 0.16 MSSA, n (%) 12 (16) 4 (5.3) Streptoccocus, n (%) 3 (4) 2 (2.7) Other Staphylococcus, n (%) 4 (9.3) 9 (12) Enterococcus, n (%) 3 (4) 4 (5.3) Gram negative rods, n (%) 23 (30.7) 22 (29.3) Fungal, n (%) 0 (0) 1 (1.3) Negative Culture, n (%) 15 (20) 13 (17.3) TIME TO GOAL ATTAINMENT CONTINUOUS INFUSION INTERMITTENT INFUSION days Time to Goal Duration of Therapy THERAPEUTIC OUTCOMES Dose Adjustments Adjustments, median (IQR) 0 (0-1) 0 (0-1) adjustments, n (%) 2 (2.7) 18 (24) <0.001 Missed dose, n (%) - 33 (44%) - Infusion hold, n (%) 4 (5.3) - - Vancomycin Serum Levels Goal Achievement, n (%) 45 (60) 30 (40) 0.02 Time to goal (days), mean (SD) 2.5 (1.4) 3.8 (2.7) 0.04 Levels to goal, median (IQR) 1 (1-2) 2 (1-2) 0.03 Total levels, median (IQR) 1 (1-2) 3 (1-5) <0.001 Subtherapeutic, mean (SD) 1 (1) 1 (1) 0.04 Supratherapeutic, median (IQR) 0 (0-0) 0 (0-0) <0.001 SERUM CONCENTRATIONS CONTINUOUS INFUSION INTERMITTENT INFUSION 27% 47.5% 47.5% 44% 5% 29% Subtherapeutic Supratherapeutic Therapeutic THERAPEUTIC OUTCOMES MRSA RATES DC Reason Therapy Failure, n (%) 1 (1.3) 4 (5.3) 0.37 De-escalation, n (%) 45 (60) 44 (58.7) ADE, n (%) 1 (1.3) 9 (12) 0.01 Clinical Success, n (%) 26 (34.7) 17 (22.7) Death or discharge, n (%) 2 (2.7) 1 (1.3) Clinical Endpoints Nephrotoxicity, n (%) 16 (21.3) 32 (42.7) 0.01 Mortality 7 (9.3) 13 (17.3) 0.23 Duration (days), median (IQR) 3.83 ( ) 6.8 ( ) Pneumonia Treatment Duration (days), median (IQR) 3.8 ( ) 5 (3.7-7) 0.18 ICU LOS 37 (23-73) 31 (25-64)

4 MRSA RATES CONCLUSIONS Continuous infusion resulted improved goal attainment, decreased number of blood samples required and therapy duration Limitations include lack of a weight-based dosing intermittent infusion protocol and minimal clinical pharmacy services within the TICU prior to July 2013 Continuous infusion vancomycin may be of benefit in the trauma population Further research may validate these outcomes in a broad patient group, confirm the clinical implications and cost savings Proven difficulties with intermittent infusion vancomycin include trough collection and a demonstrated underestimation of AUC. Continuous infusion vancomycin has proven to decrease risk of kidney injury as well as number of blood samples required. Intermittent dosing goal troughs of mg/l ensure an appropriate target AUC 24 :MIC >40 for all infections. REFERENCES Rybak M, Lomaestro B, Rotschafer JC et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66: Davis SL, Scheetz MH, Bosso JA, Goff DA, Rybak MA. Adherence to the 2009 consensus guidelines for vancomycin dosing and monitoring practices: a cross-sectional survey of U.S. hospitals. Pharmacotherapy. 2013;33: Morrison AP, Melanson SE, Carty MG, Bates WD, Szumita PM, Tanasijevic MJ. What proportion of vancomycin trough levels are drawn too early? Am J Clin Pathol. 2012;137: Neely MN, Youn G, Jones B, Jelliffe RW, Drusano GL, Rodvold KA, Lodise TP. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother. 2014;58: Byl B, Jacobs F, Wallemacq P et al. Vancomycin penetration of uninfected pleural fluid exudate after continuous or intermittent infusion. Antimicrob Agents Chemother. 2003;47: Wysocki M, Delatour F, Faurisson F et al. Continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother. 2001;45: Saugel B, Nowack MC, Hapfelmeier A et al. Continuous intravenous administration of vancomycin in medical intensive care unit patients. JCritCare. 2013;28:9 13. Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillos N. Continuous versus intermittent infusion of vancomycin for the treatment of gram positive infections: systemic review and meta-analysis. J Antimicrob Chemother, 2012;67: DiMondi VP, Rafferty K. Review of continuous-infusion vancomycin. Ann Pharmacother. 2013;47: Rello J, Sole-Violan J, Sa-Borges M et al. Pneumonia caused by oxacillin-resistant Staphylococcus aureus treated with glycopeptides. Crit Care Med. 2005;33:

5 Evaluation of Vancomycin Continuous Infusion in Trauma Patients Brittany D. Bissell, Pharm.D. PGY-2 Critical Care Pharmacy Resident Jackson Memorial Hospital Miami, Florida 5