Approved by: SMG Origination Date: 06/14 Expiration Date: 06/17 Review Date: Revision Date: POLICY and PROCEDURE Archived Date: Page 1 of 14

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1 POLICY and PROCEDURE Archived Date: Page 1 of 14 PURPOSE In order to provide consistent and optimal vancomycin and aminoglycoside dosing and monitoring, a pharmacokinetic (PK) service will be provided for adult patients receiving parenteral vancomycin or aminoglycosides while in the hospital. The Clinical and Patient Care Service (CPCS) division has worked in collaboration with the Antimicrobial Stewardship and Evaluation Team (ASET) and the Division of Infectious Diseases to develop the following protocol. POLICY To establish a standardized protocol for dosing and monitoring vancomycin and aminoglycosides in adult patients to optimize efficacy while reducing the potential for adverse events. Based on the following protocol, the credentialed pharmacist will be able to write orders for dosing, concentrations, and related laboratory studies as specified. Pre-admission emergency department patients and patients receiving vancomycin or aminoglycosides as part of surgical prophylaxis will not be included in this protocol. DEFINITIONS Credentialed pharmacist- a pharmacist deemed competent in performing vancomycin and aminoglycoside dosing and monitoring RESPONSIBILITY Inpatient Pharmacy Staff Medical Staff PROCEDURES I. Processing New Orders 1. A Pharmacy Consult: Vancomycin/Aminoglycoside order will be linked to the respective antibiotic and should be appropriately ordered for patients starting vancomycin or an aminoglycoside in whom therapy is planned to continue. a. The verifying pharmacist will review and verify the consult order and initiate an appropriate initial dosing regimen. i. Loading doses will be reviewed and provided within 2 hours. ii. Recommendations and orders for maintenance regimens and any related follow-up interventions will be provided by a credentialed pharmacist prior to the next dose due. b. Any order stating consult pharmacy or pharmacy to dose in regards to a PK consult for vancomycin and/or aminoglycosides will be interpreted as full dosing privileges as stated within this protocol. c. Providers will have the option to opt out of a pharmacy consult by not ordering the consult, discontinuing the consult order or notifying the pharmacist. II. Data collection/patient assessment/monitoring 1. Upon receiving a new consult, the credentialed pharmacist will thoroughly review the appropriateness of the provider-ordered indication and dose of antibiotic: a. Clinical indication (site/severity of infection) b. Age c. Sex d. Height/weight e. Renal function (including its stability) f. Estimated PK parameters (if applicable)

2 POLICY and PROCEDURE Archived Date: Page 2 of 14 g. Medication history, including time/amount of prior dose (if applicable) h. Current/last known serum drug concentration (if applicable) 2. Following the initial evaluation, the credentialed pharmacist shall continue to collect information related to the patient s vancomycin or aminoglycoside therapy. 3. The pharmacist s routine monitoring for all patients on vancomycin or an aminoglycoside (regardless of formal consult) includes evaluation of clinical status, interpretation of relevant labs, drug concentrations, changes in renal function or fluid status, microbiology results, concurrent antimicrobial therapy, and specified length of therapy. This information is recorded in a PK I-vent in Epic or on a PK monitoring worksheet. 4. The credentialed pharmacist is expected provide the dosing and/or monitoring services until the vancomycin or aminoglycoside course is completed (if an inpatient) or until discharged. III. Pharmacist Ordering 1. Doses a. Upon selecting a dosing regimen, the credentialed pharmacist will enter applicable orders. b. All orders in response to a Pharmacy Consult will be entered or discontinued per protocol no cosign required. 2. Serum Drug Concentrations a. The credentialed pharmacist will order serum drug concentrations for the consult drug as warranted, per protocol no cosign required. b. When the patient has a serum drug concentration resulted, the credentialed pharmacist will write a Pharmacy Consult note. In addition, if clinically warranted, the primary medical team will be notified of serum concentrations via page or face-to-face communication (i.e. for supratherapeutic vancomycin trough levels). 3. Labs a. The credentialed pharmacist will ensure that each patient with a consult will have relevant labs ordered (CBC, SCr, BUN). b. Any labs ordered by the credentialed pharmacist in response to a Pharmacy Consult will be entered per protocol no cosign required. IV. Chart Documentation 1. The credentialed pharmacist will provide a progress note in the patient s chart with each resulted concentration and/or subsequent dose change within 24 hrs of the concentration returning/dose change. This serves as the direct communication to the primary provider/team. Further communication, such as phone calls, pages or face-to-face communication will be dependent on the clinical situation and the pharmacist s discretion. 2. The credentialed pharmacist shall also provide PK progress notes for patients without formal consults; however, any recommended laboratory studies, dose or frequency changes must be relayed to the physician (verbally or via page) prior to any changes being made. 3. The chart note, titled Pharmacokinetic Consult drug (ex: Pharmacokinetic Consult Vancomycin) must include: a. Patient assessment (age, provider-ordered indication, day of therapy, estimated CrCl) b. Concentration and provider-ordered goal concentration (linked to indication)

3 POLICY and PROCEDURE Archived Date: Page 3 of 14 c. Dose recommendation and/or recommendation of next serum drug concentration d. Other recommendations (i.e. SCr monitoring frequency) e. Signature/name of covering pharmacist and pager number 4. Notes written by students and non-credentialed pharmacists/residents must be co-signed by a credentialed pharmacist within 24 hours. V. Competency Standard 1. Pharmacists performing PK consults must be deemed competent in this function through completion and successful passing of the pharmacokinetic training and written examination. 2. Clinical managers and/or designated clinical pharmacists shall monitor a sample of vancomycin and aminoglycoside patients periodically to assess compliance with policies and procedures and the quality of service provided. PROCEDURE FOR VANCOMYCIN I. Choose the Appropriate Method of Dosing A. Vancomycin Nomogram (Table 1): Use the nomogram to determine empiric dose and frequency. It is recommended to exclude the following patient populations from empiric nomogram dosing due to the concern for variable volume of distribution and/or drug clearance: ICU status Rapidly declining or changing renal function Pregnancy Liver failure, including ascites Weight < 50 kg or >100 kg Burns (>20%) Transplant patients acutely post-transplant (within 30 days) Cystic fibrosis B. Patient-specific Dosing: shall be considered for patients meeting the vancomycin nomogram exclusion criteria. Refer to Appendix A for estimated PK parameters and dosing regimen calculations. C. Dialysis: see Table 2 II. Initial Empiric Dosing A. Determine creatinine clearance using the normalized CrCl equation in Appendix A. B. In critically ill patients or patients with suspected severe infections, calculate a loading dose of 25 mg/kg with total body weight (TBW), up to a max single dose of 3g. C. Determine the maintenance dose with TBW, or if obese (>125% IBW), then ABW should be used. D. Doses will be rounded to the nearest 250 mg increment. III. A. Refer to Table 3 for vancomycin infusion rate recommendations. Peripheral line concentrations must not exceed 500 mg per 100 ml of compatible diluent. Central line concentrations may be up to 1000 mg in 100 ml of compatible diluent.

4 POLICY and PROCEDURE Archived Date: Page 4 of 14 B. Red man s syndrome may occur if the infusion is too rapid. It is not an allergic reaction, but may be characterized by hypotension and/or a maculopapular rash appearing on the face, neck, trunk, and/or upper extremities. If this should occur, slow the infusion rate. Reactions are often treated with antihistamines and (less frequently) steroids. IV. Therapeutic Monitoring A. Goal trough concentrations: refer to Table 4 for vancomycin goal trough recommendations. B. Clinical situations to obtain serum trough concentrations Patients likely to receive vancomycin beyond 72 hours Patients with rapidly changing renal function Concomitant administration of nephrotoxic medication (i.e. aminoglycosides, amphotericin B, IV contrast dye, vasopressors, ACE inhibitors, loop diuretics, NSAIDS, etc.) Patients requiring higher than usual doses of vancomycin (>40 mg/kg/day) Altered volume of distribution (i.e. morbidly obese) C. Timing of serum trough concentrations: Refer to Table 5. D. Frequency of trough concentrations: If patient has achieved a goal trough concentration at steady state and renal function is stable, vancomycin concentrations will be ordered at least weekly and renal function labs will be ordered at a minimum of every 3 days. If renal function is unstable, consider checking trough every 3 rd day In circumstances of acute renal failure or concern for subtherapeutic/supratherapeutic regimen, random concentrations may be utilized to determine the vancomycin concentration at which point to re-dose. E. Vancomycin peak concentrations are not routinely recommended. V. Vancomycin Dosing Adjustments A. Before adjusting doses, verify that the vancomycin concentration was drawn appropriately and that recent doses have not been missed. B. Refer to Appendix A for vancomycin adjustment calculations. C. Refer to Table 6 for IHD dosage adjustments Extrapolate post-hd trough by assuming 40-50% drug removal during a 4-hour dialysis session (high-flux dialysis).

5 POLICY and PROCEDURE Archived Date: Page 5 of 14 PROCEDURE FOR AMINOGLYCOSIDES I. Choose the Appropriate Method of Dosing A. High-dose Extended-Interval Therapy Aminoglycosides are concentration-dependent antibiotics, meaning that as aminoglycoside concentration increases, the rate and extent of bacterial killing increases. Optimum bactericidal activity for the aminoglycosides is achieved when the exposure concentration is approximately 8 to 10 times the MIC. B. Traditional Dosing Traditional dosing includes reduced doses and frequent administration of aminoglycosides using PK parameters to determine dose and frequency to achieve target peak values C. Gram-positive Synergy Dosing Synergy dosing is a low dose of aminoglycoside in conjunction with an antimicrobial agent that exhibits activity against the cell wall of the Gram-positive bacteria (i.e. betalactams) for the treatment of Gram-positive infections. Refer to Table 7 to determine method of dosing. Extended-interval dosing can be utilized under the discretion of the credentialed pharmacist and primary team. II. Initial Empiric Dosing A. Determine creatinine clearance using the normalized CrCl equation in Appendix A. B. Calculate the correct dosing weight (DW) based on Table 8. C. Refer to Tables 9 11 for loading dose and maintenance dose recommendations. D. Gentamicin and tobramycin doses will be rounded to the nearest 20 mg for doses >40 mg. Amikacin doses will be rounded to the nearest 50 mg. III. Therapeutic Monitoring A. Goal peak and trough concentrations: Refer to Table 12 B. Timing of concentrations: Extended-interval dosing: single concentration drawn 6-14 hours after the FIRST dose (see Hartford Nomogram in Appendix C) Traditional and Synergy dosing: refer to Table 13. C. Frequency of concentrations: Maintenance concentrations should be monitored at least once weekly, and considered at least every 3 rd day in patients demonstrating acute changes in renal function, fluid status, etc. D. Laboratory monitoring: SCr and BUN should be measured at baseline and at least 2x weekly IV. Aminoglycoside Dosing Adjustments A. Before adjusting doses, verify that the aminoglycoside concentrations were drawn appropriately and that recent doses have not been missed. B. Refer to Appendix A aminoglycoside adjustment calculations.

6 POLICY and PROCEDURE Archived Date: Page 6 of 14 REFERENCES 1. Bates RD, et al. Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis. Chest.1997; 112: Del Priore et al. A comparison of once-daily and 8-hour gentamicin dosing in the treatment of postpartum endometritis. Obstet Gynecol. 1996;87: Gilbert DN and Leggett JE. Aminoglycosides. Principles and Practice of Infectious Diseases, 7 th ed, Mandell GL, Bennett JE, Dolin R (Eds), Churchill Livingstone, New York pp Hazelwood KA et al. Vancomycin-associated nephrotoxicity: grave concern or death by character assassination? Am J Med. 2010; 23: Livingston et al. Gentamicin and clindamycin therapy in postpartum endometritis: the efficacy of daily dosing versus dosing every 8 hours. Am J Obstet Gynecol. 2003; 188: Lodise TP, et al. Larger vancomycin doses ( 4 grams/day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother. 2008; 52: Lomaestro BM. Vancomycin dosing and monitoring 2 years after the guidelines. Expert Rev Anti Infect Ther. 2011; 9: Mavros MN et al. Once versus multiple daily dosing of aminoglycosides for patients with febrile neutropenia: a systematic review and meta-analysis. J Antimicrob Chemother. 2011; 66: Nicolau DP, et al. Experience with once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents and Chemother.1995; 39: Pai AB and Pai MP. Vancomycin dosing in high-flux hemodialysis: a limited-sampling algorithm. Am J Health-Syst Pharm. 2004: 61: Rybak M, 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: Smyth A, et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis the TOPIC study: a randomized controlled trial. Lancet.2005; 365: Sorger JI, et al. Once daily versus divided, low dose gentamicin for open fractures. Clin Orthop Relat Res 1999; 366: Vandecasteele SJ and Vriese AS. Vancomycin dosing in patients on intermittent hemodialysis. Semin Dial. 2011; 24: Zelenitsky SA, et al. Initial vancomycin dosing protocol to achieve therapeutic serum concentrations in patients undergoing hemodialysis. Clin Infect Dis.2012; 55:

7 POLICY and PROCEDURE Archived Date: Page 7 of 14 APPENDICES Appendix A: Equations Ideal Body Weight Adjusted Body Weight Creatinine Clearance Vancomycin Males: IBW (kg) = (# inches over 5 feet) Females: IBW (kg) = (# inches over 5 feet) ABW = IBW + 0.4(TBW-LBW) CrCl (ml/min) = 140-age (x 0.85 if female) SCr ** Situations when SCr may not be predictive of CrCl: malnutrition/cachexia, liver disease, paralysis, bed-ridden, tacrolimus/cyclosporine, hypervolemia. Age >70 may consider correcting SCr to 1.0. k e k e = (CrCl) t ½ t ½ = 0.693/ke V d V d = 0.7 L/kg Dosing Interval (T) Dose (Xo) Estimated Cmax & Cmin T = ln {Cmax(desired) k e Cmin(desired)} + t' Xo = (Ke)(t')(Vd){Cmax (desired)} ( 1 - e -ke T ) ( 1 - e -ke t' ) Cmax = Xo ( 1 - e -ke t' ) (t )(ke)(vd) ( 1 - e -ke T ) t' = infusion time Cmin = Cmax {e -ke (T - t' ) } Single-Point Estimate for k e (for trough estimate) k e = -ln { [(Cp)(Vd)] [1+ (Cp)(Vd)]} Xo Xo _ T Aminoglycosides k e k e = (CrCl) t ½ V d t ½ = 0.693/ke V d = 0.33 L/kg (dosing weight) T = ln {Cmax(desired) Dosing Interval (T) k e Cmin(desired)} + t' t' = infusion time Dose (Xo) Estimated Cmax & Cmin Xo = (Ke)(t')(Vd){Cmax(desired)} (1 - e -ke T ) Cmax = Xo ( 1 - e -ke t' ) (t )(ke)(vd) ( 1 - e -ke T ) (1 - e -ke t' ) Cmin = Cmax {e -ke (T - t' ) }

8 POLICY and PROCEDURE Archived Date: Page 8 of 14 Appendix B: Vancomycin Table 1: DUH Initial Empiric Vancomycin Nomogram based on Target Trough, Weight and Renal Function MAINTENANCE DOSE: based on estimated creatinine clearance, weight and target trough (see below)* TARGET TROUGH MCG/ML Weight (actual) 50-59kg 60-69kg 70-79kg 80-89kg 90-99kg 100kg Creatinine clearance (ml/min)** < 10 repeat dose when spot serum concentration < 20 mcg/ml) mg q48h 1000mg q48h 1000mg q48h 1250mg q48h 1250mg q48h 1500mg q48h mg q24h 750mg q24h 1000mg q36h 1250mg q36h 1250mg q36h 1250mg q36h mg q24h 750mg q24h 1000mg q24h 1250mg q24h 1250mg q24h 1250mg q24h mg q18h 750mg q18h 1000 mg q18h 1250mg q18h 1250mg q18h 1250mg q18h mg q18h 1000mg q18h 1000mg q18h 1250mg q18h 1250mg q18h 1500mg q18h mg q12h 750mg q12h 1000mg q12h 1000mg q12h 1250mg q12h 1250mg q12h mg q12h 1000mg q12h 1000mg q12h 1250mg q12h 1250mg q12h 1500mg q12h mg q12h 1000mg q12h 1250mg q12h 1250mg q12h 1500mg q12h 1500mg q12h mg q12h 1000mg q12h 1250mg q12h 1500mg q12h 1500mg q12h 1500mg q12h >= mg q8h 750mg q8h 1000mg q8h 1000mg q8h 1250mg q8h 1250mg q8h TARGET TROUGH MCG/ML 50-59kg 60-69kg 70-79kg 80-89kg 90-99kg 100kg <10ml/min repeat dose when spot serum concentration < 15 mcg/ml mg q72h 1250mg q72h 1250mg q72h 1500mg q72h 1500mg q72h 1750mg q72h mg q48h 1000mg q48h 1250mg q48h 1500mg q48h 1500mg q48h 1750mg q48h mg q36h 1000mg q36h 1250mg q36h 1500mg q36h 1500mg q36h 1750mg q36h mg q24h 1000mg q24h 1250mg q24h 1250mg q24h 1500mg q24h 1500mg q24h mg q24h 1250mg q24h 1250mg q24h 1500mg q24h 1500mg q24h 1750mg q24h mg q18h 1250mg q18h 1250mg q18h 1500mg q18h 1500mg q18h 1750mg q18h mg q18h 1250mg q18h 1250mg q18h 1500mg q18h 1500mg q18h 1750mg q18h mg q18h 1250mg q18h 1250mg q12h 1250mg q12h 1500mg q12h 1500mg q12h mg q12h 1000mg q12h 1250mg q12h 1500mg q12h 1500mg q12h 1500mg q12h >= mg q12h 1000mg q12h 1250mg q12h 1500mg q12h 1500mg q12h 1500mg q12h * Individualize dose and interval based on serum concentration monitoring (when indicated) **CrCl estimated using CrCl equation in Appendix A

9 POLICY and PROCEDURE Archived Date: Page 9 of 14 Table 2: Vancomycin Dosing in Patients Undergoing Dialysis Type of Dialysis Empiric Dose CRRT 15 mg/kg q24h IHD Following a loading dose, give 10 mg/kg. This dose is administered during each dialysis treatment in the last 1-2 hours of the session. PD For most indications, vancomycin should be administered intravenously. Following an IV loading dose of 25mg/kg, intermittent IV doses of 15 mg/kg x 1 should be given based on goal trough concentrations (see Table 5). For peritonitis in a peritoneal dialysis patient only, intraperitoneal administration is the preferred route. Confirm whether any IV doses have been administered before deciding upon a loading dose. For use with Automated Peritoneal Dialysis (cycler): Loading dose of 30 mg/kg IP in a long dwell (6 hours). Maintenance dose 15 mg/kg IP in a long dwell. Goal is serum trough concentrations >15 mcg/ml. For use with Continuous Ambulatory Peritoneal Dialysis (manual exchanges): Treatment path 1(intermittent dosing): Loading dose of 30 mg/kg IP once administered in a dwell, maintenance doses of 15 mg/kg IP once administered in a dwell when serum concentrations </=15 mcg/ml Treatment path 2(continuous dosing): Loading dose of 1 gram per liter of dialysate administered IP once in a dwell. Maintenance dose of 25 mg per liter of dialysate administered IP in every exchange. *NOTE: dosing for this treatment path is not based on body weight* Table 3: Vancomycin Infusion Rates Vancomycin Dose Infusion Rate 750 mg 45 min 1,000 mg 60 min 1,250 mg 90 min 1,500 mg 105 min 1,750 mg 120 min 2,000 mg 3,000 mg 240 min

10 POLICY and PROCEDURE Archived Date: Page 10 of 14 Table 4: Vancomycin Goal Trough Concentration Based on Indication Indication Target Trough Concentrations (mcg/ml) Bacteremia (uncomplicated), culture-negative pneumonia, culture-negative line infection, skin and soft tissue (excluding necrotizing fasciitis or other severe cases), febrile neutropenia, urinary tract infections Bacteremia (complicated and/or Staph aureus bacteremia), endocarditis, culture-positive pneumonia, osteomyelitis, sepsis (empiric), severe SSTI Meningitis Table 5: Timing of Vancomycin Concentrations CrCl (ml/min) What is considered an appropriately drawn concentration >50 Trough immediately prior to at least 4 th dose Trough immediately prior to at least 3 rd dose* <30 Trough immediately prior to at least 2 rd dose* CRRT IHD Trough immediately prior to the 3 rd dose* Trough immediately prior to the 3 rd IHD session. If the patient is being dialyzed intermittently and dialysis treatments are not performed for >48hours, a random level may be required between treatments to ensure adequate serum concentrations. Re-dose for trough levels < 15 mcg/ml or based on indication. PD Random concentration 48 hours after the dose Using the lab draw times and dosing administration time in Epic, verify that the concentration was in fact appropriately obtained in relation to the dose as stated above. *Note that trough levels are not at steady state, and further accumulation may occur Table 6: Dosage Adjustments for Patients on IHD Pre-dialysis vancomycin concentration Dosage adjustment (mcg/ml) <15 dose by mg No change in current therapy dose by mg >35 HOLD vancomycin dose The following recommendations assume that the patient is receiving high-flux IHD three times weekly.

11 POLICY and PROCEDURE Archived Date: Page 11 of 14 Appendix C: Aminoglycosides Table 7: Choosing Appropriate Method of Dosing Traditional Bone and joint infection Endocarditis Gram-positive infection (synergy) Septic shock Indications Skin/soft tissue infection Urinary tract infection When extended interval is contraindicated Contraindications IHD, CRRT Peritoneal dialysis (see PD recommendations below) Use traditional dosing For peritonitis in a peritoneal dialysis patient only, intraperitoneal administration is the preferred route. Confirm whether any IV doses have been administered before deciding upon a loading dose. Extended Interval Cystic fibrosis Febrile neutropenia GNR bacteremia Open fracture infection GNR Pneumonia Postpartum endometritis Morbid obesity CrCl < 30 ml/min or rapidly declining renal function Pregnancy Ascites Burns (>20%) Extended interval dosing contraindicated PD For use with Automated Peritoneal Dialysis (cycler): Tobramycin loading dose of 1.5 mg/kg IP in a long dwell (6 hours). Maintenance dose 0.5 mg/kg IP in a long dwell. For use with Continuous Ambulatory Peritoneal Dialysis (manual exchanges): Treatment path 1(Intermittent dosing with gentamicin or tobramycin): no loading dose. Maintenance doses of 0.6 mg/kg IP once administered in a dwell Treatment path 2(continuous dosing with gentamicin or tobramycin): Loading dose of 8 mg per liter of dialysate administered IP once in a dwell. Maintenance dose of 4 mg per liter of dialysate administered IP in every exchange. *NOTE: dosing for this treatment path is not based on body weight* Extended interval dosing contraindicated

12 POLICY and PROCEDURE Archived Date: Page 12 of 14 Table 8: Determination of Dosing Weight for Aminoglycosides Definition Use this Dosing Weight (DW) Underweight TBW < IBW TBW Normal Weight TBW = % IBW IBW Obese TBW > 125% IBW ABW Table 9: Loading dose for Traditional Aminoglycoside Dosing Indication Gentamicin/Tobramycin Amikacin Gram-positive infection synergy Urinary tract infection 1 mg/kg 5 mg/kg Bone/joint infection, cystic fibrosis, febrile neutropenia, GNR bacteremia, GNR pneumonia, septic shock Skin/soft tissue infection mg/kg mg/kg Table 10: Empiric Gentamicin and Tobramycin Maintenance Dose CrCL (ml/min) Extended Interval* Traditional > 60 7 mg/kg Q24H Gram-Positive Synergy 1 mg/kg Q8H mg/kg Q36H 1 mg/kg Q12H mg/kg Q48H Load, then refer to Appendix A for individualized PK calculations 1 mg/kg Q24H Not recommended 1 mg/kg Q24H < 20 Not recommended Hemodialysis Not recommended Load, then 1.5 mg/kg post- HD (moderate infection) Load, then dose by concentration (severe GNR infection) Load, then dose by concentration Load, then 1 mg/kg post-hd CRRT Not recommended mg/kg Q24-48H 1 mg/kg Q24H *Lower extended interval doses including 3 mg/kg for endocarditis synergy and 5 mg/kg for postpartum endometritis or open fracture infections may be utilized; however, plotting concentrations on the Hartford Nomogram based on these regimens on the will not provide accurate drug clearance estimates.

13 POLICY and PROCEDURE Archived Date: Page 13 of 14 Table 11: Empiric Amikacin Maintenance Dose CrCL (ml/min) Extended Interval Traditional > mg/kg Q24H mg/kg Q36H mg/kg Q48H Load, then refer to Appendix A for individualized PK calculations Not recommended < 20 Not recommended Load, then dose by concentration Hemodialysis Not recommended Load, then mg/kg post-hd (adjust by concentration if needed for severe GNR infection) CRRT Not recommended Load, then 7.5 mg/kg Q24-48H Table 12: Peak and Trough Concentration Goals for Traditional Aminoglycoside Therapy Gentamicin/Tobramycin Amikacin Indication Peak (mcg/ml) Trough (mcg/ml) Peak (mcg/ml) Trough (mcg/ml) Uncomplicated UTI, synergy in GP 3 5 <1 < 5 infections GN sepsis, other 8 10 serious GN (10 13 for cystic < infections including fibrosis) pneumonia Table 13: Timing of Concentrations Traditional and Gram-Positive Synergy PEAK TROUGH Q8H Q12H Q24H Hemodialysis CRRT 30 min after 4 th dose* min before 4 th dose 30 min after 4 th dose* min before 4 rth dose 30 min after 3 rd dose* min before 3 rd dose 2 hrs after 2 nd dose Target peak Cp post HD ~ 8 mg/l (6-10 mg/l) ~ 3-5 mg/l (synergy) Immediately before HD; Re-dose for pre-hd: Cp <1 mg/l (mild UTI and synergy) Cp <2-3 mg/l (moderate-severe UTI) Cp <3-5 mg/l (severe GNR infection) *Peaks are drawn min after the end of the infusion; Cp = concentration in plasma 30 min after 3 rd dose* min before 3 rd dose

14 POLICY and PROCEDURE Archived Date: Page 14 of 14 Hartford Hospital Nomogram (Extended Interval Therapy) Gentamicin/tobramycin (7 mg/kg/dose): Plot concentration on graph Amikacin (15 mg/kg/dose): divide concentration in half, then plot on graph Plotting doses lower or higher than 7mg/kg may under or overestimate clearance. May 2014 Prepared by: Christina Sarubbi, PharmD Reviewed by: Richard Drew, PharmD, MS; Justin Geurink, PharmD; Jennifer Gommer, PharmD; Tim Lassiter, PharmD, MBA; Bo Latour, PharmD; Aaron Will, PharmD Members of Evaluation Team: Deverick Anderson, MD, Christina Sarubbi, PharmD, Michelle Sharp, PharmD, David Warner, PharmD, Lisa Bendz, PharmD, Tara Bell, PharmD, John Boreyko, PharmD, Richard Drew, PharmD, Melissa Johnson, PharmD, Joanne Latour, PharmD, Crystal Hahn, PharmD, Luke Chen, MD, Coleen Cunningham, MD, John Engemann, MD, Richard Frothingham, MD, Edward Hendershot, MD, Paul Lantos, MD, Charles Livengood III, MD, Rebekah Moehring, MD, Tereza Martinu MD, John Perfect MD, Kevin Hazen, PhD, Justin Spivey, PharmD, Rachel Rogers, PharmD, Michael Durkin, MD, Kristen Dicks, MD, Arthur Baker, MD, Sarah Lewis, MD