Page 32 - Christiana Care Health System Focus September 2018
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Pharmacy Services | Therapeutic Notes
Aminoglycoside dosing by pharmacy
   Aminoglycosides are a class of antibiotics which inhibit protein synthesis at the 30S ribosomal subunit. Through this mechanism, aminoglycosides facilitate a concentration-dependent, bactericidal effect. Aminoglycosides, which include amikacin, gentamicin, tobramycin and streptomycin, have a notable side effect profile, including nephrotoxicity and ototoxicity. Other antimicrobial agents that have a more tolerable side effect profile, do not require therapeutic monitoring and have fewer concerns with tissue penetration (for example, aminoglycosides have relatively poor lung penetration) may be preferred over aminoglycosides.
Despite these potential limitations, aminoglycosides have a very important role in the management of infections in hospitalized patients. Aminoglycosides may be used for the treatment of multi- drug resistant (MDR) Gram negative infections as well as in combination with other agents to provide empiric double coverage for Pseudomonas aeruginosa. These agents may also be applied in synergy with other active antibiotics for management of endocarditis caused by gram positive bacteria such as Enterococcus spp, Staphylococcus spp, and Streptococcus spp.
The Aminoglycoside Dosing by Pharmacy Program (AGDBP) was designed to provide a pharmacy-driven protocol for included indications when ordered by providers, similar in many ways to the current-state vancomycin dosing by pharmacy program (VDBP). This program is being implemented because aminoglycosides can be difficult to dose due to their narrow therapeutic index, and require close therapeutic monitoring to optimize efficacy and minimize the potential for toxicity. Often, an Infectious Disease provider will be involved in the management of patients in whom aminoglycosides are ordered. Notable patient populations that are excluded from the AGDBP program include:
• Cystic fibrosis.
• Pediatric/neonates (<18 years of age).
• Pregnant patients (OB patients are usually on units 3A, 3B, 3C, 4A, 4B, CLBR and are excluded; GYN patients are included).
• Surgical prophylaxis.
• Gram positive synergy – once daily dosing for Streptococcus endocarditis (3 mg/kg/daily).
Each of the dosing strategies has a specific dosing protocol and requirements for therapeutic monitoring, which will be ordered by
Stephen May, Pharm.D.; Sarah Maheady, Pharm.D.
pharmacy staff. The three general dosing strategies for AGDBP are briefly reviewed, as follows:
           1. Gonzalez L, Spencer J. Aminoglycosides: a practical review. Am Fam Physician 1998; 58(8):1811-1820.
2. Baddour LM, Wilson WR, Bayer AS et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for health- care professionals from the american heart association. Circulation 2015;132(15):1435-86.
3. Barlam TF, Cosgrove SE, Abbom LM et al. Implementing an antibiotic stewardship program: guidelines by the infectious diseases society of america and the society for health- care epidemiology of america. Clin Infect Dis 2016; 15;62(10):e51-77.
Gram Negative Infection
Type of Coverage Desired
Traditional Dosing
The IDSA Antibiotic Stewardship guideline recommends that hospitals implement pharmacokinetic monitoring and adjustment programs for aminoglycosides, and this program is a step directly towards that goal. The AGDBP program seeks to benefit patients and providers by providing pharmacy-driven optimization of aminoglycoside treatment; the program will provide patient-specific monitoring and dose adjustments to enhance antimicrobial efficacy and minimize the potential for side effects.
Nursing, prescribers, laboratory and phlebotomy have all been targeted in our educational efforts. The program has received en- dorsement from service lines as well as the P&T Committee. AGDBP requires an order from a provider in PowerChart which can be found by searching the drug they would like to use (ex. gentamicin); other key elements will be required within the order, such as indication. Guidelines are available for reference on the Antimicrobial Steward- ship section of the Pharmacy Department collaboration site, listed under Christiana Care Infectious Diseases Guidelines. 
Gram Positive Synergy Dosing
   CrCl < 20 mL/min Dialysis (HD, PD, SLED)
CrCl > 20 mL/min
 Nomogram-Extended Interval Dosing

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