Utility Assessment of a Pharmacy-to-Dose Daptomycin Protocol: A Retrospective Cohort Study

A pharmacy-to-dose (PTD) service, also referred to as pharmacy-based dosing, describes an established practice where providers can consult pharmacists for the dosing of various medications. Consulted pharmacists develop a treatment regimen utilizing protocols that are evaluated and approved by the relevant multidisciplinary committees of an institution. The Institute for Healthcare Improvement (IHI) recommends implementing pharmacy-based dosing to improve core processes for ordering medications.

Consults for PTD services that require a provider to enter the desired medication and indication have been evaluated in prior studies. This type of consultation requires a clinical or staff pharmacist to implement a patient-specific dosing regimen in addition to ordering of pertinent labs for therapeutic monitoring. Literature on PTD is most prominent regarding pharmacist led services for the dosing and monitoring of vancomycin and aminoglycosides. This is expected because appropriate use of both vancomycin and aminoglycosides relies on ordering and assessment of pharmacokinetic (PK) measurements. As new recommendations for vancomycin dosing and monitoring evolve in complexity, these services are becoming even more valuable. Hospitals with pharmacist-managed vancomycin and aminoglycoside therapy have shown lower drug costs, hearing and renal impairment, and death rates in Medicare patients compared to hospitals without these services.

Other medications that either require renal adjustments, have a narrow therapeutic index, include a wide range of dosing for various indications, or require careful consideration of patient-specific factors are excellent candidates for expanded PTD services. Pharmacists serve as institutions' medication experts and are equipped with knowledge and references needed to apply patient specific characteristics to the selection of a dosing regimen. Medications that require monitoring for the prevention of adverse effects or changes in dosing, often due to the dynamic nature of hospitalized patients' renal function, sometimes go unaddressed. Delegating tasks of therapy monitoring and dose selection to pharmacists resolves providers from this burden and ensures necessary changes are not unnoticed. Daptomycin was a medication that our facility included in PTD because of the required adjustments for renal dysfunction, indication dependent dosing, and its impact on clinical outcomes.

Daptomycin is a cyclic lipopeptide antibiotic that exhibits rapid bactericidal activity against Gram-positive organisms, including various drug resistant isolates of Enterococcus and Staphylococcus. The mechanism does not involve entrance into the bacterial cytoplasm but rather the dissipation of the membrane potential, which occurs through permeable oligomeric lesions in a calcium-dependent fashion. Peak concentration (Cmax)/minimum inhibitory concentration (MIC) and area under the curve (AUC24h)/MIC ratios have been shown in vivo to correlate best with efficacy. Doses of 4 and 6 mg/kg/dose are Food and Drug Administration (FDA)-approved to treat complicated skin and skin structure infections and S. aureus bloodstream infections including right-sided infective endocarditis, respectively. The MICs of daptomycin for Gram-positive cocci differ. Enterococcus faecalis is marked susceptible with MICs ≤ 2 µg/mL; however, strains of Enterococcus faecium display intrinsically higher MICs, and dose-dependent susceptibility based on treatment doses of 8-12 mg/kg/day.

In 2019, our institution approved a PTD daptomycin protocol which allowed pharmacists to select a dose based on provider-selected indications, patient renal function, and body mass index. Pharmacists were also authorized to order creatine phosphokinase (CPK) levels at baseline and every 7 days, if the patient remained on daptomycin. Rounding the dose to the nearest 50 mg or vial size, as deemed appropriate, was also allowed. Daptomycin was one antimicrobial to be added to our growing list of PTD-approved medications. As such, pharmacists were already well acclimated to PTD processes by the time daptomycin was approved for this service.