Antimicrobial Stewardship Intervention and Feedback to Infectious Disease Specialists: A Case Study in High-Dose Daptomycin.

Jennifer Ross,Carla Walraven,Patricia Marshik,Renée-Claude Mercier,Meghan Brett,Shannon Rankin

doi:10.3390/antibiotics4030309

Jennifer Ross, Carla Walraven + Show 4 more

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https://doi.org/10.3390/antibiotics4030309

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Abstract

Infectious Diseases specialists have used high-dose daptomycin (≥6 mg/kg/day) in select patients with difficult to treat methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) infections to optimize outcomes. Antimicrobial stewardship programs enforce antimicrobial formulary restrictions; however, interventions specifically aimed at Infectious Disease specialists can be particularly challenging. The purpose of this study was to create a high-dose daptomycin algorithm for Infectious Disease specialists that are consistent with best-practices. Daptomycin prescribing habits pre- and post-daptomycin algorithm implementation were evaluated using a quasi-experimental study design. Patients were included if ≥18 years of age and received daptomycin for ≥48 h. Patients were excluded if daptomycin was initiated on an outpatient setting. During the 12-month pre-intervention phase, 112 patients were included, with 73 patients in the 12-month post-intervention phase. A statistically significant decrease in the mean daptomycin dose from 9.01 mg/kg to 7.51 mg/kg (p < 0.005) was observed, resulting in an annual drug cost-savings of over $75,000 without adversely affecting readmission rates due to infection. Creation of a daptomycin algorithm with consideration of pathogen, disease state, and prior treatment, is an effective means of influencing prescribing habits of Infectious Disease specialists.

Highlights

Daptomycin is a novel lipopeptide antibiotic that has activity against a variety of Gram positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), heteroresistant vancomycin-intermediate S. aureus and Enterococcus spp., including vancomycin-resistantEnterococci (VRE) [1,2]
Daptomycin is approved by the United States Food and Drug Administration (FDA) at 4 mg/kg for the treatment of complicated skin and soft tissue infections (SSTI) caused by Gram positive bacteria and 6 mg/kg for S.aureus bacteremia, including those associated with right-sided endocarditis [3]
Repeat blood culture results indicated that the daptomycin minimum inhibitory concentration (MIC) had increased from 0.75 μg/mL at baseline to 4 μg/mL

Summary

Introduction

Daptomycin is a novel lipopeptide antibiotic that has activity against a variety of Gram positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), heteroresistant vancomycin-intermediate S. aureus (hVISA) and Enterococcus spp., including vancomycin-resistantEnterococci (VRE) [1,2]. Daptomycin is reserved for patients who have failed, or are intolerant to vancomycin therapy In disease states such as endocarditis and osteomyelitis, which often require prolonged durations of therapy, daptomycin is used since it is dosed once-daily, does not cause nephrotoxicity, and does not require drug concentration monitoring for safety or efficacy. In vivo and in vitro studies of clinical S. aureus strains have described a phenomenon in which prior exposure to vancomycin resulted in reduced daptomycin susceptibilities [7,8]. This phenomenon was documented in a case report by Bennett et al [9], of a 94-year old woman with persistent MRSA bacteremia despite optimization of vancomycin to obtain serum levels >15 μg/mL. The patient’s daptomycin was increased to 8 mg/kg/day to overcome the elevated MICs but the patient had a poor outcome [9]

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