Category: Professional Posters
Purpose: Polymyxins have been on the market for many years, but little is known about their pharmacokinetics and pharmacodynamics (PK/PD) and appropriate dosing for multidrug resistant (MDR) Gram-negative bacteria beyond the manufacturer recommendations (Kalil 2016; Kassamali 2015;Sandri 2013).The purpose of this medication use evaluation (MUE) was to assess the use of polymyxin B and to develop and implement recommendations in a secondary care hospital.
Methods: A retrospective MUE was conducted for all patients prescribed polymyxin B between January 2018 and July 2018. Data was collected from electronic medical records and analyzed with descriptive statistics. For each polymyxin B order, the following data were recorded: indication for use, isolated pathogens, polymyxin B total daily dose, duration of therapy, concomitant nephrotoxic medications, length of stay, and development of acute kidney injury. After completion of the MUE, the onsite clinical pharmacist performed interventions for polymyxin B orders received between August 2018 and April 2019. For the pharmacist intervention group post-MUE, the same data was collected from medical records and average daily dose was compared to the pre-intervention MUE average daily dose. Dosing of 25,000 units/kg/day divided every 12 hours was use for recommendations and as reference to assess dose appropriateness. (Sandri 2013)
Results: Twenty-four patients were included in the MUE (pre-intervention group). All patients received polymyxin B for the treatment of systemic MDR Gram-negative infections. All patients reported positive cultures for MDR Gram-negative bacteria including: Acinetobacter baumannii (45.7%), Klebsiella pneumoniae (42.9%) and Pseudomonas aeruginosa (11.4%). Patients received either 250,000 units (8.3%), 500,000 units (45.8%) or 1,000,000 units (45.8%) per day as a 24hour continuous infusion. All patients were sub-therapeutic based on units per kilogram of total body weight. Of the 24 evaluated patients, approximately one-half (13; 54.2%) were discharged home. After the MUE and during the period of August 2018 to April 2019, the pharmacist intervened in a total of eight polymyxin B orders for the treatment of systemic MDR Gram-negative infections. The isolated organisms were the following: Pseudomonas aeruginosa (50%), Klebsiella pneumoniae (25%), Acinetobacter baumannii (16%), and Proteus mirabilis (8.33%). Approximately 62% of the interventions were partially accepted in terms of dosage and frequency. The average daily dose was greater in the post-MUE pharmacist intervention group: 17,931 vs10,333 units/kg/day. This represents a 73.5 % increase in dose in the post-MUE pharmacist intervention group. Approximately 75% of the patients were discharge home in the post-MUE pharmacist intervention group.
Conclusion: Overall, the use of polymyxin B was appropriate in terms of indication; however, there is an opportunity to improve medication dosing based on the patient’s total body weight.Clinical outcomes and PK studies demonstrate that polymyxin B total body clearance is not dependent on renal clearance; therefore, there is no PK rationale for renal dose adjustments. Based on these results and with the support of the new consensus guidelines, institutional recommendations will be developed to improve polymyxin B with the goal of optimizing clinical outcomes.