Getting it Right the First Time: Relating Pharmacokinetic-Pharmacodynamic Target Attainment and Patient Outcomes

Abstract

BackgroundThe importance of delivering appropriate therapy to patients at the onset of treatment is well established. However, this goal is easier said than done given the complexity and uniqueness of each patient case. Nonetheless, treatment decisions driven by pharmacokinetic-pharmacodynamic (PK-PD) can account for patient variability and assist in selecting patient-specific therapies. Using data obtained from electronic decision support software (EDSS), we evaluated the relationship between the probability of PK-PD target attainment (PTA) and patient outcomes.MethodsData obtained over a 20-month period from an EDSS were evaluated and included: (1) patient demographics; (2) infection type; (3) pathogen; (4) clinician-selected antimicrobials; (4) pathogen susceptibility; (5) clinician-provided early and late outcomes. Data calculated by the EDSS included the PTA for all evaluated antimicrobial regimens. Using logistic regression, relationships between the probability of PTA and clinical improvement and clinical success at 48 hours and Days 7–10, respectively, were assessed.ResultsData for 121 patient cases with various infection types were available. The most common pathogens reported were MRSA (14.9%) and K. pneumoniae (14.9%). Overall, 76.3% of patients demonstrated clinical improvement at 48 hours while 70.3% of patients demonstrated clinical success at Days 7–10. Based on the relationship between the probability of PTA and clinical improvement at 48 hours (Figure 1), for every 10% increase in PTA, patients were 1.74 times more likely to demonstrate clinical improvement (OR [95% CI] 1.74 [1.28–2.37], P < 0.001). At Days 7–10 (Figure 2), patients were 1.82 times more likely to have a successful response (OR [95% CI] 1.82 [1.29–2.58], p < 0.001). Based on these relationships, the predicted percent probability of a positive outcome at 48 hours and Days 7–10 for an initial treatment regimen with PTA of 90% was 77.2% and 76.1%, respectively.ConclusionStatistically significant positive relationships between PTA and clinical outcomes at 48 hours and Days 7–10 were identified. These data demonstrate the value of PK-PD in dosing regimen selection and provide a path toward delivering appropriate initial therapy to optimize patient outcomes.Disclosures S. M. Bhavnani, ICPD Technologies: Shareholder, stock options; C. M. Rubino, ICPD Technologies: Shareholder, stock options; P. G. Ambrose, ICPD Technologies: Shareholder, stock options