A Retrospective Cohort Study to Optimize Piperacillin/Tazobactam Dosing in Routine Intensive-Care Patients via a Newly Designed Clinical Pharmacy Service Including TDM- and Algorithm-Based Recommendations

Background: Therapeutic drug monitoring (TDM) for piperacillin/tazobactam has become established in intensive care. TDM should be used in a structured approach to optimize dosing. We evaluated a newly designed TDM- and algorithm-based clinical-pharmacy-service to determine whether it is appropriate for optimization. Methods: We developed a clinical pharmacy service providing algorithmic recommendations for optimizing piperacillin/tazobactam dosing based on piperacillin TDM. After implementing the clinical pharmacy service, we evaluated the treatment of intensive-care patients with piperacillin/tazobactam in terms of achieving the minimum-inhibitory-concentration-(MIC)-related target concentration at the following four time points: t1, t2, t3, and t4 (1–4 working days after piperacillin/tazobactam therapy was started). Results: A total of 132 patients (including 36% women), median age 78 years, received piperacillin/tazobactam therapy. Sepsis or septic shock was the most common indication (43%), while a pulmonary focus was most frequent (40%). From 132 patients (t1), 19% had “too low piperacillin concentrations”, 20% “appropriate concentrations”, and 61% “too high concentrations”. After recommendations were given (acceptance rate 100%) the corresponding numbers from 93 remaining patients (t2) were 16%, 35%, and 48%, from 49 patients (t3) 8%, 53%, and 39% and from 29 patients (t4) 38%, 45%, and 17%. In (t1), dose reduction was the main recommendation (49%). The number of patients with “appropriate concentrations” increased in one comparison (t1–t2: n.s.; t1–t3: p = 0.0013; t1–t4: n.s.; Bonferroni-corrected McNemar test), while “too high concentrations” decreased (t1–t2: p = 0.0080; t1–t3: p = 0.0056; t1–t4: p = 0.0095). “too low concentrations” were not influenced (t1–t2: n.s.; t1–t3: n.s.; t1–t4: n.s.). Conclusions: Inappropriate piperacillin plasma concentrations were common. A TDM- and algorithm-based clinical-pharmacy-service especially decreased the number of overdosed patients in routine practice.