Objectives: The primary aim of the study was to compare environmental and external (cross-) contamination of traces of cytostatics, during preparation of 5-fluorouracil and cyclophosphamide using a robotic system (APOTECAchemo) or the conventional manual compounding procedure. The secondary aim was to validate the cleaning procedure of the robot. Methods: Eighty ready-to-administer (RTA) infusion bags with 5-fluorouracil, cyclophosphamide or sodium chloride were compounded using both techniques on 3–5 days. Wipe samples were taken from several locations in the compounding room before and after cleaning, and also from the technician’s gloves. These samples were analysed for 5-fluorouracil and cyclophosphamide concentrations using GC/MS/MS. Key findings: A total of 284 wipe samples were collected during the study (113 from the manual and 171 from the robotic process). External contamination on the outside of infusion bags was 3.75% for both manual and robotic compounding. For manual compounding, external cross-contamination occurred on 2.5% of the prepared infusion bags. External cross-contamination occurred on 1.25% of the infusion bags for the robotic procedure. Inside the compounding room, 9% of the environmental wipe samples were contaminated in case of manual production and 24% for robotic compounding. Since 50% of the contaminated environmental samples for the robotic system were taken after cleaning, the cleaning procedure was extended and parameter setting for cyclophosphamide handling was performed. After this, residual environmental or external contamination was no longer detectable. Conclusion: Comparison of both preparation methods showed that external (cross-)contamination of infusion bags was lower using the robotic system. An optimized cleaning procedure showed the best results in environmental contamination for the robot.

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected Pseudomonas aeruginosa infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement. A population PK model was constructed, and probability of target attainment (PTA) was assessed for targets 100% T > MIC and 100% T > 4 × MIC in the first 24 h. Ninety-six patients yielded 368 ceftazidime concentrations. In a one-compartment model, variability in ceftazidime clearance (CL) showed association with CVVH. For patients not receiving CVVH, variability in ceftazidime CL was 103.4% and showed positive associations with creatinine clearance and with the comorbidities hematologic malignancy, trauma or head injury, explaining 65.2% of variability. For patients treated for at least 24 h and assuming a worst-case MIC of 8 mg/L, PTA was 77% for 100% T > MIC and 14% for 100% T > 4 × MIC. Patients receiving loading doses before continuous infusion demonstrated higher PTA than patients who did not (100% T > MIC: 95% (n = 65) vs. 13% (n = 15); p < 0.001 and 100% T > 4 × MIC: 20% vs. 0%; p = 0.058). The considerable IIV in ceftazidime PK in ICU patients could largely be explained by renal function, CVVH use and several comorbidities. Critically ill patients are at risk for underexposure to ceftazidime when empirically aiming for the breakpoint MIC for P. aeruginosa. A loading dose is recommended.