Piperacillin - Tazobactam penetration into human pancreatic juice

The use of piperacillin-tazobactam (Pip-Taz) has not been established for pancreatic infections, and it is unclear whether the level of Pip-Taz penetration into human pancreatic juice (PJ) is high enough to eradicate relevant pathogens. Pip-Taz levels were measured in serum (S) and PJ of five patients with high-output external pancreatic fistulas by HPLC and bioassay (agar-well diffusion, P. aeruginosa test microorganism). A single dose of Pip-Taz (4.0+0.5 g) was administered as a 30 min i.v. infusion. S and PJ samples were collected simultaneously at different times. Subsequently, clinical surgical isolates were exposed to Pip-Taz concentrations according to in-vivo data. Pip and Taz showed good penetration in PJ. The S and PJ curves showed similar trends for both Pip and Taz. The AUC ratio from 0 to 8 h, AUCPJ:AUCs, ranged from 0.07 to 0.12. High intersubject variability was recorded. Pip-Taz concentrations in PJ achieved therapeutic levels 0.5–1 h after the end of infusion. PJ concentrations (range 5.2–27.4 mg/l, min–max) were maintained above the MIC of the majority of clinical isolates tested for a period of 2–3 h. More frequent drug administration may be required to maintain adequate prolonged therapeutic Pip-Taz levels in severe pancreatic infections.