Table 2.

Safety analysis

High-dose P-T regimena	Corresponding piperacillin trough concentration (mg/L)	Adverse event	Naranjo score-attributable to high-dose P-T?	Resolution/notes
6.75 g q6h	undetectable	Nausea, vomiting	6—Probable	Nausea with one episode of vomiting, which resolved upon dose reduction
6.75 g q6h	0.6	AKI (SCr 0.8 → 2.5)	3—Possible	AKI in the setting of septic shock, recent IV contrast, and vancomycin. Team reduced dose for renal function, then switched to ceftriaxone – SCr returned to baseline
6.75 g q6h	127	AKI (SCr 2.7 → 4.8)	2—Possible	AKI in the setting of septic shock and vancomycin prior to initiation of high P-T dose. Vancomycin was discontinued – no P-T dose adjustment made since SCr returned to baseline on P-T
6.75 g q6h	4	Nausea, abdominal pain	2—Possible	Mild, not requiring dose reduction, and resolved after 2 days without intervention; patient finished 6 days of therapy on high dose
6.75 g q6h	39	Neurotoxicity—delirium	3—Possible	Severe delirium during which patient bit off his nails. Patient was also receiving oral lorazepam 1mg scheduled every 6 h. P-T dose was decreased, lorazepam discontinued and patient subsequently returned to his baseline
9 g q6h	undetectable	Abdominal pain	1—Possible	Significant abdominal pain and distension on study dose while being treated for cholecystitis and an intra-abdominal abscess. Completed 6 days without dose reduction, symptoms subsided during treatment course
4.5 g q6h	115	Diarrhea	2—Possible	One episode of diarrhea after first dose of 4.5 g, which resolved upon subsequent dosing—no dose reduction needed
6.75 g q6h	5	AKI (SCr 0.5 → 1.6)	2—Possible	AKI in the setting of IV contrast and vancomycin. Team reduced dose for renal function, SCr returned to baseline
6.75 g q6h	4	AKI (SCr 0.6 → 1.5) Diarrhea	3—Possible 4—Possible	AKI in the setting of IV contrast, vancomycin, and furosemide. P-T discontinued due to updated culture information. SCr returned to baseline Patient also reported mild diarrhea, which improved upon P-T discontinuation
6.75 g q6h	45	Anemia (Hgb 11.2 → 7.3)	2—Possible	Patient received transfusion of 2 units packed red blood cells, which resolved the anemia

Hgb hemoglobin (mg/dL), SCr serum creatinine (mg/dL), AKI acute kidney injury, P-T piperacillin–tazobactam, q6h every 6 h, IV intravenous

^aEach row represents a unique patient (n = 10)