UMEM Educational Pearls

Category: Pharmacology & Therapeutics

Title: Beware of piperacillin-tazobactam dose reductions in septic shock

Keywords: sepsis, piperacillin-tazobactam (PubMed Search)

Posted: 9/29/2022 by Ashley Martinelli (Emailed: 10/3/2022) (Updated: 2/4/2023)
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Piperacillin-tazobactam is one of the most commonly used antipseudomonal antibiotics in the empiric management of patients with septic shock. The package insert recommends dose reductions for renal impairment in other infectious etiologies, but the impact of dose reduction has not been previously studied in patients with septic shock.

A recent retrospective, observational cohort study compared outcomes of patients with septic shock who received ≥ 27 grams (at least 3.375 gm q6 hours x 48 h-“NORM”) versus those who received < 27 grams (“LOW”) over the initial 48 h of septic shock (defined as concomitant norepinephrine infusion).  

Patients were excluded if they had death or hospice disposition within the 48h study period. The primary outcome was the number of norepinephrine free days (NFD) at day 28. Propensity matching was utilized to account for confounders.

Results: 351 in the LOW group, 928 in the NORM group with 608 pairs in the propensity matched assessment.

  • Patients in the LOW group were
    • Older (65 v 61, p < 0.001)
    • More likely to have lower renal function (20% with CrCl < 20, 35% with CrCl 20-40) which corresponds to package insert dose reduction recommendations
    • Received lower doses of piperacillin/tazobactam (20.3 g v 30.4 g, < 0.001)
  • Norepinephrine free days were statistically significantly higher in the NORM dosing group when looking at all patients and the propensity score matched patients.
  • In-hospital mortality/hospice disposition was also lower in the NORM group (25.9% v 35.5%, p=0.014

Bottom Line: Dose reductions of piperacillin-tazobactam appears to be harmful early in the management of patients with septic shock.

 

References

JM Allen, Surajbali D, Ngyuen DQ, et al. Impact of piperacillin-tazobactam dosing in septic shock patients using real-world evidence: an observational retrospective cohort study. Ann Pharmacotherapy; 2022: Sep 25:10600280221125919. doi: 10.1177/10600280221125919. Epub ahead of print. PMID: 36154486.