Clinical Trials - Antibiotics + Sepsis

Antipseudomonal Antibiotics

ACORN Trial:

• PICO Question: In acutely ill adults (ED / ICU) does the administration of cefipime or piperacillin-tazobactam (pip-taz) result in an increased incidence of AKI or death by day 14?
• Design: Single-center open label RCT
  • Randomization not stratified
  • Intervention: 2g cefepime IVP q8h
  • Control: Zosyn 3.375g IVPB over 30min for first dose => 3.375g infused over 4h q8h for subsequent doses
• Population: 2500 adults within 12 hours of hospital presentation with need for anti-pseudomonal abx without recent use (within 7d)
• Outcomes:
  • Primary: Death, AKI
  • Secondary: Delirium/coma free days; vasopressor/vent/ICU/hospital free days by day 28
• Results: (Cefepime vs Zosyn)
  • Primary:
    • Death or severe AKI (OR, 0.95; 95% CI, 0.80 to 1.13; P = .56)
    • Death: 7.6 vs 6.0% (ARR 1.6%, 95% CI -0.5 to 3.6)
  • Secondary:
    • Major Adverse Kidney Event (death, RRT, persistent renal dysfxn): 10.2% vs 8.8% (ARR 1.4%; 95% CI, −1.0% to 3.8%)
    • Avg # Delirium/Coma Free Days: 11.9d vs 12.2d (OR, 0.79; 95% CI, 0.65 to 0.95)
• Conclusions:
  • No statistically significant difference in rates of death or severe AKI between groups
  • Statistically significant difference in avg # of delirium/coma free days, though the difference is clinically insignificant (abs difference = 0.3 days)
• Critiques:
  • Bit strange to have the composite AKI + death outcome on ordinal scale, but shouldn't hugely change stat analysis
• References:
  • https://www.thebottomline.org.uk/summaries/icm/acorn/

Cochrane Review: Anti‐pseudomonal beta‐lactams for the initial, empirical, treatment of febrile neutropenia: comparison of beta‐lactams

• PICO Question: Among all patients with febrile neutropenia, which antipseudomonal antibiotic resulted in lowest all-cause mortality.
• Design: Meta-analysis
• Population: 44 clinical trials published before 2010
  • Comparing: cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem
• Results:
  • The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants),
  • Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants),
• Conclusions:
  • Piperacillin‐tazobactam is a good choice for empiric coverage of neutropenic fever unless carbapenems are indicated due to clinical concern for resistance
• Critiques:
  • Bit of an older study at this point, only including data up until 2010