Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Ceftriaxone-Resistant E. coli or Klebsiella pneumoniae Bloodstream Infection
JAMA, 2018 · International, multicenter, open-label, randomized noninferiority trial.
Clinical question
In patients with ceftriaxone-resistant E. coli or Klebsiella pneumoniae bloodstream infection susceptible to both study drugs, is definitive piperacillin-tazobactam noninferior to meropenem for 30-day mortality?
What the trial found
For ceftriaxone-resistant E. coli or Klebsiella pneumoniae bloodstream infection, piperacillin-tazobactam did not meet the noninferiority criterion compared with meropenem and had higher observed 30-day mortality.
Current guideline position
Consistent with current IDSA AMR guidance favoring carbapenems for ESBL-producing Enterobacterales bloodstream infection or other infections outside the urinary tract.
Clinical interpretation
MERINO supports carbapenem therapy for serious ESBL-producing Enterobacterales bloodstream infection rather than relying on piperacillin-tazobactam as definitive treatment, while susceptibility method, source, inoculum and newer beta-lactam/beta-lactamase inhibitor options still matter clinically.
Molecular resistance mechanisms (ESBL, AmpC, KPC, NDM, OXA-48, DTR-Pseudomonas, CRAB), the MERINO trial, and modern novel beta-lactamase inhibitor therapeutics.
Life-threatening organ dysfunction caused by a dysregulated host response to infection — recognized by an acute rise in SOFA score, not by infection plus fever alone.