Can piperacillin-tazobactam be used as a carbapenem-sparing treatment for bloodstream infections with extended-spectrum beta-lactamase–producing gram-negative bacteria?

Piperacillin-tazobactam leads to higher mortality and should not be used as an alternative to carbapenems for bloodstream infections due to extended-spectrum beta-lactamase (ESBL)–producing gram-negative bacteria. (LOE = 1b)

Harris PNA, Tambyah PA, Lye DC, et al, for the MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Effect of piperacillin-tazobactam vs. meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection an ceftriaxone resistance. JAMA 2018;320(10):984-994.  [PMID:30208454]

Randomized controlled trial (nonblinded)

Government

Concealed

Inpatient (any location) with outpatient follow-up

The increased use of carbapenems for the treatment of infections due to ESBL-producing bacteria may lead to carbapenem-resistant gram-negative bacilli. As such, a search for an alternative agent with similar efficacy is important. ESBL-producing bacteria can be susceptible to beta-lactam/beta-lactamase inhibitor antibiotics, such as piperacillin-tazobactam, at least in vitro. These authors tested the efficacy of an extended-spectrum penicillin (piperacillin-tazobactam) as compared with meropenem for the treatment of bloodstream infections due to Escherichia coli and Klebsiella pneumoniae species resistant to ceftriaxone or cefotaxime, but susceptible to piperacillin-tazobactam and meropenem. Adults with at least one blood culture positive for ESBL E coli or K pneumoniae were randomized to receive either piperacillin-tazobactam (n = 188) or meropenem (n = 191). Patients in each group received the study drug for 4 to 14 days as determined by the treating clinician. The 2 groups were balanced, except for greater incidence of diabetes, urosepsis, and higher APACHE II scores in the meropenem group, and more immunocompromised patients in the piperacillin-tazobactam group. For the primary outcome of 30-day mortality, there were more deaths in the piperacillin-tazobactam group than in the meropenem group with an intention-to-treat analysis (12.3% vs 3.7%; risk difference 8.6%; P = 0.90 for noninferiority) and comparable results with a per-protocol analysis. In fact, the study was suspended early because of harm and futility.