Current evidence for therapy of ceftriaxone-resistant Gram-negative bacteremia

This article aims to give a state-of-the-art assessment of treatment options for bloodstream infection because of ceftriaxone-resistant Gram-negative bacilli, especially those caused by extended-spectrum beta-lactamase (ESBL) or AmpC-producing Enterobacteriaceae. In particular, this review assesses whether current data support 'carbapenem-sparing options' for treatment of these serious infections.

The MERINO trial refuted earlier observational studies some of which showed equivalence in outcomes between beta-lactam/beta-lactamase inhibitor combinations and carbapenems for treatment of bloodstream infection because of ceftriaxone-resistant Escherichia coli or Klebsiella spp. Although numerous factors influence mortality following bloodstream infection, the variability in piperacillin/tazobactam MICs observed in the MERINO trial make this a less secure option than meropenem. However, the search for carbapenem-sparing options continues with four randomized controlled trials (RCTs) in progress and a number of other options in clinical development.

Hard outcomes from RCTs are still needed before intravenous carbapenems can be displaced as the treatment of choice for ceftriaxone-resistant Gram-negative bacilli.