Meropenem and Piperacillin-tazobactam have Comparable Outcomes in Treatment of Bloodstream Infections Caused by Extended Spectrum Beta-lactamase Producing E.coli and Klebsiellae

Background:

Widespread use of carbapenems for treatment of infections caused by extended-spectrum β-lactamase (ESBL) producing Gram-negative bacilli has contributed to increasing carbapenem resistance. Despite some studies suggesting that β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics are non-inferior to carbapenems, their use has been limited by concerns of clinical efficacy.

We compared outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by ceftriaxone non-susceptible E coli and Klebsiella spp., in an institution with a relative high incidence of ESBL-producing isolates.

Methods:

The study was conducted in the Singapore National University Hospital, a tertiary referral hospital with approximately 1,000 beds. All adult patients with a BSI caused by E. coli or Klebsiella spp. which were confirmed as third generation cephalosporin non-susceptible, but piperacillin-tazobactam and meropenem susceptible between May 2012 to May 2013 were included. Data recorded include demographic information, co-morbidities, presence of any devices, antibiotic therapy within 30 days of BSI and outcomes including subsequent isolation of carbapenem resistant organisms or Clostridium difficile, relapsed BSI and dates of discharge or death.

Results:

During the study period there were 92 BSIs that fulfilled the microbiological inclusion criteria.  79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. The patients had a median age of 74.5 years [range 23-100].  53.3% were female.  For patients given definitive monotherapy with either a carbapenem (n=23) or a BLBLI (n=24), 7 and 30 day mortality was similar in both groups (8.7% vs 8.3%, p=1.0 and 17.4% vs. 8.3%, p=0.42 respectively). There were no significant differences in subsequent isolation of carbapenem resistant organisms (4.3% vs. 4.2%, p=1.0), C. difficile infection (13.0% vs. 8.3%, p=0.67) or relapsed BSI (0% vs. 2%, p=0.23).

Conclusion:

BLBLIs appear to have a similar efficacy to carbapemens in treatment of susceptible ESBL E.coli and K.pneumoniae bloodstream infections. Larger randomized clinical trials are needed especially in this era of carbapenem resistance.