Early Treatment Outcomes for Bloodstream Infections Caused by Potential AmpC Beta-Lactamase-Producing Enterobacterales with Focus on Piperacillin/Tazobactam: A Retrospective Cohort Study.

Lena Herrmann,Stefan Hagel,Mathias W Pletz,Christina Bahrs,Norman Rose,Jürgen Rödel,Aurelia Kimmig

doi:10.3390/antibiotics10060665

Abstract

The Gram-negative bacilli Serratia spp., Providencia spp., Morganella morganii, Citrobacter freundii complex, Enterobacter spp. and Klebsiella aerogenes are common Enterobacterales that may harbor inducible chromosomal AmpC beta-lactamase genes. The purpose of the present study was to evaluate treatment outcomes and identify predictors of early treatment response in patients with bloodstream infection caused by potential AmpC beta-lactamase-producing Enterobacterales (SPICE-BSI). This cohort study included adult patients with SPICE-BSI hospitalized between 01/2011 and 02/2019. The primary outcome was early treatment response 72 h after the start of active treatment, defined as survival, hemodynamic stability, improved or stable SOFA score, resolution of fever and leukocytosis and microbiologic resolution. Among 295 included patients, the most common focus was the lower respiratory tract (27.8%), and Enterobacter spp. (n = 155) was the main pathogen. The early treatment response rate was significantly lower (p = 0.006) in the piperacillin/tazobactam group (17/81 patients, 21.0%) than in the carbapenem group (40/82 patients, 48.8%). Independent negative predictors of early treatment response (p < 0.02) included initial SOFA score, liver comorbidity and empiric piperacillin/tazobactam treatment. In vitro piperacillin/tazobactam resistance was detected in three patients with relapsed Enterobacter-BSI and initial treatment with piperacillin/tazobactam. In conclusion, our findings show that piperacillin/tazobactam might be associated with early treatment failure in patients with SPICE-BSI.

Highlights

Over an 8-year study period, we screened a total of 340 adult patients with bloodstream infection (BSI) caused by any SPICE organism for inclusion in the study
In 4 patients (1.4%), two different SPICE species were detected in the initial blood cultures (BCs)
SPICE-BSI was defined as the presence of at least one positive BC for any SPICE organism in patients with any suspicion of an infection

Summary

Introduction

Organisms) are common Enterobacterales that may harbor inducible chromosomal AmpC beta-lactamase genes [1,2]. The AmpC beta-lactamase genes are initially suppressed, but exposure to antibiotics, broad-spectrum cephalosporins, can induce their expression. SPICE organisms can cause a variety of severe, mostly hospitalacquired infections [5,6], including bloodstream infection (BSI), urinary tract infection, pneumonia, biliary and abdominal infection, surgical site infection and device-associated infection [7,8,9]. There is strong agreement that third-generation cephalosporin treatment should be avoided for SPICE infections irrespective of in vitro susceptibility; piperacillin/tazobactam treatment as a carbapenem-sparing regimen is still a matter of debate [10,11,12,13]

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