Clinical Failure and Emergence of Resistance during Third Generation Cephalosporin Therapy for Enterobacter spp. Infection: Is the Risk Overestimated? A Prospective Multicentric Study

Benoît Pilmis,Assaf Mizrahi,Thibaud Delerue,Anna Belkacem,Solen Kernéis,Sophie Alviset,Pauline Caraux-Paz,Jean-Ralph Zahar,Etienne Canoui,Matthieu Lafaurie,Etienne Carbonnelle,Alexandre Bleibtreu

doi:10.3390/hygiene1020007

Abstract

Background: Clinical and microbiological guidelines recommend treating infections caused by Enterobacter spp. with cefepime or carbapenems. The main objective of this study was to assess the risk of clinical failure with third generation cephalosporin (3GC) therapy compared to other β-lactams for infections caused by Enterobacter spp. Our secondary objective was to evaluate the risk of emergence of resistance during therapy. Methods: We conducted a prospective observational study in seven French hospitals over an 18-month period including all patients with a pulmonary and/or bloodstream infection due to Enterobacter spp. susceptible to 3GC. Results: Seventy-four patients were included in our study. Among them, 26 (35%) received a 3GC as a first-line treatment, and clinical improvements were observed for 13/21 (62%) of them. Four (5%) cases of emergence of 3GC resistance were observed during therapy including one in the 3GC group. 3GC therapy can be safely used as first-line therapy especially for non-severe patients suffering from pulmonary or bloodstream infections due to Enterobacter spp. Conclusions: Emergence of 3GC resistance remains a rare event, and there is a lack of evidence of the benefit of last-line antibiotics therapies.

Highlights

The Enterobacteriaceae family is a major cause of community and healthcare related infections
79 cases were reported; among them, five (6%) were excluded because of lack of sufficient data, resulting in a final total of 74 infections related to Enterobacter spp. susceptible to 3GC (Figure 1)
The most frequent sources of infection were intra-abdominal infections (IAIs) (n = 16, 32%) and urinary tract infections (UTIs) (n = 16, 32%), whereas primary bacteremia was observed in seven cases (14%) (Figure 1)

Summary

Introduction

The Enterobacteriaceae family is a major cause of community and healthcare related infections. Previous studies reported a high risk of resistance reaching 19% in patients with infections related to Enterobacter spp. during 3GC antibiotic therapy [3,4]. Among the different species possessing AmpC β-lactamase, Enterobacter spp. seems to have the highest risk of emergence of resistance under treatment compared to Morganella morganii and Serratia marcescens. The main objective of this study was to assess the risk of clinical failure with third generation cephalosporin (3GC) therapy compared to other β-lactams for infections caused by Enterobacter spp. Methods: We conducted a prospective observational study in seven French hospitals over an 18-month period including all patients with a pulmonary and/or bloodstream infection due to Enterobacter spp. susceptible to 3GC. Conclusions: Emergence of 3GC resistance remains a rare event, and there is a lack of evidence of the benefit of last-line antibiotics therapies

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