Abstract
Extended spectrum β-lactamase (ESBL)-producing bacteria are prevalent worldwide and correlated with hospital infections, but they have been evolving as an increasing cause of community acquired infections. The spread of ESBL constitutes a major threat for public health, and infections with ESBL-producing organisms have been associated with poor outcomes. Established therapeutic options for severe infections caused by ESBL-producing organisms are considered the carbapenems. However, under the pressure of carbapenem overuse and the emergence of resistance, carbapenem-sparing strategies have been implemented. The administration of carbapenem-sparing antibiotics for the treatment of ESBL infections has yielded conflicting results. Herein, the current available knowledge regarding carbapenem-sparing strategies for ESBL producers is reviewed, and the optimal conditions for the “when and how” of carbapenem-sparing agents is discussed. An important point of the review focuses on piperacillin–tazobactam as the agent arousing the most debate. The most available data regarding non-carbapenem β-lactams (i.e., ceftolozane–tazobactam, ceftazidime–avibactam, temocillin, cephamycins and cefepime) are also thoroughly presented as well as non β-lactams (i.e., aminoglycosides, quinolones, tigecycline, eravacycline and fosfomycin).
Highlights
The spread of extended spectrum β-lactamase (ESBL)-producing bacteria has increased the last two decades in the hospital setting as well as in the community, emerging as a serious threat of public health [1].In particular, infections caused by antimicrobial-resistant Escherichia coli proportionally contributed the most to the burden of antimicrobial resistance in Europe, both as number of cases and number of attributable deaths [2]
Antibiotics 2020, 9, 61 for the treatment of ESBL-producing Enterobacterales (ESBL-PE) and have been associated with improved outcomes, even when in vitro activity to other β-lactams is exhibited [9]. These findings cannot be extrapolated to all patients, as a considerable amount of literature has been published on the use of β-lactams/β-lactamase inhibitor combinations (BLBLI) and piperacillin–tazobactam [10,11,12,13]
In the effort to evaluate the efficacy of BLBLI versus carbapenems in patients with a non-urinary source of ESBL-PE bacteremia, Ofer-Friedman et al [11] performed a multicenter, multinational efficacy analysis from 2008 to 2012 comparing outcomes in patients given a carbapenem (69) versus those treated with PTZ (10)
Summary
The spread of extended spectrum β-lactamase (ESBL)-producing bacteria has increased the last two decades in the hospital setting as well as in the community, emerging as a serious threat of public health [1]. Antibiotics 2020, 9, 61 for the treatment of ESBL-PE and have been associated with improved outcomes, even when in vitro activity to other β-lactams is exhibited [9] These findings cannot be extrapolated to all patients, as a considerable amount of literature has been published on the use of β-lactams/β-lactamase inhibitor combinations (BLBLI) and piperacillin–tazobactam [10,11,12,13]. The current review is focused on the current state of evidence regarding carbapenem-sparing antibiotic options including non-carbapenem β-lactams as well as non β-lactams options for the treatment of ESBL-PE infections. ESBL, extended spectrum β-lactamases, carbapenem-sparing agents, bacteremia, septic shock, non b-lactams, carbapenems, meropenem, imipenem–cilastatin, ertapenem, β-lactams/β-lactamase inhibitor combinations, piperacillin–tazobactam, ceftolozane–tazobactam, ceftazidime–avibactam, fosfomycin, tigecycline, eravacycline, aminoglycosides and quinolones. Evidence on non β-lactams (i.e., fosfomycin, tigecycline, eravacycline, aminoglycosides and quinolones) is thoroughly discussed, and suggestions on their proper use are indicated
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