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Mono vs. combo regimens with novel beta-lactam/beta-lactamase inhibitor combinations for the treatment of infections due to carbapenemase-producing Enterobacterales: insights from the literature

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A Correction to this article was published on 19 March 2021

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Abstract

Ceftazidime–avibactam (CZA), meropenem–vaborbactam (MVB) and imipenem–relebactam (I–R) are combinations of old ß-lactams with novel non-ß-lactam ß-lactamase inhibitors (BLBLIs) able to inhibit some carbapenemases, such as the KPC-type, thus are becoming the standard for difficult-to-treat carbapenemase-producing Enterobacterales (CPE); a practical question is whether these novel BLBLIs should be used as monotherapy or as part of a combination regimen with other antibiotics, and if so, with which ones, to reduce the emergence of resistant strains and to optimize their efficacy. In this short review, we assessed clinical outcomes in patients with CPE-infections treated with the novel BLBLIs as mono- or combo-regimens, and laboratory studies on the synergistic effects with other antimicrobials. Available evidence on combination therapy is scarce and mainly limited to retrospective studies involving 630 patients treated with CZA: aminoglycosides were used in 39.6% of 336 patients treated with combo-regimens, followed by polymyxin B/colistin (24.4%), tigecycline (24.1%), carbapenems (13.4%) and fosfomycin (5.4%). Aminoglycosides could be useful in case of bloodstream and severe urinary infections. Pneumonia is a risk factor for CZA-resistance emergence: fosfomycin, due to favorable lung pharmacokinetics/pharmacodynamics, could represent an interesting partner; fosfomycin could be added also for osteomyelitis. Tigecycline could be preferred for intrabdominal and skin-soft tissue infections. Due to nephrotoxicity and lack of in vitro synergy, the association CZA/colistin seems not optimal. MVB and I–R were mostly used as monotherapies. Currently, there is no definitive evidence whether combinations are more effective than monotherapies; further studies are warranted, and to date only personal opinions can be provided.

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Funding

No funding has been received for this work. This study was carried out as part of our routine work.

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Authors and Affiliations

  1. Internal Medicine Unit, Felice Lotti Hospital, Pontedera, Azienda USL Toscana Nord-Ovest, Pisa, Italy

    Simone Meini

  2. Department of Anesthesiology, Neuro Intensive Care Unit, Careggi University Hospital, Florence, Italy

    Bruno Viaggi

  3. Infectious Disease Unit, Department of Medicine, University of Udine, Udine, Italy

    Carlo Tascini

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  1. Simone Meini
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  2. Bruno Viaggi
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  3. Carlo Tascini
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Correspondence to Simone Meini.

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The original online version of this article was revised: The presentation of Table 1 was incorrect. The corrected table is given below.

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Meini, S., Viaggi, B. & Tascini, C. Mono vs. combo regimens with novel beta-lactam/beta-lactamase inhibitor combinations for the treatment of infections due to carbapenemase-producing Enterobacterales: insights from the literature. Infection 49, 411–421 (2021). https://doi.org/10.1007/s15010-021-01577-x

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