Rationale and evidence for the use of new beta-lactam/beta-lactamase inhibitor combinations and cefiderocol in critically ill patients

Annals of Intensive Care

Review

Damien Roux¹  Jean-Ralph Zahar²  François Barbier³  Julien Poissy⁴  Sami Hraiech⁵  Olivier Pajot⁶  Solen Kernéis⁷  Nathanaël Veluppillai⁷ 

[1]Institut Maurice Rapin, Hôpital Henri Mondor, Créteil, France

[2]DMU ESPRIT, Médecine Intensive Réanimation, Hôpital Louis Mourier, Assistance Publique – Hôpitaux de Paris, Colombes, and INSERM/CNRS, Institut Necker Enfants Malades, Université Paris Cité, Paris, France

[3]Institut Maurice Rapin, Hôpital Henri Mondor, Créteil, France

[4]Département de Microbiologie Clinique, Hôpital Avicenne, Assistance Publique – Hôpitaux de Paris, Bobigny and INSERM/IAME, Université de Paris, Paris, France

[5]Médecine Intensive Réanimation, Centre Hospitalier Régional d’Orléans, 14, Avenue de l’Hôpital, 45000, Orléans, France

[6]Institut Maurice Rapin, Hôpital Henri Mondor, Créteil, France

[7]Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Lille, Inserm U1285, Université de Lille, and CNRS/UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France

[8]Médecine Intensive Réanimation, Hôpital Nord, Assistance Publique – Hôpitaux de Marseille, and Centre d’Études et de Recherche sur les Services de Santé et la Qualité de Vie, Université Aix-Marseille, Marseille, France

[9]Réanimation Polyvalente, Hôpital Victor Dupouy, Argenteuil, France

[10]Équipe de Prévention du Risque Infectieux, Hôpital Bichat-Claude Bernard, Assistance Publique – Hôpitaux de Paris, and INSERM/IAME, Université Paris Cité, Paris, France

关键词: Cefiderocol;    Ceftolozane–tazobactam;    Ceftazidime–avibactam;    Meropenem–vaborbactam;    Imipenem–relebactam;    Aztreonam;    Enterobacterales;    Pseudomonas aeruginosa;    Carbapenem resistance;    Intensive care unit;   

DOI  :  10.1186/s13613-023-01153-6

 received in 2023-04-20, accepted in 2023-06-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHealthcare-associated infections involving Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) phenotype are associated with impaired patient-centered outcomes and poses daily therapeutic challenges in most of intensive care units worldwide. Over the recent years, four innovative β-lactam/β-lactamase inhibitor (BL/BLI) combinations (ceftolozane–tazobactam, ceftazidime–avibactam, imipenem–relebactam and meropenem–vaborbactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of certain DTR-GNB infections. The literature addressing their microbiological spectrum, pharmacokinetics, clinical efficacy and safety was exhaustively audited by our group to support the recent guidelines of the French Intensive Care Society on their utilization in critically ill patients. This narrative review summarizes the available evidence and unanswered questions on these issues.MethodsA systematic search for English-language publications in PUBMED and the Cochrane Library database from inception to November 15, 2022.ResultsThese drugs have demonstrated relevant clinical success rates and a reduced renal risk in most of severe infections for whom polymyxin- and/or aminoglycoside-based regimen were historically used as last-resort strategies—namely, ceftazidime–avibactam for infections due to Klebsiella pneumoniae carbapenemase (KPC)- or OXA-48-like-producing Enterobacterales, meropenem–vaborbactam for KPC-producing Enterobacterales, ceftazidime–avibactam/aztreonam combination or cefiderocol for metallo-β-lactamase (MBL)-producing Enterobacterales, and ceftolozane–tazobactam, ceftazidime–avibactam and imipenem–relebactam for non-MBL-producing DTR Pseudomonas aeruginosa. However, limited clinical evidence exists in critically ill patients. Extended-infusion scheme (except for imipenem–relebactam) may be indicated for DTR-GNB with high minimal inhibitory concentrations and/or in case of augmented renal clearance. The potential benefit of combining these agents with other antimicrobials remains under-investigated, notably for the most severe presentations. Other important knowledge gaps include pharmacokinetic information in particular situations (e.g., pneumonia, other deep-seated infections, and renal replacement therapy), the hazard of treatment-emergent resistance and possible preventive measures, the safety of high-dose regimen, the potential usefulness of rapid molecular diagnostic tools to rationalize their empirical utilization, and optimal treatment durations. Comparative clinical, ecological, and medico-economic data are needed for infections in whom two or more of these agents exhibit in vitro activity against the causative pathogen.ConclusionsNew BL/BLI combinations and cefiderocol represent long-awaited options for improving the management of DTR-GNB infections. Several research axes must be explored to better define the positioning and appropriate administration scheme of these drugs in critically ill patients.

【 授权许可】

CC BY   
© The Author(s) 2023

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