An evidence-based multidisciplinary approach focused at creating algorithms for targeted therapy of infection-related ventilator associated complications (IVACs) caused by Enterobacterales in critically ill adult patients

ABSTRACT

Introduction

Prompt implementation of appropriate targeted antibiotic therapy representsa valuable approach in improving clinical and ecological outcome in critically septic patients. Thismultidisciplinary opinion article aims to develop evidence-based algorithms for targeted antibiotictherapy of infection-related ventilator associated complications (IVACs) caused by Enterobacterales,which are among the most common pathogens associated with these conditions.

Areas covered

A multidisciplinary team of four experts had several rounds of assessment for developingalgorithms devoted to targeted antimicrobial therapy of IVACs caused by Enterobacterales.A literature search was performed on PubMed-MEDLINE (until March 2021) to provide evidence forsupporting therapeutic choices. Quality and strength of evidence was established according toa hierarchical scale of the study design. Six different algorithms with associated recommendations concerning therapeutic choice and dosing optimization were suggested according to the susceptibilitypattern of Enterobacterales: multi-susceptible, extended-spectrum beta-lactamase (ESBL)-producing,AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and metallo-beta-lactamase (MBL)-producing Enterobacterales.

Expert opinion

The implementation of algorithms focused on prompt revision of antibiotic regimensguided by results of conventional and rapid diagnostic methodologies, appropriate place in therapy ofnovel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and PK/PD optimization of antibiotic dosing regimens is strongly suggested.

KEYWORDS:

• Antimicrobial stewardship
• critically ill patients
• infection-related ventilator associated complications
• multidisciplinary taskforce
• PK/PD dosing optimization
• targeted antibiotic therapy

Article highlights

• A multidisciplinary task force involving in the implementation of a targeted antibiotic therapy in critically ill patients affected by IVACs due to Enterobacterales may contribute to maximizing efficacy, reducing antibiotic overconsumption, and minimizing the development of resistance

• Ampicillin or ceftriaxone represent the first therapeutic choice in IVACs caused by multi-susceptible Enterobacterales

• A carbapenem-sparing approach including novel beta-lactam/beta-lactamase inhibitors or cefepime should be considered in the management of IVACs caused by ESBL-producing or AmpC-producing Enterobacterales, respectively.

• According to real-world evidence and ELF penetration, meropenem-vaborbactam should be used as first therapeutic choice in IVACs due to KPC-producing Enterobacterales, being imipenem-relebactam, ceftazidime-avibactam in combination therapy, and cefiderocol reasonable alternatives

• Ceftazidime-avibactam, in monotherapy or in association with aztreonam, and cefiderocol represent the first therapeutic choice in IVACs caused by OXA-48-producing or MBL-producing Enterobacterales

Declaration of interest

B. Viaggi. participated in advisory boards and in speaker’s bureau for, and received research contracts, contributions and study events from Abbott, Accelerate Diagnostics, Ada, Alifax, Angelini, Becton Dickinson, Bellco, Biomerieux, Biotest, Cepheid, Correvio, Gilead, Menarini, MSD Italia, Nordic Pharma, Pfizer, Shionogi, Thermo Fisher Scientific; G.M. Rossolini participated in advisory boards and speaker’s bureau for, and received research contracts, contributions and travel grants from Accelerate, Angelini, Arrow, Beckman Biomedical Service, Coulter, Becton-Dickinson, bioMérieux, Cepheid, Hain Life Sciences, Menarini, Meridian, MSD, Nordic Pharma, Pfizer, Qiagen, Q-linea, Qpex, Quidel, Qvella, Roche, Seegene, Set-Lance, Shionogi, Symcel, ThermoFisher, VenatorX, Zambon; F.Pea participated in speaker bureau for Angelini, Basilea Pharmaceutica, Gilead, Hikma, Merck Sharp & Dohme, Nordic Pharma, Pfizer, and Sanofi Aventis, and in advisory board for Angelini, Basilea Pharmaceutica, Correvio, Gilead, Merck Sharp & Dohme, Nordic Pharma, Novartis, Pfizer, and Thermo-Fisher. P. Viale has served as a consultant for Biomerieux, Gilead, Merck Sharp & Dohme, Nabriva, Nordic Pharma, Pfizer, Thermo-Fisher, and Venatorx, and received payment for serving on the speaker’s bureau for Correvio, Gilead, Merck Sharp & Dohme, Nordic Pharma and Pfizer. M. Gatti has no conflict of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

BV, GMR, FP and PV made substantial contributions to conception of the manuscript. MG was involved in searching literature and drafting the manuscript. BV, GMR, FP and PV made substantial contributions in revising the manuscript critically for important intellectual content. All authors approved the final version of the manuscript.

Additional information

Funding

This paper was not funded.