An Evidence-Based Multidisciplinary Approach Focused on Creating Algorithms for Targeted Therapy of Infection-Related Ventilator-Associated Complications (IVACs) Caused by Pseudomonas aeruginosa and Acinetobacter baumannii in Critically Ill Adult Patients.

Milo Gatti,Pierluigi Viale,Federico Pea,Bruno Viaggi,Gian Maria Rossolini

doi:10.3390/antibiotics11010033

Abstract

(1) Background: To develop evidence-based algorithms for targeted antibiotic therapy of infection-related ventilator-associated complications (IVACs) caused by non-fermenting Gram-negative pathogens. (2) Methods: A multidisciplinary team of four experts had several rounds of assessments for developing algorithms devoted to targeted antimicrobial therapy of IVACs caused by two non-fermenting Gram-negative pathogens. A literature search was performed on PubMed-MEDLINE (until September 2021) to provide evidence for supporting therapeutic choices. Quality and strength of evidence was established according to a hierarchical scale of the study design. Six different algorithms with associated recommendations in terms of therapeutic choice and dosing optimization were suggested according to the susceptibility pattern of two non-fermenting Gram-negative pathogens: multi-susceptible Pseudomonas aeruginosa (PA), multidrug-resistant (MDR) metallo-beta-lactamase (MBL)-negative-PA, MBL-positive-PA, carbapenem-susceptible Acinetobacter baumannii (AB), and carbapenem-resistant AB. (3) Results: Piperacillin–tazobactam or fourth-generation cephalosporins represent the first therapeutic choice in IVACs caused by multi-susceptible PA. A carbapenem-sparing approach favouring the administration of novel beta-lactam/beta-lactamase inhibitors should be pursued in the management of MDR-MBL-negative PA infections. Cefiderocol should be used as first-line therapy for the management of IVACs caused by MBL-producing-PA or carbapenem-resistant AB. Fosfomycin-based combination therapy, as well as inhaled colistin, could be considered as a reasonable alternative for the management of IVACs due to MDR-PA and carbapenem-resistant AB. (4) Conclusions: The implementation of algorithms focused on prompt revision of antibiotic regimens guided by results of conventional and rapid diagnostic methodologies, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens is strongly suggested.

Highlights

Infection-related ventilator-associated complications (IVACs) represent the most prevalent infective events in patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation [1], accounting approximately for one-third of hospital-acquired pneumonia (HAP) cases [2]
We recently showed in a descriptive case series of PK/PD target attainment and microbiological outcome in critically ill patients with documented severe XDR Acinetobacter baumannii BSI and/or ventilator-associated pneumonia (VAP) treated with cefiderocol that the standard 3 h infusion was ineffective in achieving the aggressive PK/PD of
The definitive agreement for each therapeutic algorithm was reached by the multidisciplinary team after thoroughly discussion based on specific long-standing experience and on the specific expertise of each single member in terms of management of critically ill patients affected by IVACs, in appropriately placing in therapy of the old and novel antimicrobial agents, in implementing appropriate target antibiotic therapy and antimicrobial stewardship strategies in challenging scenarios, in applying traditional and novel microbiological methods and in interpreting microbiological findings and susceptibility test according to the specific clinical scenarios, and in optimizing and individualizing antibiotic dosing regimens according to the specific pathophysiological alterations

Summary

Introduction

Infection-related ventilator-associated complications (IVACs) represent the most prevalent infective events in patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation [1], accounting approximately for one-third of hospital-acquired pneumonia (HAP) cases [2]. Gram-negative pathogens are responsible for the majority of HAP and ventilator-associated pneumonia (VAP), and among these, the non-fermenting Gram-negative pathogens (especially Pseudomonas aeruginosa and Acinetobacter baumannii) are responsible for a remarkable amount of IVACs in critically ill patients, second only to Staphylococcus aureus in terms of prevalence [6,7]. Pseudomonas aeruginosa and Acinetobacter baumannii are both characterized by innate resistance mechanisms against multiple antimicrobials. These pathogens may acquire new resistances by different mobile elements, making extremely challenging the choice of appropriate antibiotic therapy in this setting [6,7,8,9]. Once that the causative pathogen has been identified and its susceptibility pattern has been defined, therapy should be revised and targeted, as recommended by the Surviving Sepsis Campaign guidelines [11]

Methods

Results

Conclusion