Carbapenem-Resistant Acinetobacter spp Infection in Critically Ill Patients With Limited Treatment Options: A Descriptive Study of Cefiderocol Therapy During the COVID-19 Pandemic
Authors: Giannella Maddalena , Verardi Stefano , Karas Andreas , Abdel Hadi Hasania , Dupont Hervé , Soriano Alex , Santerre Henriksen Anne , Cooper Andrew , Falcone Marco ,   ARES Study Group, Viale Pierluigi , Giannella Maddalena , Pascale Renato , Falcone Marco , Tiseo Giusy , Bandera Alessandra , Muheberimana Toussaint , Pastore Valeria , Saracino Alessandra , Bavaro Davide Fiore , Dalfino Lidia , Guerra Luca , Barchiesi Francesco , Farinaccio Ylenia , Temperoni Chiara , Parruti Giustino , Coladonato Simona , Rapacchiale Giorgia , Ferraris Laurenzia , Meloni Alessandro , Bruni Andrea , Garofalo Eugenio , Torti Carlo , Grossi Paolo , Mangoni Emanuele Durante , Massa Alessia , D’Amico Fabiana , Iossa Domenico , Karruli Arta , Carannante Novella , Merli Marco , Pallotto Carlo , Seminari Elena Maria , Sottotetti Samantha , Carbone Roberto , Casolari Stefania , Vanino Elisa , Cristini Francesco , Raumer Luigi , De Pascale Gennaro , di Chiaro Agnese , Cubattoli Lucia , Bartoloni Alessandro , Lauria Nicoletta Di , Venditti Mario , Oliva Alessandra , Cultrera Rosario , Hadi Hasania Abdel , Tenorio Carmen Hidalgo , Torres David Pérez , Canas-Pérez Isabel , Lorente Luis López-Urrutia , Rodriguez Montserrat , Balandin Barbara , Lepeule Raphaël , Wichmann Dominic , König Christina , Jarczak Dominik 
Published: July 2023

Abstract

Background
Carbapenem-resistant Acinetobacter baumannii infections are difficult to treat and are a significant public health threat due to intrinsic/acquired resistance and limited treatment options.

Methods
A retrospective, observational cohort study in patients receiving cefiderocol via Shionogi's early access program for Acinetobacter spp infections (1 April 2020–30 April 2021; 27 sites; Italy, Spain, Germany, France). Primary outcome was clinical success, defined as clinical resolution of infection at day 14 or day 28 survival.

Results
Overall, 147 patients were included. Primary infection sites were respiratory (65.3%) and bloodstream (unknown source [15.6%]; catheter-related [10.9%]); 24.5% of patients had polymicrobial infection. Of 136 patients in intensive care (92.5%), 85.3% (116/136) received mechanical ventilation. Septic shock (55.6% [70/126]) and coronavirus disease 2019 (COVID-19) (81.6%) were prevalent. Prior to cefiderocol, 85.0% of patients received gram-negative treatment, 61.2% received ≥2 antimicrobials, and most received colistin (58.5%; median duration, 11.5 days). Cefiderocol monotherapy was used in 30.6% of patients. Clinical success rate was 53.1% and was higher in patients without septic shock (62.5%), without COVID-19 (77.8%), and with lower Sequential Organ Failure Assessment (SOFA) scores (quartile 1 [median, 3; range, 0–5]: 82.9%). Day 28 survival was 44.9% and was higher in patients without septic shock (60.7%), without COVID-19 (59.3%), with lower SOFA score (quartile 1: 82.9%), and receiving first-line cefiderocol (68.2% [15/22]). Resolution of infection at day 14 occurred in 39.5% of patients.

Conclusions
Despite use in complex patients with limited treatment options and high septic shock/COVID-19 rates, cefiderocol treatment was associated with an overall clinical success rate of 53%.