Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

Abstract

Objectives To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. Methods Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model. Results In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8–20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1–4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15–1.38, P < 0.001). Cefiderocol was associated with a non-significant lower mortality risk (HR 0.64, 95% CI 0.38–1.08, P = 0.10). Conclusions Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.

Empiric treatment of patients with sepsis and septic shock and place in therapy of cefiderocol: a systematic review and expert opinion statement

“…Consistent results were reported by a comparative study on COVID-19 patients, which compared cefiderocol to BAT in patients with bacteremia and nosocomial pneumonia due to A. baumannii [ 27 ]; 107 patients were enrolled: 42 treated with cefiderocol and 65 with other therapies (among others colistin). No differences in mortality at day 28 were reported (55% vs 58%, p = 0.706).…”

“…Due to its recent approval and the exiguity of published studies, the place in therapy of cefiderocol has to be still defined, thus conveying its strength in guidelines [ 7 , 9 ]. Anyways, even more evidence is coming to light among literature, since recent clinical studies have demonstrated the important role that cefiderocol can play in the eradication of infections caused by Gram-negative MDR pathogens [ 17 , 27 – 29 , 37 ]. Beta lactamase antibiotics, as carbapenems, are still considered the best available therapy against Gram-negative extended-spectrum β-lactamase (ESBL)-producing pathogens.…”

Efficacy and In Vitro Activity of Novel Antibiotics for Infections With Carbapenem-Resistant Gram-Negative Pathogens

“…All-cause 28-day mortality rate was 57%, without differences between groups ( P = 0.70). In this study, cefiderocol was associated with a non-significant lower mortality risk ( P = 0.10) ( Pascale et al., 2021 ).…”

Outcomes with Cefiderocol Treatment in Patients with Bacteraemia Enrolled into Prospective Phase 2 and Phase 3 Randomised Clinical Studies

“…Our post hoc analysis data are complemented by efficacy findings for cefiderocol in real-life cases of difficult-to-treat severe gram-negative infections. Microbiological clearance from repeat blood cultures was seen in around 67% of a total of 60 patients with BSI due mainly to CR or XDR A. baumannii and difficult-to-treat resistant P. aeruginosa [34][35][36][37][38][39][40][41][42]. A more complete picture of the real-world efficacy of cefiderocol in gram-negative BSI patients will be provided by the ongoing Phase 2 GAMECHANGER study, an open-label, prospective, randomised, controlled, non-inferiority trial, comparing cefiderocol and standard of care in the treatment of healthcare-associated or hospital-acquired BSI (NCT03869437; [43]).…”