Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Nov 5;13(11):1048.
doi: 10.3390/antibiotics13111048.

Cefiderocol Versus Best Available Therapy in the Treatment of Critically Ill Patients with Severe Infections Due to Resistant Gram-Negative Bacteria: A Systematic Review and Meta-Analysis

Carlos Risco-Risco  1 , César Henriquez-Camacho  2   3 , Marta Herrera-Rueda  2 , José Barberán  4   5 , David Andaluz-Ojeda  6   7   8
Affiliations
Review

Cefiderocol Versus Best Available Therapy in the Treatment of Critically Ill Patients with Severe Infections Due to Resistant Gram-Negative Bacteria: A Systematic Review and Meta-Analysis

Carlos Risco-Risco et al. Antibiotics (Basel). .

Abstract

Background: This study aims to assess the effectiveness and safety of cefiderocol in treating severe infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) in critically ill patients, particularly those in intensive care units (ICUs).

Methods: A meta-analysis of studies, including randomized clinical trials and observational studies in adult patients, was performed. Studies with at least 50% of critically ill patients were included. Studies with small sample size or without comparison groups were excluded. Sources included PubMed, Scopus, or Google Scholar, up to 14 August 2024. Risk of bias was assessed according to the Cochrane tool. The main outcome examined was 30-day mortality, while secondary outcomes assessed included clinical cure rates and adverse effects. Results were expressed with odds ratios. No funding was received for this study. It was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with reference CRD42024563041.

Results: eight studies, with 1339 patients were included in the meta-analysis. Cefiderocol treatment was associated with a lower 30-day mortality rate than other available therapies (pooled OR 0.47; 95% CI: 0.23-0.97, p = 0.04), particularly in cases of carbapenem-resistant A. baumannii infections (pooled OR 0.29; 95% CI: 0.14-0.60, p < 0.001). Although there was a non-significant trend toward higher clinical cure rates in the cefiderocol group (OR 1.59; 95% CI: 0.96-2.62, p = 0.07), the drug demonstrated at least non-inferiority when compared to other treatment options. Study limitations included moderate heterogeneity between studies, and a high risk of bias in non-RCT studies. (Five cohort studies were included). Another limitation is that five of the eight studies compared cefiderocol versus colistine, an antibiotic with known toxicity.

Conclusions: The findings suggest that cefiderocol is a promising therapeutic option for managing severe MDR-GNB infections in critically ill patients, offering a potential global benefit on mortality and at least non-inferiority in the cure rate when compared with other therapies.

Keywords: Acinetobacter baumannii; Gram-negative bacteria; ICU; MDR; cefiderocol; critically ill; severe infections.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram of the process of identification and selection of articles included in the meta-analysis.
Figure 2
Figure 2
Risk of bias summary and bias graph.
Figure 3
Figure 3
Meta-analysis of studies evaluating the 30-day mortality rate in patients treated with cefiderocol.
Figure 3
Figure 3
Meta-analysis of studies evaluating the 30-day mortality rate in patients treated with cefiderocol.
Figure 4
Figure 4
Meta-analysis of studies evaluating the curation rate in patients treated with cefiderocol vs. best available therapy.
Figure 4
Figure 4
Meta-analysis of studies evaluating the curation rate in patients treated with cefiderocol vs. best available therapy.
See this image and copyright information in PMC

References

    1. World Health Organization World Health Organization Publishes List of Bacteria for Which New Antibiotics Are Urgently Needed. [(accessed on 14 August 2024)]. Available online: https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-....
    1. Kazmierczak K.M., Tsuji M., Wise M.G., Hackel M., Yamano Y., Echols R., Sahm D.F. In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study) Int. J. Antimicrob. Agents. 2019;53:177–184. - PubMed
    1. Wang C., Yang D., Wang Y., Ni W. Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence. Front Pharmacol. 2022;13:896971. doi: 10.3389/fphar.2022.896971. - DOI - PMC - PubMed
    1. Fendian Á.M., Albanell-Fernández M., Tuset M., Pitart C., Castro P., Soy D., Bodro M., Soriano A., Del Río A., Martínez J.A. Real-Life Data on the Effectiveness and Safety of Cefiderocol in Severely Infected Patients: A Case Series. Infect. Dis. Ther. 2023;12:1205–1216. doi: 10.1007/s40121-023-00776-3. - DOI - PMC - PubMed
    1. Barbier F., Hraiech S., Kernéis S., Veluppillai N., Pajot O., Poissy J., Roux D., Zahar J.-R., French Intensive Care Society Rationale and evidence for the use of new beta-lactam/beta-lactamase inhibitor combinations and cefiderocol in critically ill patients. Ann. Intensive Care. 2023;13:65. doi: 10.1186/s13613-023-01153-6. - DOI - PMC - PubMed

LinkOut - more resources