Available online 5 December 2023, 107047

Author links open overlay panel, , , , AbstractObjectives

To perform a systematic review with meta-analysis for assessing the clinical efficacy of cefiderocol-based regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections.

Methods

Two authors independently searched PubMed-MEDLINE, Scopus, and Cochrane database up to 02 July 2023, to retrieve randomized controlled trials (RCTs) or observational studies comparing clinical efficacy of cefiderocol-based regimens in patients affected by CRAB infections compared to those treated with non-cefiderocol-based regimens. Data were independently extracted by the two authors, and the quality of included studies was independently assessed according to ROB 2.0 or ROBINS-I tools. Mortality rate was selected as primary outcome. Meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity.

Results

A total of 530 articles were screened, and 6 studies (one RCT and five observational; N=561; 247 cefiderocol-based regimens vs. 314 non-cefiderocol-based regimens) were included. Cefiderocol did not significantly reduce in-hospital mortality compared to alternative therapies (predominantly colistin based), but the confidence intervals around the effect estimate includes a clinically important benefit (N=5; OR 0.64; 95%CI 0.40-1.04; I2=57.5%). When only observational studies providing adjustment for confounders were considered, a lower risk of mortality rate was found in patients treated with cefiderocol-based regimens (N=4; OR 0.53; 95%CI 0.39-0.71; I2=0.0%).

Conclusions

Cefiderocol-based regimens were associated with a significant lower risk of mortality rate in patients affected by CRAB infections in observational studies providing proper adjustment for confounders.

Section snippetsBackground

Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a major cause of healthcare-associated infections in hospitalized patients, and has been recently classified by the World Health Organization in the critical category of pathogens requiring urgent new antibiotic treatment options [1]. CRAB infections are responsible for high rates of clinical failure and mortality compared to other difficult-to-treat Gram-negative pathogens, causing death in more than 45% of cases in clinical trials

Methods

A systematic review with meta-analysis was conducted for investigating the clinical efficacy of cefiderocol-based regimens compared to other therapeutic regimens in patients with CRAB infections. The meta-analysis was registered in the PROSPERO database (CRD42023441850), and performed following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines [8].

Literature search

A total of 530 studies was identified by search, and 169 were removed as being duplicates. Subsequently, 335 studies were excluded after screening at title/abstract level. Overall, 26 full-text articles were assessed for eligibility, and finally six studies met the inclusion criteria (Supplementary Figure 1). Twenty studies were excluded according to the pre-defined exclusion criteria: lack of comparator group (seventeen studies), and lack of outcome data for CRAB subgroup (three studies).

Characteristics of the included studies

One

Discussion

Our meta-analysis found a trend to significant lower mortality rate in patients affected by severe CRAB infections treated with cefiderocol-based treatment regimens compared to those receiving colistin-based regimens. Furthermore, after excluding the CREDIBLE-CR trial [6] and considering only observational studies from Italy performing proper adjustment for confounders, we found a significant lower mortality rate among patients receiving cefiderocol-based regimens. Notably, these findings are

Declarations

Funding: This research was supported by EU funding within the NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT).

Competing Interests: Mi.Ga. reports grants from Angelini S.p.A., outside the submitted work. F.P. reports personal fees from Angelini, Basilea Pharmaceutica, Gilead, Hikma, MSD, Pfizer, Sanofi-Aventis, Shionogi, Thermo Fisher, and Accelerate Diagnostics, outside the submitted work; has participated in speaker's

References

[1] Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018;18:318–27. https://doi.org/10.1016/S1473-3099(17)30753-3.

[2] Shields RK, Paterson DL, Tamma PD. Navigating Available Treatment Options for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections. Clin Infect Dis 2023;76:S179–93. //doi.org/10.1093/cid/ciad094

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