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Review
. 2022 Apr 12:13:896971.
doi: 10.3389/fphar.2022.896971. eCollection 2022.

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

Chuanhai Wang  1 , Deqing Yang  2 , Yifan Wang  3 , Wentao Ni  3
Affiliations
Review

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

Chuanhai Wang et al. Front Pharmacol. .

Erratum in

Abstract

Cefiderocol is a novel synthetic siderophore-conjugated antibiotic that hijacks the bacterial iron transport systems facilitating drug entry into cells, achieving high periplasmic concentrations. This systematic review analyzed the currently available literature on cefiderocol. It summarized in vitro susceptibility data, in vivo antimicrobial activity, pharmacokinetics/pharmacodynamics (PK/PD), clinical efficacy, safety and resistance mechanisms of cefiderocol. Cefiderocol has potent in vitro and in vivo activity against multidrug-resistant (MDR) Gram-negative bacteria, including carbapenem-resistant isolates. But New Delhi Metallo-β-lactamase (NDM)- positive isolates showed significantly higher MICs than other carbapenemase-producing Enterobacterales, with a susceptible rate of 83.4% for cefiderocol. Cefiderocol is well-tolerated, and the PK/PD target values can be achieved using a standard dose regimen or adjusted doses according to renal function. Clinical trials demonstrated that cefiderocol was non-inferiority to the comparator drugs in treating complicated urinary tract infection and nosocomial pneumonia. Case reports and series showed that cefiderocol was a promising therapeutic agent in carbapenem-resistant infections. However, resistant isolates and reduced susceptibility during treatment to cefiderocol have already been reported. In conclusion, cefiderocol is a promising powerful weapon for treating MDR recalcitrant infections.

Keywords: carbapenem-resistant; cefiderocol; gram-negative bacteria; multidrug resistant; systematic review.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of literature search.
FIGURE 2
FIGURE 2
The cefiderocol MIC50 and MIC90 distribution of Enterobacterales, Acinetobacter spp, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia spp.
FIGURE 3
FIGURE 3
The cefiderocol MIC profile of Enterobacterales, Acinetobacter spp and Pseudomonas aeruginosa with or without carbapenem-resistance. (A), the MIC90 distribution of the three Gram-negative bacteria; (B), the cumulative curves of MICs of 9305 isolates (n = 13). CRE, carbapenem-resistant Enterobacterales; CR-A, carbapenem-resistant Acinetobacter spp; CR-PA, carbapenem-resistant P. aeruginosa.
FIGURE 4
FIGURE 4
The cefiderocol MIC profile of different species of Enterobacterales, (A), the MIC90 distribution; (B), the cumulative curves of MICs of 1264 isolates (n = 15) harboring different β-lactamase.
FIGURE 5
FIGURE 5
Forest plot for the pooled analysis of clinical response at test of cure, microbiological response and 28-days all-cause mortality between cefiderocol and comparators for the treatment of complicated urinary tract infection (cUTI) or nosocomial pneumonia (NP).
FIGURE 6
FIGURE 6
Forest plot for the pooled analysis of clinical response at test of cure between cefiderocol and comparators for the treatment of infections caused by specific pathogens. Complicated urinary tract infection, cUTI; Nosocomial pneumonia, NP.
FIGURE 7
FIGURE 7
Forest plot for the pooled analysis of microbiological eradication at test of cure between cefiderocol and comparators for the treatment of infections caused by specific pathogens. Complicated urinary tract infection, cUTI; Nosocomial pneumonia, NP.
See this image and copyright information in PMC

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