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Published on: August 30, 2018
In Vitro Activity of Cefiderocol against Clinical Gram-Negative Isolates Originating from Germany in 2016/17
Esther Wohlfarth1, Michael Kresken1, Fabian Deuchert1
1Antiinfectives Intelligence GmbH, c/o Rechtsrheinisches Technologie- und Gründerzentrum, Gottfried-Hagen-Straße 60-62, 51105 Cologne, Germany.
Abstract:
Antimicrobial resistance poses a global threat to public health. Of great concern are Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales with resistance to carbapenems or third-generation cephalosporins. The aim of the present study was to investigate the in vitro activity of the novel siderophore cephaloporin cefiderocol (CID) and four comparator β-lactam-β-lactamase-inhibitor combinations and to give insights into the genetic background of CID-resistant isolates. In total, 301 clinical Enterobacterales and non-fermenting bacterial isolates were selected for this study, including randomly chosen isolates (set I, n = 195) and challenge isolates (set II, n = 106; enriched with ESBL and carbapenemase producers, as well as colistin-resistant isolates). Isolates displayed CID MIC50/90 values of 0.12/0.5 mg/L (set I) and 0.5/1 mg/L (set II). Overall, the CID activity was superior to the comparators against A. baumannii, Stenotrophomonas maltophilia and set II isolates of P. aeruginosa. There were eight CID-resistant isolates detected (MIC > 2 mg/L): A. baumannii (n = 1), E. cloacae complex (n = 5) and P. aeruginosa (n = 2). Sequencing analyses of these isolates detected the acquired β-lactamase (bla) genes blaNDM-1,blaSHV-12 and naturally occurring blaOXA-396, blaACT-type and blaCMH-3. In conclusion, CID revealed potent activity against clinically relevant organisms of multidrug-resistant Enterobacterales and non-fermenters.
Insights
The novel siderophore cephalosporin cefiderocol shows potent in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales and non-fermenters. This study investigated cefiderocol
Area of Science:
- Microbiology and Infectious Diseases
- Antimicrobial Resistance Research
- Pharmacology and Therapeutics
Background:
- Antimicrobial resistance (AMR) is a critical global health challenge, particularly concerning carbapenem- or third-generation cephalosporin-resistant Gram-negative bacteria like *Acinetobacter baumannii*, *Pseudomonas aeruginosa*, and Enterobacterales.
- Novel antimicrobial agents are urgently needed to combat the rising threat of multidrug-resistant (MDR) pathogens.
- Cefiderocol (CID), a siderophore cephalosporin, has emerged as a potential therapeutic option against difficult-to-treat Gram-negative infections.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of cefiderocol (CID) against a collection of clinically relevant Enterobacterales and non-fermenting bacteria.
- To compare the efficacy of CID with four β-lactam-β-lactamase-inhibitor combinations.
- To explore the genetic basis of CID resistance in selected bacterial isolates.
Main Methods:
- A total of 301 clinical isolates were tested, comprising randomly selected strains (set I, n=195) and challenge strains (set II, n=106) enriched for carbapenemase producers and colistin-resistant isolates.
- Minimum Inhibitory Concentrations (MICs) for CID and comparator agents were determined using standard microbiological methods.
- Whole-genome sequencing was performed on CID-resistant isolates to identify relevant β-lactamase genes.
Main Results:
- Cefiderocol (CID) demonstrated potent in vitro activity, with MIC50/90 values of 0.12/0.5 mg/L (set I) and 0.5/1 mg/L (set II).
- CID exhibited superior activity compared to comparator agents against *Acinetobacter baumannii*, *Stenotrophomonas maltophilia*, and carbapenem-resistant *Pseudomonas aeruginosa* isolates.
- Eight CID-resistant isolates were identified, including *A. baumannii*, *E. cloacae* complex, and *P. aeruginosa*. Sequencing revealed various acquired and naturally occurring β-lactamase genes, such as *bla*NDM-1, *bla*SHV-12, *bla*OXA-396, *bla*ACT-type, and *bla*CMH-3.
Conclusions:
- Cefiderocol (CID) displays significant in vitro potency against a broad spectrum of multidrug-resistant Enterobacterales and non-fermenting Gram-negative bacteria.
- CID's activity profile suggests its potential utility in treating infections caused by challenging MDR pathogens.
- Understanding the genetic mechanisms of CID resistance is crucial for guiding its clinical application and monitoring resistance development.
