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Xeruborbactam + Cefiderocol

S-649228 Therapeutic Area: Infections Due to Gram-Negative Bacteria Delivery Method: Intravenous Infusion

Our approach here is to combine a highly stable beta-lactam antibiotic with an investigational beta-lactamase inhibitor. S-649228 is a combination of the beta-lactamase inhibitor xeruborbactam with cefiderocol, a first-in-class siderophore cephalosporin antibiotic. It is administered intravenously and may have the potential to address serious infections due to Acinetobacter spp., Enterobacterales and Pseudomonas aeruginosa, including carbapenem-resistant strains in an inpatient setting.

Cefiderocol, developed by Shionogi, can overcome the three major mechanisms of carbapenem resistance by entering cells via the iron active transport system and passive porin diffusion, overcoming efflux pump-up regulation and being stable against all classes of beta-lactamases. While infrequently reported, resistance can occur.1,2,3,4,5

In the U.S., cefiderocol is available under the brand name Fetroja® and is indicated in patients 18 years of age or older for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia (HABP/VABP) and complicated urinary tract infections (cUTIs) caused by certain susceptible Gram-negative microorganisms.

These compounds and their uses are investigational and have not all been approved by the U.S. Food and Drug Administration. This information is presented only for purposes of providing a general overview and should not be construed as a recommendation for use of any product for unapproved uses.

References

  1. Fetroja (cefiderocol) [package insert]. Florham Park, NJ: Shionogi Inc. ↩︎
  2. Davies TA, Queenan AM, Morrow BJ, et al. Longitudinal survey of carbapenem resistance and resistance mechanisms in Enterobacteriaceae and non-fermenters from the USA in 2007–09. J Antimicrob Chemother. 2011;66(10):2298-2307. ↩︎
  3. Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2007;51(10):3471-3484. ↩︎
  4. Rodríguez-Martínez J-M, Poirel L, Nordmann P. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009;53(11):4783-4788. ↩︎
  5. Iregui A, Khan Z, Landman D, Quale J. Activity of cefiderocol against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii endemic to medical centers in New York City. Microb Drug Resist. 2020;26(7):722-726. ↩︎
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