With Potent In Vitro Activity, Cefiderocol a Promising Option for Treating Resistance

With antimicrobial resistance on the rise, the need for new antibiotics is more urgent than ever. Investigators with Shinogi in Japan report positive in vitro activity of cefiderocol against a wide variety of gram-negative pathogens.

In data presented in a poster session at the European Congress of Clinical Microbiology and Infectious Disease (ECCMID 2019), the research team detailed the activity of cefiderocol, a novel parenteral siderophore cephalosporin, against carbapenem-resistant clinical isolates collected in 2014-2016 from 24 European countries.

The samples included 545 Enterobacteriaceae, 267 Acinetobacter baumannii, 182 Pseudomonas aeruginosa, and 1 Stenotrophomonas maltophilia. Using Clinical & Laboratory Standards Institute guidelines and broth microdilution, investigators determined minimum inhibitory concentrations (MICs) for cefiderocol, cefepime, ceftazidime-avibactam, ceftolozane-tazobactam, ciprofloxacin, colistin, and meropenem.

The carbapenem non-susceptible strain of all bacterial species was defined as meropenem MIC ≥ 4 mg/L.

Activity of cefiderocol against a variety of gram-negative bacteria with MIC₉₀ of ≤8 mg/L was found to be potent. Against K pneumoniae and P aeruginosa, MIC₉₀ ranged from 2 to 4, and 0.5 to 2 mg/L among EU countries, but showed wide range against A baumannii (0.25 to 32 mg/L), including 16 mg/L against the isolates from Russia and 32 mg/L against the samples from Turkey.

Cefiderocol non-susceptible strains (MIC: ≥ 8 mg/L) represented 4.7% (45/995 strains), most of which were A baumannii from Russia and Turkey (31 isolates), investigators wrote in the abstract.

“The potent in vitro activity of cefiderocol was demonstrated against carbapenem non-susceptible isolates of Enterobacteriaceae, A baumannii, and P aeruginosa collected from Europe, with greater than 95.3% of isolates having MIC values ≤ 4 mg/L,” the team concluded. “These results indicate this agent has high potential for treating infections caused by these problematic organisms.”

Health care providers appear encouraged by the early data on cefiderocol.

“Here’s one agent, cefiderocol, which is a very interesting molecule,” Jason Pogue, PharmD, BCPS-AQID, said in a Contagion® Peer Exchange program last year on the future treatment of Pseudomonas infections. “We don’t know a lot about it yet. There are not a lot of data out there about it yet, but it seems to retain activity. It has a very unique mechanism that actually uses iron transport to get into the gram-negative cell. Again, the in vitro data are incredibly encouraging. You name your carbapenem-resistant organism of choice, and it seems to have activity.”

The study, “Cefiderocol in Vitro Activity Against Gram-Negative Clinical Isolates Collected in Europe: Result From SIDERO-CR-2014/2016,” was presented in a poster session on Monday, April 15, 2019, at ECCMID 2019 in Amsterdam, the Netherlands.