Cefiderocol-Xeruborbactam Active Against Carbapenem-Resistant Bacteria

News | Articles | October 22, 2026 Investigational cefiderocol-xeruborbactam inhibited 98.5% of carbapenem-nonsusceptible Acinetobacter and nearly all Enterobacterales in global surveillance data. Cefiderocol-xeruborbactam (Shionogi/Qpex Biopharma) inhibited nearly all Enterobacterales and Pseudomonas aeruginosa , and 98.5% of carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex isolates, in 2024 global surveillance data.

1-3 A fourth poster showed the combination restored bactericidal activity in a mouse urinary tract infection model. 4 Investigators from Element Iowa City (JMI Laboratories) and Shionogi presented the 4 posters at IDWeek 2026 , held October 21-24 in Washington, DC. The investigational combination pairs cefiderocol (Fetroja; Shionogi), a siderophore-conjugated cephalosporin, with xeruborbactam, a boronate β-lactamase inhibitor active against serine and metallo-β-lactamases (MBLs).

1,4 The program targets antimicrobial resistance driven by New Delhi metallo-β-lactamase (NDM) and other carbapenemases, which reduce susceptibility to cefiderocol alone. 4 Cefiderocol-Xeruborbactam Activity Against Enterobacterales and Pseudomonas aeruginosa Investigators tested 7995 Enterobacterales from 69 hospitals in 20 countries through the SENTRY Surveillance Program.

1 All isolates, including extensively drug-resistant (XDR) and carbapenem-nonsusceptible strains, had cefiderocol-xeruborbactam MICs of 4 mg/L or lower (MIC50/90, ≤0.015/0.12 mg/L). Comparator susceptibility ranged from 83.1% to 99.9%. 1 Gaps appeared among resistant subsets for most comparators.

Against XDR Enterobacterales, comparators reached only 38.2% to 67.2% susceptibility, except cefiderocol (96.3%) and aztreonam-avibactam (99.2%). 1 Against MBL producers, most comparators were active against 0% to 13.5% of isolates. 1 KPC and MBL producers came from both US and European centers, while OXA-48-like producers and isolates carrying more than 1 carbapenemase appeared only in Europe.

1 Against isolates with multiple carbapenemases, comparators reached 0% to 55.6% susceptibility, except cefiderocol (92.1%) and aztreonam-avibactam (100%). 1 European Enterobacterales were less susceptible than US isolates to imipenem-relebactam, meropenem-vaborbactam, and ceftazidime-avibactam.

1 Most comparators remained active against carbapenemase-negative isolates, with susceptibility of 88.1% to 100%, except colistin. 1 Among 2185 P aeruginosa isolates, 99.6% had cefiderocol-xeruborbactam MICs of 4 mg/L or lower (MIC50/90, ≤0.06/0.25 mg/L). 2 Against carbapenemase producers, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam, and ceftazidime-avibactam showed 2.4% to 4.8% susceptibility, compared with 76.2% for cefiderocol.

Cefiderocol-xeruborbactam inhibited 92.9% to 99.2% of resistant subsets, including XDR and ceftolozane-tazobactam-nonsusceptible isolates. 2 Carbapenemase-positive P aeruginosa came mostly from Europe, with a single carbapenemase producer identified among US isolates. 2 European isolates were less susceptible than US isolates to cefiderocol-xeruborbactam, cefiderocol, and ceftazidime-avibactam, but more susceptible to ceftolozane-tazobactam, imipenem-relebactam, and meropenem-vaborbactam.

2 Frequently Asked Questions What is cefiderocol-xeruborbactam? It is an investigational combination of cefiderocol, a siderophore-conjugated cephalosporin, and xeruborbactam, a β-lactamase inhibitor active against serine and metallo-β-lactamases. 1,4 How active was cefiderocol-xeruborbactam against carbapenem-resistant Acinetobacter?

The combination inhibited 98.5% of carbapenem-nonsusceptible A baumannii-calcoaceticus isolates collected in 2024, including 93.1% of NDM producers. 3 Does xeruborbactam add to cefiderocol activity in vivo? In a mouse urinary tract infection model, the combination reduced bacterial counts by more than 1 log10 against 4 isolates where cefiderocol alone did not.

4 Activity Against Carbapenem-Resistant Acinetobacter and Mouse UTI Model Results Of 1307 A baumannii-calcoaceticus isolates from 93 medical centers in 20 countries, 41.2% were carbapenem nonsusceptible, with higher rates in Europe (50.5%) than North America (28.8%). 3 Cefiderocol-xeruborbactam inhibited 98.5% of carbapenem-nonsusceptible isolates, compared with 0.2% for meropenem and 92.8% for colistin.

Activity reached 98.9% against OXA-23-like producers and 93.1% against NDM producers. 3 Xeruborbactam restored cefiderocol activity against PER-producing isolates, inhibiting 100% vs 4.8% with cefiderocol alone. 3 The combination also inhibited 84.0% of cefiderocol-nonsusceptible and 90.2% of sulbactam-durlobactam-nonsusceptible isolates.

Against sequence type 2, which accounted for 69.7% of carbapenem-nonsusceptible isolates, cefiderocol-xeruborbactam inhibited 98.7% vs 87.7% for cefiderocol and 92.8% for sulbactam-durlobactam. 3 Nonsusceptibility to cefiderocol (5.7%) and sulbactam-durlobactam (3.9%) was far less common than carbapenem nonsusceptibility.

3 Only 23 isolates (1.8%) had cefiderocol-xeruborbactam MICs above 4 mg/L. 3 In the mouse model, investigators infected neutropenic mice with 4 Enterobacterales isolates with cefiderocol MICs of 4 mg/L or higher, including an NDM producer. 4 Adding xeruborbactam lowered cefiderocol MICs against all 4 isolates in vitro, and bacterial burdens in untreated controls rose by about 2 to 3 log10 colony-forming units per kidney.

4 Cefiderocol alone, given at a humanized regimen, did not achieve a reduction of more than 1 log10 in kidney bacterial counts, and xeruborbactam alone showed no efficacy. 4 The combination produced more than a 1-log10 reduction against all 4 strains. 4 For the combination, MICs in the mouse model study were also determined in cation-adjusted Mueller-Hinton broth, consistent with the susceptibility testing methodology approved by CLSI and EUCAST in 2026.

4 References Papp-Wallace KM, Kimbrough JH, Maher JM, Mendes RE, Sader HS, Castanheira M. Activity of cefiderocol-xeruborbactam and comparator agents against Enterobacterales, including molecularly characterized isolates recovered globally in 2024. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC.

Poster P-166. Papp-Wallace KM, Kimbrough JH, Maher JM, Mendes RE, Sader HS, Castanheira M. Activity of cefiderocol-xeruborbactam and comparator agents against Pseudomonas aeruginosa, including molecularly characterized isolates recovered globally in 2024.

Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-168. Kimbrough JH, Papp-Wallace KM, Castanheira M.

Activity of cefiderocol-xeruborbactam and comparator agents against global Acinetobacter baumannii-calcoaceticus species complex isolates. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-167.

Mizusawa E, Toba S, Takagi F, et al. Bactericidal activity of cefiderocol/xeruborbactam in a murine urinary tract infection model. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC.

Poster P-163. Related to this article