Trial finds cefiderocol isn't superior to standard antibiotics for bloodstream infections

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IV drip with antibiotics — sudok1 / iStock

The results of a phase 3 trial show cefiderocol is noninferior, but not superior, to currently used standard-of-care antibiotics in patients with gram-negative bloodstream infections, researchers reported today in The Lancet Infectious Disease.

In The GAME CHANGER trial, investigators enrolled patients with healthcare-associated or hospital-acquired gram-negative bloodstream infections in six countries (Australia, Malaysia, Singapore, Taiwan, Thailand, and Turkey) and randomly assigned them 1:1 to receive either cefiderocol (2 grams every 8 hours) or the standard-of-care antibiotic chosen by the patient's clinical team.

Approved by the US Food and Drug Administration in 2017, Cefiderocol is a broad-spectrum siderophore antibiotic that has demonstrated in vitro activity against carbapenem-resistant pathogens, which are among the most difficult to treat. But previous trial results in patients with carbapenem-resistant infections have been inconclusive.

The primary outcome of the trial was all-cause mortality at 14 days after randomization. The noninferiority margin was 10 percentage points, and superiority was to be assessed if noninferiority was shown.

More evidence needed for efficacy against carbapenem-resistant bacteria

Of the 504 patients who were included in the final analysis, 250 were in the cefiderocol group and 254 in the standard-of-care group. A subset of 127 patients had at least one bacterial isolate with resistance to carbapenems. At 14 days, 20 (8%) of 250 patients in the cefiderocol group had died, compared with 17 (7%) of 254 patients in the standard-of-care group, for an absolute risk difference of 1 percentage point (95% confidence interval [CI], –3 to 6).

Within the carbapenem-resistant subset, 9 (14%) of 64 patients in the cefiderocol group died within 14 days, compared with 6 (10%) of 63 patients in the standard-of-care group, for an absolute risk difference of 5 percentage points (95% CI, –7 to 16).

Five treatment-emergent serious adverse events were reported that were either probably or possibly related to the study drug, all in the cefiderocol group.

"This evidence suggests that cefiderocol is efficacious in patients with health-care-associated gram-negative bloodstream infection who are at high risk of antibiotic resistance, but more evidence is required to define its efficacy when carbapenem-resistant organisms are the cause," the investigators wrote.

West Nile death reported in California

News brief

Chris Dall, MA

California yesterday reported its fifth West Nile virus–related death this year, in a man from Placer County in the Central Valley.

There have been 54 confirmed human West Nile virus cases in the state this year, 5 of them in Placer County, where county officials said high numbers of West Nile virus-positive mosquitoes and dead birds have been found. It's the first West Nile virus–related death in the county this year.

Slight risk of neuroinvasive disease

Though the risk of serious illness from West Nile virus is low, less than 1% of those infected can develop a serious illness known as neuroinvasive West Nile, which is fatal for about 10% of patients. People 50 years of age and older have a higher chance of getting sick and are more likely to develop complications.

"When there is a higher than normal proportion of West Nile virus infected mosquitoes as there has been this year, despite our efforts to reduce these populations, the risk of disease transmission to people also gets higher," Joel Buettner, general manager of the Placer Mosquito and Vector Control District, said in a county news release. "West Nile virus can be a deadly disease and we encourage everyone to take precautions to reduce their risk of mosquito bites."

West Nile is the leading mosquito-borne illness in the continental United States. The Centers for Disease Control and Prevention has tracked 1,137 cases so far in 2025 in 42 states. Activity is up about 40% from last year.