CDC official urges focus on 'therapeutic non-responsiveness' alongside antimicrobial resistance

Dr. Clifford McDonald of the Centers for Disease Control and Prevention told the council that clinical failure sometimes occurs even when laboratory tests indicate an organism should respond to therapy, and he urged the field to name and measure that phenomenon. “Therapeutic — we call this therapeutic non-responsiveness. And simply defined, it's when a poor clinical outcome occurs despite receiving current standard of care treatment,” McDonald said during the panel's presentation.

McDonald outlined a patient-centered framework that places the host at the center and treats pathogen characteristics, antimicrobials, infection context, the microbiome and other therapeutics as interacting domains that can compound to cause poor outcomes. He highlighted recurrent Clostridioides difficile infection—with roughly one in five patients experiencing recurrence after apparently appropriate treatment—as an example where microbiome disruption, not classical resistance, can drive poor results. To address these gaps McDonald described a suite of approaches he calls pathogen reduction, microbiome restoration (PRMR), including selective live biotherapeutic products, bacteriophage, antiseptics and fecal microbiota transplantation. “The goal of this is to eliminate colonizing pathogens while preserving or restoring a healthy microbiome,” he said.

McDonald also summarized CDC infrastructure that supports these aims — the AR Lab Network for detection, the ARCH consortium for international colonization studies, stewardship programs, and diagnostic innovation platforms — and urged the council to consider how regulatory pathways, applied research, investment, and coordination could accelerate PRMR from promise to practice. He stressed this broader focus should not detract from traditional AMR control because genetically conferred resistance is transmissible and persistent across settings.