Rethinking Treatment for Invasive Stenotrophomonas maltophilia Infections

Body:The 2026 guidance designates cefiderocol monotherapy as the preferred treatment for invasive S maltophilia infections, acknowledging the suggestion rests on susceptibility data and neutropenic animal studies with very little supportive clinical data. Aztreonam-avibactam, preferably combined with a second agent, is now listed as an alternative. As in the CRAB section, the panel added the term “invasive infections” throughout the section to clarify its suggestions apply to infection rather than colonization.

In this final episode, Pranita D. Tamma, MD, MHS, of the Department of Pediatrics at the University of Pennsylvania School of Medicine, explains why the panel moved away from trimethoprim-sulfamethoxazole as the default choice. She points to concerns raised by the FDA, EUCAST, and CLSI during breakpoint reviews, along with animal data showing stasis at best, even at very low MICs. Cefiderocol, by contrast, consistently achieved a 1- to 2-log kill across four separate animal models, though clinical outcomes data remain limited.

“In my own practice, I’ve definitely felt comfortable using cefiderocol for invasive steno infections as monotherapy,” said Tamma

Emily L. Heil, PharmD, MS, FIDP, BCIDP, AAHIVP, professor in the Department of Practice, Sciences, and Health Outcomes Research at the University of Maryland School of Pharmacy and pharmacy director of the Antimicrobial Stewardship Program at the University of Maryland Medical Center, notes the field still lacks a true gold standard for Stenotrophomonas, because most clinical studies are retrospective, single center, and unable to reliably distinguish infection from colonization. Both clinicians support starting with combination therapy for critically ill patients, then moving to a single agent once the patient stabilizes or source control is achieved.

The discussion closes with an update on aztreonam-avibactam, for which CLSI set S maltophilia breakpoints in June; they will appear in the M100 document in early 2027. Tamma and Heil encourage clinicians to publish their experiences with these agents and to share feedback on the guidance ahead of its next update.