A randomized controlled trial evaluating a novel individualized treatment strategy for carbapenem-resistant Gram-negative bacteria infections

Why clinicians should know about it

• Picked for Microbiology (medical) (paper of the day, 18 September 2026): iACT‑guided therapy trial for carbapenem‑resistant infections

Abstract

OBJECTIVE: We assessed the impact of in vitro antibiotic combination testing (iACT)-guided therapy compared to standard therapy on carbapenem-resistant Gram-negative infections. METHODS: In this two-centre, open-label randomized trial, patients were randomized 1:1 to iACT-guided or standard therapy. The primary endpoint was 30-day all-cause mortality in the intention-to-treat (ITT) population. Exploratory analyses compared patients who received iACT-matched therapy with those who did not, irrespective of randomized assignment. FINDINGS: 102 patients were randomized and 98 included in the ITT analysis (49 per arm). The study was discontinued early due to substantial crossover: 31 (63%) patients assigned to the control arm switched to iACT-guided therapy at physician request due to anticipated intolerance to standard therapy. The 30-day mortality was 33% in both groups (difference 0%; 95% CI -18 to 18). Drug-related adverse events were 37% (iACT arm) versus 27% (control arm). Exploratory analysis showed that receipt of iACT-matched therapy (n=91) was associated with a larger absolute risk difference for 30-day all-cause mortality (difference -42%; 95% CI, -64 to -5) compared to the non-matched arm (n=7) but should be interpreted with caution due to the imbalanced groups and other confounding risks. CONCLUSIONS: Accrual in this trial was poor due to physicians' preference to adopt iACT-guided therapy. Randomized comparisons showed no mortality benefit, which was affected by significant treatment crossover. While exploratory analysis suggests potential utility of iACT-guided therapy for CRGNB infections, the findings is at most hypothesis-generating and needs to be validated with further investigations.

Abstract as published, via PubMed.