A randomised controlled trial evaluating a novel individualised treatment strategy for carbapenem-resistant...

To assess the impact of in vitro antibiotic combination testing (iACT)-guided therapy compared with standard therapy on carbapenem-resistant Gram-negative infections.

In this two-centre, open-label randomised trial, patients were randomised 1:1 to iACT-guided or standard therapy. The primary endpoint was 30-d all-cause mortality in the intention-to-treat population. Exploratory analyses compared patients who received iACT-matched therapy with those who did not, irrespective of randomised assignment.

In total, 102 patients were randomised, with 98 included in the intention-to-treat 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-d 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-d all-cause mortality (difference, -42%; 95% CI, -64 to -5) compared with the non-matched arm (n = 7); however, this should be interpreted with caution due to the imbalanced groups and other confounding risks.

Accrual in this trial was poor due to physicians' preference to adopt iACT-guided therapy. Randomised comparisons showed no mortality benefit, which was affected by significant treatment crossover. While exploratory analysis suggests the potential utility of iACT-guided therapy for carbapenem-resistant Gram-negative bacterial infections, the findings are at most hypothesis-generating and need to be validated with further investigations.