Background and Rationale
Carbapenem-resistant Enterobacterales (CRE) pose a growing threat in healthcare settings due to limited treatment options and high mortality. Colistin, often used as a backbone of therapy, is frequently combined with carbapenems like meropenem in attempts to broaden antimicrobial activity and suppress resistance. The AIDA randomized trial investigates whether colistin monotherapy or a colistin-meropenem combination influences the subsequent acquisition of CRE and the molecular characteristics of any isolates that emerge after therapy. Understanding these dynamics is critical for guiding clinical decisions and stewardship strategies.
Study Design and Methods
The AIDA trial enrolled patients with confirmed CRE infections deemed eligible for colistin-based therapy. Participants were randomized to receive either colistin monotherapy or a colistin-meropenem combination. Researchers collected serial clinical samples to monitor CRE acquisition following treatment, and performed molecular analyses on isolates to characterize resistance genes, plasmids, and clonal relationships. The study aimed to determine both the rate of new CRE isolation after treatment and the diversity of resistance mechanisms that arise in each arm.
Key Findings: CRE Acquisition After Therapy
Across the cohort, the incidence of subsequent CRE isolation after completing therapy was a central outcome. The colistin monotherapy arm showed a certain rate of CRE acquisition, while the colistin-meropenem combination arm demonstrated a comparable or differential rate depending on patient subgroups and infection sites. Importantly, the trial sought to determine whether adding meropenem to colistin suppresses or inadvertently selects for particular CRE strains in subsequent infections, with implications for both patient outcomes and hospital transmission risk.
Molecular Characterization and Resistance Mechanisms
Misolates obtained after therapy underwent comprehensive molecular profiling. Analyses focused on carbapenemase genes (such as bla genes), plasmid types associated with resistance, and multilocus sequence typing to trace clonal lineages. Findings highlighted the spectrum of resistance determinants that can emerge after different colistin-based strategies. In some cases, novel or dominant plasmid-mediated resistance elements were observed, underscoring the adaptive potential of CRE under selective pressure from antimicrobial regimens.
Clinical Implications
The results inform several practical considerations for clinicians and infection control teams. If colistin monotherapy and colistin-meropenem combination similarly affect CRE acquisition, decisions may hinge more on immediate clinical response, toxicity, and pharmacokinetic/pharmacodynamic goals rather than long-term CRE emergence alone. Conversely, a detectable difference in subsequent CRE acquisition or specific resistance patterns between arms could steer therapy toward regimens that minimize future risk of hard-to-treat infections. The study also emphasizes the importance of rapid diagnostics and stewardship to tailor regimens and monitor for resistance evolution during and after treatment.
Limitations and Future Directions
As with any randomized trial, the generalizability of findings may be influenced by patient selection, local epidemiology, and infection sites. The molecular landscape of CRE is diverse, and results may vary across regions with different prevalent carbapenemases and plasmids. Future work should explore longer follow-up periods, broader geographic representation, and the impact of alternative combination strategies on CRE dynamics and patient outcomes.
Conclusion
The AIDA trial provides valuable insights into how colistin-based therapies shape subsequent CRE acquisition and the molecular underpinnings of emergent resistance. While the optimal strategy may depend on individual patient factors and local resistance patterns, the study reinforces the need for integrated approaches combining antimicrobial stewardship, rapid diagnostics, and ongoing surveillance to curb the spread of CRE while effectively treating those with severe infections.
