Overview
Carbapenem-resistant Enterobacterales (CRE) infections pose a major challenge across healthcare settings due to limited treatment options and high mortality. The AIDA randomized trial investigates how initial treatment choices—specifically colistin monotherapy versus a combination of colistin with meropenem—may influence subsequent acquisition and molecular characteristics of CRE isolates. This article summarizes the study’s aims, methods, key results, and clinical implications for managing CRE infections while considering antimicrobial stewardship and patient outcomes.
Background and Rationale
Colistin remains a backbone therapy for many multidrug-resistant Gram-negative infections. In practice, clinicians often pair colistin with a carbapenem such as meropenem in the hope of synergistic activity or to broaden antimicrobial coverage. Yet, the impact of these strategies on later recovery of CRE organisms—particularly their genetic profiles and resistance determinants—has been less clear. The AIDA trial sought to determine whether initial colistin monotherapy or a colistin-meropenem combination influences the emergence or selection of CRE during or after therapy, with a focus on acquisition rates and molecular characteristics of isolates recovered in subsequent clinical samples.
Study Design and Methods
The trial randomized patients with documented or suspected carbapenem-resistant Gram-negative infections to receive either colistin alone or colistin with meropenem. Researchers collected clinical isolates before, during, and after therapy to assess CRE acquisition events. Molecular characterization included whole-genome sequencing of CRE isolates to identify resistance genes, sequence types, and potential clonal spread. The analysis aimed to answer whether combination therapy alters the likelihood of acquiring new CRE strains and whether the resistance mechanisms differ between treatment arms.
Key Findings: CRE Acquisition Rates
Initial results indicate that the choice between colistin monotherapy and colistin-meropenem therapy may influence CRE acquisition dynamics. In the colistin monotherapy arm, CRE isolates obtained during follow-up showed a certain distribution of resistance determinants and genetic backgrounds. In contrast, the colistin-meropenem combination arm demonstrated a distinct pattern in the recovered CRE population, with potential shifts in the prevalence of specific resistance genes or sequence types. Overall, the data suggest that initial combination therapy could modify the ecological landscape of CRE in treated patients, potentially affecting subsequent infection risk.
Molecular Characterization and Resistance Mechanisms
Whole-genome sequencing revealed both shared and unique features between CRE isolates from the two arms. Common carbapenemase genes, such as KPC, NDM, or OXA-type enzymes, were observed, but their distribution varied by treatment group. Some isolates carried multiple resistance determinants or mobile genetic elements that facilitate gene transfer, underscoring the complexity of CRE evolution under selective antibiotic pressure. The study’s molecular insights help explain observed differences in clinical outcomes and may guide future therapy choices and surveillance strategies.
Clinical Implications
From a clinical perspective, these findings emphasize that antimicrobial strategy can shape not only immediate efficacy but also the risk and nature of subsequent CRE infections. If colistin-meropenem therapy is associated with a distinct CRE profile or altered acquisition risk, clinicians might tailor initial regimens based on individual patient risk factors, infection site, and local resistance patterns. Additionally, the results highlight the importance of ongoing microbiological sampling and molecular surveillance during and after therapy to promptly detect and respond to emergent CRE strains.
Limitations and Future Directions
As with any randomized study, patient heterogeneity and local epidemiology influence generalizability. The molecular analyses, while informative, may be limited by sample size or the breadth of resistance determinants assessed. Future work should validate these findings across diverse settings, explore the impact on patient-centered outcomes such as mortality and length of stay, and investigate optimization strategies that minimize CRE emergence while preserving therapeutic efficacy.
Bottom Line
The AIDA trial contributes important evidence on how colistin-based regimens might shape CRE acquisition and its molecular underpinnings. By integrating clinical outcomes with detailed genomic profiling, researchers and clinicians can better balance immediate treatment success with long-term resistance management, ultimately improving care for patients facing carbapenem-resistant infections.
