Imipenem/Cilastatin/Relebactam for MDR Pseudomonas aeruginosa: Real-World Clinical Effectiveness and Contexts of Use
Emre Yücel, Dionysios Ntais, Mike Allen, David W. Hilbert, Mary R. Motyl, Fakhar Siddiqui, Katherine Young, Hannah Collings, Medi StoneBackground: Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with substantial morbidity, mortality and therapeutic uncertainty, particularly in critically ill and immunocompromised patients. Imipenem/cilastatin/relebactam (IMI/REL) combines the established carbapenem imipenem with cilastatin, a dehydropeptidase-I inhibitor, and relebactam, a diazabicyclooctane beta-lactamase inhibitor that restores imipenem activity against selected class A and class C beta-lactamase-mediated resistance mechanisms. Methods: A targeted narrative review was undertaken to identify and provide an overview of published observational studies and conference abstracts reporting clinical outcomes with IMI/REL in patients with confirmed or suspected MDR P. aeruginosa infection. Evidence was summarized descriptively, because the available studies were heterogeneous in design, infection site, patient severity, pathogen mix, susceptibility testing and outcome definitions. Results: Real-world IMI/REL data remain limited but are increasingly informative. IMI/REL was commonly used in high-risk patients, including those with pneumonia, bacteremia, intensive care admission, prior antimicrobial exposure, polymicrobial infection or limited alternative treatment options. Reported clinical success or clinical cure was observed in approximately 56–70.2% of patients, although interpretation is limited by non-comparative designs, small patient populations and mixed-pathogen populations. Thirty-day all-cause mortality varied widely, broadly reflecting baseline severity, infection site and salvage-therapy use. Emergence of IMI/REL non-susceptibility was variably reported, but some recent studies report high rates of treatment-emergent resistance; this requires caution and remains an important area for surveillance. Conclusions: IMI/REL appears to be a clinically useful option for susceptible MDR P. aeruginosa infections, particularly in patients with limited alternatives. Available real-world evidence should be interpreted cautiously, because most data derive from retrospective uncontrolled cohorts.