Meropenem-Vaborbactam vs. Best Available Therapy for Carbapenem-Resistant Enterobacteriaceae Infections in TANGO II: Outcomes in Immunocompromised Patients

Abstract

Background. Immunocompromised patients are at high risk for mortality due to carbapenem‐resistant Enterobacteriaceae (CRE). Meropenem‐vaborbactam (M‐V) is a novel cyclic boronic acid β‐lactamase inhibitor combination being developed for treatment of serious gram‐negative infections, including CRE. This analysis reports outcomes among immunocompromised subjects in TANGO II, a randomized, open‐label comparative trial with best available therapy (BAT) in subjects with complicated urinary tract infection (cUTI), acute pyelonephritis (AP), HABP/VABP, bacter‐emia, and cIAI, due to known or suspected CRE. Methods. Eligible subjects were randomized 2:1 to M‐V (2g/2g every 8h) or BAT for 7 to 14 days. BAT included any of the following, alone or in combination: car‐bapenems, aminoglycosides, polymyxin B, colistin, tigecycline, or cefazidime‐avibac‐tam (monotherapy only). Clinical cure was defined as complete resolution of signs or symptoms such that no further antimicrobial therapy was required. Results. Of the 50 subjects who had a baseline pathogen (m‐MITT population), 19 (38.0%) were immunocompromised (4 leukemia/lymphoma, 5 medication, 10 transplant). Among the 43 subjects with a baseline CRE pathogen (mCRE‐MITT), 18 (41.9%) were immunocompromised. The most common infection types among immunocompromised subjects (mCRE‐MITT) were bacteremia (61.1%), cUTI/AP (16.7%), HABP/VABP (11.1%), and cIAI (11.1%). Clinical effcacy and mortality among immunocompromised in the mCRE‐MITT population are shown. M‐V was associated with fewer drug‐related adverse events (30.8% vs. 40.0%), serious adverse events (38.5% vs. 50.0%), and renal‐related adverse events (7.7% vs. 40.0%) than BAT. [Figure Presented] Conclusion. In immunocompromised subjects, receipt of M‐V was associated with higher clinical cure rates and a lower mortality rate than BAT (m‐MITT, mCRE‐MITT populations). M‐V is a promising treatment option for CRE in this population.