Meropenem-Vaborbactam vs. Best AvailableTherapy for Carbapenem-ResistantEnterobacteriaceae Infections in TANGO II: PrimaryOutcomes by Site of Infection

Abstract

Background. Meropenem-vaborbactam (M-V) is a β-lactamase inhibitor combination active against Klebsiella pneumoniaecarbapenemase (KPC)-producing CRE. Few clinical trials of new agents have been conducted in patients with CRE. Methods. TANGO II is a randomized, Phase 3, open-label trial in patients with infections due to known or suspected CRE, including complicated urinary tract infection (cUTI), acute pyelonephritis (AP), HABP/VABP, bacteremia, or complicated intra-abdom-inal infection (cIAI). Eligible subjects were randomized 2:1 to monotherapy with M-V or Best Available Terapy (BAT) for 7-14 days. BAT could include (alone or in combination): a carbapenem, aminoglycoside, polymyxin B, colistin, tigecycline or cefazidime-avibactam (monotherapy only). Enrollment was stratifed by infection type and geographic region. Endpoints difered by infection: overall success (clinical cure + microbial eradication) in cUTI/AP, 28-day all-cause mortality in HABP/VABP + bacteremia, and clinical cure in cIAI. It was not powered for inferential statistical testing; results are presented descriptively. Results. 72 patients were enrolled: 43 (59.7%) had baseline CRE and comprised the microbiologic CRE modified intent-to-treat population (mCRE-MITT, primary population). In mCRE-MITT, 20 had bacteremia, 15 had cUTI/AP, 5 had HABP/VABP, and 3 had cIAI. [Figure Presented] ∗4 M-V subjects were indeterminate/not assessed at TOC. AEs occurred in 84.4% of M-V patients vs. 92% on BAT. M-V was associated with fewer drug-related AEs (24.4% vs. 44%), severe AEs (13.3% vs. 28%), and serious AEs (33.3% vs. 44%) vs. BAT. Conclusion. In this first prospective comparative trial of a β-lactam/β-lactamase inhibitor combination as monotherapy of CRE infections, M-V showed consistent improvement over BAT in effcacy endpoints across infections, and improved safety/tolerability. M-V appears to be an improved treatment option for CRE infections.