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

• Published in: Open forum infectious diseases Vol. 4; no. suppl_1; p. S537
• Main Authors: Paterson, David L, Kwak, Eun J, Bhowmick, Tanaya, Alexander, Elizabeth, Loutit, Jeffrey S, Zhang, Shu, Dudley, Michael N, Walsh, Thomas J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.10.2017
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofx163.1398

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, bacteremia, 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: carbapenems, aminoglycosides, polymyxin B, colistin, tigecycline, or ceftazidime-avibactam (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 efficacy 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. 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. Disclosures D. L. Paterson, Achaogen: Consultant, Consulting fee; Merck: Consultant and Investigator, Consulting fee and Research grant; Shionogi: Consultant, Consulting fee; GlaxoSmithKline: Consultant, Consulting fee; E. Alexander, The Medicines Company: Shareholder, Salary; J. S. Loutit, The Medicine’s Company: Employee and Shareholder, Salary; S. Zhang, The Medicines Company: Shareholder, Salary; M. N. Dudley, The Medicine’s Company: Employee and Shareholder, Salary; T. J. Walsh, The Medicines Company: Consultant and Investigator, Consulting fee and Research grant; Astellas: Consultant and Investigator, Consulting fee and Research grant; Allergan: Consultant and Investigator, Consulting fee and Research grant; Merck: Consultant and Investigator, Consulting fee and Research grant Outcomes in mCRE-MITT M-V (n = 10) BAT (n = 8) ALL (n = 18) Difference (95% CI) Clinical Cure at End of Therapy (EOT) 6 (60%) 2 (25%) 8 (44.4%) +35% (-13.5% to 72.8%) Clinical Cure at Test of Cure (EOT+7 days) 7 (70%) 0 (0%) 7 (38.9%) +70% (26.9% to 93.3%) All-Cause Mortality Day 28 2 (20%) 3 (37.5%) 5 (27.8%) -17.5% (-59.2% to 29.3%)