Background: Widespread antibiotic resistance among Enterobacteriaceae limits treatment options for cUTI and AP. Outcomes data for aminoglycoside treatment of cUTI and AP are lacking. Plazomicin, a next-generation aminoglycoside, has in vitro activity against multidrug-resistant (MDR) Enterobacteriaceae, including aminoglycoside nonsusceptible, ESBL-producing, and carbapenem-resistant strains. Here, we report diagnosis-specific baseline characteristics and efficacy and safety results from the EPIC study evaluating once-daily plazomicin versus meropenem for patients with cUTI or AP.
Methods: EPIC was a randomized, double-blind study. With stratification by diagnosis and region, hospitalized patients with cUTI or AP received IV plazomicin (15 mg/kg q24h) or IV meropenem (1 g q8h) for 4-7 days, followed by optional oral therapy, for a total of 7-10 days of therapy. Microbiological eradication (reduction of baseline pathogen to <104 CFU/mL), clinical cure (based on baseline symptoms), and composite cure (combined microbiological eradication and clinical cure) rates at the end-of-IV therapy (EOIV) and test-of-cure (TOC; Day 15-19) visits in the microbiological modified intent-to-treat (mMITT) population were analyzed for cUTI and AP subgroups.
Results: 58.2% of the mMITT population had cUTI and 41.8% had AP. cUTI patients were older, with a higher proportion of males, renal impairment, and resistant pathogens relative to patients with AP (Table 1). Composite cure, microbiological eradication, and clinical cure rates at EOIV were high for both treatment groups across diagnoses (Table 2). At TOC, plazomicin achieved higher composite cure rates than meropenem in cUTI and AP, driven by higher microbiological eradication rates in each subgroup. The incidence of AEs, including serious AEs and AEs leading to discontinuation of IV study drug, was low and comparable between treatment arms.
Conclusion: Plazomicin was well tolerated in patients with cUTI or AP, and demonstrated higher microbiological eradication rates for both diagnoses at the TOC visit than meropenem, a preferred agent for treatment of infections due to MDR Enterobacteriaceae. The results support plazomicin as a potential treatment option for cUTI and AP.
D. J. Cloutier,
D. S. Cebrik, Achaogen, Inc.: Employee , Salary
T. R. Keepers, Achaogen, Inc.: Employee , Salary
K. M. Krause, Achaoge, Inc.: Employee , Salary
L. E. Connolly, Achaogen, Inc.: Employee and Shareholder , Salary
F. M. E. Wagenlehner, Achaoge, Inc.: Consultant and Investigator , Consulting fee
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