124. Microbiological Outcomes With Plazomicin (PLZ) Versus Meropenem (MEM) in Patients (pts) With Complicated Urinary Tract Infections (cUTI), Including Acute Pyelonephritis (AP) in the EPIC Study
Session: Oral Abstract Session: What's Hot in UTIs and STIs
Thursday, October 4, 2018: 8:45 AM
Room: S 158

Background: PLZ is a next-generation aminoglycoside (AG) that is structurally protected from common AG-modifying enzymes (AMEs) in Enterobacteriaceae and with in vitro activity against multidrug-resistant Enterobacteriaceae, including ESBL-producing, AG-resistant, and carbapenem-resistant isolates. We report microbiological outcomes in the EPIC study, including outcomes for resistant pathogens and by the PLZ MIC.

Methods: EPIC was a multinational, randomized, double-blind study in hospitalized pts with cUTI or AP. Pts received IV PLZ (15 mg/kg q24h) or IV MEM (1 g q8h) for 4-7 days, followed by optional oral therapy, for a total of 7-10 days of therapy. The extended mMITT population included pts with 1 qualifying baseline pathogen (105 CFU/mL urine) who received study drug. Microbiological outcomes were assessed at TOC (day 15-19). Isolate identification and susceptibility testing were conducted by a central laboratory. Whole-genome sequencing was used to identify AME and β-lactamase genes.

Results: Of 609 pts enrolled, 407 (66.8%) were included in the extended mMITT population. The most common uropathogen was Escherichia coli (63.4%) followed by Klebsiella pneumoniae (19.7%). PLZ and MEM MIC50/90 for Enterobacteriaceae were 0.5/2 μg/mL (range: ≤0.06->128 mg/mL) and 0.015/0.06 mg/mL (range: ≤0.004-128 mg/mL), respectively. ESBL and AG-NS phenotypes were found in 29% and 27% of isolates, respectively. Genotyping detected β-lactamase and AME genes in 32.5% and 36.8% of isolates, respectively, most commonly blaCTX-M-15 (n = 98), blaOXA-1/OXA-30 (n = 82), aac(6`)Ib-cr (n = 79), and aac(3)-IIa (n = 56). Rates of microbiological eradication are shown in Table 1. All Enterobacteriaceae in the PLZ group with a PLZ MIC of 4 µg/mL (6/6) were eradicated at TOC (Table 2). Across 49 pts with concurrent bacteremia, 100% (27/27) and 96% (24/25) of Enterobacteriaceae were cleared from the blood at TOC in the PLZ and MEM groups, respectively.

Conclusion: PLZ demonstrated comparable or higher microbiological eradication rates compared to MEM for common gram-negative uropathogens, including resistant pathogens. The results support PLZ as a potential treatment option for cUTI, including AP, caused by Enterobacteriaceae with PLZ MICs of ≤4 mg/mL.

Tiffany R. Keepers, PhD, Deborah S. Cebrik, MS, MPH, Daniel J. Cloutier, PharmD, Allison Komirenko, PharmD, Lynn Connolly, MD, PhD and Kevin Krause, MBA, Achaogen, Inc., South San Francisco, CA

Disclosures:

T. R. Keepers, Achaogen, Inc.: Employee , Salary .

D. S. Cebrik, Achaogen, Inc.: Employee , Salary .

D. J. Cloutier, Achaogen, Inc.: Employee and Shareholder , Salary .

A. Komirenko, Achaogen, Inc.: Employee and Shareholder , Salary .

L. Connolly, Achaogen, Inc.: Consultant , Consulting fee .

K. Krause, Achaogen, Inc.: Employee , Salary .

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