Improved Outcomes with Plazomicin (PLZ) Compared with Colistin (CST) in Patients with Bloodstream Infections (BSI) Caused by Carbapenem-resistant Enterobacteriaceae (CRE): Results from the CARE Study. (4th October 2017)

• Record Type: Journal Article
• Authors: McKinnell, James A; Connolly, Lynn E; Pushkin, Richard; Jubb, Adrian M; O'Keeffe, Bridget; Serio, Alisa W; Smith, Alex; Gall, Jonathan; Riddle, Valerie; Krause, Kevin M; Pogue, Jason M
• Is Part Of: Open forum infectious diseases. Volume 4(2017)Supplement 1
• Page Start: S531
• Page End: S531
• Publication Date: 2017-10-04
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx163.1383
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: CRE BSIs have high mortality and limited treatment options. PLZ is a next-generation aminoglycoside with activity against multidrug-resistant Enterobacteriaceae. CARE was a phase 3, open-label study that evaluated the efficacy and safety of PLZ in patients with infections due to CRE. The aim of this exploratory analysis was to evaluate outcomes in the subgroup with CRE BSI. Methods: CARE enrolled 2 cohorts: Cohort 1 (C1), a randomized comparison of PLZ vs. CST and Cohort 2 (C2), a single-arm study of PLZ in patients ineligible for C1. Patients in C1 received PLZ (15 mg/kg q24h) or CST (300-mg load [colistin base activity] then 5 mg/kg/d) plus tigecycline or meropenem. Patients in C2 received PLZ plus investigator's choice of adjunctive agent. Treatment was 7–14 days. The primary endpoint was all-cause mortality (ACM) at Day 28 or significant disease-related complications (SDRCs) in patients with confirmed CRE who received ≥1 dose of study drug (mMITT population). Clearance of bacteremia by Day 5 required 2 negative cultures ≥24 hours apart with sustained clearance through the study period. Serum creatinine levels were assessed by a central lab. Results: Of 39 patients enrolled in C1, 30 had BSI (29 mMITT). PLZ patients had lower ACM at Day 28 or SDRCs and ACM at Day 28 compared with CST patients and higher rates of bacteremia clearance by Day 5 (Table). Lack of clearance in PLZ patients was due to recurrence beyond Day 5 (1 pt) and insufficient follow-up to demonstrate clearance (1 pt); 6 CST patients failed to clear by Day 5 and 2 had recurrence beyond Day 5. 10%(1/10) of PLZ and 25% (3/12) of CST patients experienced a ≥0.5 mg/dL increase in serum creatinine from baseline through the end of therapy. Of 30 patients enrolled in C2, 15 had BSI (14 mMITT). ACM at Day 28 or SDRCs and ACM at Day 28 were 35.7% (5/14) and 14.3% (2/14), respectively. Clearance of bacteremia at Day 5 was observed in 64.3% (9/14); of the 5 whose bacteremia did not clear, 1 failed to clear by Day 5 and 4 had recurrence beyond Day 5. A ≥0.5 mg/dL increase in serum creatinine through the end of therapy was reported in 33.3% (4/12). Conclusion: PLZ was associated with improved survival and microbiological clearance compared with CST in C1 patients with BSI; outcomes in C2 were supportive of these findings. PLZ may be an important potential new treatment option for patients with CRE BSI. Disclosures: J. A. McKinnell, Achaogen, Inc.: Consultant and Shareholder, Consulting fee; L. E. Connolly, Achaogen, Inc.: Employee and Shareholder, Salary; R. Pushkin, Achaogen, Inc.: Employee, Salary; A. M. Jubb, Achaogen, Inc.: Employee and Shareholder, Salary; B. O'Keeffe, Achaogen, Inc: Employee, Salary; A. W. Serio, Achaogen, Inc.: Employee and Shareholder, Salary; A. Smith, Achaogen, Inc.: Employee and Shareholder, Salary; J. Gall, Achaoge, Inc.: Employee, Salary; V. Riddle, Achaogen, Inc.: Consultant and Independent Contractor, Consulting fee; K. M. Krause, Achaogen, Inc.: Employee, Salary; J. M. Pogue, Achaogen, Inc.: Consultant, Consulting fee