2247. Real-world Experience with Meropenem–Vaborbactam (M/V) for Treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections

• Published in: Open forum infectious diseases Vol. 6; no. Supplement_2; p. S768
• Main Authors: Shields, Ryan K, McCreary, Erin K, Marini, Rachel V, Kline, Ellen G, Jones, Chelsea E, Hao, Binghua, Clancy, Cornelius J, Nguyen, Minh-Hong
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 23.10.2019
• Subjects: Abstracts
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofz360.1925

Abstract Background M/V demonstrates in vitro activity against KPC-producing CRE, but real-world clinical experience is limited. Methods Patients treated for > 48 hours with M/V for CRE infections were included. Success was defined as improved symptoms, absence of recurrent infection, and survival at 30 days. Microbiologic failures (MF) were defined as isolation of the same species post-treatment (tx). KPC and ompK36 mutations were detected by sequencing of PCR products. Results 19 patients were included; 58% were men; median age was 53. 11% were transplant recipients and median Charlson score was 3 (range: 0–10). Infection types included bacteremia (n = 7), pneumonia (6; 5 ventilator-associated), soft tissue (2), tracheobronchitis (2), intra-abdominal (1), and pyelonephritis (1). 68% of patients were in the ICU; median APACHE II and SOFA scores were 18 (7–40) and 4 (1–13), respectively. CR pathogens included K. pneumoniae (14), K. oxytoca (2), E. coli (2), and C. freundii (1); 89% harbored KPC, including KPC-2 (6), KPC-3 (10), and KPC-3 with a D179Y mutation (1). All were susceptible to M/V (median MIC = 0.03 µg/mL [0.015–0.12]). Median duration of tx was 8 days (3 – 28); 89% received monotherapy. Success and survival rates at 30d were 63% and 89%, respectively. Failures were due to death (2), recurrent infection (2), worse symptoms (2), and persistent bacteremia (1). Success rates for bacteremia and pneumonia were 57% and 67%, respectively. MF within 90 days occurred in 32% due to K. pneumoniae (5) or E. coli (1). MF were classified as intra-abdominal abscess (3), pneumonia (1), and respiratory (1) or urinary (1) colonization. The median time to MF was 32 days (15 – 67). M/V MICs were increased ≥8-fold against 67% (4/6) of recurrent isolates. 1 pt developed intra-abdominal infection due to M/V non-susceptible KPC-3 K. pneumoniae isolate (MIC = 8) following a 12-day of M/V; the recurrent isolate differed from the parent by an IS5 insertion in the ompK36 gene promoter. M/V was well-tolerated, 1 patient developed eosinophilia. Conclusion In this cohort of critically-ill patients with CRE infection, tx with M/V yielded outcomes comparable to prior cohorts treated with ceftazidime–avibactam. M/V non-susceptibility emerged in 1 isolate. Our findings require validation in future studies. Disclosures All authors: No reported disclosures.