2266. Management of Ertapenem-Resistant, Meropenem-Susceptible Enterobacteriaceae

Abstract

Background. Carbapenemases are the most frequent mechanism of carbapenem resistance in Enterobacteriaceae. However, alternative mechanisms such as loss of porin channels or up-regulation of efflux pumps can cause intermediate- to high-level resistance to ertapenem (ERTA) and possibly reduced susceptibilities to meropenem (MERO) leading to discordant phenotypic profiles. Clinical implications of discordant carbapenem susceptibilities and optimal therapy options are yet unknown. We sought to describe our experience with carbapenem-discordant Enterobacteriaceae (CDE). Methods. Descriptive study of hospitalized adult patients with a CDE positive culture from December 1/16 - December 1/18. Discordance was defined as Enterobacteriaceae with an ERTA-resistant and MERO-susceptible phenotype. Primary objective was to describe antibiotic use patterns for CDE infections. Secondary outcomes included infectious diseases (ID) involvement and clinical outcomes. Clinical failure was defined as a composite of in-hospital mortality, switch of definitive therapy due to clinical worsening, re-hospitalization within 30 days for re-infection, or failure to achieve blood culture clearance for ≥7 days. Results. A total of 55 patients with CDE were identified. Most common organisms were Enterobacter cloacae complex (72%) and Klebsiella pneumoniae (9%). Of 21 isolates tested, 1 (4.8%) was positive for a carbapenemase. Mean age of patients was 61 ± 16 years, 51% were admitted to a medicine service, and 18% were immunocompromised. ID was involved in 82% of CDE cases. Most common sites were urine (33%), wound/tissue (27%), and respiratory (18%). 43/55 (78%) patients were treated - 17/43 (40%) with MERO, 14/43 (33%) with fluoroquinolones. Ceftazidime/avibactam and tigecycline were used in 4 (9%) patients each. Combination therapy was used in 8 (19%) patients, most commonly with MERO or tigecycline. Clinical failure occurred in 21/43 (49%) patients - 8/43 (19%) were receiving MERO-based therapy, 13/43 (30%) were receiving a non-MERO-based therapy. Conclusion. Discordance between ERTA and MERO susceptibility was more common in Enterobacter spp. Majority of isolates tested negative for a carbapenemase. MERO and fluoroquinolones were the most frequently used antibiotics for treatment of CDE infections.