142. Evaluation of Meropenem-Vaborbactam Susceptibility and Underlying Resistance Mechanisms among Clinical KPC-producing <i>Klebsiella pneumoniae</i>

Abstract Background Meropenem-vaborbactam (MV) is the first carbapenem/β-lactamase inhibitor combination developed to restore meropenem susceptibility against KPC-producing carbapenem-resistant Enterobacterales(CRE). Vaborbactam (VAB) potently inhibits Ambler class A and C β-lactamases by reversible covalent binding of boronate serine side chains β-lactamases. Resistance MV in non-metallo-β-lactamase (MBL) producing Klebsiella pneumoniae (KP) isolates has been described but remains rare. We sought identify major molecular mechanisms associated with resistance KP (KPC-KP) isolates. Methods Clinical elevated MICs were identified consult service. Additional clinical mutations ompK35 or ompK36 genes selected from a historic database. Isolates MBL OXA-48-like excluded. Controls comprised susceptible KPC-KP determination was done using Sensititre automated broth microdilution (BMD) according CLSI. VAB avibactam concentrations held at 8 µg/ml 4 µg/ml, respectively. Whole genome sequencing (WGS) performed on all Genome libraries prepared Illumina Nextera XT MiSeq MinION. Results total 119 included study. All resistant meropenem. Twenty-one identified. harbored genes. Glycine/aspartate (GD 134-135) insertion, premature stop codon genes, concomitantly blaKPC copy number predominant among No insertion elements gene promoter region found. Two exhibited unique envZ See table for WGS MIC results. Table 1.Whole isolatesα: Truncated nodes 14 76, partial genotype consistent blaSHV-12WT: Wild type*: Premature codonGD: Duplication Glycine (G134) Aspartate (D135)FS: Frameshift mutationins: insertionMEM: meropenemMVB: meropenem-vaborbactamCZA: ceftazidime-avibactamCFD: cefiderocolN/A: not availableTable 2.Whole Conclusion reliably analyzed reveal contribution omp this phenotype. Elevated additionally recognized database preceding availability. In absence production, caution warranted use empirically due non-β-lactamase mediated mechanisms. Disclosures Daniel D. Rhoads, M.D. PhD, Luminex: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|Thermo Fisher: Advisor/Consultant Federico Perez, M.D., Accelerate: Grant/Research Support|Merck: Support|Pfizer: Support Robert A. Bonomo, MD, NIH VA: Support|VenatoRx Merck Wockhardt Cystic Fibrosis Foundation: Support.