1589. Activity of Meropenem-Vaborbactam and Comparators against Globally Disseminated Klebsiella pneumoniae Sequence Type 258
Authors: Shorttidge Dee , Deshpande Lalitagauri M , Doyle Timothy B , Streit Jennifer M , Castanheira Mariana 
Published: January 2021

Abstract

Background
Meropenem-vaborbactam (MVB) is a combination of a carbapenem and a b-lactamase inhibitor active against β-lactamases including serine carbapenemases. MVB recently was approved in the US and Europe for the treatment of complicated UTIs, including acute pyelonephritis, and is approved in Europe for treatment of complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, and bacteremia. Carbapenemase-producing Enterobacterales (ENT) isolates, particularly Klebsiella pneumoniae (KPN), have disseminated worldwide and are considered endemic in various countries. Carbapenem-resistant (CR) KPN outbreaks have been associated with KPN sequence-type 258 (ST258). Globally, 60-70% of KPC-producing KPN belong to ST258. In this study, we examined the susceptibilities of ST258 isolates collected as a part of the SENTRY global surveillance program.

Methods
KPN isolates from 2016-2019 were susceptibility tested by reference broth microdilution methods. The results were interpreted using CLSI 2020 breakpoints. The sequence type and presence of carbapenemases were determined by whole genome sequencing and analysis.

Results
130 KPN ST258 isolates were identified in 6 countries. All isolates were extremely drug resistant (XDR, susceptible to &lt; = 1 agent in 2 or fewer drug classes). 76.2% were CR, and 71 isolates contained blaKPC-2, 25 blaKPC-3 and 1 blaKPC-12. One isolate contained blaNDM-1. The US had the most ST258 isolates (n=56), of which 22 produced KPC-2 and 19 produced KPC-3. Greece had 32 isolates, with 17 KPC-2 and 5 KPC-3. Brazil had 22 isolates, 17 with KPC-2. The single NDM-1 producing isolate was from Argentina. Susceptibilities to MVB and comparators by country are shown in the table. MVB inhibited 99.2% of the isolates and was the most active agent overall, only 23.1% were meropenem susceptible. Tigecycline was the most active comparator with 98.5% susceptible.

Conclusion
These results demonstrate MVB has potent activity against the internationally disseminated KPN clone ST258 including those producing KPC. MVB may be useful for the treatment of infections caused by XDR K. pneumoniae.
Table 1

Disclosures
Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)