1677. In vitro Activity of SPR206 and Comparator Compounds against Enterobacterales Isolates Responsible for Infections in United States Hospitals
Authors: Mendes Rodrigo E , Sader Helio S , Ryan Arends S J , Cotroneo Nicole , Critchley Ian A , Critchley Ian A , Castanheira Mariana 
Published: December 2022

Abstract

Background
SPR206 is a next generation polymyxin under clinical development to treat infections, such as pneumonia, bloodstream, and urinary tract infections caused by Gram-negative (GN) multidrug-resistant (MDR) pathogens. The in vitro activity of SPR206 and comparators was monitored against GN pathogens causing infection in US and European hospitals during 2021 as part of the SENTRY Antimicrobial Surveillance Program. This study reports the activity of SPR206 against Enterobacterales (ENT) from US hospitals.

Methods
A total of 1,614 ENT recovered from clinical samples during the SENTRY Program for 2021 were included in the study. Isolates were collected from medical centers in all 9 US Census Divisions and centrally tested for susceptibility using the CLSI broth microdilution method and interpretations.

Results
E. coli (EC; 425) and K. pneumoniae (KP; 425) were the most common pathogens included in this surveillance study, followed by E. cloacae (215), Citrobacter spp. (120), K. oxytoca (110), S. marcescens (104), K. aerogenes (65), P. mirabilis (60), M. morganii (60), and other 11 species (30). Overall, SPR206 and colistin (COL) had MIC50 of 0.06 and 0.25 mg/L against all ENT, respectively. Indole-positive Proteae, Proteus species and Serratia spp., which are intrinsically resistant to COL (MIC values, ≥8 mg/L), also had an elevated MIC for SPR206 (MIC, ≥8 mg/L). Excluding these organisms, SPR206 (MIC50/90, 0.06/0.12 mg/L) and meropenem (MIC50/90, 0.03/0.06 mg/L) showed the lowest MIC against this ENT subset, followed by COL (MIC50/90, 0.25/0.25 mg/L) and ceftazidime-avibactam (MIC50/90, 0.12/0.5 mg/L). SPR206 (MIC50/90, 0.06/0.12 mg/L) had MIC 2- to 4-fold lower than COL (MIC50/90, 0.25/0.25 mg/L) against EC and KP. Finally, SPR206 (MIC50/90, 0.06/0.25 mg/L) showed the lowest MIC against MDR and extremely drug-resistant (XDR) isolates.

Conclusion
SPR206 was consistently more potent than COL against ENT pathogens causing various infections in US hospitals. SPR206 remained active against the MDR and XDR subsets, where limited intravenous options were available. These SPR206 data, combined with its favorable safety and tolerability profiles in Phase 1 studies, support the continued clinical advancement and development of SPR206.

Disclosures
Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.