1676. Activity of SPR206 and Comparator Agents Against Pseudomonas aeruginosa and Acinetobacter baumannii Causing Infections in United States Hospitals

Abstract Background SPR206 is a next generation polymyxin being developed to treat serious infections caused by Gram-negative (GN) multidrug-resistant (MDR) pathogens. The in vitro activity of SPR206 and comparators were 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 A. baumannii-calcoaceticus species complex (ACB) and P. aeruginosa (PSA) recovered from patients hospitalized in the USA. Methods A total of 238 ACB and 450 PSA recovered from clinical samples during the SENTRY Program for 2021 were included in the study. Isolates were collected from sites in all 9 US Census Divisions and centrally tested for susceptibility by CLSI broth microdilution method and interpretations. Results A total of 34.9% (83/238) and 14.7% (35/238) ACB displayed an MDR or XDR phenotype, whereas 17.8% (80/450) and 8.0% (36/450) PSA had these phenotypes, respectively. Overall, SPR206 had MIC50/90 of 0.12/0.5 mg/L against all ACB, whereas colistin (COL) had MIC50/90 results of 0.5/1 mg/L. SPR206 and COL inhibited, respectively, 98.0% and 97.0% of ACB at MIC of ≤2 mg/L. Other agents tested against ACB showed MIC90 of >16 mg/L. SPR206 remained active against the MDR (MIC50/90, 0.12/1 mg/L) and XDR (MIC50/90, 0.12/0.25 mg/L) subsets of ACB, as did COL (MIC50/90, 0.5/1 mg/L). MIC50, MIC90, and MIC100 of 0.25 mg/L, 0.25 mg/L, and 2 mg/L were obtained for SPR206 against all PSA, respectively. COL (MIC50/90, 1/1 mg/L), ceftazidime-avibactam (MIC50/90, 2/8 mg/L; 94.9% susceptible), and ceftolozane-tazobactam (MIC50/90, 0.5/2 mg/L; 96.9% susceptible) were active against PSA. SPR206 (MIC50/90, 0.25/0.5 mg/L) and COL (MIC50/90, 1/1 mg/L) remained active against the MDR and XDR PSA subsets. Conclusion SPR206 showed potent in vitro activity against these recent collections of ACB and PSA from the USA. SPR206 potency was consistently greater than clinically available in-class and other comparator agents. These results, and favorable safety and tolerability profiles of SPR206 in Phase 1 studies, support the clinical development of SPR206 for the usually difficult-to-treat infections caused by these pathogens and their resistant subsets. 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.