Antimicrobial Activity and Spectrum of a Seachaid Pharmaceuticals Investigational Compound (SP2078) Tested against Gram-positive Pathogens

• SP2078 inhibited all MRSA and MSSA strains at ≤0.12 µg/mL (MIC 50/90 , 0.06/0.06 µg/mL), and exhibited MIC 50 results four- to eight-fold lower than the direct comparators daptomycin (MIC 50 , 0.25 µg/mL), vancomycin (MIC 50 , 0.5 µg/mL) and teicoplanin (MIC 50 , 0.5 µg/mL; Table 1). • Similarly, all hVISA and VISA strains were inhibited by SP2078 at ≤0.12 µg/mL (MIC 50 values of 0.06 and 0.12 µg/mL, respectively; Table 1). SP2078 displayed MIC 50 values eight-fold lower than daptomycin (MIC 50 , 0.5-1 µg/mL) and 16- to 64-fold lower than vancomycin (MIC 50 , 1-4 µg/mL) and teicoplanin (MIC 50 , 2-8 µg/mL) when tested against hVISA and VISA, respectively. • Higher MIC values were observed for SP2078 when tested against VRSA strains (MIC 50 , 2 µg/mL), while daptomycin remained in vitro active (MIC 50 , 0.25 µg/mL; Table 1). • SP2078 (MIC 50/90 , 0.03/0.06 µg/mL) was eight-fold more potent than daptomycin (MIC 50/90 , 0.25/0.5 µg/mL), and 32- to 64-fold more potent than vancomycin (MIC 50/90 , 1/2 µg/mL) and teicoplanin (MIC 50/90 , 2/4 µg/mL) tested against S. epidermidis (Table 1). • Overall, the SP2078 compound exhibited higher MIC results (MIC 50/90 , 8/8 µg/mL) when tested against vancomycin-resistant VanA-type E. faecalis (Table 2); while daptomycin (MIC 50/90 , 1/2 µg/mL) and linezolid (MIC 50/90 , 1/1 µg/mL) remained very active. • When tested against vancomycin-resistant VanB-type E. faecalis, SP2078 (MIC 50/90 , 0.12/0.12 µg/mL) demonstrated in vitro activity comparable to the wildtype vancomycin-susceptible control strains (MIC 50/90 , 0.06/0.12 µg/mL; Table 2). • SP2078 was active when tested against vancomycin-susceptible (MIC 50/90 , 0.03/0.03 µg/mL) and -resistant (VanB) E. faecium (MIC 50/90 , 0.015/0.03 µg/mL; Table 3). However, SP2078 was less active against vancomycin-resistant (VanA) E. faecium strains (MIC 50/90 , 4/8 µg/mL). • Enterococcal isolates intrinsically harboring the vanC gene were very susceptible to SP2078 (MIC 50/90 , 0.06/0.25 µg/mL; Table 4). In addition, teicoplanin and daptomycin (MIC 50/90 , 1/2 µg/mL for both) showed MIC 50 values 16-fold higher than SP2078, whereas the vancomycin MIC 50 value obtained (MIC 50/90 , 4/4 µg/mL) was 64-fold higher than SP2078. • SP2078 (MIC 50/90 , 0.03/0.06 µg/mL) was four-fold more potent than teicoplanin (MIC 50/90 , 0.12/0.25 µg/mL) and daptomycin (MIC 50/90 , 0.12/0.25 µg/mL), and eight-fold more active than vancomycin (MIC 50/90 , 0.25/0.5 µg/mL) when tested against β-hemolytic streptococci (Table 5).