In the course of our continuing search for novel antimicrobial agents, we isolated a new antibacterial compound Sch 575948 (1) along with a known alkaloid ptilomycalin A (2) from the marine sponge Ptilocaulis spiculifer. Sch 575948 was identified as a bicyclic bis-guanidine alkaloid, a homolog of crambescin A, based on extensive NMR and HRMS analyses, with the molecular formula established as C₁₈H₃₂N₆O₂ (found m/z 365.2665; calcd. m/z 365.2659 for [M+H]⁺). The stereochemistry at the C-13 position could not be defined due to the limited amount of compound available. Compound 1 exhibited antibacterial activity against a genetically engineered super sensitive strain of Staphylococcus aureus (RN4220) with the NorA efflux pump knockout, showing inhibition zones of 13, 15, and 18 mm in diameter at 25, 50, and 100 μg respectively in an agar diffusion assay. Ptilomycalin A (2) showed antifungal activity against Saccharomyces cerevisiae with inhibition zones of 10, 11, 12, and 13 mm at 10, 20, 40, and 80 μg respectively.