The main distinction between Streptococcus pyogenes and Streptococcus pneumoniae lies in their hemolytic patterns on blood agar. S. pyogenes is beta-hemolytic, causing complete lysis of red blood cells, resulting in a clear zone around colonies. In contrast, S. pneumoniae is alpha-hemolytic, partially lysing red blood cells and producing a greenish discoloration on the agar. This difference is crucial for laboratory identification and subsequent clinical management. Both are Gram-positive cocci, but their hemolysis type distinguishes their pathogenic mechanisms and treatment protocols.

Reference: Medical Microbiology, Murray et al., 9th Edition.