The key idea is that Gram-negative bacteria have an extra protective layer that Gram-positive bacteria do not. Their outer membrane, which contains lipopolysaccharide, sits outside a thin peptidoglycan layer and acts as a strong barrier to many antimicrobial agents. This outer membrane limits what can diffuse into the cell, thanks to selective porin channels that restrict entry of larger or certain charged molecules. Once anything gets past the outer membrane, there’s still a periplasmic space with enzymes such as beta-lactamases that can inactivate antibiotics, and active efflux pumps that remove drugs that do manage to get in. Put together, these multiple defensive layers make Gram-negative bacteria much more resistant to many treatments compared with organisms that lack this outer membrane.