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"Activity against Gram-negative bacteria" refers to the efficacy of an antibiotic or antimicrobial agent to inhibit or kill bacteria classified as Gram-negative on the basis of their cell envelope structure. Gram-negative bacteria possess an outer membrane with lipopolysaccharide, making them intrinsically more resistant to many antibiotics; successful drugs must penetrate this barrier and reach intracellular targets such as penicillin-binding proteins, ribosomes, or DNA gyrase. "Activity against gram-negative bacteria" therefore does not correspond to a unique molecular target but rather to the ability of an agent to circumvent or overcome multiple, distinct bacterial defense mechanisms
For drugs with activity against Gram-negative bacteria, mechanisms of action reflect their molecular targets: - Inhibition of cell wall synthesis (e.g., penicillins, cephalosporins, carbapenems, monobactams) - Disruption of bacterial outer membrane integrity (e.g., polymyxins/colistin) - Inhibition of protein synthesis (e.g., aminoglycosides, tetracyclines) - Inhibition of DNA gyrase/topoisomerase (e.g., quinolones) - Inhibition of folate biosynthesis (e.g., trimethoprim, sulfonamides)
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