USMLE Step 2 Antibiotics and Treatments Practice Exam 2025 – Complete Prep Resource

The third and fourth generations of cephalosporins are known for their expanded Gram-negative coverage. This is largely due to their enhanced ability to penetrate the outer membrane of Gram-negative bacteria and their improved affinity for penicillin-binding proteins (PBPs) found in these organisms.

Third-generation cephalosporins, such as ceftriaxone and ceftazidime, offer significant coverage against a variety of Gram-negative pathogens, including those that produce extended-spectrum beta-lactamases (ESBLs) to some extent. They are often utilized in the treatment of serious infections caused by Gram-negative bacteria, including pneumonia, meningitis, and sepsis.

Fourth-generation cephalosporins, such as cefepime, are even broader in their Gram-negative coverage. They provide excellent efficacy against Pseudomonas aeruginosa and other multidrug-resistant Gram-negative organisms, making them a choice for hospital-acquired infections and in settings where resistant strains are prevalent.

Overall, selecting the third and fourth generations for their superior Gram-negative coverage reflects their position in the cephalosporin class as agents with enhanced activity against these challenging pathogens.