Cephalosporins comprise a β-lactam antibiotic class whose first members were discovered in 1945 from the fungus Cephalosporium acremonium. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as Neisseria gonorrhoeae. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.

头孢菌素属于 β-内酰胺类抗生素，其首批成员于 1945 年从真菌顶头孢霉中发现。由于它们能够通过孔蛋白穿过外膜进入周质并破坏肽聚糖合成，因此它们在革兰氏阴性细菌感染的临床用途广泛。最新的头孢菌素类药物被用作治疗复杂性尿路感染、MRSA 和其他多重耐药病原体（例如淋病奈瑟菌。不幸的是，全球头孢菌素耐药菌株不断增加，对此类药物的异质耐药性已成为日益关注的话题，而耐受性和持续性被认为是头孢菌素治疗失败的潜在原因。在这篇综述中，我们总结了头孢菌素类抗生素从发现到其作用机制的整个过程，并讨论了头孢菌素治疗失败的原因，包括耐药性、耐受性以及仅少数细菌培养亚群表现出这些品质的现象（异抗性和耐药性）。坚持）。此外，我们还讨论了最近在头孢菌素结合物和联合治疗方面所做的努力如何旨在重振此类抗生素的活力。