Miller Keith, Storey Christopher, Stubbings William J, Hoyle Anthony M, Hobbs Joanne K, Chopra Ian
Antimicrobial Research Centre and School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK.
J Antimicrob Chemother. 2005 Apr;55(4):579-82. doi: 10.1093/jac/dki003. Epub 2005 Feb 18.
We examined the antistaphylococcal activity of the novel cephalosporin CB-181963 (formerly known as CAB-175), with emphasis on its microbiological activity and penicillin-binding protein specificities.
Using established procedures, we examined the activity of CB-181963 against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains of Staphylococcus aureus in both planktonic and biofilm culture. We also determined whether CB-181963 exhibited a post-antibiotic effect (PAE). A radioactive competition assay with (3)H-labelled benzylpenicillin was used to determine penicillin-binding protein (PBP) affinities of CB-181963, including binding to PBP2a from MRSA. The potential for emergence of CB-181963-resistant mutants in MSSA and MRSA strains was examined using plating procedures.
CB-181963 showed excellent activity against MRSA strains resistant to other cephalosporins in both planktonic and biofilm cultures. However, in common with other cephalosporins it was unable to eradicate biofilms. CB-181963 had a short PAE compared with other beta-lactam antibiotics. CB-181963 retained activity against a strain expressing type A beta-lactamase and demonstrated affinity for PBP2a of MRSA. Mutants resistant to CB-181963 were not recovered in either MSSA or MRSA.
CB-181963 is a potent antistaphylococcal agent with better activity against MRSA than other cephalosporins. The anti-MRSA activity is correlated with elevated binding to PBP2a. CB-181963 may have a role in the treatment of staphylococcal infections, including those caused by MRSA and in the prophylaxis of biofilm-associated MSSA and MRSA infections. However, because of its short PAE, CB-181963 may have to be administered more frequently than other beta-lactam antibiotics, or given via prolonged infusion.
我们研究了新型头孢菌素CB - 181963（原称CAB - 175）的抗葡萄球菌活性，重点关注其微生物活性和青霉素结合蛋白特异性。
采用既定程序，我们检测了CB - 181963在浮游菌和生物膜培养中对甲氧西林敏感（MSSA）和甲氧西林耐药（MRSA）金黄色葡萄球菌菌株的活性。我们还确定了CB - 181963是否表现出抗生素后效应（PAE）。使用放射性竞争试验和³H标记的苄青霉素来确定CB - 181963的青霉素结合蛋白（PBP）亲和力，包括与MRSA的PBP2a的结合。使用平板接种程序检测MSSA和MRSA菌株中CB - 181963耐药突变体出现的可能性。
CB - 181963在浮游菌和生物膜培养中对耐其他头孢菌素的MRSA菌株均表现出优异的活性。然而，与其他头孢菌素一样，它无法根除生物膜。与其他β - 内酰胺类抗生素相比，CB - 181963的PAE较短。CB - 181963对表达A类β - 内酰胺酶的菌株仍具有活性，并对MRSA的PBP2a表现出亲和力。在MSSA或MRSA中均未获得对CB - 181963耐药的突变体。
CB - 181963是一种强效的抗葡萄球菌药物，对MRSA的活性优于其他头孢菌素。其抗MRSA活性与对PBP2a的结合增加相关。CB - 181963可能在葡萄球菌感染的治疗中发挥作用，包括由MRSA引起的感染以及预防与生物膜相关的MSSA和MRSA感染。然而，由于其PAE较短，CB - 181963可能需要比其他β - 内酰胺类抗生素更频繁地给药，或通过延长输注给药。
