Analysis of synergy between beta-lactams and anti-methicillin-resistant Staphylococcus aureus agents from the standpoint of strain characteristics and binding action. Issue 4 (April 2019)

• Record Type: Journal Article
• Authors: Ono, Daisuke; Yamaguchi, Tetsuo; Hamada, Masakaze; Sonoda, Shiro; Sato, Ayami; Aoki, Kotaro; Kajiwara, Chiaki; Kimura, Soichiro; Fujisaki, Momoko; Tojo, Hiroyuki; Sasaki, Masakazu; Murakami, Hinako; Kato, Keisuke; Ishii, Yoshikazu; Tateda, Kazuhiro
• Is Part Of: Journal of infection and chemotherapy. Volume 25:Issue 4(2019:Apr.)
• Page Start: 273
• Page End: 280
• Publication Date: 2019-04
• Subjects: MRSA -- Synergistic effect -- Beta-lactam -- Anti-MRSA agent; MSE Maximum Synergistic Effect; Chemotherapy -- Periodicals; Infection -- Periodicals; Communicable diseases -- Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1016/j.jiac.2018.12.007
• Languages: English
• ISSNs: 1341-321X

Abstract

Abstract: In light of the increasing number of clinical cases resistant to traditional monotherapies and the lack of novel antimicrobial agents, combination therapy is an appealing solution for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we evaluated the efficacy of anti-MRSA agents, such as vancomycin (VAN), daptomycin (DAP), and linezolid (LZD), in conjunction with 13 beta-lactams and non-beta-lactams. We assessed the in vitro activities of the various combinations against 40 MRSA strains based on the maximum synergistic effect (MSE), an index calculated from the MIC change with a combination agent. Nearly all the anti-MRSA agents, which were combined with beta-lactams as well as VAN and DAP, showed a synergistic effect with arbekacin. VAN also exhibited varying degrees of synergy depending on the type of beta-lactam, whereas DAP and LZD showed similar synergy with different beta-lactams. These effects were confirmed by antibiotic kill curves, except for the apparent interaction between LZD and beta-lactams. The MSE results were analyzed according to strain characteristics including susceptibility to combination agents, staphylococcal cassette chromosome mec type, and presence of the blaZ gene; however, no obvious correlations were observed. In a fluorescence binding assay, the fluorescence intensity of boron-dipyrromethene (BODIPY)-VAN decreased, whereas that of BODIPY-DAP increased in combination with a beta-lactam agent. These findings suggest that beta-lactam combinations are promising treatment options for MRSA infections and that the type of beta-lactam combined with VAN is important for the synergistic effect.