Antagonistic Effect of Colistin on Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus in and Studies.
Sungim Choi, Song Mi Moon, Su-Jin Park, Seung Cheol Lee, Kyung Hwa Jung, Heung-Sup Sung, Mi-Na Kim, Jiwon Jung, Min Jae Kim, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, Jin-Yong Jeong, Jun Hee Woo, Yang Soo Kim, Yong Pil Chong
Author Information
Sungim Choi: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Song Mi Moon: Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do, Republic of Korea.
Su-Jin Park: Center for Antimicrobial Resistance and Microbial Genetics, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Seung Cheol Lee: Department of Infectious Diseases and Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Kyung Hwa Jung: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Heung-Sup Sung: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. ORCID
Mi-Na Kim: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. ORCID
Jiwon Jung: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Min Jae Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Sung-Han Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Sang-Oh Lee: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. ORCID
Sang-Ho Choi: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jin-Yong Jeong: Department of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jun Hee Woo: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Yang Soo Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Yong Pil Chong: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea drchong@amc.seoul.kr.
As concerns arise that the vancomycin MIC of methicillin-resistant (MRSA) could be increased by concurrent colistin administration, we evaluated the effect of colistin on vancomycin efficacy against MRSA via and studies. Among MRSA blood isolates collected in a tertiary-care hospital, we selected representative strains from community-associated MRSA strains (CA-MRSA; ST72-MRSA-SCC IV) and hospital-acquired MRSA strains (HA-MRSA; ST5-MRSA-SCC II). USA CA-MRSA (USA300), HA-MRSA (USA100), N315 (New York/Japan clone), and a MRSA standard strain (ATCC 43300) were used for comparison. We performed checkerboard assays to identify changes in the vancomycin MIC of MRSA following colistin exposure and evaluated the effect of a vancomycin-colistin combination using time-kill assays. We also assessed the antagonistic effect by administering vancomycin, colistin, and a combination of these two in a neutropenic murine thigh infection model. In the checkerboard assays, vancomycin MICs of all MRSA strains except N315 were increased by from 0.25 to 0.75 μg/ml following colistin exposure. However, the time-kill assays indicated antagonism only against ST5-MRSA and USA100, when the vancomycin concentration was twice the MIC. In the murine thigh infection model with ST5-MRSA and USA100, vancomycin monotherapy reduced the number of CFU/muscle >1 log compared to a combination treatment after 24 h in ST5-MRSA, indicating an antagonistic effect of colistin on vancomycin treatment. This study suggests that exposure to colistin may reduce the susceptibility to vancomycin of certain MRSA strains. Combination therapy with vancomycin and colistin for multidrug-resistant pathogens might result in treatment failure for concurrent MRSA infection.
