Efficacy of a multimechanistic monoclonal antibody combination against staphylococcus aureus surgical site infections in mice

Roger V. Ortines; Yu Wang; Haiyun Liu; Dustin A. Dikeman; Bret L. Pinsker; Robert J. Miller; Sophia E. Kim; Nicole E. Ackerman; Joe F. Rizkallah; Lee Ann T. Marcello; Taylor S. Cohen; Christine Tkaczyk; Bret R. Sellman; Lloyd S. Miller

doi:10.1128/AAC.00346-19

Efficacy of a multimechanistic monoclonal antibody combination against staphylococcus aureus surgical site infections in mice

Roger V. Ortines, Yu Wang, Haiyun Liu, Dustin A. Dikeman, Bret L. Pinsker, Robert J. Miller, Sophia E. Kim, Nicole E. Ackerman, Joe F. Rizkallah, Lee Ann T. Marcello, Taylor S. Cohen, Christine Tkaczyk, Bret R. Sellman, Lloyd S. Miller

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Surgical site infections (SSIs) are commonly caused by Staphylococcus aureus. We report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus alpha-toxin, clumping factor A, and four leukocidins (LukSF, LukED, HlgAB, and HlgCB) plus vancomycin had enhanced efficacy compared with control antibody plus vancomycin in two mouse models of S. aureus SSI. Therefore, monoclonal antibody-based neutralization of multiple S. aureus virulence factors may provide an adjunctive perioperative approach to combat S. aureus SSIs.

Original language	English (US)
Article number	e00346-19
Journal	Antimicrobial agents and chemotherapy
Volume	63
Issue number	8
DOIs	https://doi.org/10.1128/AAC.00346-19
State	Published - Jan 1 2019

Keywords

Alpha-toxin
ClfA
Clumping factor A
HLA
Leukocidin
MRSA
Staphylococcus aureus
Surgical

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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10.1128/AAC.00346-19

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Ortines, R. V., Wang, Y., Liu, H., Dikeman, D. A., Pinsker, B. L., Miller, R. J., Kim, S. E., Ackerman, N. E., Rizkallah, J. F., Marcello, L. A. T., Cohen, T. S., Tkaczyk, C., Sellman, B. R., & Miller, L. S. (2019). Efficacy of a multimechanistic monoclonal antibody combination against staphylococcus aureus surgical site infections in mice. Antimicrobial agents and chemotherapy, 63(8), [e00346-19]. https://doi.org/10.1128/AAC.00346-19

Efficacy of a multimechanistic monoclonal antibody combination against staphylococcus aureus surgical site infections in mice. / Ortines, Roger V.; Wang, Yu; Liu, Haiyun; Dikeman, Dustin A.; Pinsker, Bret L.; Miller, Robert J.; Kim, Sophia E.; Ackerman, Nicole E.; Rizkallah, Joe F.; Marcello, Lee Ann T.; Cohen, Taylor S.; Tkaczyk, Christine; Sellman, Bret R.; Miller, Lloyd S.

In: Antimicrobial agents and chemotherapy, Vol. 63, No. 8, e00346-19, 01.01.2019.

Research output: Contribution to journal › Article › peer-review

Ortines, RV, Wang, Y, Liu, H, Dikeman, DA, Pinsker, BL, Miller, RJ, Kim, SE, Ackerman, NE, Rizkallah, JF, Marcello, LAT, Cohen, TS, Tkaczyk, C, Sellman, BR & Miller, LS 2019, 'Efficacy of a multimechanistic monoclonal antibody combination against staphylococcus aureus surgical site infections in mice', Antimicrobial agents and chemotherapy, vol. 63, no. 8, e00346-19. https://doi.org/10.1128/AAC.00346-19

Ortines, Roger V. ; Wang, Yu ; Liu, Haiyun ; Dikeman, Dustin A. ; Pinsker, Bret L. ; Miller, Robert J. ; Kim, Sophia E. ; Ackerman, Nicole E. ; Rizkallah, Joe F. ; Marcello, Lee Ann T. ; Cohen, Taylor S. ; Tkaczyk, Christine ; Sellman, Bret R. ; Miller, Lloyd S. / Efficacy of a multimechanistic monoclonal antibody combination against staphylococcus aureus surgical site infections in mice. In: Antimicrobial agents and chemotherapy. 2019 ; Vol. 63, No. 8.

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