Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis. / Aung, Thet Tun; Chor, Wei Hong Jeff; Yam, Joey Kuok Hoong; Givskov, Michael; Yang, Liang; Beuerman, Roger W.

In: Ocular Surface, Vol. 15, No. 4, 2017, p. 770-783.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Aung, TT, Chor, WHJ, Yam, JKH, Givskov, M, Yang, L & Beuerman, RW 2017, 'Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis', Ocular Surface, vol. 15, no. 4, pp. 770-783. https://doi.org/10.1016/j.jtos.2017.06.002

APA

Aung, T. T., Chor, W. H. J., Yam, J. K. H., Givskov, M., Yang, L., & Beuerman, R. W. (2017). Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis. Ocular Surface, 15(4), 770-783. https://doi.org/10.1016/j.jtos.2017.06.002

Vancouver

Aung TT, Chor WHJ, Yam JKH, Givskov M, Yang L, Beuerman RW. Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis. Ocular Surface. 2017;15(4):770-783. https://doi.org/10.1016/j.jtos.2017.06.002

Author

Aung, Thet Tun ; Chor, Wei Hong Jeff ; Yam, Joey Kuok Hoong ; Givskov, Michael ; Yang, Liang ; Beuerman, Roger W. / Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis. In: Ocular Surface. 2017 ; Vol. 15, No. 4. pp. 770-783.

Bibtex

@article{b3d62c3867fa4ee2819adc37f97329bb,
title = "Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis",
abstract = "Purpose The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. Methods Sensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening. Anti-biofilm effects were evaluated in an 8-well chamber slide biofilm model. The efficacy of a new treatment strategy was validated using the novel neutropenic mouse keratitis model and monitored by slit-lamp microscopy, confocal microscopy, and colony forming unit measurements. Results We reported the very first evidence that these organisms develop corneal biofilms by the accumulation of extracellular DNA (eDNA) and the presence of microcolonies using a novel mycobacterial neutropenic mouse keratitis model. The combination of amikacin and gatifloxacin or besifloxacin was more effective than the current gold-standard drug, amikacin, and we developed a novel treatment strategy (amikacin + gatifloxacin + DNase), the destruction of biofilm matrix component, eDNA, which increased the efficacy of the new antibiotic combination for treating mycobacterial infection in in vitro (P = 0.002) and in vivo (P = 0.001) compared to its respective control. Conclusion Biofilms have a role in mycobacterial keratitis leading to poor treatment outcomes in clinical practice and the use of combination therapy (amikacin + gatifloxacin + DNase) could be a useful new treatment option.",
keywords = "Amikacin, Biofilm, Combination therapy, DNase, Keratitis, Nontuberculous mycobacteria",
author = "Aung, {Thet Tun} and Chor, {Wei Hong Jeff} and Yam, {Joey Kuok Hoong} and Michael Givskov and Liang Yang and Beuerman, {Roger W.}",
note = "Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2017",
doi = "10.1016/j.jtos.2017.06.002",
language = "English",
volume = "15",
pages = "770--783",
journal = "The Ocular Surface",
issn = "1542-0124",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Discovery of novel antimycobacterial drug therapy in biofilm of pathogenic nontuberculous mycobacterial keratitis

AU - Aung, Thet Tun

AU - Chor, Wei Hong Jeff

AU - Yam, Joey Kuok Hoong

AU - Givskov, Michael

AU - Yang, Liang

AU - Beuerman, Roger W.

N1 - Publisher Copyright: © 2017 The Authors

PY - 2017

Y1 - 2017

N2 - Purpose The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. Methods Sensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening. Anti-biofilm effects were evaluated in an 8-well chamber slide biofilm model. The efficacy of a new treatment strategy was validated using the novel neutropenic mouse keratitis model and monitored by slit-lamp microscopy, confocal microscopy, and colony forming unit measurements. Results We reported the very first evidence that these organisms develop corneal biofilms by the accumulation of extracellular DNA (eDNA) and the presence of microcolonies using a novel mycobacterial neutropenic mouse keratitis model. The combination of amikacin and gatifloxacin or besifloxacin was more effective than the current gold-standard drug, amikacin, and we developed a novel treatment strategy (amikacin + gatifloxacin + DNase), the destruction of biofilm matrix component, eDNA, which increased the efficacy of the new antibiotic combination for treating mycobacterial infection in in vitro (P = 0.002) and in vivo (P = 0.001) compared to its respective control. Conclusion Biofilms have a role in mycobacterial keratitis leading to poor treatment outcomes in clinical practice and the use of combination therapy (amikacin + gatifloxacin + DNase) could be a useful new treatment option.

AB - Purpose The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. Methods Sensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening. Anti-biofilm effects were evaluated in an 8-well chamber slide biofilm model. The efficacy of a new treatment strategy was validated using the novel neutropenic mouse keratitis model and monitored by slit-lamp microscopy, confocal microscopy, and colony forming unit measurements. Results We reported the very first evidence that these organisms develop corneal biofilms by the accumulation of extracellular DNA (eDNA) and the presence of microcolonies using a novel mycobacterial neutropenic mouse keratitis model. The combination of amikacin and gatifloxacin or besifloxacin was more effective than the current gold-standard drug, amikacin, and we developed a novel treatment strategy (amikacin + gatifloxacin + DNase), the destruction of biofilm matrix component, eDNA, which increased the efficacy of the new antibiotic combination for treating mycobacterial infection in in vitro (P = 0.002) and in vivo (P = 0.001) compared to its respective control. Conclusion Biofilms have a role in mycobacterial keratitis leading to poor treatment outcomes in clinical practice and the use of combination therapy (amikacin + gatifloxacin + DNase) could be a useful new treatment option.

KW - Amikacin

KW - Biofilm

KW - Combination therapy

KW - DNase

KW - Keratitis

KW - Nontuberculous mycobacteria

U2 - 10.1016/j.jtos.2017.06.002

DO - 10.1016/j.jtos.2017.06.002

M3 - Journal article

C2 - 28662943

AN - SCOPUS:85021812045

VL - 15

SP - 770

EP - 783

JO - The Ocular Surface

JF - The Ocular Surface

SN - 1542-0124

IS - 4

ER -

ID: 340025694