Statistical Metamodeling for revealing synergistic antimicrobial interactions

Chia Hsiang Chen, Vincent Gau, Donna D. Zhang, Joseph C. Liao, Fei Yue Wang, Pak Kin Wong

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future.

Original languageEnglish (US)
Article numbere15472
JournalPLoS One
Volume5
Issue number11
DOIs
StatePublished - Dec 9 2010

Fingerprint

Trimethoprim
Gentamicins
anti-infective agents
trimethoprim
gentamicin
Validation Studies
Microbial Sensitivity Tests
Public health
Pathogens
Growth
Bacterial Infections
Sensitivity analysis
Screening
Public Health
Anti-Bacterial Agents
synergists
minimum inhibitory concentration
bacterial infections
Pharmaceutical Preparations
microbial growth

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chen, Chia Hsiang ; Gau, Vincent ; Zhang, Donna D. ; Liao, Joseph C. ; Wang, Fei Yue ; Wong, Pak Kin. / Statistical Metamodeling for revealing synergistic antimicrobial interactions. In: PLoS One. 2010 ; Vol. 5, No. 11.
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Statistical Metamodeling for revealing synergistic antimicrobial interactions. / Chen, Chia Hsiang; Gau, Vincent; Zhang, Donna D.; Liao, Joseph C.; Wang, Fei Yue; Wong, Pak Kin.

In: PLoS One, Vol. 5, No. 11, e15472, 09.12.2010.

Research output: Contribution to journalArticle

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