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Susceptibility

Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa

Phillip J. Bergen, Jian Li, Craig R. Rayner, Roger L. Nation
Phillip J. Bergen
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia
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Jian Li
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia
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Craig R. Rayner
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia
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Roger L. Nation
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia
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  • For correspondence: Roger.Nation@vcp.monash.edu.au
DOI: 10.1128/AAC.00035-06
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  • FIG. 1.
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    FIG. 1.

    (a) Structures of colistin A and B; (b) structures of sodium colistin A and B methanesulfonate (CMS). Fatty acid, 6-methyloctanoic acid for colistin A and 6-methylheptanoic acid for colistin B; Thr, threonine; Leu, leucine; Dab, α,γ-diaminobutyric acid. α and γ indicate the respective —NH2 involved in the peptide linkage.

  • FIG. 2.
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    FIG. 2.

    (a) Concentration-time course of colistin produced from CMS spiked at 8.0 mg/liter and 32 mg/liter (n = 3) and from incremental spiking with colistin (n = 3); (b) time-kill curves for P. aeruginosa obtained by using colistin methanesulfonate spiked at 8.0 mg/liter and 32 mg/liter (n = 3) at zero time, spiked incrementally with colistin to mimic the colistin concentration-time course achieved after spiking of the sample with colistin methanesulfonate at 8.0 mg/liter and 32 mg/liter (n = 3), and colistin spiked at 6.0 mg/liter at zero time (n = 1; control experiment).

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  • TABLE 1.

    AUC0-240 of killing curves normalized by baseline log10 CFU/mlt = 0

    Colistin formAUC0-240/(log10 CFU/mlt = 0) (n = 3)
    8.0 mg/liter32 mg/liter
    CMS186.3 ± 6.090.4 ± 4.1
    Colistina192.8 ± 10.470.0 ± 7.4
    • ↵ a Spiked incrementally to achieve the same concentration-time course of colistin observed from hydrolysis of CMS spiked initially at 8.0 mg/liter or 32 mg/liter.

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Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa
Phillip J. Bergen, Jian Li, Craig R. Rayner, Roger L. Nation
Antimicrobial Agents and Chemotherapy May 2006, 50 (6) 1953-1958; DOI: 10.1128/AAC.00035-06

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Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa
Phillip J. Bergen, Jian Li, Craig R. Rayner, Roger L. Nation
Antimicrobial Agents and Chemotherapy May 2006, 50 (6) 1953-1958; DOI: 10.1128/AAC.00035-06
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KEYWORDS

Anti-Bacterial Agents
colistin
Prodrugs
Pseudomonas aeruginosa

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