Interaction of colistin with lipids in liposomes and monolayers

Mestres, C.; Alsina, M. A.; Busquets, Maria Antònia; Murányi, I; Reig, F.

doi:10.1016/s0378-5173(97)00301-3

Cited by 24 publications

(27 citation statements)

References 12 publications

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“…Another characteristic of colistin which is of potential benefit is its unique anti-endotoxin activity, being able to neutralize bacterial lipopolysaccharides [80][81][82]. In vitro it was shown that colistin formed mixed monolayers with phospholipids and coexisted in mixed micelles [83].…”

Section: Mechanism Of Actionmentioning

confidence: 98%

Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria

Nation

Milne

et al. 2005

International Journal of Antimicrobial Agents

494

442

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Section: Mechanism Of Actionmentioning

confidence: 98%

Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria

Nation

Milne

et al. 2005

International Journal of Antimicrobial Agents

494

442

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“…A potential reason for the inoculum effect of colistin might arise from its antiendotoxin activity in neutralizing bacterial LPS (26,29,72). Colistin forms mixed monolayers with phospholipids and is incorporated in micelles in vitro (46). "Binding" of colistin to LPS fragments of killed bacteria might decrease the free colistin concentration in vitro and contribute to the inoculum effect.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Colistin Bactericidal Activity by High Inoculum of Pseudomonas aeruginosa Characterized by a New Mechanism-Based Population Pharmacodynamic Model

Bulitta

Yang

Yohonn

et al. 2010

Antimicrob Agents Chemother

119

130

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Colistin is increasingly being utilized against Gram-negative pathogens, including Pseudomonas aeruginosa, resistant to all other antibiotics. Since limited data exist regarding killing by colistin at different initial inocula (CFUo), we evaluated killing of Pseudomonas aeruginosa by colistin at several CFUo and developed a mechanism-based mathematical model accommodating a range of CFUo. In vitro time-kill experiments were performed using >8 concentrations up to 64 ؋ the MIC of colistin against P. aeruginosa PAO1 and two clinical P. aeruginosa isolates at CFUo of 10 6 , 10 8 , and 10 9 CFU/ml. Serial samples up to 24 h were simultaneously modeled in the NONMEM VI (results shown) and S-ADAPT software programs. The mathematical model was prospectively "validated" by additional time-kill studies assessing the effect of Ca 2؉ and Mg 2؉ on killing of PAO1 by colistin. Against PAO1, killing of the susceptible population was 23-fold slower at the 10 9 CFUo and 6-fold slower at the 10 8 CFUo than at the 10 6 CFUo. The model comprised three populations with different second-order killing rate constants (5.72, 0.369, and 0.00210 liters/h/mg). Bacteria were assumed to release signal molecules stimulating a phenotypic change that inhibits killing. The proposed mechanism-based model had a good predictive performance, could describe killing by colistin for all three studied strains and for two literature studies, and performed well in a prospective validation with various concentrations of Ca 2؉ and Mg 2؉ . The extent and rate of killing of P. aeruginosa by colistin were markedly decreased at high CFUo compared to those at low CFUo. This was well described by a mechanism-based mathematical model, which should be further validated using dynamic in vitro models.

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“…2). Colistin is a polycation with 5 free amino groups that may, in part, be responsible for its ability to bind electrostatically to negatively charged tissue phospholipids (42,43). Animal studies have shown that colistin and polymyxin B accumulate in tissues, including the lungs (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Substantial Targeting Advantage Achieved by Pulmonary Administration of Colistin Methanesulfonate in a Large-Animal Model

Landersdorfer

Nguyen

Lieu

et al. 2017

Antimicrob Agents Chemother

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Colistin, administered as its inactive prodrug colistin methanesulfonate (CMS), is often used in multidrug-resistant Gram-negative pulmonary infections. The CMS and colistin pharmacokinetics in plasma and epithelial lining fluid (ELF) following intravenous and pulmonary dosing have not been evaluated in a large-animal model with pulmonary architecture similar to that of humans. Six merino sheep (34 to 43 kg body weight) received an intravenous or pulmonary dose of 4 to 8 mg/kg CMS (sodium) or 2 to 3 mg/kg colistin (sulfate) in a 4-way crossover study. Pulmonary dosing was achieved via jet nebulization through an endotracheal tube cuff. CMS and colistin were quantified in plasma and bronchoalveolar lavage fluid (BALF) samples by high-performance liquid chromatography (HPLC). ELF concentrations were calculated via the urea method. CMS and colistin were comodeled in S-ADAPT. Following intravenous CMS or colistin administration, no concentrations were quantifiable in BALF samples. Elimination clearance was 1.97 liters/h (4% interindividual variability) for CMS (other than conversion to colistin) and 1.08 liters/h (25%) for colistin. On average, 18% of a CMS dose was converted to colistin. Following pulmonary delivery, colistin was not quantifiable in plasma and CMS was detected in only one sheep. Average ELF concentrations (standard deviations [SD]) of formed colistin were 400 (243), 384 (187), and 184 (190) mg/liter at 1, 4, and 24 h after pulmonary CMS administration. The population pharmacokinetic model described well CMS and colistin in plasma and ELF following intravenous and pulmonary administration. Pulmonary dosing provided high ELF and low plasma colistin concentrations, representing a substantial targeting advantage over intravenous administration. Predictions from the pharmacokinetic model indicate that sheep are an advantageous model for translational research.

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Interaction of colistin with lipids in liposomes and monolayers

Cited by 24 publications

References 12 publications

Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria

Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria

Attenuation of Colistin Bactericidal Activity by High Inoculum of Pseudomonas aeruginosa Characterized by a New Mechanism-Based Population Pharmacodynamic Model

Substantial Targeting Advantage Achieved by Pulmonary Administration of Colistin Methanesulfonate in a Large-Animal Model

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