Rapid, simple, and clinically applicable high-performance liquid chromatography method for clinical determination of plasma colistin concentrations

Hanai, Yuki; Matsuo, Kazuhiro; Kosugi, Tadayoshi; Kusano, Ayumu; Ohashi, Hayato; Kimura, Itsuki; Hirayama, S.; Nanjo, Yuta; Ishii, Yoshikazu; Sato, Takahiro; Miyazaki, Taito; Nishizawa, Kenji; Yoshino, Takashi

doi:10.1186/s40780-018-0119-x

Cited by 16 publications

(18 citation statements)

References 25 publications

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“…Detection of colistin can be achieved using several methods, including chromatography with fluorescence after derivatization 20 – 23 or mass spectrometry 19 , 24 – 27 detection, microbiological assays 28 , 29 , enzyme-linked (ELISA) 6 , 30 and derivative spectrophotometry 31 . Here, analysis of FPLC chromatograms was achieved by monitoring absorbance at 210 nm.…”

Section: Discussionmentioning

confidence: 99%

A physicochemical assessment of the thermal stability of dextrin–colistin conjugates

Chiron

Varache

Stokniene

et al. 2021

Sci Rep

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Attachment of polysaccharide carriers is increasingly being used to achieve precision delivery and improved effectiveness of protein and peptide drugs. Although it is clear that their clinical effectiveness relies on the purity and integrity of the conjugate in storage, as well as following administration, instability of polysaccharide-based conjugates can reduce the protective efficacy of the polymer, which may adversely affect the bioactive’s potency. As a model, these studies used dextrin–colistin conjugates, with varying degrees of polymer modification (1, 2.5 and 7.5 mol% succinoylation) to assess the effect of storage temperature (− 20, 4, 21 and 37 °C) and duration (up to 12 months) on saccharide and colistin release and antimicrobial activity. Estimation of the proportion of saccharide release (by comparison of area under the curve from size exclusion chromatograms) was more pronounced at higher temperatures (up to 3 and 35% at − 20 °C and 37 °C, respectively after 12 months), however, repeated freeze–thaw did not produce any measurable release of saccharides, while addition of amylase (20, 100, 500 IU/L) caused rapid release of saccharides (> 70% total within 24 h). At all temperatures, conjugates containing the lowest degree of succinoylation released the highest proportion of free colistin, which increased with storage temperature, however no trend in saccharide release was observed. Despite the clear physical effects of prolonged storage, antimicrobial activity of all samples was only altered after storage at 37 °C for 12 months (> threefold decreased activity). These results demonstrate significant release of saccharides from dextrin–colistin conjugates during prolonged storage in buffered solution, especially at elevated temperature, which, in most cases, did not affect antimicrobial activity. These findings provide vital information about the structure–activity relationship of dextrin–colistin conjugates, prior to full-scale commercial development, which can subsequently be applied to other polysaccharide-protein and -peptide conjugates.

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Section: Discussionmentioning

confidence: 99%

A physicochemical assessment of the thermal stability of dextrin–colistin conjugates

Chiron

Varache

Stokniene

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Detection of colistin can be achieved using several methods, including chromatography with uorescence after derivatization [20][21][22][23] or mass spectrometry 19,24−27 detection, microbiological assays 28,29 , enzymelinked (ELISA) 6,30 and derivative spectrophotometry 31 . Here, analysis of FPLC chromatograms was achieved by monitoring absorbance at 210 nm.…”

Section: Discussionmentioning

confidence: 99%

A physicochemical assessment of the thermal stability of dextrin-colistin conjugates

Chiron

Varache

Stokniene

et al. 2021

Preprint

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Attachment of polysaccharide carriers is increasingly being used to achieve precision delivery and improved effectiveness of protein and peptide drugs. Although it is clear that their clinical effectiveness relies on the purity and integrity of the conjugate in storage, as well as following administration, instability of polysaccharide-based conjugates can reduce the protective efficacy of the polymer, which may adversely affect the bioactive’s potency. As a model, these studies used dextrin-colistin conjugates, with varying degrees of polymer modification (1, 2.5 and 7.5 mol% succinoylation) to assess the effect of storage temperature (-20, 4, 21 and 37°C) and duration (up to 12 months) on saccharide and colistin release and antimicrobial activity. Estimation of the proportion of saccharide release (by comparison of area under the curve from size exclusion chromatograms) was more pronounced at higher temperatures (up to 3 and 35% at -20°C and 37°C, respectively after 12 months), however, repeated freeze-thaw did not produce any measurable release of saccharides, while addition of amylase (20, 100, 500 IU/L) caused rapid release of saccharides (> 70% total within 24 h). At all temperatures, conjugates containing the lowest degree of succinoylation released the highest proportion of free colistin, which increased with storage temperature, however no trend in saccharide release was observed. Despite the clear physical effects of prolonged storage, antimicrobial activity of all samples was only altered after storage at 37°C for 12 months (> 3-fold decreased activity). These results demonstrate significant release of saccharides from dextrin-colistin conjugates during prolonged storage in buffered solution, especially at elevated temperature, which, in most cases, did not affect antimicrobial activity. These findings provide vital information about the structure-activity relationship of dextrin-colistin conjugates, prior to full-scale commercial development, which can subsequently be applied to other polysaccharide-protein and -peptide conjugates.

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“…The samples were centrifuged and chilled, and the plasma was stored at −20 • C until assayed. Concentrations of colistin in the plasma of patients were determined using a modified HPLC method [39][40][41][42][43], Supplementary Materials File S1. The Ethics Committee of the Universidad de La Sabana Clinic approved this study (Act 12 September 2017), and signed written informed consent was obtained from all patients who participated in the study.…”

Section: Determination Of the Plasma Colistin Concentrationsmentioning

confidence: 99%

Estimation of the Difference in Colistin Plasma Levels in Critically Ill Patients with Favorable or Unfavorable Clinical Outcomes

et al. 2021

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In recent decades, antimicrobial resistance (AMR) has led to an increased use of therapeutic alternatives. Among these options, colistin continues to be an option for the treatment of multi-resistant (MDR) Gram-negative bacterial infections. However, due to its high toxicity (nephrotoxicity and neurotoxicity) and narrow therapeutic window, colistin treatment must be utilized carefully. Colistin-treated patients have been observed to have higher mortality due to inadequate therapeutic levels. The objective of this study was to estimate the difference in colistin plasma levels in critically ill patients, and its relationship to favorable or unfavorable clinical outcomes. This prospective observational study was conducted between September 2017 and June 2020 at the Universidad de La Sabana Clinic, in patients who had been treated with colistimethate sodium (CMS) for at least 72 h until day 7 of drug treatment in the critical care unit of a university hospital. There were no statistically significant differences in colistin levels between groups with favorable or unfavorable clinical outcomes (0.16 SD vs. 0.54 SD p-value = 0.167). There was higher mortality in patients with subtherapeutic levels (18% vs. 0%), and additionally, there was a greater rate of renal failure in the group with higher therapeutic levels (50% vs. 20.7%). Due to the loss of power of the study, we were unable to demonstrate a possible difference between colistin levels related to favorable or unfavorable clinical outcomes at day 7. However, we recommend further studies to evaluate the impact of measuring levels in terms of mortality and security.

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Rapid, simple, and clinically applicable high-performance liquid chromatography method for clinical determination of plasma colistin concentrations

Cited by 16 publications

References 25 publications

A physicochemical assessment of the thermal stability of dextrin–colistin conjugates

A physicochemical assessment of the thermal stability of dextrin–colistin conjugates

A physicochemical assessment of the thermal stability of dextrin-colistin conjugates

Estimation of the Difference in Colistin Plasma Levels in Critically Ill Patients with Favorable or Unfavorable Clinical Outcomes

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