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Quantifying combine...
Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model
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- Zhao, Chenyan (author)
- Uppsala universitet,Institutionen för farmaci
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- Kristoffersson, Anders N., 1985- (author)
- Uppsala universitet,Institutionen för farmaci
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- Khan, David D. (author)
- Uppsala universitet,Institutionen för farmaci
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- Lagerbäck, Pernilla (author)
- Uppsala universitet,Infektionsmedicin
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- Lustig, Ulrika (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Cao, Sha (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Annerstedt, Charlotte (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Cars, Otto (author)
- Uppsala universitet,Infektionsmedicin
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- Andersson, Dan I. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Hughes, Diarmaid, 1956- (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Nielsen, Elisabet I., 1973- (author)
- Uppsala universitet,Institutionen för farmaci
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- Friberg, Lena E. (author)
- Uppsala universitet,Institutionen för farmaci
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(creator_code:org_t)
- Springer Nature, 2024
- 2024
- English.
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Co-administering a low dose of colistin (CST) with ciprofloxacin (CIP) may improve the antibacterial effect against resistant Escherichia coli, offering an acceptable benefit-risk balance. This study aimed to quantify the interaction between ciprofloxacin and colistin in an in silico pharmacokinetic-pharmacodynamic model from in vitro static time-kill experiments (using strains with minimum inhibitory concentrations, MICCIP 0.023–1 mg/L and MICCST 0.5–0.75 mg/L). It was also sought to demonstrate an approach of simulating concentrations at the site of infection with population pharmacokinetic and whole-body physiologically based pharmacokinetic models to explore the clinical value of the combination when facing more resistant strains (using extrapolated strains with lower susceptibility). The combined effect in the final model was described as the sum of individual drug effects with a change in drug potency: for ciprofloxacin, concentration at half maximum killing rate (EC50) in combination was 160% of the EC50 in monodrug experiments, while for colistin, the change in EC50 was strain-dependent from 54.1% to 119%. The benefit of co-administrating a lower-than-commonly-administrated colistin dose with ciprofloxacin in terms of drug effect in comparison to either monotherapy was predicted in simulated bloodstream infections and pyelonephritis. The study illustrates the value of pharmacokinetic-pharmacodynamic modelling and simulation in streamlining rational development of antibiotic combinations.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- Farmaceutisk vetenskap
- Pharmaceutical Science
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Zhao, Chenyan
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Kristoffersson, ...
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Khan, David D.
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Lagerbäck, Perni ...
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Lustig, Ulrika
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Cao, Sha
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Annerstedt, Char ...
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Cars, Otto
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Andersson, Dan I ...
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Hughes, Diarmaid ...
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Nielsen, Elisabe ...
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Friberg, Lena E.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
- Articles in the publication
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Scientific Repor ...
- By the university
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Uppsala University