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Pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following nebulisation of CMS among patients with ventilator-associated pneumonia

Gkoufa, Aikaterini (författare)
Natl & Kapodistrian Univ Athens, Laikon Gen Hosp, Dept Med 1, Athens, Greece.
Sou, Tomas (författare)
Uppsala Univ, Dept Pharm, Uppsala, Sweden.
Karaiskos, Ilias (författare)
Hygeia Gen Hosp, Dept Internal Med & Infect Dis, Athens, Greece.;Hygeia Gen Hosp, Dept Internal Med & Infect Dis 1, 4 Erythrou Stavrou Str & Kifisias,Marousi, Athens 15123, Greece.
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Routsi, Christina (författare)
Natl & Kapodistrian Univ Athens, Evangelismos Hosp, Dept Crit Care 1, Athens, Greece.
Lin, Yu-Wei (författare)
Monash Univ, Biomed Discovery Inst, Dept Microbiol, Clayton, Vic, Australia.
Psichogiou, Mina (författare)
Natl & Kapodistrian Univ Athens, Laikon Gen Hosp, Dept Med 1, Athens, Greece.
Zakynthinos, Spyros (författare)
Natl & Kapodistrian Univ Athens, Evangelismos Hosp, Dept Crit Care 1, Athens, Greece.
Giamarellou, Helen (författare)
Li, Jian (författare)
Monash Univ, Biomed Discovery Inst, Dept Microbiol, Clayton, Vic, Australia.
Friberg, Lena (författare)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för farmaci
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Natl & Kapodistrian Univ Athens, Laikon Gen Hosp, Dept Med 1, Athens, Greece Uppsala Univ, Dept Pharm, Uppsala, Sweden. (creator_code:org_t)
Elsevier, 2022
2022
Engelska.
Ingår i: International Journal of Antimicrobial Agents. - : Elsevier. - 0924-8579 .- 1872-7913. ; 59:6
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https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • There has been accumulating interest in nebulised colistin methanesulfonate (CMS) for the treatment of ventilator-associated pneumonia (VAP). In this study, pulmonary and systemic pharmacokinetics following nebulisation of CMS at a dose of 3 MIU and 5 MIU, using a vibrating mesh nebuliser, for VAP caused by extensively drug-resistant Gram-negative pathogens was assessed. Blood samples and minibronchoalveolar lavage (mini-BAL) was performed post-dose at 1, 4 and 8 h. Concentrations of CMS and formed colistin in mini-BAL and plasma were determined by liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis was conducted using a population approach. The study population included three groups ( n = 10 per group): (A) intravenous CMS and concomitantly nebulised CMS at a dose of 3 MIU (30 min duration); (B) nebulised CMS at a dose of 3 MIU (30 min duration) as monotherapy; and (C) nebulised CMS 5 MIU (45 min duration) as monotherapy. Mean plasma formed colistin concentrations were < 1 mg/L following CMS nebulisation as monotherapy (groups B and C). Predicted trough concentrations of formed colistin in the epithelial lining fluid (ELF) following 24-h dosing of 3 MIU and 5 MIU nebulised CMS were 120.4 mg/L and 200.7 mg/L, respectively. The model predicted that concomitant intravenous CMS (group A) had minimal impact on the formed colistin concentration in ELF. This study demonstrated high ELF formed colistin concentrations following nebulised CMS (constantly above colistin MICs), while plasma concentrations were lower than those associated with nephrotoxicity. Our results provide important information for optimisation of nebulised colistin therapy. (c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Nyckelord

CMS
Colistin
Nebulised
VAP
Pharmacokinetics
Modelling

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