Combination of polymyxin B and minocycline against multidrug-resistant Klebsiella pneumoniae: interaction quantified by pharmacokinetic/pharmacodynamic modelling from in vitro data

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: onr:"swepub:oai:DiVA.org:uu-420030" > Combination of poly...

1 of 1
Previous record
Next record
To hitlist

Combination of polymyxin B and minocycline against multidrug-resistant Klebsiella pneumoniae : interaction quantified by pharmacokinetic/pharmacodynamic modelling from in vitro data

Zhao, Chenyan (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap

Wistrand-Yuen, Pikkei (author): Uppsala universitet,Infektionssjukdomar

Lagerbäck, Pernilla (author): Uppsala universitet,Institutionen för cell- och molekylärbiologi,Infektionssjukdomar

Tängdén, Thomas (author): Uppsala universitet,Infektionssjukdomar

Nielsen, Elisabet I., 1973- (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap

Friberg, Lena E. (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap

show less...

(creator_code:org_t)

ELSEVIER, 2020
2020
English.
In: International Journal of Antimicrobial Agents. - : ELSEVIER. - 0924-8579 .- 1872-7913. ; 55:6

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://doi.org/10.1...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Lack of effective treatment for multidrug-resistant Klebsiella pneumoniae (MDR-Kp) necessitates finding and optimising combination therapies of old antibiotics. The aims of this study were to quantify the combined effect of polymyxin B and minocycline by building an in silico semi-mechanistic pharmacokinetic/pharmacodynamic (PKPD) model and to predict bacterial kinetics when exposed to the drugs alone and in combination at clinically achievable unbound drug concentration-time profiles. A clinical K. pneumoniae strain resistant to polymyxin B [minimum inhibitory concentration (MIC) = 16 mg/L] and minocycline (MIC = 16 mg/L) was selected for extensive in vitro static time-kill experiments. The strain was exposed to concentrations of 0.0625-48 ? MIC, with seven samples taken per experiment for viable counts during 0-28 h. These observations allowed the development of the PKPD model. The final PKPD model included drug-induced adaptive resistance for both drugs. Both the minocycline-induced bacterial killing and resistance onset rate constants were increased when polymyxin B was co-administered, whereas polymyxin B parameters were unaffected. Predictions at clinically used dosages from the developed PKPD model showed no or limited antibacterial effect with monotherapy, whilst combination therapy kept bacteria below the starting inoculum for 20 h at high dosages [polymyxin B 2.5 mg/kg + 1.5 mg/kg every 12 h (q12h); minocycline 400 mg + 200 mg q12h, loading + maintenance doses]. This study suggests that polymyxin B and minocycline in combination may be of clinical benefit in the treatment of infections by MDR-Kp and for isolates that are non-susceptible to either drug alone. (C) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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 -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

Polymyxin B
Minocycline
Combination therapy
Pharmacokinetic
pharmacodynamic model
In vitro time-kill study
Multidrug-resistant Klebsiella pneumoniae

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

International Journal of Antimicrobial Agents (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Zhao, Chenyan; Wistrand-Yuen, P ...; Lagerbäck, Perni ...; Tängdén, Thomas; Nielsen, Elisabe ...; Friberg, Lena E.

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

Articles in the publication: International Jo ...

By the university: Uppsala University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se