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A New Pharmacokinet...
A New Pharmacokinetic-Pharmacodynamic Model To Characterize the Inoculum Effect of Acinetobacter baumannii on Polymyxin B In Vitro
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- Akrong, Grace (författare)
- INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.
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- Chauzy, Alexia (författare)
- INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.
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- Aranzana-Climent, Vincent (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för farmaci,INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.
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- Lacroix, Mathilde (författare)
- INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.;Inst ROCHE, Boulogne Billancourt, France.
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- Deroche, Luc (författare)
- INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.
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- Prouvensier, Laure (författare)
- INSERM U1070, Poitiers, France.;CHU Poitiers, Dept Toxicol & Pharmacocinet, Poitiers, France.
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- Buyck, Julien M. (författare)
- INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.
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- Couet, William (författare)
- INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.;CHU Poitiers, Dept Toxicol & Pharmacocinet, Poitiers, France.
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- Marchand, Sandrine (författare)
- INSERM U1070, Poitiers, France.;Univ Poitiers, Poitiers, France.;CHU Poitiers, Dept Toxicol & Pharmacocinet, Poitiers, France.
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INSERM U1070, Poitiers, France;Univ Poitiers, Poitiers, France. Institutionen för farmaceutisk biovetenskap (creator_code:org_t)
- American Society for Microbiology, 2022
- 2022
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 66:1
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The inoculum effect (i.e., reduction in antimicrobial activity at large starting inoculum) is a phenomenon described for various pathogens. Given that limited data exist regarding inoculum effect of Acinetobacter baumannii, we evaluated killing of A. baumannii by polymyxin B, a last-resort antibiotic, at several starting inocula and developed a pharmacokinetic-pharmacodynamic (PKPD) model to capture this phenomenon. In vitro static time-kill experiments were performed using polymyxin B at concentrations ranging from 0.125 to 128 mg/L against a clinical A. baumannii isolate at four starting inocula from 10(5) to 10(8) CFU/mL. Samples were collected up to 30 h to quantify the viable bacterial burden and were simultaneously modeled in the NONMEM software program. The expression of polymyxin B resistance genes (lpxACD, pmrCAB, and wzc), and genetic modifications were studied by RT-qPCR and DNA sequencing experiments, respectively. The PKPD model included a single homogeneous bacterial population with adaptive resistance. Polymyxin B effect was modeled as a sigmoidal E-max model and the inoculum effect as an increase of polymyxin B EC50 with increasing starting inoculum using a power function. Polymyxin B displayed a reduced activity as the starting inoculum increased: a 20-fold increase of polymyxin B EC50 was observed between the lowest and the highest inoculum. No effects of polymyxin B and inoculum size were observed on the studied genes. The proposed PKPD model successfully described and predicted the pronounced in vitro inoculum effect of A. baumannii on polymyxin B activity. These results should be further validated using other bacteria/antibiotic combinations and in vivo models.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- A. baumannii
- PKPD model
- inoculum effect
- polymyxin B
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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