Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Scientific reports - 11(2021), 1 vom: 31. Mai, Seite 11339 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fedrigo, Nayara Helisandra [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 19.11.2021 Date Revised 02.02.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-021-90709-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM326083138 |
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| 245 | 1 | 0 | |a Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy |
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| 500 | |a Date Revised 02.02.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Polymyxin B |2 NLM | |
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| 700 | 1 | |a Shinohara, Danielle Rosani |e verfasserin |4 aut | |
| 700 | 1 | |a Mazucheli, Josmar |e verfasserin |4 aut | |
| 700 | 1 | |a Nishiyama, Sheila Alexandra Belini |e verfasserin |4 aut | |
| 700 | 1 | |a Carrara-Marroni, Floristher Elaine |e verfasserin |4 aut | |
| 700 | 1 | |a Martins, Frederico Severino |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Peijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Mingming |e verfasserin |4 aut | |
| 700 | 1 | |a Sy, Sherwin Kenneth B |e verfasserin |4 aut | |
| 700 | 1 | |a Tognim, Maria Cristina Bronharo |e verfasserin |4 aut | |
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