Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens
Abstract The dosage of colistin for the treatment of enteric E. coli in animals necessitates considering the heteroresistant (HR) nature of the targeted inoculum, described by the presence of a major susceptible population (S1, representing 99.95% of total population) mixed with an initial minor sub...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39727-w |
| _version_ | 1797452817852530688 |
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| author | Andrew Mead Pierre-Louis Toutain Pascal Richez Ludovic Pelligand |
| author_facet | Andrew Mead Pierre-Louis Toutain Pascal Richez Ludovic Pelligand |
| author_sort | Andrew Mead |
| collection | DOAJ |
| description | Abstract The dosage of colistin for the treatment of enteric E. coli in animals necessitates considering the heteroresistant (HR) nature of the targeted inoculum, described by the presence of a major susceptible population (S1, representing 99.95% of total population) mixed with an initial minor subpopulation of less susceptible bacteria (S2). Herein, we report the 1-compartment population pharmacokinetics (PK) of colistin in chicken intestine (jejunum and ileum) and combined it with a previously established pharmacodynamic (PD) model of HR in E. coli. We then computed probabilities of target attainment (PTA) with a pharmacodynamic target (AUC24h/MIC) that achieves 50% of the maximal kill of bacterial populations (considering inoculums of pure S1, S2 or HR mixture of S1 + S2). For an MIC of 1 mg/L, PTA > 95% was achieved with the registered dose (75,000 IU/kg BW/day in drinking water) for the HR mixture of S1 + S2 E. coli, whether they harboured mcr or not. For an MIC of 2 mg/L (ECOFF), we predicted PTA > 90% against the dominant susceptible sub-population (S1) with this clinical dose given (i) over 24 h for mcr-negative isolates or (ii) over 6 h for mcr-positive isolates (pulse dosing). Colistin clinical breakpoint S ≤ 2 mg/L (EUCAST rules) should be confirmed clinically. |
| first_indexed | 2024-03-09T15:14:09Z |
| format | Article |
| id | doaj.art-dc4671f4357e4bc985b450e41f9cd91b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:14:09Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dc4671f4357e4bc985b450e41f9cd91b2023-11-26T13:14:33ZengNature PortfolioScientific Reports2045-23222023-08-0113111410.1038/s41598-023-39727-wTargeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickensAndrew Mead0Pierre-Louis Toutain1Pascal Richez2Ludovic Pelligand3Comparative Biomedical Sciences, The Royal Veterinary CollegeComparative Biomedical Sciences, The Royal Veterinary CollegeTranspharmComparative Biomedical Sciences, The Royal Veterinary CollegeAbstract The dosage of colistin for the treatment of enteric E. coli in animals necessitates considering the heteroresistant (HR) nature of the targeted inoculum, described by the presence of a major susceptible population (S1, representing 99.95% of total population) mixed with an initial minor subpopulation of less susceptible bacteria (S2). Herein, we report the 1-compartment population pharmacokinetics (PK) of colistin in chicken intestine (jejunum and ileum) and combined it with a previously established pharmacodynamic (PD) model of HR in E. coli. We then computed probabilities of target attainment (PTA) with a pharmacodynamic target (AUC24h/MIC) that achieves 50% of the maximal kill of bacterial populations (considering inoculums of pure S1, S2 or HR mixture of S1 + S2). For an MIC of 1 mg/L, PTA > 95% was achieved with the registered dose (75,000 IU/kg BW/day in drinking water) for the HR mixture of S1 + S2 E. coli, whether they harboured mcr or not. For an MIC of 2 mg/L (ECOFF), we predicted PTA > 90% against the dominant susceptible sub-population (S1) with this clinical dose given (i) over 24 h for mcr-negative isolates or (ii) over 6 h for mcr-positive isolates (pulse dosing). Colistin clinical breakpoint S ≤ 2 mg/L (EUCAST rules) should be confirmed clinically.https://doi.org/10.1038/s41598-023-39727-w |
| spellingShingle | Andrew Mead Pierre-Louis Toutain Pascal Richez Ludovic Pelligand Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens Scientific Reports |
| title | Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens |
| title_full | Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens |
| title_fullStr | Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens |
| title_full_unstemmed | Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens |
| title_short | Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens |
| title_sort | targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens |
| url | https://doi.org/10.1038/s41598-023-39727-w |
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