Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever
Abstract Background Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β‐lactam concentrations. Aims This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin‐tazobacta...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.1585 |
| _version_ | 1811237879193534464 |
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| author | Sabine F. Maarbjerg Anders Thorsted Lena E. Friberg Elisabet I. Nielsen Mikala Wang Henrik Schrøder Birgitte K. Albertsen |
| author_facet | Sabine F. Maarbjerg Anders Thorsted Lena E. Friberg Elisabet I. Nielsen Mikala Wang Henrik Schrøder Birgitte K. Albertsen |
| author_sort | Sabine F. Maarbjerg |
| collection | DOAJ |
| description | Abstract Background Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β‐lactam concentrations. Aims This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin‐tazobactam, in order to optimize the dosing regimen. Methods This prospective PK study included children with cancer, aged 1–17 years, who were treated with piperacillin‐tazobactam for suspected or verified infection. A piperacillin‐tazobactam loading dose (100 mg/kg) was administered followed by continuous infusion (300 mg/kg/day). The unbound fraction of piperacillin was quantified by high‐performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100% fT > MIC) and 50% fT > 4xMIC. Results We included 68 fever episodes among 38 children with a median (IQR) age of 6.5 years and body weight of 27.4 kg (15.1–54.0). A three‐compartment model adequately described the concentration‐time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2 L/h/70 kg (13.0; 15.3) and 47.6 mg/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the P. aeruginosa breakpoint (16 mg/L) with the target of 100% fT > MIC, and a daily dose of 300 mg/kg reached optimal PTA. The strict target of 50% fT > 4xMIC (64 mg/L) was not feasibly attained by any dosing regimen at recommended doses. Conclusion Unlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100% fT > MIC to be reached for children with febrile neutropenia. |
| first_indexed | 2024-04-12T12:32:13Z |
| format | Article |
| id | doaj.art-916249ee1e794aab95228646445fc11e |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-04-12T12:32:13Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-916249ee1e794aab95228646445fc11e2022-12-22T03:33:00ZengWileyCancer Reports2573-83482022-10-01510n/an/a10.1002/cnr2.1585Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and feverSabine F. Maarbjerg0Anders Thorsted1Lena E. Friberg2Elisabet I. Nielsen3Mikala Wang4Henrik Schrøder5Birgitte K. Albertsen6Department of Pediatrics and Adolescent Medicine Aarhus University Hospital Aarhus DenmarkDepartment of Pharmacy Uppsala University Uppsala SwedenDepartment of Pharmacy Uppsala University Uppsala SwedenDepartment of Pharmacy Uppsala University Uppsala SwedenDepartment of Clinical Microbiology Aarhus University Hospital Aarhus DenmarkDepartment of Pediatrics and Adolescent Medicine Aarhus University Hospital Aarhus DenmarkDepartment of Pediatrics and Adolescent Medicine Aarhus University Hospital Aarhus DenmarkAbstract Background Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β‐lactam concentrations. Aims This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin‐tazobactam, in order to optimize the dosing regimen. Methods This prospective PK study included children with cancer, aged 1–17 years, who were treated with piperacillin‐tazobactam for suspected or verified infection. A piperacillin‐tazobactam loading dose (100 mg/kg) was administered followed by continuous infusion (300 mg/kg/day). The unbound fraction of piperacillin was quantified by high‐performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100% fT > MIC) and 50% fT > 4xMIC. Results We included 68 fever episodes among 38 children with a median (IQR) age of 6.5 years and body weight of 27.4 kg (15.1–54.0). A three‐compartment model adequately described the concentration‐time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2 L/h/70 kg (13.0; 15.3) and 47.6 mg/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the P. aeruginosa breakpoint (16 mg/L) with the target of 100% fT > MIC, and a daily dose of 300 mg/kg reached optimal PTA. The strict target of 50% fT > 4xMIC (64 mg/L) was not feasibly attained by any dosing regimen at recommended doses. Conclusion Unlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100% fT > MIC to be reached for children with febrile neutropenia.https://doi.org/10.1002/cnr2.1585continuous infusiondose optimizationfebrile neutropeniapharmacokineticspiperacillintarget attainment |
| spellingShingle | Sabine F. Maarbjerg Anders Thorsted Lena E. Friberg Elisabet I. Nielsen Mikala Wang Henrik Schrøder Birgitte K. Albertsen Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever Cancer Reports continuous infusion dose optimization febrile neutropenia pharmacokinetics piperacillin target attainment |
| title | Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever |
| title_full | Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever |
| title_fullStr | Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever |
| title_full_unstemmed | Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever |
| title_short | Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever |
| title_sort | continuous infusion of piperacillin tazobactam significantly improves target attainment in children with cancer and fever |
| topic | continuous infusion dose optimization febrile neutropenia pharmacokinetics piperacillin target attainment |
| url | https://doi.org/10.1002/cnr2.1585 |
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