β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.26/45740 |
Resumo: | Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time -lactam antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion of -lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to -lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that -lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time -lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome. |
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β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicityb-lactampharmacokineticspharmacodynamicscritical caredosingorgan failuretoxicityresistanceAntimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time -lactam antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion of -lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to -lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that -lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time -lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.Repositório ComumPereira, João GonçalvesFernandes, JoanaDuarte, Ana RitaFernandes, Susana Mendes2023-07-27T10:23:22Z2022-12-182022-12-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.26/45740eng10.3390/antibiotics11121839info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-10T05:02:05Zoai:comum.rcaap.pt:10400.26/45740Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:35:40.527501Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity |
title |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity |
spellingShingle |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity Pereira, João Gonçalves b-lactam pharmacokinetics pharmacodynamics critical care dosing organ failure toxicity resistance |
title_short |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity |
title_full |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity |
title_fullStr |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity |
title_full_unstemmed |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity |
title_sort |
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity |
author |
Pereira, João Gonçalves |
author_facet |
Pereira, João Gonçalves Fernandes, Joana Duarte, Ana Rita Fernandes, Susana Mendes |
author_role |
author |
author2 |
Fernandes, Joana Duarte, Ana Rita Fernandes, Susana Mendes |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Repositório Comum |
dc.contributor.author.fl_str_mv |
Pereira, João Gonçalves Fernandes, Joana Duarte, Ana Rita Fernandes, Susana Mendes |
dc.subject.por.fl_str_mv |
b-lactam pharmacokinetics pharmacodynamics critical care dosing organ failure toxicity resistance |
topic |
b-lactam pharmacokinetics pharmacodynamics critical care dosing organ failure toxicity resistance |
description |
Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time -lactam antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion of -lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to -lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that -lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time -lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-18 2022-12-18T00:00:00Z 2023-07-27T10:23:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.26/45740 |
url |
http://hdl.handle.net/10400.26/45740 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.3390/antibiotics11121839 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134921643524096 |