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Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis

We systematically reviewed the efficacy and safety of an extended or continuous infusion (EI/CI) versus short-term infusion (STI) of carbapenems in children with severe infections. Databases, including PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure,...

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Autores principales: Zhou, Pengxiang, Zhang, Yahui, Wang, Zhenhuan, Ying, Yingqiu, Xing, Yan, Tong, Xiaomei, Zhai, Suodi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470113/
https://www.ncbi.nlm.nih.gov/pubmed/34572670
http://dx.doi.org/10.3390/antibiotics10091088
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author Zhou, Pengxiang
Zhang, Yahui
Wang, Zhenhuan
Ying, Yingqiu
Xing, Yan
Tong, Xiaomei
Zhai, Suodi
author_facet Zhou, Pengxiang
Zhang, Yahui
Wang, Zhenhuan
Ying, Yingqiu
Xing, Yan
Tong, Xiaomei
Zhai, Suodi
author_sort Zhou, Pengxiang
collection PubMed
description We systematically reviewed the efficacy and safety of an extended or continuous infusion (EI/CI) versus short-term infusion (STI) of carbapenems in children with severe infections. Databases, including PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, WanFang Data, and SinoMed, were systematically searched from their inceptions to 10 August 2020, for all types of studies (such as randomized controlled trials (RCTs), retrospective studies, and pharmacokinetic or population pharmacokinetic (PK/PPK) studies) comparing EI/CI versus STI in children with severe infection. There was no limitation on language, and a manual search was also conducted. The data were screened, evaluated, extracted, and reviewed by two researchers independently. Quantitative (meta-analysis) or qualitative analyses of the included studies were performed. Twenty studies (including two RCTs, one case series, six case reports, and 11 PK/PPK studies) were included in this review (CRD42020162845). The RCTs’ quality evaluation results revealed a risk of selection and concealment bias. Qualitative analysis of RCTs demonstrated that, compared with STI, an EI (3 to 4 h) of meropenem in late-onset neonatal sepsis could improve the clinical effectiveness and microbial clearance rates, and reduce the rates of mortality; however, the differences in the incidence of other adverse events were not statistically significant. Retrospective studies showed that children undergoing an EI of meropenem experienced satisfactory clinical improvement. In addition, the results of the PK/PPK study showed that an EI (3 or 4 h)/CI of carbapenems in severely infected children was associated with a more satisfactory goal achievement rate (probability of target attainment) and a cumulative fraction of response than STI therapy. In summary, the EI/CI of carbapenems in children with severe infection has a relatively sufficient PK or pharmacodynamic (PD) basis and satisfactory efficacy and safety. However, due to the limited quantity and quality of studies, the EI/CI therapy should not be used routinely in severely infected children. This conclusion should be further verified by more high-quality controlled clinical trials or observational studies based on PK/PD theories.
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spelling pubmed-84701132021-09-27 Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis Zhou, Pengxiang Zhang, Yahui Wang, Zhenhuan Ying, Yingqiu Xing, Yan Tong, Xiaomei Zhai, Suodi Antibiotics (Basel) Review We systematically reviewed the efficacy and safety of an extended or continuous infusion (EI/CI) versus short-term infusion (STI) of carbapenems in children with severe infections. Databases, including PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, WanFang Data, and SinoMed, were systematically searched from their inceptions to 10 August 2020, for all types of studies (such as randomized controlled trials (RCTs), retrospective studies, and pharmacokinetic or population pharmacokinetic (PK/PPK) studies) comparing EI/CI versus STI in children with severe infection. There was no limitation on language, and a manual search was also conducted. The data were screened, evaluated, extracted, and reviewed by two researchers independently. Quantitative (meta-analysis) or qualitative analyses of the included studies were performed. Twenty studies (including two RCTs, one case series, six case reports, and 11 PK/PPK studies) were included in this review (CRD42020162845). The RCTs’ quality evaluation results revealed a risk of selection and concealment bias. Qualitative analysis of RCTs demonstrated that, compared with STI, an EI (3 to 4 h) of meropenem in late-onset neonatal sepsis could improve the clinical effectiveness and microbial clearance rates, and reduce the rates of mortality; however, the differences in the incidence of other adverse events were not statistically significant. Retrospective studies showed that children undergoing an EI of meropenem experienced satisfactory clinical improvement. In addition, the results of the PK/PPK study showed that an EI (3 or 4 h)/CI of carbapenems in severely infected children was associated with a more satisfactory goal achievement rate (probability of target attainment) and a cumulative fraction of response than STI therapy. In summary, the EI/CI of carbapenems in children with severe infection has a relatively sufficient PK or pharmacodynamic (PD) basis and satisfactory efficacy and safety. However, due to the limited quantity and quality of studies, the EI/CI therapy should not be used routinely in severely infected children. This conclusion should be further verified by more high-quality controlled clinical trials or observational studies based on PK/PD theories. MDPI 2021-09-09 /pmc/articles/PMC8470113/ /pubmed/34572670 http://dx.doi.org/10.3390/antibiotics10091088 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zhou, Pengxiang
Zhang, Yahui
Wang, Zhenhuan
Ying, Yingqiu
Xing, Yan
Tong, Xiaomei
Zhai, Suodi
Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis
title Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis
title_full Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis
title_fullStr Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis
title_full_unstemmed Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis
title_short Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis
title_sort extended or continuous infusion of carbapenems in children with severe infections: a systematic review and narrative synthesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470113/
https://www.ncbi.nlm.nih.gov/pubmed/34572670
http://dx.doi.org/10.3390/antibiotics10091088
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