Julia Laporte-Amargos, Francisco Carmona-Torre, Maria Huguet, Pedro Puerta-Alcalde, Raul Rigo-Bonnin, Marta Ulldemolins, Montserrat Arnan, Jose Luis Del Pozo, Anna Torrent, Carolina Garcia-Vidal, Natàlia Pallarès, Cristian Tebé, Carme Muñoz, Fe Tubau, Ariadna Padullés, Ana-Maria Sureda, Jordi Carratalà, Carlota Gudiol
{"title":"延长输注β-内酰胺类抗生素治疗血液病患者发热性中性粒细胞减少症的疗效(BEATLE):一项随机、多中心、开放标签、优势临床试验。","authors":"Julia Laporte-Amargos, Francisco Carmona-Torre, Maria Huguet, Pedro Puerta-Alcalde, Raul Rigo-Bonnin, Marta Ulldemolins, Montserrat Arnan, Jose Luis Del Pozo, Anna Torrent, Carolina Garcia-Vidal, Natàlia Pallarès, Cristian Tebé, Carme Muñoz, Fe Tubau, Ariadna Padullés, Ana-Maria Sureda, Jordi Carratalà, Carlota Gudiol","doi":"10.1016/j.cmi.2024.10.006","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia.</p><p><strong>Methods: </strong>We performed a randomized, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50%, 75%, and 100%ƒ<sub>u</sub>T <sub>> MIC</sub>, and 30-day mortality.</p><p><strong>Results: </strong>From November 19, 2019 to June 22, 2022, 295 patients were screened for eligibility, of whom 150 were randomly assigned to receive EI (n = 77) or II (n = 73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference, -12.4%; 95% CI, -29.4 to 4.7; p 0.17). The pharmacokinetic/pharmacodynamic targets of 75% and 100% ƒ<sub>u</sub>T <sub>> MIC</sub> for empirical treatment were achieved more frequently in the EI group. No statistically significant differences were found between groups in terms of adverse events or 30-day mortality.</p><p><strong>Discussion: </strong>Our findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis or septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.</p>","PeriodicalId":10444,"journal":{"name":"Clinical Microbiology and Infection","volume":" ","pages":""},"PeriodicalIF":10.9000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomized, multicentre, open-label, superiority clinical trial.\",\"authors\":\"Julia Laporte-Amargos, Francisco Carmona-Torre, Maria Huguet, Pedro Puerta-Alcalde, Raul Rigo-Bonnin, Marta Ulldemolins, Montserrat Arnan, Jose Luis Del Pozo, Anna Torrent, Carolina Garcia-Vidal, Natàlia Pallarès, Cristian Tebé, Carme Muñoz, Fe Tubau, Ariadna Padullés, Ana-Maria Sureda, Jordi Carratalà, Carlota Gudiol\",\"doi\":\"10.1016/j.cmi.2024.10.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia.</p><p><strong>Methods: </strong>We performed a randomized, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50%, 75%, and 100%ƒ<sub>u</sub>T <sub>> MIC</sub>, and 30-day mortality.</p><p><strong>Results: </strong>From November 19, 2019 to June 22, 2022, 295 patients were screened for eligibility, of whom 150 were randomly assigned to receive EI (n = 77) or II (n = 73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference, -12.4%; 95% CI, -29.4 to 4.7; p 0.17). The pharmacokinetic/pharmacodynamic targets of 75% and 100% ƒ<sub>u</sub>T <sub>> MIC</sub> for empirical treatment were achieved more frequently in the EI group. No statistically significant differences were found between groups in terms of adverse events or 30-day mortality.</p><p><strong>Discussion: </strong>Our findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis or septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.</p>\",\"PeriodicalId\":10444,\"journal\":{\"name\":\"Clinical Microbiology and Infection\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":10.9000,\"publicationDate\":\"2024-10-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Microbiology and Infection\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cmi.2024.10.006\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Microbiology and Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.cmi.2024.10.006","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomized, multicentre, open-label, superiority clinical trial.
Objectives: The efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia.
Methods: We performed a randomized, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50%, 75%, and 100%ƒuT > MIC, and 30-day mortality.
Results: From November 19, 2019 to June 22, 2022, 295 patients were screened for eligibility, of whom 150 were randomly assigned to receive EI (n = 77) or II (n = 73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference, -12.4%; 95% CI, -29.4 to 4.7; p 0.17). The pharmacokinetic/pharmacodynamic targets of 75% and 100% ƒuT > MIC for empirical treatment were achieved more frequently in the EI group. No statistically significant differences were found between groups in terms of adverse events or 30-day mortality.
Discussion: Our findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis or septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.
期刊介绍:
Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.