Extended vs Bolus Infusion of Broad-Spectrum β-Lactams for Febrile Neutropenia: An Unblinded, Randomized Trial

Ram, Ron; Halavy, Yael; Amit, Odelia; Paran, Yael; Katchman, Eugene; Yachini, Bruria; Svetlana, Kor; Avivi, Irit; Ben‐Ami, Ronen

doi:10.1093/cid/ciy258

Cited by 46 publications

(57 citation statements)

References 27 publications

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“…However, other studies found different outcomes: in a large study on 213 patients, Tamma et al reported that the 14-day and 30-day mortality rates of patients given βL-βLIs were higher than those administered carbapenem (respectively: 17 vs 8% and 26 vs 11%) [8]. Moreover, although that study included the largest number of ICU patients, no patients received βL-βLI extended-infusion therapy, which could have yielded poorer outcomes [17,18].…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit patients

Luyt

Faure

Bonnet

et al. 2019

International Journal of Antimicrobial Agents

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Purpose. To evaluate the use of non-carbapenem antibiotics to treat severe extendedspectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit (ICU) patients. Methods. This retrospective observational study conducted in 2 ICUs compared outcomes of patients with extended-spectrum β-lactamase-producing Enterobacteriaceae infections administered a carbapenem or a non-carbapenem antibiotic as their definitive treatment. The primary outcome was treatment failure within 30 days, a composite endpoint of extendedspectrum β-lactamase-producing Enterobacteriaceae-infection recurrence and day-30 mortality. Secondary outcomes included day-30 and in-hospital mortality rates, extended-spectrum betalactamase-producing Enterobacteriaceae-infection recurrence, and infection(s) due to other pathogen(s). Results: Among the 107 patients included, 67 received a carbapenem and 40 a noncarbapenem antibiotic as their definitive treatment. Clinical characteristics of the 2 groups were similar. Comparing patients given a non-carbapenem antibiotic to those administered carbapenem, respectively, the former had similar day-30 treatment-failure (43% vs. 60%, P =0.06) and extended-spectrum β-lactamase-producing Enterobacteriaceae-infection-recurrence rates (25% vs. 22%, P = 0.8), but lower day-30 (23% vs. 45%, P = 0.02) and in-hospital (23% vs. 49%, P = 0.002) mortality rates. Secondary infection rates caused by other pathogen(s), including Clostridium difficile, were comparable. Outcomes were comparable regardless of whether or not patients received empirical carbapenem. Conclusions. For ICU patients with severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections, treatment with a non-carbapenem antibiotic was not associated with poorer outcome, compared to a carbapenem.

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Section: Discussionmentioning

confidence: 95%

“…Second, the infection origins and responsible pathogens differed markedly, as the Merino trial enrolled a large proportion of patients with predominantly E. coli urinary tract infections. Third, the duration of piperacillin-tazobactam infusion in the Merino trial (ie over 30 minutes) may not be optimal for severe infection [17,18].…”

Section: Discussionmentioning

confidence: 99%

Use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit patients

Luyt

Faure

Bonnet

et al. 2019

International Journal of Antimicrobial Agents

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“…Due to difficulties to ensure an adequate intravenous access in this study, four patients in the continuous infusions group were eliminated due to suspension of the infusion for ≥ 4 h and were not included in the analysis, which may constitute a bias. This is one of the limitations of the continuous infusion strategy because a central venous catheter is needed to comply with it; other issues are that the mobility of the patient may be limited and that the administration of non-compatible IV medications could require placing an additional peripheral short catheter 14,15 . To ensure that this strategy is successful, a trained staff and the availability of a pump infusion system are required 20 .…”

Section: Discussionmentioning

confidence: 99%

Piperacillin/Tazobactam in Continuous Infusion versus Intermittent Infusion in Children with Febrile Neutropenia

Solórzano-Santos

Quezada-Herrera

Fuentes-Pacheco

et al. 2019

RIC

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Background: Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective: The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/ tazobactam (TZP) in febrile neutropenic pediatric patients. Methods: This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results: There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions: There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

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“…The sample size calculation is based on determining whether the administration of BLA by EI (study group) will be clinically more effective than the administration of BLA by II (control group), for the treatment of FN in haematological patients. Previous data suggest that the clinical efficacy rate in the control group is expected to be 0.45 [20,21]. A relevant clinical efficacy rate in the study group is expected to be 0.70.…”

Section: Sample Sizementioning

confidence: 92%

“…A retrospective study with 164 patients found clinical efficacy with the use of meropenem by EI compared to II [20]. Similarly, a recent single-centre, randomised clinical trial found that EI was associated with superior treatment outcomes compared with II, and the benefit was greatest for patients with pneumonia [21]. Nevertheless, the study had some methodological flaws, and no PK studies were performed to support the clinical results [22].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)

Laporte-Amargós

Gudiol

Arnán

et al. 2020

Trials

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Background: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal βlactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. Methods: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK

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Extended vs Bolus Infusion of Broad-Spectrum β-Lactams for Febrile Neutropenia: An Unblinded, Randomized Trial

Abstract: NCT02463747.

Cited by 46 publications

References 27 publications

Use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit patients

Use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit patients

Piperacillin/Tazobactam in Continuous Infusion versus Intermittent Infusion in Children with Febrile Neutropenia

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)

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