拡張スペクトルβラクタマーゼ - 産生病原体に感染している、または感染のリスクがある患者の発熱性好中球減少症に対するセフトロザン/タゾバクタムとメロペネムの比較 (CLEMENT)

実験的：Intervention

In the intervention arm 3g of ceftolozane-tazobactam are given intravenously every 8 hours. Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.

Colonized patients will be considered those identified through positive routine rectal swabs and/or positive culture of a clinical sample) or at risk of infection by an ESBL-producing pathogen due to use of 3rd/4th gen cephalosporin or piperacillin/tazobactam for at least 48 hours. in the last 30 days.

薬：Ceftolozane-Tazobactam

In the intervention arm 3g of ceftolozane-tazobactam are given intravenously every 8 hours. Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.

アクティブコンパレータ：Control

The comparator arm consists of 2g of meropenem given intravenously every 8 hours.Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.

Colonized patients will be considered those identified through positive routine rectal swabs and/or positive culture of a clinical sample) or at risk of infection by an ESBL-producing pathogen due to use of 3rd/4th gen cephalosporin or piperacillin/tazobactam for at least 48 hours. in the last 30 days.

薬：Meropenem

The comparator arm consists of 2g of meropenem given intravenously every 8 hours.Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.

Percentage of Participants with regards to clinical failure of antimicrobial therapy at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population

To compare the clinical response rates at the EOT visit for ceftolozane/tazobactam versus meropenem. Clinical response at the EOT visit was defined as cure (complete resolution of fever and symptoms related to Febrile Neutropenia episode), failure (non-resolution, relapse or recurrence of Febrile Neutropenia) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate.

Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population

To compare the clinical response rates at the EOT visit for ceftolozane/tazobactam versus meropenem in the Microbiological Intent-to-Treat (mITT) Population. Clinical response at the EOT visit was defined as cure (complete resolution of fever and symptoms related to Febrile Neutropenia episode), failure (non-resolution, relapse or recurrence of Febrile Neutropenia) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate.

Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population

To demonstrate the non-inferiority of ceftolozane/tazobactam versus meropenem in participants with Febrile Neutropenia on Patients Colonized With or at Risk for Infection With Extended Spectrum Beta Lactamase - Producing Pathogens at the TOC visit (7 to 14 days after the end-of-therapy [EOT] visit) using a non-inferiority margin of 12.5%. Clinical response at the TOC visit was defined as cure (complete resolution of fever and symptoms related to Febrile Neutropenia), failure (non-resolution, relapse or recurrence of Febrile Neutropenia) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate unless the clinical outcome at the EOT visit was failure.

Incidence of microbiologically documented infections and identification of causative organisms in culture

The incidences of microbiologically documented infections, along with the identification of causative organisms in culture, will be recorded. The measure will be assessed through the counting of cases confirmed by positive cultures.

In-hospital mortality

In-hospital mortality in the first 100 days after allogenic hematopoietic stem cell transplant (HSCT)

Occurrence of graft versus host disease (GVHD)

Occurrence of GVHD In the first 100 days after allogenic HSCT

Frequency of multidrug resistant-pathogen infections or colonization

Frequency of multidrug resistant-pathogen infections or colonization by weekly rectal swab screening

Faecal microbiota analysis

Patients will also undergo faecal microbiota analysis on baseline and at the end of therapy as a surrogate marker for future GVHD.

Percentage of Participants Who Report 1 or More Adverse Event (AE)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Percentage of Participants With Any Serious Adverse Event (SAE)

A serious adverse event (SAE) is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment.

Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.