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The goals of this observational study are to identify risk factors for ESBL-producing Enterobacterales and carbapenemase-producing Enterobacterales (CPE) colonization in oncohematological patients with severe neutropenia, and to develop and validate a predictive model of infection caused by ESBL-producing Enterobacterales and CPE in patients previously colonized by the same bacteria.
The main questions the study aims to answer are:
Study Design & Participants: Participants will be screened after receiving neutropenia-inducing treatment (e.g., chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy, or others). A baseline rectal swab will be collected to assess initial colonization status, followed by weekly swabs throughout the duration of neutropenia. Patients will be followed for 90 days from initial screening, during which the study team will record any infections, with an additional 30-day follow-up period. All hospitalization data will be recorded.
An exploratory metagenomics sub-study will be conducted within the study. Its goal is to describe the intestinal microbiome in patients and analyze any correlation between the microbiome and infection and mortality. For logistical reasons, this sub-study will be performed only on patients in the Seville area. This analysis will be performed via sequencing of the 16S ribosomal ribonucleic acid (rRNA) gene.
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| Measure | Description | Time Frame |
|---|---|---|
| Number of patients colonized by ESBL-producing Enterobacterales and Carbapenem-resistant Enterobacterales (CRE) detected by rectal swab | A weekly control of colonizations status will be performed via rectal swabs, while the patient is hospitalized. | 90 days follow-up. In case of infection a security follow-up of 30 days will be performed |
| Number of Neutropenic fever (NF) and/or clinically relevant infection events caused by ESBL-producing Enterobacterales and CPE | Due to the observational nature of the study, all cases of NF or infection will be registered in the electronic case report form (eCRF) | 90 days follow-up. In case of infection a security follow-up of 30 days will be performed |
| Measure | Description | Time Frame |
|---|---|---|
| All cause mortality at 30 and 90 days | Mortality at 30-days after inclusion and mortality at 90-days after inclusion | 90 day follow-up since inclusion |
| In case of infection, mortality related to the infection at day 30 and/or recurrence of infection until day 90 |
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Inclusion criteria
Exclusion criteria
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Patients with hematological diseases, including: myelodysplastic syndrome, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, chronic lymphocytic leukemia, chronic myeloproliferative leukemias, lymphomas, or other hematological disorders.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zaira Palacios Baena R. MD/PhD | Contact | 0034 609320301 | zaira.palacios.baena@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Zaira R. Palacios Baena, MD/PhD | Virgen Macarena hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Torrecárdenas | Almería | Andalusia | 04009 | Spain |
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Microbiological isolates will be frozen and forwarded to the coordinating centre for Whole Genome Sequencing (WGS). These isolates shall be stored for a maximum period of 25 years
For patients with an infection episode, mortality related to the infection and recurrence will be assessed at day 30 of the security follow-up |
| 90 days follow-up. In case of infection a security follow-up of 30 days will be performed |
| Length of hospitalisation(s) (in days) | Total number of hospitalisation days during the 90 day follow-up. | 90 days follow up since inclusion |
| Data collection on antibiotic usage in Days of treatment (DOT) | Data collection on antibiotic usage in days of treatment | 90 days follow-up. In case of infection a security follow-up of 30 days will be performed |
| Number of appropiate empirical and targeted treatment. | Data will be obtained from the participat's clinical history. Appropriate treatment is defined as confirmed activity in vitro of the treatment against the infectious agent. | 90 days follow-up. In case of infection a security follow-up of 30 days will be performed |
| C. difficile infection | Rate of patients presenting confirmed Clostridioses difficile toxin presence | 90 days follow-up. In case of infection a security follow-up of 30 days will be performed |
| Number of fungal infections caused by yeast or mold | Proven, probable or possible fungal infection confirmed by growth of specimen in culture or fungal biomarkers. | 90 days follow-up. In case of infection a security follow-up of 30 days will be performed |
| Hospital Universitario De Jerez | Jerez de la Frontera | Cádiz | 11407 | Spain |
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| Hospital Universitario de Vigo | Vigo | Galicia | 36310 | Spain |
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| Clinica Universidad de Navarra | Pamplona | Navarre | 31008 | Spain |
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| Hospital Universitario Vall d'Hebron | Barcelona | 08035 | Spain |
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| Hospital Universitario Puerta del Mar | Cadiz | 11009 | Spain |
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| Hospital Universitario Virgen de las Nieves Ruiz de Alda | Granada | 18014 | Spain |
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| Hospital Universitario Juan Ramón Jiménez | Huelva | 21005 | Spain |
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| Hospital Universitario Ramón y Cajal | Madrid | 28034 | Spain |
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| Hospital Universitario La Paz | Madrid | 28046 | Spain |
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| Hospital Regional Universitario de Málaga | Málaga | 29010 | Spain |
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| Hospital Clínico Universitario de Salamanca | Salamanca | 37007 | Spain |
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| Hospital Universitario Virgen Macarena | Seville | 41009 | Spain |
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| Hospital Universitario Virgen del Rocío | Seville | 41013 | Spain |
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| Hospital Universitario Nuestra Señora de Valme | Seville | 41014 | Spain |
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| ID | Term |
|---|---|
| D009503 | Neutropenia |
| ID | Term |
|---|---|
| D000380 | Agranulocytosis |
| D007970 | Leukopenia |
| D000095542 | Cytopenia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007960 | Leukocyte Disorders |
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