Prospective Study on Febrile Batteries in Pediatric Oncohaematological Patients (SuBiTo)

Bacterial Infections Clinical Trial

— SuBiTo  

Official title:

Studio Prospettico Sulle Batteriemie Febbrili Nei Pazienti Oncoematologici Pediatrici

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06419426
• Other study ID #: SuBiTO
• Status: Active, not recruiting
• Start date: April 22, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Associazione Italiana Ematologia Oncologia Pediatrica
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study is to define prospectively the incidence of multi-resistant germ batteries in paediatric oncoematological patients, to assess associated mortality, antibiotic resistance profile and the type of implemented therapy.

Description:

Bacterial infections are the most frequent cause of infectious morbidity and mortality in the patient undergoing chemotherapy or hemopoietic stem cell transplantation (TCSE). The main predisposing factor is the impairment of innate immunity as a result of the alteration of mucous barriers (mucositis/enteritis from chemotherapy or radiotherapy), skin (CVC) and neutropenia (non-specific haematological toxicity due to chemotherapy or radiotherapy on bones with hemopoietic marrow). The most frequent form of infection is represented by fever whose cause remains indeterminate in 60-80% of cases. In about 10-15% of cases fever is accompanied by the positivization of hemoculture and is configured as a microbiologically determined infection (IMD). In the remaining cases, infectious episodes may be clinically documented such as pneumonia or bronchitis confirmed for radiological examination or CT scans, without the identification of the causative agent; these are defined as clinically determined infections (ICDs).

The knowledge, through hemoculture, of the germs responsible for febrile batteries over a given period of time, allows the definition of the predominant typology of germs responsible for systemic infection. On this basis, it is used to define the empirical antibiotic treatment that is given to the patient within a few hours of the onset of fever. Empirical antibiotic therapy must be effective with regard to the germs most represented in the department or in the area in question. Once the result of hemoculture has been received, usually within 48-72 hours, empirical antibiotic therapy can be maintained or modified in relation to the type of isolated germ and its susceptibility to antibiotics included in the empirical scheme. In fact, there is ample evidence that ready-to-treat with broad-spectrum antibiotics reduces mortality from bacterial infection in the immunocompromised patient, so this procedure is now a recommended approach by the guidelines. In addition to the knowledge of prevalent bacterial epidemiology for a certain type of immunocompromised patients in a given geographical area, a second tool capable of allowing appropriate empirical antibiotic therapy is the choice of therapy based on the presence or not of asymptomatic bacterial colonization of the patient. In fact, it is estimated that in 20-30% of cases the colonizing germ can become the cause of a batteriemia, facilitated by favoring factors such as the rupture of skin-mucous reefs or the appearance of neutropenia. The need to start empirical antibiotic therapy with effective molecules against causal germ (appropriate empirical therapy) has been shown to reduce bacterial infectious mortality at a time when antibiotic resistance is gradually increasing. It has been shown that inappropriate empirical antibiotic therapy, based on antibiotics to which the germ is not sensitive, is associated with increased infectious mortality from sepsis and septic shock. Among the adjuvant therapies used in immunosuppressed patients, in addition to antibiotic therapy, especially in patients with septic shock, there is the administration of opsonizing immunoglobulins and able to activate the complement such as, for example, immunoglobulins enriched in IgM. This practice is generally more established in immunocompetent patients while there are no prospective data in immunocompromised patients.

Primary objective Incidence of febrile batteries from antibiotic-resistant gram negative germs (MDR)

Secondary objectives Incidence of batteries from negative Gram germs; Incidence of batteries from gram positive germs; Incidence of fungemie; Incidence of septic shock; Incidence of batteries from colonising germs; Incidence of resistance to the main classes of antibiotics used empirically: cephalosporins of 3 and 4 generation (ceftazidime, cefipime), semisitical penicillins (piperacillin/tazobactam), carbapenemas (meropenem, imipenem), aminoglycosides (aminoglycosides (aikacin), second generation fluorquinolones; Response to empirical antibiotic therapy within 72 hours, without modification of empirical antibiotic therapy and without the use of Pentablobin; Response to empirical antibiotic therapy within 72 hours with the use of Pentaglobin within 72 hours of the onset of fever; Response to empirical antibiotic therapy with modification of the antibiotic (without the addition of antifungal), without the use of Pentaglobin; Response to empirical antibiotic therapy with modification of the antibiotic (without the addition of antifungal), with the use of Pentaglobin; Response of antibiotic therapy with empirical addition of antifungal with or without the use of Pentaglobin; Mortality at 30 days; Mortality at 90 days

Design of the study Prospective, observational, non-interventional study to determine the incidence of febrile batteries from MDR germs in febrile oncohaematological patients.

The study is aimed at the centers belonging to the Italian Society of Pediatric Oncology Hematology (IAEOP). Patients will be enrolled prospectively from the date of activation of the center.

Eligible patients will include patients who develop fever after chemotherapy (either after first diagnosis or relapse) or after hemopoietic stem cell transplantation (TCSE) autologhe or allogenic, managed in ordinary hospitalization, subjected to endovenous antibiotic therapy for at least 72 hours for the treatment of the febrile episode. These patients will be the denominator of the study population. Patients who turn out to have positive hemoculture will represent the cases of the study population. A patient may be enrolled several times in the study both as "denominator/control" (hospitalization and example for several febrile episodes) and as a "case" (second episode of febrile batteriemia). In the latter case, the interval between the conclusion of a febrile episode (stable slibration, negative hemoculture) and the subsequent febrile episode must be at least 7 days. The febrile episodes considered will be only those in ordinary hospitalization (minimum 2 nights of hospitalization) while febrile episodes managed exclusively in day-care (Day-Hospital) or with home, oral or endovenous antibiotic therapy are excluded.

Each participating centre must declare at the opening the standard procedure relating to:

1. Study of colonization: yes, no, method of investigation;

2. Standard antibiotic prophylaxis in acute myeloid leukemia (LLA), acute myeloid leukemia (LMA), non-Hodgkin lymphoma (LNH), allogenic TCSE, autologous TCSE;

3. Standard empirical therapy in non-colonized patient (first 48-72 hours);

4. Use of Pentaglobin (yes/no, criteria for use, dose).

In the study patients, hospitalized by febrile episode in endovenous antibiotic therapy, the following information will be collected: sex, age at the time of the febrile episode, age at diagnosis of the basic disease, type of tumor, stage of treatment in hospitalization, type of transplant, presence or not of transplant disease against the host (only for allogenic transplantation), colonization or not, CVC or not, type of CVC, presence or not of urinary catheter, clinical characteristics of the febrile episode, date onset fever-date end fever, date start-date end of antibiotic therapy, date start-date end antifungal therapy, date start-date end therapy with Pentaglobin, result of haemoculture and antibiogram, number of neutrophils, number of lymphocytes, hypotension (in relation to normal values for age, saturation O2, need or not of hospitalization in intensive care , whether or not fluids are used, ventilatory support, renal replacement therapy, , maximum PCR-value (in the first 72 hours), PCT-value (maximum in the first 72 hours), Galactomanane (maximum value during the episode), β-D glucan (maximum value during the episode), survival at 30 and 90 days, final definition of the infectious episode (FUO, ICD, IMD), and possible toxicity related to antibiotic therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2000
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

Inclusion Criteria:

• written informed consent,- onset of fever after chemotherapy or after hemopoietic stem cell transplantation (TCSE),

• endovenous antibiotic therapy for at least 72 hours for the treatment of the febrile episode.

• ordinary hospitalization scheme

• age < 18

Related Conditions & MeSH terms

• Bacterial Infections

Intervention

Other:
• Battery incidence
Incidence of batteries from negative Gram germs; Incidence of batteries from gram positive germs; Incidence of fungemie; Incidence of septic shock; Incidence of batteries from colonising germs; Incidence of resistance to the main classes of antibiotics

Locations

Country	Name	City	State
Italy	Azienda Ospedali Riuniti Presidio "G. Salesi"	Ancona
Italy	AOU Policlinico	Bari
Italy	Policlinico Sant'Orsola Malpighi Clinica	Bologna
Italy	Ospedale Regionale	Bolzano
Italy	Spedali Civili, Presidio Ospedale Dei Bambini	Brescia
Italy	Ospedale Pediatrico Microcitemico "Antonio Cao", Azienda Ospedaliera Brotzu	Cagliari
Italy	AOU Policlinico Vittorio Emanuele	Catania
Italy	Azienda Ospedaliero Universitaria Sant'Anna	Ferrara
Italy	Azienda Ospedaliero-Universitaria "Anna Meyer"	Firenze
Italy	Istituto G.Gaslini	Genova
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milano
Italy	Azienda Policlinico Di Modena	Modena
Italy	Fondazione MBBM / AO San Gerardo Clinica	Monza
Italy	A.O.R.N. Santobono - Pausilipon	Napoli
Italy	Oncoematologia Pediatrica AOU di Padova	Padova
Italy	ARNAS Civico Di Cristina E Benfratelli	Palermo
Italy	Azienda Ospedaliero Universitaria Di Parma	Parma
Italy	Fondazione IRCCS, Policlinico San Matteo	Pavia
Italy	A.O.U. "S.M. Della Misericordia"	Perugia
Italy	Ospedale Civile Dello Spirito Santo Dipartimento Di Ematologia, Medicina Trasfusionale E Biotecnologie	Pescara
Italy	IRCCS Ospedale Pediatrico Bambino Gesù Dip.to di Oncoematologia e Terapia cellulare e Genica	Roma
Italy	IRCCS Ospedale "Casa Sollievo Della Sofferenza"	San Giovanni Rotondo
Italy	AOU Citta' Della Salute E Della Scienza Di Torino	Torino
Italy	IRCCS Materno Infantile "Burlo Garofolo"	Trieste
Italy	Azienda Ospedaliera Universitaria Integrata	Verona	Italia

Sponsors (1)

Lead Sponsor	Collaborator
Associazione Italiana Ematologia Oncologia Pediatrica

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of febrile bacteremia due to Gram-negative germs multi-resistant to antibiotics (MDR)	The evaluation of the incidence of febrile bacteremia due to MDR Gram-negative germs, i.e. bacteria that present resistance to at least 3 of the 5 classes of main antibiotics (3rd and 4th generation cephalosporins, beta-lactams, aminoglycosides, carbapenems and quinolones).	2020-2023
Secondary	Incidence of various types of febrile episodes	Incidence of various types of febrile episodes: fever of unknown origin (FUO), microbiologically determined infection (MDI) with positive blood culture and without positive blood culture, clinically determined infection (CDI).; The incidence of the various types of febrile episodes was obtained as the ratio of cases of FUO, IMD with and without bacteremia, fungemia and CDI to total febrile episodes	2020-2023
Secondary	Bacteremia	Incidence of bacteremia due to Gram-negative germs and bacteremia due to Gram-positive germs. The incidence of Gram-negative bacteremia and Gram-positive bacteremia was calculated by the ratio of different events to total IMDs with positive blood culture and total bacteremia.	2020-2023
Secondary	Fungaemia	The incidence of fungemia was calculated as the ratio of fungemia cases to total microbiologically determined infection with positive blood culture.	2020-2023
Secondary	Risk factors for bacteremia and microbiologically documented infection (MDI)	Risk factor analysis for incidence for bacteremia and IMD was performed by logistic regression models	2020-2023
Secondary	Mortality at 30 days	Evaluate clinical responce and mortality at 30 days. Mortality was derived from the ratio of the number of deaths to the total number of eligible patients.	30 days
Secondary	Mortality at 90 days	Evaluate clinical response and mortality at 90 days. Mortality was derived from the ratio of the number of deaths to the total number of eligible patients.	90 days