Study to Optimize the Use of New Antibiotics

Bacterial Infections Clinical Trial

— NEW_SAFE  

Official title:

Quasi-experimental Intervention Study to Optimize the Use of New Antibiotics (Project NEW_SAFE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03941951
• Other study ID #: FIS-TED-2019-01
• Status: Recruiting
• Phase: N/A
• Start date: July 9, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2020
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: Zaira Palacios Baena
• Phone: 34 653276353
• Email: zaira.palacios.baena[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Quasi-experimental intervention multicenter trial of patients treated with new antibiotics (before-after study).

The study will be carried out in 14 hospitals of the Andalusian Public Health System with representation from all the provinces and has been designed in two phases:

1. A first phase in which an observational study of historical preintervention cohorts of patients who have received either empirical or targeted treatment with ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam, ceftolozane-tazobactam and isavuconazole from January 2016 to December 2019 will be developed. Case detection will be carried out by locating the antimicrobial prescriptions in the electronic prescribing systems and / or pharmaceutical management systems of each hospital. A set of epidemiological, clinical, microbiological and prognostic variables will be completed in each case.

2. A second phase or intervention period that will be applied to the cohort of patients treated with new antibiotics (intervention cohort) from January 2020 to June 2021. A quasi-experimental intervention study will be carried out through the development of a Program for Optimizing the use of Antibiotics (PROA) in Spanish, Antimicrobial Stewardship Program (ASP) in English, in the participating hospitals. It will consist in the development of a consensus document on the use of new antibiotics following a Delphi methodology, dissemination of the consensus document / guide among the participating hospitals and audit on the prescription of new antimicrobials after the implementation of the guide based on providing non-imposition advice and positive reinforcement to the prescriber. The recommendations will be consigned in a structured form, which will allow to evaluate the degree of follow-up of the recommendations. The audit will be performed on day 0-1 of the prescription.

3. Cohort of bacteremia due to multiresistant microorganisms ("safety" cohort): In order to evaluate the safety of the use of new antimicrobials against therapeutic alternatives in syndromes where they are potentially a preferred option and parallel to the two phases, episodes for bacteremia by carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, carbapenem-resistant enterobacteria, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus occurred in participating hospitals from 2017 to 2021 will be collected.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Pre-intervention cohort (historical):

Inclusion criteria:

• All patients treated with ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam, ceftolozane-tazobactam or isavuconazole.

• In a hospital or ambulatory regime.

• That they have received at least 1 dose of treatment of any of the antimicrobials mentioned, either as empirical or directed treatment.

• Adults (18 years).

• Between January 1, 2016 and December 31, 2019.

Exclusion criteria:

• There are no exclusion criteria except for age.

Intervention cohort:

Inclusion criteria:

• All patients treated with ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam, ceftolozane-tazobactam or isavuconazole.

• In a hospital or ambulatory regime.

• That they have received at least 1 dose of treatment of any of the antimicrobials mentioned, either as empirical or directed treatment.

• Adults (18 years).

• From January 1, 2020 to December 31, 2021.

• Since the publication and diffusion of the recommendation guide.

Exclusion criteria:

• There are no exclusion criteria except for age.

Safety cohort:

Inclusion criteria:

• All episodes of clinically significant bacteremia (that have received any treatment) produced by:

• Acinetobacter baumannii resistant or with intermediate susceptibility to any carbapenem.

• Pseudomonas aeruginosa resistant or with intermediate susceptibility to any carbapenem.

• Enterobacteria resistant or with intermediate susceptibility to any carbapenem.

• Vancomycin-resistant Enterococcus faecium.

• Methicillin-resistant Staphylococcus aureus.

• From January 1, 2017 to December 31, 2021.

• Adult patients (18 years old).

Exclusion criteria:

• There are no exclusion criteria except for age.

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Fungal Infection
• Infection
• Mycoses

Intervention

Behavioral:
• Non-impositive Program for Optimizing the Use of Antimicrobials
Quasi-experimental intervention through the development of a Program for Optimizing the Use of Antimicrobials in the participating hospitals. The intervention will consist of the development of a consensus guide on the use of new antibiotics, its dissemination in Andalusian hospitals and an audit on the prescription of new antibiotics.

Locations

Country	Name	City	State
Spain	Hospital de Poniente-El Ejido	Almería
Spain	University Hospital Puerta del Mar	Cadiz
Spain	University Hospital Reina Sofía	Córdoba
Spain	Hospital Clínico Universitario San Cecilio	Granada
Spain	University Hospital Virgen de las Nieves	Granada
Spain	Área Hospitalaria Juan Ramón Jiménez	Huelva
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	University Hospital de Jerez de la Frontera	Jerez De La Frontera
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	University Hospital Virgen de la Victoria	Málaga
Spain	Hospital de Puerto Real	Puerto Real
Spain	University Hospital Virgen de Valme	Sevilla
Spain	University Hospital Virgen del Rocío	Sevilla
Spain	University Hospital Virgen Macarena (Sevilla).	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Country where clinical trial is conducted

Spain, 

References & Publications (34)

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Ficha técnica de ceftazidima-avibactam. http://www.ema.europa.eu/docs/es_ES /document_library /EPAR_-_Product_Information/human/004027/WC500210234.pdf

Ficha técnica de ceftolozano-tazobactam. https://ec.europa.eu/health/documents /communityregister/2015/20150918132786/anx_132786_es.pdf

Ficha técnica de isavuconazol. https://ec.europa.eu/health/documents/community-register/2015/20151015132781/anx_132781_es.pdf.

Ficha técnica de tedizolid. http://www.ema.europa.eu/docs/es_ES/document_library /EPAR_-_Product_Information/human/002846/WC500184802.pdf

Gaibani P, Campoli C, Lewis RE, Volpe SL, Scaltriti E, Giannella M, Pongolini S, Berlingeri A, Cristini F, Bartoletti M, Tedeschi S, Ambretti S. In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniae during ceftazidime/avibactam treatment. J Antimicrob Chemother. 2018 Jun 1;73(6):1525-1529. doi: 10.1093/jac/dky082. — View Citation

Gofman N, To K, Whitman M, Garcia-Morales E. Successful treatment of ventriculitis caused by Pseudomonas aeruginosa and carbapenem-resistant Klebsiella pneumoniae with i.v. ceftazidime-avibactam and intrathecal amikacin. Am J Health Syst Pharm. 2018 Jul 1;75(13):953-957. doi: 10.2146/ajhp170632. — View Citation

Hernández-García I, Sáenz-González MC, Meléndez D. [Assessment of an educational program for the prevention of healthcare-associated infections]. Rev Calid Asist. 2013 Mar-Apr;28(2):96-108. doi: 10.1016/j.cali.2012.09.001. Epub 2012 Nov 2. Spanish. — View Citation

Iacovelli A, Spaziante M, Al Moghazi S, Giordano A, Ceccarelli G, Venditti M. A challenging case of carbapenemase-producing Klebsiella pneumoniae septic thrombophlebitis and right mural endocarditis successfully treated with ceftazidime/avibactam. Infection. 2018 Oct;46(5):721-724. doi: 10.1007/s15010-018-1166-9. Epub 2018 Jun 20. Erratum in: Infection. 2018 Jul 10;:. — View Citation

Informa de posicionamiento terapéutico de dalbavancina. https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/IPTdalbavancina-Xydalba.pdf

López Cortés LE, Mujal Martínez A, Fernández Martínez de Mandojana M, Martín N, Gil Bermejo M, Solà Aznar J, Villegas Bruguera E, Peláez Cantero MJ, Retamar Gentil P, Delgado Vicente M, González-Ramallo VJ, Ponce González MÁ, Mirón Rubio M, Gómez Rodríguez de Mendarozqueta MM, Goenaga Sánchez MÁ, Sanroma Mendizábal P, Delgado Mejía E, Pajarón Guerrero M; Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), the Sociedad Española de Hospitalización a Domicilio (SEHAD) Group. Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society. Enferm Infecc Microbiol Clin. 2019 Jun - Jul;37(6):405-409. doi: 10.1016/j.eimc.2018.03.012. Epub 2018 May 18. English, Spanish. — View Citation

López-Cerero L, Egea P, Gracia-Ahufinger I, González-Padilla M, Rodríguez-López F, Rodríguez-Baño J, Pascual A. Characterisation of the first ongoing outbreak due to KPC-3-producing Klebsiella pneumoniae (ST512) in Spain. Int J Antimicrob Agents. 2014 Dec;44(6):538-40. doi: 10.1016/j.ijantimicag.2014.08.006. Epub 2014 Sep 26. — View Citation

Mensa J, Soriano A, Llinares P, Barberán J, Montejo M, Salavert M, Alvarez-Rocha L, Maseda E, Moreno A, Pasquau J, Gómez J, Parra J, Candel J, Azanza JR, García JE, Marco F, Soy D, Grau S, Arias J, Fortún J, de Alarcón CA, Picazo J; Sociedad Española de Quimioterapia (SEQ); Sociedad Española de Medicina Interna (SEMI); GTIPO-Sociedad Española de Anestesiología y Reanimación. [Guidelines for antimicrobial treatment of the infection by Staphylococcus aureus]. Rev Esp Quimioter. 2013 Jan;26 Suppl 1:1-84. Review. Spanish. — View Citation

Nigo M, Luce AM, Arias CA. Long-term Use of Tedizolid as Suppressive Therapy for Recurrent Methicillin-Resistant Staphylococcus aureus Graft Infection. Clin Infect Dis. 2018 Jun 1;66(12):1975-1976. doi: 10.1093/cid/ciy041. — View Citation

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Plant AJ, Dunn A, Porter RJ. Ceftolozane-tazobactam resistance induced in vivo during the treatment of MDR Pseudomonas aeruginosa pneumonia. Expert Rev Anti Infect Ther. 2018 May;16(5):367-368. doi: 10.1080/14787210.2018.1473079. — View Citation

Rodríguez-Baño J, Cisneros JM, Cobos-Trigueros N, Fresco G, Navarro-San Francisco C, Gudiol C, Horcajada JP, López-Cerero L, Martínez JA, Molina J, Montero M, Paño-Pardo JR, Pascual A, Peña C, Pintado V, Retamar P, Tomás M, Borges-Sa M, Garnacho-Montero J, Bou G; Study Group of Nosocomial Infections (GEIH) of the Spanish Society of Infectious Diseases, Infectious Diseases (SEIMC). Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology. Enferm Infecc Microbiol Clin. 2015 May;33(5):337.e1-337.e21. doi: 10.1016/j.eimc.2014.11.009. Epub 2015 Jan 15. — View Citation

Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Machuca I, Pascual A. Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae. Clin Microbiol Rev. 2018 Feb 14;31(2). pii: e00079-17. doi: 10.1128/CMR.00079-17. Print 2018 Apr. Review. — View Citation

Rodríguez-Baño J, Paño-Pardo JR, Alvarez-Rocha L, Asensio Á, Calbo E, Cercenado E, Cisneros JM, Cobo J, Delgado O, Garnacho-Montero J, Grau S, Horcajada JP, Hornero A, Murillas-Angoiti J, Oliver A, Padilla B, Pasquau J, Pujol M, Ruiz-Garbajosa P, San Juan R, Sierra R; GEIH-SEIMC; SEFH; SEMPSPH. [Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document]. Farm Hosp. 2012 Jan-Feb;36(1):33.e1-30. doi: 10.1016/j.farma.2011.10.001. Epub 2011 Dec 1. Spanish. — View Citation

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* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total antibiotic consumption	Defined daily doses (DDD) of each antibiotic per 1000 stays	Yearly from date of intervention up to 24 months of follow-up
Secondary	Total cost per antimicrobial	Total expense in euros of each antimicrobial per 1000 stays	Yearly from date of intervention up to 24 months of follow-up
Secondary	Mortality rate	Mortality from any cause at 7, 14 and 30 days after the start of the treatment.	At 7, 14 and 30 days after the start of the treatment.
Secondary	Total length of hospital stay	Duration of a single episode of hospitalization defined as the time between hospital admission and discharge measured in days. During this episode the patient has to be prescribed with one of the antibiotics included in the study.	Monthly from date of intervention up to 24 months of follow-up
Secondary	Incidence of colitis due to Clostridium difficile.	Clostridium difficile infection documented during treatment with any of the antibiotics described	Monthly from date of intervention up to 24 months of follow-up
Secondary	Percentage of patients with infections by multiresistant microorganisms. Colonization during treatment by resistant microorganisms	Percentage of patients with infections by multiresistant microorganisms in each cohort.	Monthly from date of intervention up to 24 months of follow-up
Secondary	Percentage of patients colonized by multiresistant microorganisms	Percentage of patients colonized by multiresistant microorganisms in each cohort after completion of treatment with antibiotic under study.	Monthly from date of intervention up to 24 months of follow-up
Secondary	Re-admission rate	Re-admission of the patient in the hospital at 90 days after the start of the antibiotic treatment.	90 days after the start of the antibiotic treatment.