Bacterial Infections Clinical Trial
— NEW_SAFEOfficial title:
Quasi-experimental Intervention Study to Optimize the Use of New Antibiotics (Project NEW_SAFE)
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla |
Spain,
Bouza E, Valerio M, Soriano A, Morata L, Carus EG, Rodríguez-González C, Hidalgo-Tenorio MC, Plata A, Muñoz P, Vena A; DALBUSE Study Group (Dalbavancina: Estudio de su uso clinico en España). Dalbavancin in the treatment of different gram-positive infections: a real-life experience. Int J Antimicrob Agents. 2018 Apr;51(4):571-577. doi: 10.1016/j.ijantimicag.2017.11.008. Epub 2017 Nov 24. — View Citation
Cosimi RA, Beik N, Kubiak DW, Johnson JA. Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review. Open Forum Infect Dis. 2017 May 2;4(2):ofx084. doi: 10.1093/ofid/ofx084. eCollection 2017 Spring. Review. — View Citation
Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, Gould IM, Ramsay CR, Michie S. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2017 Feb 9;2:CD003543. doi: 10.1002/14651858.CD003543.pub4. Review. — View Citation
De León-Borrás R, Álvarez-Cardona J, Vidal JA, Guiot HM. Ceftazidime/Avibactam for Refractory Bacteremia, Vertebral Diskitis/Osteomyelitis with Pre-Vertebral Abscess and Bilateral Psoas Pyomyositis Secondary to Klebsiella Pneumoniae Carbapenemase-Producing Bacteria (KPC). P R Health Sci J. 2018 Jun;37(2):128-131. — View Citation
Diamond IR, Grant RC, Feldman BM, Pencharz PB, Ling SC, Moore AM, Wales PW. Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol. 2014 Apr;67(4):401-9. doi: 10.1016/j.jclinepi.2013.12.002. Review. — View Citation
Dietl B, Sánchez I, Arcenillas P, Cuchi E, Gómez L, González de Molina FJ, Boix-Palop L, Nicolás J, Calbo E. Ceftolozane/tazobactam in the treatment of osteomyelitis and skin and soft-tissue infections due to extensively drug-resistant Pseudomonas aeruginosa: clinical and microbiological outcomes. Int J Antimicrob Agents. 2018 Mar;51(3):498-502. doi: 10.1016/j.ijantimicag.2017.11.003. Epub 2017 Nov 20. — View Citation
European Centre for Disease Prevention and Control. Rapid risk assessment: Carbapenem-resistant Enterobacteriaceae - first update 4 June 2018. Stockholm: ECDC; 2018. https://ecdc.europa.eu/sites/portal/files/documents/RRA-Enterobacteriaceae-Carbapenems-European-Union-countries.pdf
Ficha técnica de ceftarolina. https://ec.europa.eu/health/documents/communityregister/2012/20120823123835/anx_123835_es.pdf
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
PIRASOA: actividad laboratorio de referencia. Accesible en: pirasoa.iavante.es/mod/resource/view.php?id=797
Plan estratégico y de acción para reducir el riesgo de selección y diseminación de la resistencia a los antibióticos http://www.resistenciaantibioticos.es/es/system/files/ content_images/plan_nacional_resistencia_antibioticos.pdf
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
Si S, Durkin MJ, Mercier MM, Yarbrough ML, Liang SY. Successful Treatment of Prosthetic Joint Infection due to Vancomycin-resistant Enterococci with Tedizolid. Infect Dis Clin Pract (Baltim Md). 2017 Mar;25(2):105-107. doi: 10.1097/IPC.0000000000000469. — View Citation
Spellberg B, Bonomo RA. Editorial Commentary: Ceftazidime-Avibactam and Carbapenem-Resistant Enterobacteriaceae: "We're Gonna Need a Bigger Boat". Clin Infect Dis. 2016 Dec 15;63(12):1619-1621. Epub 2016 Sep 13. — View Citation
Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318-327. doi: 10.1016/S1473-3099(17)30753-3. Epub 2017 Dec 21. — View Citation
Tobudic S, Forstner C, Burgmann H, Lagler H, Ramharter M, Steininger C, Vossen MG, Winkler S, Thalhammer F. Dalbavancin as Primary and Sequential Treatment for Gram-Positive Infective Endocarditis: 2-Year Experience at the General Hospital of Vienna. Clin Infect Dis. 2018 Aug 16;67(5):795-798. doi: 10.1093/cid/ciy279. — View Citation
Versporten A, Zarb P, Caniaux I, Gros MF, Drapier N, Miller M, Jarlier V, Nathwani D, Goossens H; Global-PPS network. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: results of an internet-based global point prevalence survey. Lancet Glob Health. 2018 Jun;6(6):e619-e629. doi: 10.1016/S2214-109X(18)30186-4. Epub 2018 Apr 23. Erratum in: Lancet Glob Health. 2018 Sep;6(9):e968. — View Citation
Vickery SB, McClain D, Wargo KA. Successful Use of Ceftolozane-Tazobactam to Treat a Pulmonary Exacerbation of Cystic Fibrosis Caused by Multidrug-Resistant Pseudomonas aeruginosa. Pharmacotherapy. 2016 Oct;36(10):e154-e159. doi: 10.1002/phar.1825. Epub 2016 Sep 1. — View Citation
Zasowski EJ, Trinh TD, Claeys KC, Casapao AM, Sabagha N, Lagnf AM, Klinker KP, Davis SL, Rybak MJ. Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections. Antimicrob Agents Chemother. 2017 Jan 24;61(2). pii: e02015-16. doi: 10.1128/AAC.02015-16. Print 2017 Feb. — View Citation
* Note: There are 34 references in all — Click here to view all references
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. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03726216 -
Xydalba Utilization Registry in France
|
||
Completed |
NCT03605498 -
OR PathTrac (Tracking Intra-operative Bacterial Transmission)
|
||
Withdrawn |
NCT05269121 -
Bacteriophage Therapy in First Time Chronic Prosthetic Joint Infections
|
Phase 1/Phase 2 | |
Completed |
NCT02541695 -
Characterization of Resistance Against Live-attenuated Diarrhoeagenic E. Coli
|
N/A | |
Recruiting |
NCT02074865 -
Children's Antibiotic Resistant Infections in Low Income Countries
|
N/A | |
Completed |
NCT01932034 -
Prospective Study to Optimize Vancomycin Dosing in Children and Adults Using Computer Software
|
N/A | |
Completed |
NCT01689207 -
To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)
|
Phase 1 | |
Completed |
NCT01412801 -
Magnitude of the Antibody Response to and Safety of a GBS Trivalent Vaccine in HIV Positive and HIV Negative Pregnant Women and Their Offsprings
|
Phase 2 | |
Not yet recruiting |
NCT01159470 -
The Rate of C-reactive Protein (CRP) Increase as a Marker for Bacterial Infections in Children
|
N/A | |
Completed |
NCT00983255 -
Ascending Dose Pharmacokinetic (PK) and Absolute Bioavailability (BA)
|
Phase 1 | |
Completed |
NCT00678106 -
Study Of Dalbavancin Drug Levels Achieved In Hospitalized Adolescents Who Are Receiving Antibiotic Therapy For Bacterial Infections
|
Phase 1 | |
Completed |
NCT00799591 -
French Study In ICU Patients Treated With Tigecycline
|
N/A | |
Completed |
NCT01074775 -
Human Innate Immune Responses To Mycobacterial Aerodigestive Tract Infection
|
N/A | |
Completed |
NCT00478855 -
Tazocin Intervention Study
|
Phase 4 | |
Terminated |
NCT00431028 -
Sub-Tenon's Injection of Triamcinolone and Ciprofloxacin in a Controlled-Release System for Cataract Surgery
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT03634904 -
Serum Ceftazidime Concentrations in Hemodialysis Patients
|
N/A | |
Recruiting |
NCT05684705 -
Study to Investigate the Penetration of Rifabutin Into the Lung After Multiple Intravenous Administrations of BV100
|
Phase 1 | |
Recruiting |
NCT03858387 -
PK/PD and Clinial Outcomes of Beta-lactams in ICU Patients
|
||
Enrolling by invitation |
NCT04764058 -
Efficacy and Safety of Colistin Based Antibiotic Therapy
|
Phase 1/Phase 2 | |
Recruiting |
NCT06319235 -
Clinical Trial to Demonstrate the Safety and Efficacy of DUOFAG®
|
Phase 1/Phase 2 |