In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol.
Elda Righi, Luigia Scudeller, Margherita Chiamenti, Kamilia Abdelraouf, Thomas Lodise, Elena Carrara, Alessia Savoldi, Dario Menghin, Gloria Pellizzari, Sally Ellis, Francois Franceschi, Laura Piddock, Chiara Rebuffi, Maurizio Sanguinetti, Evelina Tacconelli
Author Information
Elda Righi: Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy. ORCID
Luigia Scudeller: Clinical Epidemiology and Biostatistics, IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano Foundation, Milan, Italy. ORCID
Margherita Chiamenti: Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Kamilia Abdelraouf: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
Thomas Lodise: Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
Elena Carrara: Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Alessia Savoldi: Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Dario Menghin: Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Gloria Pellizzari: Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Sally Ellis: Global Antibiotic Research & Development Partnership (GARDP), Geneva, Switzerland.
Francois Franceschi: Global Antibiotic Research & Development Partnership (GARDP), Geneva, Switzerland.
Laura Piddock: Global Antibiotic Research & Development Partnership (GARDP), Geneva, Switzerland.
Chiara Rebuffi: Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Maurizio Sanguinetti: Microbiology, A. Gemelli Hospital, Catholic University of the Sacred Heart, Rome, Italy.
Evelina Tacconelli: Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
OBJECTIVE: There is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR , and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria. METHODS AND ANALYSIS: This protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE's risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias. DISSEMINATION: This systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42019128104(available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128104).
References
Environ Toxicol Chem. 2016 May;35(5):1297-309
[PMID: 26399705]
