Mical Paul1, Elena Carrara2, Pilar Retamar3, Thomas Tängdén4, Roni Bitterman1, Robert A Bonomo5, Jan de Waele6, George L Daikos7, Murat Akova8, Stephan Harbarth9, Celine Pulcini10, José Garnacho-Montero11, Katja Seme12, Mario Tumbarello13, Paul Christoffer Lindemann14, Sumanth Gandra15, Yunsong Yu16, Matteo Bassetti17, Johan W Mouton18, Evelina Tacconelli19, Jesús Rodríguez-Baño3. 1. Infectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel; Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. 2. Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy. 3. Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain; Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. 4. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 5. Department of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Medical Service, Research Service, and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA; VAMC Center for Antimicrobial Resistance and Epidemiology, Cleveland, OH, USA. 6. Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium. 7. First Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 8. Hacettepe University School of Medicine, Department of Infectious Diseases, Ankara, Turkey. 9. Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland. 10. Université de Lorraine, APEMAC, Nancy, France; Université de Lorraine, CHRU-Nancy, Infectious Diseases Department, Nancy, France. 11. Intensive Care Unit. Virgen Macarena University Hospital, Seville, Spain. 12. Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia. 13. Department of Medical Biotechnologies, University of Siena, Italy. 14. Haukeland University Hospital, Department of Microbiology, Bergen, Norway. 15. Division of Infectious Diseases, Washington University School of Medicine in St Louis, St Louis, MO, USA. 16. Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China; Regional Medical Centre for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 17. Department of Health Sciences, University of Genoa, Genoa, Italy; Clinica Malattie Infettive, San Martino Policlinico Hospital, Genoa, Italy. 18. Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands. 19. Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy; Division of Infectious Diseases, Department of Internal Medicine I, German Centre for Infection Research, University of Tübingen, Tübingen, Germany; German Centre for Infection Research (DZIF), Clinical Research Unit for Healthcare Associated Infections, Tübingen, Germany. Electronic address: evelina.tacconelli@univr.it.
Abstract
SCOPE: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy. METHODS: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak). RECOMMENDATIONS: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
SCOPE: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy. METHODS: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak). RECOMMENDATIONS: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
Authors: O Lima; A Sousa; A Filgueira; M Carmen González-Novoa; Celina Domínguez-López; M Ávila-Nuñez; M Represa; P Rubiñán; L Martínez-Lamas; Sonia Pérez-Castro; M Rubianes; M T Pérez-Rodríguez Journal: Eur J Clin Microbiol Infect Dis Date: 2022-10-07 Impact factor: 5.103
Authors: Massimiliano De Angelis; Maria T Mascellino; Maria C Miele; Dania Al Ismail; Marisa Colone; Annarita Stringaro; Vincenzo Vullo; Mario Venditti; Claudio M Mastroianni; Alessandra Oliva Journal: Antibiotics (Basel) Date: 2022-02-10