Alberto E Maraolo1, Silvia Corcione2, Adriano Grossi3, Alessio Signori4, Cristiano Alicino4,5, Khetam Hussein6, Enrico M Trecarichi7, Pierluigi Viale8, Jean-François Timsit9, Balaji Veeraraghavan10, Maria V Villegas11, Galia Rahav12, George L Daikos13, Konstantinos Z Vardakas14,15, Emmanuel Roilides16, Anne-Catrin Uhlemann17, Abdul K Ghafur18, Simone Mornese Pinna2, Matteo Bassetti4,19, Philipp P Kohler20, Daniele R Giacobbe4,19. 1. First Division of Infectious Diseases, Cotugno Hospital, AORN Dei Colli, Naples, Italy. albertomaraolo@mail.com. 2. Department of Medical Sciences, Infectious Diseases, University of Turin, Turin, Italy. 3. Section of Hygiene, University Department of Life Sciences and Public Health, University Cattolica del Sacro Cuore, Rome, Italy. 4. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy. 5. Medical Direction, Santa Corona Hospital, ASL 2 Regional Health System of Liguria, Pietra Ligure, Italy. 6. Infectious Diseases Unit, Rambam Health Care Campus, Haifa, Israel. 7. Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit, "Magna Graecia" University, Catanzaro, Italy. 8. Department of Medical and Surgical Sciences, Clinics of Infectious Diseases, S. Orsola-Malpighi Hospital, "Alma Mater Studiorum" University of Bologna, Bologna, Italy. 9. AP-HP, Bichat Claude Bernard Hospital, Medical and Infectious Diseases ICU (MI2), Paris, France. 10. Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India. 11. Grupo de Resistencia Antimicrobiana Y Epidemiología Hospitalaria, Universidad El Bosque, Bogotá, Colombia. 12. Infectious Diseases Unit, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 13. First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece. 14. Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece. 15. Department of Medicine, Henry Dunant Hospital Center, Athens, Greece. 16. Infectious Disease Unit and Third Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece. 17. Department of Medicine, Division of Infectious Diseases, Columbia University Irving Medical Center, New York, NY, USA. 18. Apollo Cancer Institute, Anna Salai, Chennai, India. 19. Ospedale Policlinico San Martino, IRCCS Per L'Oncologia, L. go R. Benzi 10, Genoa, Italy. 20. Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Abstract
INTRODUCTION: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. METHODS: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). RESULTS: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56-3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24-2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70-4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36-3.59; I2 = 58%). CONCLUSION: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.
INTRODUCTION: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. METHODS: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). RESULTS: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infectedpatients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56-3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24-2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70-4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36-3.59; I2 = 58%). CONCLUSION: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.
Entities:
Keywords:
Active therapy; Carbapenem-resistant Klebsiella pneumoniae; Individual patient data meta-analysis; Monotherapy