TY - JOUR
T1 - The Impact of Carbapenem Resistance on Mortality in Patients With Klebsiella Pneumoniae Bloodstream Infection
T2 - An Individual Patient Data Meta-Analysis of 1952 Patients
AU - Maraolo, Alberto E.
AU - Corcione, Silvia
AU - Grossi, Adriano
AU - Signori, Alessio
AU - Alicino, Cristiano
AU - Hussein, Khetam
AU - Trecarichi, Enrico M.
AU - Viale, Pierluigi
AU - Timsit, Jean François
AU - Veeraraghavan, Balaji
AU - Villegas, Maria V.
AU - Rahav, Galia
AU - Daikos, George L.
AU - Vardakas, Konstantinos Z.
AU - Roilides, Emmanuel
AU - Uhlemann, Anne Catrin
AU - Ghafur, Abdul K.
AU - Mornese Pinna, Simone
AU - Bassetti, Matteo
AU - Kohler, Philipp P.
AU - Giacobbe, Daniele R.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Active therapy
KW - Carbapenem-resistant Klebsiella pneumoniae
KW - Individual patient data meta-analysis
KW - Monotherapy
UR - http://www.scopus.com/inward/record.url?scp=85100865877&partnerID=8YFLogxK
U2 - 10.1007/s40121-021-00408-8
DO - 10.1007/s40121-021-00408-8
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AN - SCOPUS:85100865877
SN - 2193-8229
VL - 10
SP - 541
EP - 558
JO - Infectious Diseases and Therapy
JF - Infectious Diseases and Therapy
IS - 1
ER -