TY - JOUR
T1 - A Systems-Based Analysis of Mono- and Combination Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections
AU - Luterbach, Courtney L.
AU - Qiu, Hongqiang
AU - Hanafin, Patrick O.
AU - Sharma, Rajnikant
AU - Piscitelli, Joseph
AU - Lin, Feng Chang
AU - Ilomaki, Jenni
AU - Cober, Eric
AU - Salata, Robert A.
AU - Kalayjian, Robert C.
AU - Watkins, Richard R.
AU - Doi, Yohei
AU - Kaye, Keith S.
AU - Nation, Roger L.
AU - Bonomo, Robert A.
AU - Landersdorfer, Cornelia B.
AU - van Duin, David
AU - Rao, Gauri G.
AU - on behalf of the Antibacterial Resistance Leadership Group
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681. In addition, research reported in this publication was supported in part by the National Institutes of Health under Award Numbers R01AI143910 (D.v.D.), National Institute of Allergy and Infectious Diseases R01AI146241 (G.G.R.), and by the National Institute of General Medical Sciences T32GM086330 (C.L.L.). Lastly, H.Q. received the financial support of the visiting scholarship from the Fujian Science and Technology Innovation Joint Project (no. 2019Y9051).
Publisher Copyright:
Copyright © 2022 Luterbach et al.
PY - 2022/10
Y1 - 2022/10
N2 - Antimicrobial resistance is a global threat. As “proof-of-concept, ” we employed a system-based approach to identify patient, bacterial, and drug variables contributing to mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKp) bloodstream infections exposed to colistin (COL) and ceftazidime-avibactam (CAZ/AVI) as mono- or combination therapies. Patients (n = 49) and CRKp isolates (n = 22) were part of the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a multicenter, observational, prospective study of patients with carbapenem-resistant Enterobacterales (CRE) conducted between 2011 and 2016. Pharmacodynamic activity of mono- and combination drug concentrations was evaluated over 24 h using in vitro static time-kill assays. Bacterial growth and killing dynamics were estimated with a mechanism-based model. Random Forest was used to rank variables important for predicting.
AB - Antimicrobial resistance is a global threat. As “proof-of-concept, ” we employed a system-based approach to identify patient, bacterial, and drug variables contributing to mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKp) bloodstream infections exposed to colistin (COL) and ceftazidime-avibactam (CAZ/AVI) as mono- or combination therapies. Patients (n = 49) and CRKp isolates (n = 22) were part of the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a multicenter, observational, prospective study of patients with carbapenem-resistant Enterobacterales (CRE) conducted between 2011 and 2016. Pharmacodynamic activity of mono- and combination drug concentrations was evaluated over 24 h using in vitro static time-kill assays. Bacterial growth and killing dynamics were estimated with a mechanism-based model. Random Forest was used to rank variables important for predicting.
UR - http://www.scopus.com/inward/record.url?scp=85140256241&partnerID=8YFLogxK
U2 - 10.1128/aac.00591-22
DO - 10.1128/aac.00591-22
M3 - Article
C2 - 36125299
AN - SCOPUS:85140256241
SN - 0066-4804
VL - 66
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 10
M1 - 00591-22
ER -
