TY - JOUR
T1 - A Systems-Based Analysis of Mono- and Combination Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections
AU - the Antibacterial Resistance Leadership Group
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.
N1 - 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
UR - http://www.scopus.com/inward/citedby.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
ER -
