TY - JOUR
T1 - In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections
AU - AIDA Study Group
AU - Nutman, Amir
AU - Temkin, Elizabeth
AU - Lellouche, Jonathan
AU - Rakovitsky, Nadya
AU - Hameir, Amichay
AU - Daikos, George
AU - Durante-Mangoni, Emanuele
AU - Pavleas, Ioannis
AU - Dishon, Yael
AU - Petersiel, Neta
AU - Yahav, Dafna
AU - Eliakim, Noa
AU - Bernardo, Mariano
AU - Iossa, Domenico
AU - Friberg, Lena E.
AU - Theuretzbacher, Ursula
AU - Leibovici, Leonard
AU - Paul, Mical
AU - Carmeli, Yehuda
AU - Dickstein, Yaakov
AU - Bitterman, Roni
AU - Zayyad, Hiba
AU - Koppel, Fidi
AU - Zak-Doron, Yael
AU - Altunin, Sergey
AU - Andria, Nizar
AU - Neuberger, Ami
AU - Stern, Anat
AU - Raines, Marina
AU - Karban, Amir
AU - Eliakim-Raz, Noa
AU - Zusman, Oren
AU - Elbaz, Michal
AU - Atamna, Heyam
AU - Daitch, Vered
AU - Babich, Tanya
AU - Adler, Amos
AU - Levi, Inbar
AU - Daikos, George L.
AU - Skiada, Anna
AU - Antoniadou, Anastasia
AU - Kotsaki, Antigoni
AU - Andini, Roberto
AU - Cavezza, Giusi
AU - Bertolino, Lorenzo
AU - Giuffre, Giuseppe
AU - Giurazza, Roberto
AU - Ruocco, Giuseppe
AU - Galdo, Maria
AU - Murino, Patrizia
N1 - Publisher Copyright:
© 2021 European Society of Clinical Microbiology and Infectious Diseases
PY - 2022/1
Y1 - 2022/1
N2 - Objectives: Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections. Methods: Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes. Results: The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04–2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03–2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95–2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09–3.25). Conclusions: In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.
AB - Objectives: Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections. Methods: Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes. Results: The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04–2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03–2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95–2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09–3.25). Conclusions: In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.
KW - Bacterial fitness
KW - Carbapenem-resistant Acinetobacter baumannii
KW - Clinical outcome
KW - Murine thigh infection model
KW - Treatment failure
UR - http://www.scopus.com/inward/record.url?scp=85108656639&partnerID=8YFLogxK
U2 - 10.1016/j.cmi.2021.05.005
DO - 10.1016/j.cmi.2021.05.005
M3 - Article
C2 - 33984488
AN - SCOPUS:85108656639
SN - 1198-743X
VL - 28
SP - 73
EP - 78
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
IS - 1
ER -