In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections. (January 2022)

• Record Type: Journal Article
• Authors: Nutman, Amir; Temkin, Elizabeth; Lellouche, Jonathan; Rakovitsky, Nadya; Hameir, Amichay; Daikos, George; Durante-Mangoni, Emanuele; Pavleas, Ioannis; Dishon, Yael; Petersiel, Neta; Yahav, Dafna; Eliakim, Noa; Bernardo, Mariano; Iossa, Domenico; Friberg, Lena E.; Theuretzbacher, Ursula; Leibovici, Leonard; Paul, Mical; Carmeli, Yehuda; Paul, Mical; Benattar, Yael Dishon; Dickstein, Yaakov; Bitterman, Roni; Zayyad, Hiba; Koppel, Fidi; Zak-Doron, Yael; Altunin, Sergey; Andria, Nizar; Neuberger, Ami; Stern, Anat; Petersiel, Neta; Raines, Marina; Karban, Amir; Leibovici, Leonard; Yahav, Dafna; Eliakim-Raz, Noa; Zusman, Oren; Elbaz, Michal; Atamna, Heyam; Daitch, Vered; Babich, Tanya; Carmeli, Yehuda; Nutman, Amir; Adler, Amos; Levi, Inbar; Daikos, George L.; Skiada, Anna; Pavleas, Ioannis; Antoniadou, Anastasia; Kotsaki, Antigoni; Durante-Mangoni, Emanuele; Andini, Roberto; Iossa, Domenico; Bernardo, Mariano; Cavezza, Giusi; Bertolino, Lorenzo; Giuffre, Giuseppe; Giurazza, Roberto; Ruocco, Giuseppe; Galdo, Maria; Murino, Patrizia; Cristinziano, Adriano; Corcione, Antonio; Zampino, Rosa; Mouton, Johan; Friberg, Lena; Theuretzbacher, Ursula;
• Is Part Of: Clinical microbiology and infection. Volume 28:Number 1(2022)
• Page Start: 73
• Page End: 78
• Publication Date: 2022-01
• Subjects: Bacterial fitness -- Carbapenem-resistant Acinetobacter baumannii -- Clinical outcome -- Murine thigh infection model -- Treatment failure; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2021.05.005
• Languages: English
• ISSNs: 1198-743X

Abstract

Abstract: 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 10 5 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.