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. 2022 Jan;28(1):73-78.
doi: 10.1016/j.cmi.2021.05.005. Epub 2021 May 11.

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

Amir Nutman  1 , Elizabeth Temkin  2 , Jonathan Lellouche  3 , Nadya Rakovitsky  3 , Amichay Hameir  3 , George Daikos  4 , Emanuele Durante-Mangoni  5 , Ioannis Pavleas  6 , Yael Dishon  7 , Neta Petersiel  8 , Dafna Yahav  9 , Noa Eliakim  10 , Mariano Bernardo  5 , Domenico Iossa  5 , Lena E Friberg  11 , Ursula Theuretzbacher  12 , Leonard Leibovici  10 , Mical Paul  13 , Yehuda Carmeli  2 ; AIDA Study Group
Collaborators, Affiliations
Free article

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

Amir Nutman et al. Clin Microbiol Infect. 2022 Jan.
Free article

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 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.

Keywords: Bacterial fitness; Carbapenem-resistant Acinetobacter baumannii; Clinical outcome; Murine thigh infection model; Treatment failure.

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