Adaptation of Acinetobacter baumannii to colistin exposure: Laboratory mimicking of a clinical case

Abstract

10Adaptation of Acinetobacter baumannii to colistin use on a disease course of a patient was 11 described. Effects of colistin was mimicked in the laboratory conditions. The colistin resistant isolate 12 was identified from the patient after 25 days of colistin treatment. In the laboratory, the expressions 13 of pmrCAB were the highest at the generation which was corresponded to the duration of therapy. A. 14 baumannii can develop a stable colistin-resistant phenotype after three weeks of colistin exposure. 15 16 17The increase of colistin-resistance in Acinetobacter baumannii is a great concern in various regions of 18 the world such as Asia, Europe, and North and South America (1). Exposure to colistin is considered 19 as the most significant factor for emerging of colistin resistance (2), however, details of the in vivo 20 response of A. baumannii to colistin exposure, such as the number of days for development of 21 resistance was not described. The molecular studies about colistin resistance indicated two main 22 mechanisms: modifications in lipid A structure and complete loss of LPS (3). By this study, we 23 analyzed adaptation of A. baumannii to colistin use on a disease course of a patient. The cellular 24 effects of colistin use was mimicked in laboratory conditions to understand the relationship between 25 the clinical features and molecular resistance mechanisms. 26 27 A 45-year-old woman had a stab wound caused by penetration of the abdominal and thoracic walls 28 by a sharp object. Two days after abdominal and thoracic surgery in another hospital, she was 29 transferred to our intensive care unit (ICU). In 3 rd day of hospitalization, her body temperature was 30 elevated, and her white blood cell count was 27,280 /µL, C-reactive protein was 356.9 mg/L and 31 procalcitonin was 0.86 ng/mL. Carbapenem resistant A. baumannii (CarR-AB) was isolated from the 32 cultures of sputum and abdominal drainage in 5 th day. Colistin 300 mg/day and meropenem 3 g/day 33 were started, but clinical and laboratory response were poor. At the 15 th day of hospital stay, CarR-34 AB was isolated again from abdominal drainage. Meropenem was switched to tigecycline 100 35