26The synergistic activity of eravacycline in combination with colistin on carbapenem-resistant 27 A.baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory 28 concentrations (MICs) of eravacycline and colistin were determined by the broth 29 microdilution method. MICs values ranged between 1 to 4 mg and 0,5 to 128 mg/L for 30 eravacycline and colistin, respectively. In-vitro synergy between eravacycline and colistin 31 was evaluated by using the chequerboard methodology. Synergistic activity was found in 10 32 % of the strains, and additive effect in 20 %. No antagonism was detected. Similar activity 33 was also observed in colistin resistant CRAB isolates. The result of this study indicates that 34 eravacycline and colistin combination may be a potential therapeutic option for the treatment 35 of CRAB related infections. (CRAB) is an important nosocomial 53 pathogen causing substantial morbidity and mortality (1, 2). Current treatment options 54 (polymyxins, tigecycline, aminoglycosides) for CRAB are limited and suffer from 55 pharmacokinetic limitations such as high toxicity and low plasma levels (3). Therefore, to 56 enhance clinical efficacy and to avoid toxicity, combination therapy is often used for CRAB 57 infections (4).
58Eravacycline is a novel fluorocycline that belongs to the tetracycline class of 59 antimicrobials may be a treatment option for CRAB (5). In vitro studies were shown that 60 eravacycline minimum inhibitory concentrations (MICs) were found to be 2-8 fold lower 61 than tigecycline MICs against CRAB (6-8). The drug is also active against colistin resistant 62 strains (9). Despite in vitro activity, treatment success of eravacycline in CRAB infections are 63 unknown due to lack of clinical trials (10, 11). Management of healthcare-associated 64 infections (HCAI) caused by CRAB should be required combination therapy. There is no in 65 vitro study related to the synergism of eravacycline with other antibiotics in the literature.
66The aim of this in vitro study is to evaluate the synergistic activity of eravacycline in 67 combination with colistin on CRAB isolates.
68
Results
69Ten carbapenem-resistant A. baumannii strains were used in this study. Three of these 70 strains were also resistant to colistin. All isolates were found to have bla OXA-51 and nine 71 harbored bla OXA-23. The characteristics of 10 CRAB isolates included in chequerboard 72 experiments were shown in Table 1.
73MIC values ranged between 1 to 4 mg and 0,5 to 128 mg/L for eravacycline and 74 colistin, respectively. Chequerboard analysis showed 10% synergy, 20% additive, 70%
132This research received no specific grant from any funding agency in the public, commercial, 133 or not-for-profit sectors.