Antimicrobial activity of essential oils and synergy with colistin against colistin-susceptible and colistin-resistant Acinetobacter baumannii strains

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English. Background: A. baumannii has a high capacity to develop or acquire new antimicrobial resistancemechanisms, therefore the search for new therapeutic alternatives is necessary. One option is the use ofcombined therapies between antibiotics and adjuvants. Essential oils (EOs) are aromatic oily liquidsconsist of up to 100 secondary metabolites. Some EOs and their constituents may have someantibacterial, antifungal or antiviral activity. The aim of the study was to determine in A. baumannii whichare the best EOs candidates to use as antibiotic adjuvants and which are the best antibiotic/adjuvantcombinations in vitro and in vivo.Methods: Disc diffusion and determination of MICs assays were used to study the antimicrobial activityof 10 EOs against two representative strains of A. baumannii (ATCC 17978 and ATCC 19606). The threemost active EOs were deeply studied in more strains. The activity of this EOs in combination withantibiotics (imipenem, meropenem, colistin, tigecycline, ceftazidime and amikacin) were assessed.Checkerboard method was used and FICindex was calculated. Finally, efficacy of combined therapy wasstudied in an in vivo model of Galleria mellonella.Results: EOs of clove, thyme and eucalyptus (MIC 512 mg/L) were the most active against A. baumanniistrains. Synergy was observed with EOs of thyme and clove in combination with colistin. No synergy wasobserved with EO of eucalyptus and/or other antibiotics.Two colistin-resistant derivatives of ATCC 19606 (ATCC 19606pmrB and ATCC 19606ΔlpxC) and twoclinical isogenic pair of colistin-susceptible/colistin-resistant strains (AB248/ AB249pmrB and ABRIM/ABRIMpmrB) were studied. In ATCC 19606pmrB, colistin MICs decreased 16-fold in combination with128 mg/L of EOs of thyme or clove. In ATCC 19606ΔlpxC, colistin MICs decreased 16- and 32-fold incombination with 128 mg/L of EO of thyme and clove, respectively. In the pair AB248/ AB249pmrb, colistinMICs decreased 16- and 128-fold in combination with 128 mg/L of EO of thyme, respectively, whilecolistin MICs decreased 16- and 64-fold in combination with 128 mg/L of EO of clove. In the pair ABRIM/ABRIMpmrB, colistin MICs decreased 4- and 128-fold in combination with 128 mg/L of EO of thyme,respectively, while both strains decreased 8-fold in combination with 128 g/L of EO of clove. Preliminaryin vivo assays showed better efficacy of combination therapy compared to monotherapy in colistinsusceptible and colistin resistant strains.