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Title

Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii

AuthorsBlasco, Lucía; Ambroa, Antón; López, María; Fernández-García, Laura; Bleriot, Inés; Trastoy, Rocío; Ramos-Vivas, José; Coenye, Tom; Fernández-Cuenca, Felipe; Vila, Jordi; Martínez-Martínez, Luis; Rodríguez-Baño, Jesús; Pascual, Álvaro; Cisneros, José Miguel; Pachón, Jerónimo CSIC ORCID CVN; Bou, Germán; Tomás, María
KeywordsAcinetobacter baumannii
Multiresistant
Mutant lytic phage
Phage therapy
Antibiotic-phage synergy
Issue Date12-Nov-2019
PublisherMultidisciplinary Digital Publishing Institute
CitationMicroorganisms 7(11): 556 (2019)
AbstractPhage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) that displayed antimicrobial activity against A. baumannii clinical strain Ab177_GEIH-2000 (isolated in the GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585, and for which meropenem and imipenem MICs of respectively, 32 µg/mL, and 16 µg/mL were obtained). We observed an in vitro synergistic antimicrobial effect (reduction of 4 log–7 log CFU/mL) between meropenem and the lytic phage in all combinations analyzed (Ab105-2phiΔCI mutant at 0.1, 1 and 10 MOI and meropenem at 1/4 and 1/8 MIC). Moreover, bacterial growth was reduced by 8 log CFU/mL for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phiΔCI mutant) and by 4 log CFU/mL for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phiΔCI mutant) at both MOI 1 and 10. These results were confirmed in an in vivo model (G. mellonella), and the combination of imipenem and mutant Ab105-2phiΔCI was most effective (p < 0.05). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to antibiotics used to combat multi-resistant strains of Acinetobacter baumannii.
DescriptionThis article belongs to the Special Issue Bacteriophage Treatment as an Alternative Technology to Inactivate Pathogenic Bacteria: A Generalized Worldwide Growing Acceptance.
Publisher version (URL)http://dx.doi.org/10.3390/microorganisms7110556
URIhttp://hdl.handle.net/10261/214385
DOIhttp://dx.doi.org/10.3390/microorganisms7110556
Identifiersdoi: 10.3390/microorganisms7110556
issn: 2076-2607
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