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Article

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

1
Microbiology Department-Research Institute Biomedical A Coruña (INIBIC), Hospital A Coruña (CHUAC), University of A Coruña (UDC), 15495 A Coruña, Spain
2
Microbiology Department-Research Institute Biomedical Valdecilla (IDIVAL), Hospital Marques de Valdecilla, 39008 Santander, Spain
3
Laboratory of Pharmaceutical Microbiology, Ghent University, 9000 Gent, Belgium
4
Clinical Unit for Infectious Diseases, Microbiology and Preventive Medicine, Hospital Universitario Virgen Macarena/Department of Microbiology and Medicine, University of Seville/Biomedicine Institute of Seville (IBIS), 41009 Seville, Spain
5
Institute of Global Health of Barcelona (ISGlobal), Hospital Clínic-Universitat de Barcelona, 170, 08036 Barcelona, Spain
6
Unit of Microbiology, University Hospital Reina Sofía, Department of Microbiology, University of Córdoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
7
Clinical Unit for Infectious Diseases, Microbiology and Preventive Medicine, Hospital Universitario Virgen del Rocío/Department of Microbiology and Medicine, University of Seville/Biomedicine Institute of Seville (IBIS), 41009 Seville, Spain
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
On Behalf of Study Group on Mechanisms of Action and Resistance to Antimicrobials (GEMARA) of Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC)/Spanish Network for the Research in Infectious Diseases (REIPI).
Microorganisms 2019, 7(11), 556; https://doi.org/10.3390/microorganisms7110556
Received: 30 September 2019 / Revised: 8 November 2019 / Accepted: 9 November 2019 / Published: 12 November 2019
Phage 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. View Full-Text
Keywords: Acinetobacter baumannii; multiresistant; mutant lytic phage; phage therapy; antibiotic-phage synergy Acinetobacter baumannii; multiresistant; mutant lytic phage; phage therapy; antibiotic-phage synergy
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MDPI and ACS Style

Blasco, L.; Ambroa, A.; Lopez, M.; Fernandez-Garcia, L.; Bleriot, I.; Trastoy, R.; Ramos-Vivas, J.; Coenye, T.; Fernandez-Cuenca, F.; Vila, J.; Martinez-Martinez, L.; Rodriguez-Baño, J.; Pascual, A.; Cisneros, J.M.; Pachon, J.; Bou, G.; Tomas, M. Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii. Microorganisms 2019, 7, 556. https://doi.org/10.3390/microorganisms7110556

AMA Style

Blasco L, Ambroa A, Lopez M, Fernandez-Garcia L, Bleriot I, Trastoy R, Ramos-Vivas J, Coenye T, Fernandez-Cuenca F, Vila J, Martinez-Martinez L, Rodriguez-Baño J, Pascual A, Cisneros JM, Pachon J, Bou G, Tomas M. Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii. Microorganisms. 2019; 7(11):556. https://doi.org/10.3390/microorganisms7110556

Chicago/Turabian Style

Blasco, Lucia, Anton Ambroa, Maria Lopez, Laura Fernandez-Garcia, Ines Bleriot, Rocio Trastoy, Jose Ramos-Vivas, Tom Coenye, Felipe Fernandez-Cuenca, Jordi Vila, Luis Martinez-Martinez, Jesus Rodriguez-Baño, Alvaro Pascual, Jose Miguel Cisneros, Jeronimo Pachon, German Bou, and Maria Tomas. 2019. "Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii" Microorganisms 7, no. 11: 556. https://doi.org/10.3390/microorganisms7110556

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