Phage-antibiotic synergy to combat multidrug resistant strains of Gram-negative ESKAPE pathogens.

作者信息

Morris Tinta Carmen, Reyneke Brandon, Khan Sehaam, Khan Wesaal

机构信息

Department of Microbiology, Faculty of Science, Stellenbosch University, Private Bag X1, Stellenbosch, 7602, South Africa.

Faculty of Health Science, University of Johannesburg, PO Box 17011, Doornfontein, 2028, South Africa.

出版信息

Sci Rep. 2025 May 18;15(1):17235. doi: 10.1038/s41598-025-01489-y.

Abstract

Bacteriophage-antibiotic-synergy (PAS) was investigated to target Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Enterobacter cloacae. Whole genome sequencing indicated that bacteriophage KPW17 targeting K. pneumoniae, clustered with genus Webervirus, ECSR5 targeting E. cloacae clustered with Eclunavirus, PAW33 targeting P. aeruginosa clustered with Bruynoghevirus, while ABTW1 targeting A. baumannii clustered with Vieuvirus. PAS analysis showed that the combination of ciprofloxacin (CIP) and levofloxacin (LEV) with PAW33 resulted in the synergistic eradication of all tested P. aeruginosa strains. Similarly, the combined use of doripenem (DOR) and LEV with KPW17 resulted in the synergistic eradication of the environmental and clinical K. pneumoniae strains, while the combined use of DOR and gentamicin (CN) with ECSR5 was synergistic against the clinical E. cloacae NCTC 13406. Gentamicin with ECSR5, however, only exhibited an additive effect for E. cloacae 4L, while ABTW1 with piperacillin-tazobactam (TZP) and imipenem (IPM) resulted in an indifferent interaction between the bacteriophage and tested antibiotics against the clinical A. baumannii AB3, i.e., the activity of the combination is equal to the activity of most active agent. Thus, while the observed PAS may offer an opportunity for the re-introduction or more efficient application of certain antibiotics to combat antibiotic resistance, extensive research is required to determine the optimal phage-antibiotic combinations, dosages and treatment regiments.

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