{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:25:41Z","timestamp":1792643141136,"version":"4.5.0"},"reference-count":151,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The proliferation of multidrug-resistant (MDR) ESKAPE pathogens\u2014Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.\u2014constitutes a critical global health crisis, rendering conventional antibiotics increasingly ineffective. This comprehensive review evaluates the re-emerging potential of bacteriophage therapy as a personalized treatment for infections caused by these organisms. Phages, being viruses that specifically infect and lyse bacteria, offer significant advantages, including high specificity that spares host microbiota, self-replication at the infection site, and potent activity against biofilms. This paper synthesizes current preclinical and clinical evidence, including compassionate-use cases, for phage therapy against each of the ESKAPE pathogens. While case reports and small studies demonstrate considerable success, particularly in salvage therapy for otherwise untreatable infections, significant challenges remain. These include the narrow host range of phages, the potential for bacterial resistance, unpredictable pharmacokinetic and pharmacodynamic parameters, and a complex, non-harmonized regulatory landscape. The review highlights that phage\u2013antibiotic synergy and the use of phage cocktails are promising strategies to overcome some of these limitations. Future progress in phage therapy will depend on standardized manufacturing, robust clinical trials to establish dosing and efficacy, and the development of adaptive regulatory pathways. Phage therapy is positioned not as a replacement for antibiotics but as a vital adjunctive tool in the armamentarium against MDR infections, heralding a move towards a more personalized approach to infectious disease management.<\/jats:p>","DOI":"10.3390\/pathogens14101011","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:48:07Z","timestamp":1759834087000},"page":"1011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Phage to ESKAPE: Personalizing Therapy for MDR Infections\u2014A Comprehensive Clinical Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-6911","authenticated-orcid":false,"given":"Andrea","family":"Marino","sequence":"first","affiliation":[{"name":"Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0653-9560","authenticated-orcid":false,"given":"Stefano","family":"Stracquadanio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, \u201cKore\u201d University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-2484","authenticated-orcid":false,"given":"Federica","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7218-7762","authenticated-orcid":false,"given":"Alberto Enrico","family":"Maraolo","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8959-1403","authenticated-orcid":false,"given":"Agnese","family":"Colpani","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8265-5400","authenticated-orcid":false,"given":"Andrea","family":"De Vito","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7988-5419","authenticated-orcid":false,"given":"Nicholas","family":"Geremia","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Clinical Medicine, Ospedale \u201cdell\u2019Angelo\u201d, 30174 Venice, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9419-4064","authenticated-orcid":false,"given":"Alice","family":"Nicolosi","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-7975","authenticated-orcid":false,"given":"Alessandra","family":"Oliva","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Cacopardo","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-8452","authenticated-orcid":false,"given":"Giuseppe","family":"Nunnari","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Marino, A., Maniaci, A., Lentini, M., Ronsivalle, S., Nunnari, G., Cocuzza, S., Parisi, F.M., Cacopardo, B., Lavalle, S., and La Via, L. 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