{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:02:20Z","timestamp":1792789340660,"version":"4.5.0"},"reference-count":104,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"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 continued rise in antimicrobial resistance poses a serious threat to public health worldwide. The use of phages that can have bactericidal activity without disrupting the normal flora represents a promising alternative treatment method. This practice has been successfully applied for decades, mainly in Eastern Europe, and has recently been used as an emergency therapy for compassionate care in the United States. Here, we provide a comprehensive review of the pre-clinical and clinical applications of phage therapy concerning three major Gram-negative pathogens: Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The advantages and the challenges of expanding the usage of phages as an alternative or adjunctive treatment for antimicrobial-resistant bacterial infections are discussed. We emphasize the virologic complexities of using the highly adaptable phage populations as molecular tools, along with antibiotic chemical compounds, to effectively combat rapidly coevolving pathogenic bacteria in the host microenvironment. Pre-clinical studies, isolated clinical reports and a few randomized clinical trials have shown that bacteriophages can be effective in treating multidrug-resistant bacterial infections. The ability of some phages to revert the resistance against antibiotics, and possibly also against the human complement and other phages, appears to be a great advantage of phage therapy despite the inevitable emergence of phage-resistant strains. Bacteriophages (or specific phage-derived products) can enhance antimicrobial efficacy by reducing bacterial virulence via the alteration of basic bacterial structures, primarily of the cellular wall and membrane. Although several issues remain open regarding their effective clinical application, it appears that phage-based therapeutics in combination with antibiotics can provide an effective solution to the spread of antimicrobial resistance.<\/jats:p>","DOI":"10.3390\/pathogens13100896","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T11:28:51Z","timestamp":1729078131000},"page":"896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Phage-Based Therapy in Combination with Antibiotics: A Promising Alternative against Multidrug-Resistant Gram-Negative Pathogens"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7666-9198","authenticated-orcid":false,"given":"Cleo","family":"Anastassopoulou","sequence":"first","affiliation":[{"name":"Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4670-5786","authenticated-orcid":false,"given":"Stefanos","family":"Ferous","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Petsimeri","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Gioula","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-4715","authenticated-orcid":false,"given":"Athanasios","family":"Tsakris","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"ref_1","unstructured":"(2024, August 21). National Burreau of Economic Research. Available online: https:\/\/www.nber.org\/bh-20192\/reductions-mortality-rates-and-health-disparities-introduction-penicillin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/s41579-024-01054-w","article-title":"ESKAPE pathogens: Antimicrobial resistance, epidemiology, clinical impact and therapeutics","volume":"22","author":"Miller","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","unstructured":"Palmer, G.H., and Buckley, G.J. (2024, August 21). Combating Antimicrobial Resistance and Protecting the Miracle of Modern Medicine, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK577288\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1128\/CMR.00002-11","article-title":"Food animals and antimicrobials: Impacts on human health","volume":"24","author":"Marshall","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","unstructured":"Centers for Disease Control and Prevention (2019). Antibiotic Resistance Threats in the United States."},{"key":"ref_6","unstructured":"World Health Organization (2014). Antimicrobial Resistance: Global Report on Surveillance, World Health Organization."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4161\/bact.1.2.14590","article-title":"Pros and cons of phage therapy","volume":"1","author":"Abedon","year":"2011","journal-title":"Bacteriophage"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1001\/archpedi.1922.01910420062011","article-title":"The Bacteriolysant Therapy of Bacillary Dysentery in Children: Therapeutic Application of Bacteriolysants; D\u2019herelle\u2019s Phenomenon","volume":"23","author":"Davison","year":"1922","journal-title":"Am. J. Dis. Child."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev-virology-100422-040919","article-title":"The Cold War and Phage Therapy: How Geopolitics Stalled Development of Viruses as Antibacterials","volume":"11","author":"Summers","year":"2024","journal-title":"Annu. Rev. Virol."},{"key":"ref_10","unstructured":"ASM (2024, August 21). Bacteriophages Past, Present and Future. Available online: https:\/\/asm.org\/articles\/2022\/august\/phage-therapy-past,-present-and-future#:~:text=The%20French%2DCanadian%20microbiologist%2C%20Felix,the%20official%20discoverer%20of%20phage."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00954-17","DOI":"10.1128\/AAC.00954-17","article-title":"Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection","volume":"61","author":"Schooley","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","first-page":"83","article-title":"How Broad Is Enough: The Host Range of Bacteriophages and Its Impact on the Agri-Food Sector","volume":"2","author":"Fong","year":"2021","journal-title":"Ther. Appl. Res."},{"key":"ref_13","unstructured":"Kasman, L.M., and Porter, L.D. (2024, August 22). Bacteriophages, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK493185\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/jeb.12774","article-title":"Pre-adapting parasitic phages to a pathogen leads to increased pathogen clearance and lowered resistance evolution with Pseudomonas aeruginosa cystic fibrosis bacterial isolates","volume":"29","author":"Friman","year":"2016","journal-title":"J. Evol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48.e9","DOI":"10.1016\/j.cmi.2016.09.003","article-title":"Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States","volume":"23","author":"Bartsch","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.cmi.2023.11.008","article-title":"Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: Results from a prospective, multinational case-control-control matched cohorts study (EURECA)","volume":"30","author":"Kostyanev","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00397-20","DOI":"10.1128\/AAC.00397-20","article-title":"Metallo-\u03b2-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline","volume":"64","author":"Boyd","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1056\/NEJMoa2304748","article-title":"Cefepime-Taniborbactam in Complicated Urinary Tract Infection","volume":"390","author":"Wagenlehner","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Baqer, A.A., Fang, K., Mohd-Assaad, N., Adnan, S.N.A., and Md Nor, N.S. (2022). In Vitro Activity, Stability and Molecular Characterization of Eight Potent Bacteriophages Infecting Carbapenem-Resistant Klebsiella pneumoniae. Viruses, 15.","DOI":"10.3390\/v15010117"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"198750","DOI":"10.1016\/j.virusres.2022.198750","article-title":"Isolation, characterization, and genome analysis of bacteriophage P929 that could specifically lyase the KL19 capsular type of Klebsiella pneumoniae","volume":"314","author":"Chen","year":"2022","journal-title":"Virus Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fang, C., Dai, X., Xiang, L., Qiu, Y., Yin, M., Fu, Y., Li, Y., and Zhang, L. (2023). Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1265011"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108826","DOI":"10.1016\/j.isci.2024.108826","article-title":"Diverse bacteriophages for biocontrol of ESBL- and AmpC-\u03b2-lactamase-producing E. coli","volume":"27","author":"Vitt","year":"2024","journal-title":"iScience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"199126","DOI":"10.1016\/j.virusres.2023.199126","article-title":"BL02, a phage against carbapenem- and polymyxin-B resistant Klebsiella pneumoniae, isolated from sewage: A preclinical study","volume":"331","author":"Liang","year":"2023","journal-title":"Virus Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e0027224","DOI":"10.1128\/jvi.00272-24","article-title":"Bacteriophage cocktail shows no toxicity and improves the survival of Galleria mellonella infected with Klebsiella spp.","volume":"98","author":"Kelly","year":"2024","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.jgar.2024.01.018","article-title":"Evaluation of the therapeutic effect of a novel bacteriophage in the healing process of infected wounds with Klebsiella pneumoniae in mice","volume":"36","author":"Kelishomi","year":"2024","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00034-21","DOI":"10.1128\/mBio.00034-21","article-title":"Bacteriophage Treatment Rescues Mice Infected with Multidrug-Resistant Klebsiella pneumoniae ST258","volume":"12","author":"Hesse","year":"2021","journal-title":"mBio"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107221","DOI":"10.1016\/j.ijantimicag.2024.107221","article-title":"Bacteriophage-resistant carbapenem-resistant Klebsiella pneumoniae shows reduced antibiotic resistance and virulence","volume":"64","author":"Chen","year":"2024","journal-title":"Int. J. Antimicrob. Agents."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"756","DOI":"10.2340\/17453674.2022.4579","article-title":"Salphage: Salvage bacteriophage therapy for a recalcitrant Klebsiella pneumoniae prosthetic shoulder infection\u2014A case report","volume":"93","author":"Doub","year":"2022","journal-title":"Acta Orthop."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1093\/cid\/ciz782","article-title":"Eradication of a Multidrug-Resistant, Carbapenemase-Producing Klebsiella pneumoniae Isolate Following Oral and Intra-rectal Therapy with a Custom Made, Lytic Bacteriophage Preparation","volume":"70","author":"Corbellino","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41467-021-27656-z","article-title":"Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae","volume":"13","author":"Eskenazi","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","article-title":"The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update","volume":"81","author":"Reynolds","year":"2021","journal-title":"Drugs"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Poole, K. (2011). Pseudomonas aeruginosa: Resistance to the max. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00065"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kothari, A., Kherdekar, R., Mago, V., Uniyal, M., Mamgain, G., Kalia, R.B., Kumar, S., Jain, N., Pandey, A., and Omar, B.J. (2023). Age of Antibiotic Resistance in MDR\/XDR Clinical Pathogen of Pseudomonas aeruginosa. Pharmaceuticals, 16.","DOI":"10.3390\/ph16091230"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ferous, S., Anastassopoulou, C., Pitiriga, V., Vrioni, G., and Tsakris, A. (2024). Antimicrobial and Diagnostic Stewardship of the Novel \u03b2-Lactam\/\u03b2-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa. Antibiotics, 13.","DOI":"10.3390\/antibiotics13030285"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e0019423","DOI":"10.1128\/aac.00194-23","article-title":"Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program","volume":"67","author":"Satlin","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105847","DOI":"10.1016\/j.ijantimicag.2019.11.004","article-title":"Risk factors for mortality among patients with Pseudomonas aeruginosa bacteraemia: A retrospective multicentre study","volume":"55","author":"Babich","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e01759-19","DOI":"10.1128\/AAC.01759-19","article-title":"Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence","volume":"64","author":"Recio","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100030","DOI":"10.1016\/j.microb.2023.100030","article-title":"Phage therapy as a revolutionary treatment for multidrug-resistant Pseudomonas aeruginosa infections: A narrative review","volume":"2","author":"Nawaz","year":"2024","journal-title":"Microbe"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1136\/thoraxjnl-2016-209265","article-title":"Phage therapy is highly effective against chronic lung infections with Pseudomonas aeruginosa","volume":"72","author":"Waters","year":"2017","journal-title":"Thorax"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00029-e12","DOI":"10.1128\/mBio.00029-12","article-title":"Bacteriophages \u03c6MR299-2 and \u03c6NH-4 can eliminate Pseudomonas aeruginosa in the murine lung and on cystic fibrosis lung airway cells","volume":"3","author":"Alemayehu","year":"2012","journal-title":"mBio"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, X., Haque, A., Matsuzaki, S., Matsumoto, T., and Nakamura, S. (2021). The Efficacy of Phage Therapy in a Murine Model of Pseudomonas aeruginosa Pneumonia and Sepsis. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.682255"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e02900-18","DOI":"10.1128\/AEM.02900-18","article-title":"Two Novel Bacteriophages Improve Survival in Galleria mellonella Infection and Mouse Acute Pneumonia Models Infected with Extensively Drug-Resistant Pseudomonas aeruginosa","volume":"85","author":"Jeon","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chegini, Z., Khoshbayan, A., Taati Moghadam, M., Farahani, I., Jazireian, P., and Shariati, A. (2020). Bacteriophage therapy against Pseudomonas aeruginosa biofilms: A review. Ann. Clin. Microbiol. Antimicrob., 19.","DOI":"10.1186\/s12941-020-00389-5"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"dlac046","DOI":"10.1093\/jacamr\/dlac046","article-title":"Combination of phage therapy and cefiderocol to successfully treat Pseudomonas aeruginosa cranial osteomyelitis","volume":"4","author":"Simner","year":"2022","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Alipour-Khezri, E., Skurnik, M., and Zarrini, G. (2024). Pseudomonas aeruginosa Bacteriophages and Their Clinical Applications. Viruses, 16.","DOI":"10.3390\/v16071051"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5725","DOI":"10.1038\/s41467-022-33294-w","article-title":"Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler","volume":"13","author":"Chatzis","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1473-3099(18)30482-1","article-title":"Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): A randomised, controlled, double-blind phase 1\/2 trial","volume":"19","author":"Jault","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1749-4486.2009.01973.x","article-title":"A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy","volume":"34","author":"Wright","year":"2009","journal-title":"Clin. Otolaryngol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"33","DOI":"10.5604\/01.3001.0015.0084","article-title":"A randomized, double-blind, placebo-controlled study to investigate the use of bacteriophages in patients with chronic rhinosinusitis with nasal polyps","volume":"75","author":"Dobretsov","year":"2021","journal-title":"Otolaryngol. Pol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S1473-3099(20)30330-3","article-title":"Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: A randomised, placebo-controlled, double-blind clinical trial","volume":"21","author":"Leitner","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ebiom.2015.12.023","article-title":"Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh","volume":"4","author":"Sarker","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.2147\/IDR.S166750","article-title":"Insight into Acinetobacter baumannii: Pathogenesis, global resistance, mechanisms of resistance, treatment options, and alternative modalities","volume":"11","author":"Asif","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Novovi\u0107, K., and Jov\u010di\u0107, B. (2023). Colistin Resistance in Acinetobacter baumannii: Molecular Mechanisms and Epidemiology. Antibiotics, 12.","DOI":"10.3390\/antibiotics12030516"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1093\/jac\/dkx322","article-title":"High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial","volume":"72","author":"Nowak","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1007\/s00705-019-04208-x","article-title":"Characterization of myophage AM24 infecting Acinetobacter baumannii of the K9 capsular type","volume":"164","author":"Popova","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Turner, D., Wand, M.E., Briers, Y., Lavigne, R., Sutton, J.M., and Reynolds, D.M. (2017). Characterisation and genome sequence of the lytic Acinetobacter baumannii bacteriophage vB_AbaS_Loki. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172303"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s12250-019-00125-0","article-title":"Specific and Selective Bacteriophages in the Fight against Multidrug-resistant Acinetobacter baumannii","volume":"34","author":"Pichlak","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gordillo Altamirano, F.L., Kostoulias, X., Subedi, D., Korneev, D., Peleg, A.Y., and Barr, J.J. (2022). Phage-antibiotic combination is a superior treatment against Acinetobacter baumannii in a preclinical study. EBioMedicine, 80.","DOI":"10.1016\/j.ebiom.2022.104045"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41564-020-00830-7","article-title":"Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials","volume":"6","author":"Forsyth","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Chen, L.K., Kuo, S.C., Chang, K.C., Cheng, C.C., Yu, P.Y., Chang, C.H., Chen, T.Y., and Tseng, C.C. (2017). Clinical Antibiotic-resistant Acinetobacter baumannii Strains with Higher Susceptibility to Environmental Phages than Antibiotic-sensitive Strains. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06688-w"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Manley, R., Fitch, C., Francis, V., Temperton, I., Turner, D., Fletcher, J., Phil, M., Michell, S., and Temperton, B. (2024). Resistance to bacteriophage incurs a cost to virulence in drug-resistant Acinetobacter baumannii. J. Med. Microbiol., 73.","DOI":"10.1099\/jmm.0.001829"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Oyejobi, G.K., Zhang, X., Xiong, D., Xue, H., Shi, M., Yang, H., and Wei, H. (2024). Phage-Bacterial Interaction Alters Phenotypes Associated with Virulence in Acinetobacter baumannii. Viruses, 16.","DOI":"10.3390\/v16050743"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107220","DOI":"10.1016\/j.ijantimicag.2024.107220","article-title":"Phage therapy combats pan drug-resistant Acinetobacter baumannii infection safely and efficiently","volume":"64","author":"Wang","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.7754\/Clin.Lab.2018.180342","article-title":"In Vitro Study of Bacteriophage AB3 Endolysin LysAB3 Activity Against Acinetobacter baumannii Biofilm and Biofilm-Bound, A. baumannii","volume":"64","author":"Zhang","year":"2018","journal-title":"Clin. Lab."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Li, S., Wei, B., Xu, L., Cong, C., Murtaza, B., Wang, L., Li, X., Li, J., Xu, M., and Yin, J. (2024). A novel Saclayvirus Acinetobacter baumannii phage genomic analysis and effectiveness in preventing pneumonia. Appl. Microbiol. Biotechnol., 108.","DOI":"10.1007\/s00253-024-13208-0"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1038\/s41467-022-31455-5","article-title":"Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy","volume":"13","author":"Liu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e0082421","DOI":"10.1128\/AAC.00824-21","article-title":"Critically Ill Patient with Multidrug-Resistant Acinetobacter baumannii Respiratory Infection Successfully Treated with Intravenous and Nebulized Bacteriophage Therapy","volume":"66","author":"Rao","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/emph\/eoy005","article-title":"Phage treatment of an aortic graft infected with Pseudomonas aeruginosa","volume":"2018","author":"Chan","year":"2018","journal-title":"Evol. Med. Public Health"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Nation, R.L., Rigatto, M.H.P., Falci, D.R., and Zavascki, A.P. (2019). Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity. Antibiotics, 8.","DOI":"10.3390\/antibiotics8010024"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Hietala, V., Horsma-Heikkinen, J., Carron, A., Skurnik, M., and Kiljunen, S. (2019). The Removal of Endo- and Enterotoxins From Bacteriophage Preparations. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01674"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Manohar, P., Loh, B., Nachimuthu, R., and Leptihn, S. (2024). Phage-antibiotic combinations to control Pseudomonas aeruginosa-Candida two-species biofilms. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-59444-2"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.2217\/fmb.10.125","article-title":"Pseudomonas aeruginosa biofilms in cystic fibrosis","volume":"5","author":"Ciofu","year":"2010","journal-title":"Future Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"102287","DOI":"10.1016\/j.isci.2021.102287","article-title":"Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy","volume":"24","author":"Bichet","year":"2021","journal-title":"iScience"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"\u00c1cs, N., Gambino, M., and Br\u00f8ndsted, L. (2020). Bacteriophage Enumeration and Detection Methods. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.594868"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Glonti, T., and Pirnay, J.P. (2022). In Vitro Techniques and Measurements of Phage Characteristics That Are Important for Phage Therapy Success. Viruses, 14.","DOI":"10.3390\/v14071490"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1002\/med.21572","article-title":"Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review","volume":"39","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.healun.2019.01.001","article-title":"Novel bacteriophage therapy for treatment of left ventricular assist device infection","volume":"38","author":"Aslam","year":"2019","journal-title":"J. Heart Lung Transplant."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"142","DOI":"10.5694\/mja2.50274","article-title":"Adjunctive bacteriophage therapy for prosthetic valve endocarditis due to Staphylococcus aureus","volume":"211","author":"Gilbey","year":"2019","journal-title":"Med. J. Aust."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e0207121","DOI":"10.1128\/aac.02071-21","article-title":"Considerations for the Use of Phage Therapy in Clinical Practice","volume":"66","author":"Suh","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1007\/s12275-011-1512-4","article-title":"Antibacterial efficacy of lytic Pseudomonas bacteriophage in normal and neutropenic mice models","volume":"49","author":"Tiwari","year":"2011","journal-title":"J. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Daubie, V., Chalhoub, H., Blasdel, B., Dahma, H., Merabishvili, M., Glonti, T., De Vos, N., Quintens, J., Pirnay, J.P., and Hallin, M. (2022). Determination of phage susceptibility as a clinical diagnostic tool: A routine perspective. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1000721"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/S1473-3099(11)70241-9","article-title":"Prevalence and implications of multiple-strain infections","volume":"11","author":"Balmer","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e152472","DOI":"10.1172\/jci.insight.152472","article-title":"A population-level strain genotyping method to study pathogen strain dynamics in human infections","volume":"6","author":"Morgan","year":"2021","journal-title":"JCI Insight"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Anju, V.T., Busi, S., Imchen, M., Kumavath, R., Mohan, M.S., Salim, S.A., Subhaswaraj, P., and Dyavaiah, M. (2022). Polymicrobial Infections and Biofilms: Clinical Significance and Eradication Strategies. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121731"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Qin, J., Wu, N., Bao, J., Shi, X., Ou, H., Ye, S., Zhao, W., Wei, Z., Cai, J., and Li, L. (2021). Heterogeneous Klebsiella pneumoniae Co-infections Complicate Personalized Bacteriophage Therapy. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.608402"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1093\/cid\/ciz222","article-title":"Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection with Bacteriophages and Antibiotics Combination","volume":"69","author":"Gelman","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Fletcher, J., Manley, R., Fitch, C., Bugert, C., Moore, K., Farbos, A., Michelsen, M., Alathari, S., Senior, N., and Mills, A. (2024). The Citizen Phage Library: Rapid Isolation of Phages for the Treatment of Antibiotic Resistant Infections in the UK. Microorganisms, 12.","DOI":"10.3390\/microorganisms12020253"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Yoo, S., Lee, K.-M., Kim, N., Vu, T.N., Abadie, R., and Yong, D. (2024). Designing phage cocktails to combat the emergence of bacteriophage-resistant mutants in multidrug-resistant Klebsiella pneumoniae. Microbiol. Spectr., 12.","DOI":"10.1128\/spectrum.01258-23"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Comeau, A.M., T\u00e9tart, F., Trojet, S.N., Pr\u00e8re, M.F., and Krisch, H.M. (2007). Phage-Antibiotic Synergy (PAS): Beta-lactam and quinolone antibiotics stimulate virulent phage growth. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000799"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e01462-20","DOI":"10.1128\/mBio.01462-20","article-title":"Phage-Antibiotic Synergy Is Driven by a Unique Combination of Antibacterial Mechanism of Action and Stoichiometry","volume":"11","author":"Green","year":"2020","journal-title":"mBio"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"106951","DOI":"10.1016\/j.ijantimicag.2023.106951","article-title":"Sequential treatment effects on phage-antibiotic synergistic application against multi-drug-resistant Acinetobacter baumannii","volume":"62","author":"Mukhopadhyay","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_92","first-page":"703","article-title":"Synergistic Interaction between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence","volume":"215","author":"Oechslin","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1093\/ps\/83.12.1944","article-title":"Therapeutic efficacy of bacteriophage and Baytril [enrofloxacin] individually and in combination to treat colibacillosis in broilers","volume":"83","author":"Huff","year":"2004","journal-title":"Poult. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Loganathan, A., Bozdogan, B., Manohar, P., and Nachimuthu, R. (2024). Phage-antibiotic combinations in various treatment modalities to manage MRSA infections. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1356179"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S1473-3099(20)30464-3","article-title":"Bacteriophages: It\u2019s a medicine, Jim, but not as we know it","volume":"21","author":"Pirnay","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41564-019-0634-z","article-title":"Safety of bacteriophage therapy in severe Staphylococcus aureus infection","volume":"5","author":"Lin","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41591-019-0437-z","article-title":"Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus","volume":"25","author":"Dedrick","year":"2019","journal-title":"Nat. Med."},{"key":"ref_98","first-page":"S1198-743X(23)00528-1","article-title":"Phages and phage-borne enzymes as new antibacterial agents","volume":"2023","author":"McCallin","year":"2023","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.2174\/0929867322666150209152851","article-title":"Bacteriophages and phage-derived proteins\u2014Application approaches","volume":"22","author":"Maciejewska","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.apsb.2023.08.017","article-title":"Translating bacteriophage-derived depolymerases into antibacterial therapeutics: Challenges and prospects","volume":"14","author":"Wang","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13567-024-01311-z","article-title":"Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection","volume":"55","author":"Li","year":"2024","journal-title":"Vet. Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Huang, X., Li, X., An, H., Wang, J., Ding, M., Wang, L., Li, L., Ji, Q., Qu, F., and Wang, H. (2022). Capsule type defines the capability of Klebsiella pneumoniae in evading Kupffer cell capture in the liver. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010693"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Wu, Y., Wang, R., Xu, M., Liu, Y., Zhu, X., Qiu, J., Liu, Q., He, P., and Li, Q. (2019). A Novel Polysaccharide Depolymerase Encoded by the Phage SH-KP152226 Confers Specific Activity Against Multidrug-Resistant Klebsiella pneumoniae via Biofilm Degradation. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02768"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Chen, X., Liu, M., Zhang, P., Xu, M., Yuan, W., Bian, L., Liu, Y., Xia, J., and Leung, S.S.Y. (2022). Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter baumannii. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.845500"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/10\/896\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:13:01Z","timestamp":1760112781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/10\/896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":104,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["pathogens13100896"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13100896","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]}}}