{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:20:37Z","timestamp":1789395637034,"version":"build-2803163510"},"reference-count":103,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Antimicrobial resistance (AMR) is an urgent global threat, with bacteria developing resistance against most antibiotics currently in clinical use. Non-traditional antibacterials\u2014including bacteriophages, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), live biotherapeutic products (LBPs) and anti-virulence small molecules\u2014act through mechanisms distinct from traditional antibiotics and may exhibit mechanism-dependent differences in the propensity for resistance development. Despite growing interest, the landscape of non-traditional candidates in active clinical development against WHO priority pathogens has not been recently systematically mapped. This review aimed to characterize the current non-traditional antibacterial clinical pipeline targeting pathogens on the WHO Bacterial Priority Pathogens List (BPPL) 2024. Methods: Candidates were identified from the WHO antibacterial clinical pipeline report (October 2025) and verified through the Global AMR R&amp;D Hub, ClinicalTrials.gov, and targeted searches of peer-reviewed publications, conference abstracts, and company communications. Candidates were included if they showed documented clinical activity since January 2023. Results: Twenty-seven candidates met the inclusion criteria, of which 20 remain in active clinical development and seven have been discontinued or paused or have unverified status. The pipeline is dominated by bacteriophages and markedly skewed toward carbapenem-resistant Pseudomonas aeruginosa (CRPA) and methicillin-resistant Staphylococcus aureus (MRSA), with few or no candidates targeting carbapenem-resistant Acinetobacter baumannii (CRAB), Shigella or Salmonella. Conclusions: Non-traditional antibacterials represent a promising but underfunded and unevenly distributed pipeline\u2014with public and philanthropic investment in antibacterial R&amp;D totaling just $2.51 billion across 2017\u20132023, a seven-year total, against an estimated $251\u2013276 billion in global pharmaceutical R&amp;D spending in a single recent year. Realizing their potential will require substantially greater investment and more deliberate prioritization toward the WHO priority pathogens currently underserved by the non-traditional pipeline.<\/jats:p>","DOI":"10.3390\/antibiotics15090899","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:05:26Z","timestamp":1789391126000},"page":"899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Traditional Antibacterial Agents Relevant to the WHO 2024 Priority Pathogens: A Structured Update of the Clinical Pipeline"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7625-016X","authenticated-orcid":false,"given":"Melanie Kempf","family":"Hansen","sequence":"first","affiliation":[{"name":"Aarhus University Hospital (AUH), 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"Aarhus University Hospital (AUH), 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S1473-3099(25)00118-5","article-title":"The WHO Bacterial Priority Pathogens List 2024: A prioritisation study to guide research, development, and public health strategies against antimicrobial resistance","volume":"25","author":"Sati","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3934\/microbiol.2018.3.482","article-title":"An overview of the antimicrobial resistance mechanisms of bacteria","volume":"4","author":"Reygaert","year":"2018","journal-title":"AIMS Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jgar.2021.08.001","article-title":"Environmental antimicrobial resistance and its drivers: A potential threat to public health","volume":"27","author":"Samreen","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global burden of bacterial antimicrobial resistance 1990\u20132021: A systematic analysis with forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"ref_5","unstructured":"World Health Organization (2026, June 24). Antimicrobial Resistance. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antimicrobial-resistance."},{"key":"ref_6","unstructured":"U.S. Centers for Disease Control and Prevention (CDC) (2026, June 18). About Antimicrobial Resistance, Available online: https:\/\/www.cdc.gov\/antimicrobial-resistance\/about\/index.html."},{"key":"ref_7","unstructured":"McKinsey & Company (2026, June 24). Pharma\u2019s Rx for R&D [Industry Report]. Available online: https:\/\/www.mckinsey.com\/featured-insights\/week-in-charts\/pharmas-rx-for-r-and-d."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101288","DOI":"10.1016\/j.lanmic.2025.101288","article-title":"An overview of global public and philanthropic investments into antibacterial therapeutics (2017\u20132023)","volume":"7","author":"Czaplewski","year":"2026","journal-title":"Lancet Microbe"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/ja.2013.86","article-title":"Antibiotics in the clinical pipeline in 2013","volume":"66","author":"Butler","year":"2013","journal-title":"J. Antibiot."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e0199121","DOI":"10.1128\/aac.01991-21","article-title":"Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed","volume":"66","author":"Butler","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41579-023-00993-0","article-title":"Alternative therapeutic strategies to treat antibiotic-resistant pathogens","volume":"22","author":"MacNair","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41564-024-01891-8","article-title":"ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro","volume":"10","author":"Daruka","year":"2025","journal-title":"Nat. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s44259-025-00096-1","article-title":"Antibiotics re-booted\u2014Time to kick back against drug resistance","volume":"3","author":"Blaskovich","year":"2025","journal-title":"npj Antimicrob. Resist."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1080\/13543784.2024.2326028","article-title":"Antibacterial agents active against Gram Negative Bacilli in phase I, II, or III clinical trials","volume":"33","author":"Paterson","year":"2024","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1021\/acsinfecdis.4c00218","article-title":"A Review of Antibacterial Candidates with New Modes of Action","volume":"10","author":"Butler","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sarkar, T., Chetia, M., and Chatterjee, S. (2021). Antimicrobial Peptides and Proteins: From Nature\u2019s Reservoir to the Laboratory and Beyond. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.691532"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D1087","DOI":"10.1093\/nar\/gkv1278","article-title":"APD3: The antimicrobial peptide database as a tool for research and education","volume":"44","author":"Wang","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127822","DOI":"10.1016\/j.micres.2024.127822","article-title":"Antimicrobial peptides: Opportunities and challenges in overcoming resistance","volume":"286","author":"Bucataru","year":"2024","journal-title":"Microbiol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e02340-16","DOI":"10.1128\/AAC.02340-16","article-title":"Intracellular Targeting Mechanisms by Antimicrobial Peptides","volume":"61","author":"Le","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jmii.2016.12.005","article-title":"Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria","volume":"50","author":"Chung","year":"2017","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6603","DOI":"10.1038\/s41598-021-86155-9","article-title":"OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria","volume":"11","author":"Mandel","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Michaeli, J., Mandel, S., Maximov, S., Zazoun, J., Savoia, P., Kothari, N., Valmont, T., Ferrari, L., Duncan, L.R., and Hawser, S. (2022). In Vitro and In Vivo Antimicrobial Activity of the Novel Peptide OMN6 against Multidrug-Resistant Acinetobacter baumannii. Antibiotics, 11.","DOI":"10.3390\/antibiotics11091201"},{"key":"ref_23","unstructured":"Omnix Medical (2026, June 24). Safety and Pharmacokinetic Results from the First-in-Human Study with Intravenously Administered OMN6 [Press Release]. Available online: https:\/\/omnixmedical.com\/2024\/05\/10\/safety_and_pharmacokinetic_results_from_the_first_in_human_study\/."},{"key":"ref_24","unstructured":"Omnix Medical (2026, June 24). Omnix Medical Announces First Patients Dosed in Phase II Trial of Antimicrobial Lead Compound OMN6 [Press Release]. Available online: https:\/\/www.akampion.com\/news\/2026\/06\/omnix-medical-announces-first-patients-dosed-in-phase-ii-trial-of-antimicrobial-lead-compound-omn6\/."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e0187921","DOI":"10.1128\/Spectrum.01879-21","article-title":"Prospective Activity of PLG0206, an Engineered Antimicrobial Peptide, on Chronic Periprosthetic Joint Infection Total Knee Arthroplasty Components Ex Vivo: The Knee Explant Analysis (KnEA) Study","volume":"9","author":"Huang","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Huang, D.B., Brothers, K.M., Mandell, J.B., Taguchi, M., Alexander, P.G., Parker, D.M., Shinabarger, D., Pillar, C., Morrissey, I., and Hawser, S. (2022). Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274815"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Huang, D., Pachuda, N., Sauer, J.M., Dobbins, D., and Steckbeck, J. (2022). The Engineered Antibiotic Peptide PLG0206 Eliminates Biofilms and Is a Potential Treatment for Periprosthetic Joint Infections. Antibiotics, 11.","DOI":"10.3390\/antibiotics11010041"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e0144121","DOI":"10.1128\/AAC.01441-21","article-title":"A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of a First-in-Human Engineered Cationic Peptide, PLG0206, Intravenously Administered in Healthy Subjects","volume":"66","author":"Huang","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","unstructured":"Peptilogics Inc. (2026, June 09). Peptilogics Begins Pivotal Trial of First-Ever Drug Designed to Cure Medical Device-Related Infections [Press Release]. Available online: https:\/\/peptilogics.com\/news\/peptilogics-begins-pivotal-trial-of-first-ever-drug-designed-to-cure-medical-device-related-infections\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/SLA.0000000000005508","article-title":"Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial","volume":"277","author":"Wei","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e2415310","DOI":"10.1001\/jamanetworkopen.2024.15310","article-title":"Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial","volume":"7","author":"Wei","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41579-026-01318-7","article-title":"Revisiting the life cycle of temperate phages","volume":"24","author":"Chmielowska","year":"2026","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","first-page":"23","article-title":"Exploring bacteriophage therapy for drug-resistant bacterial infections","volume":"31","author":"Schooley","year":"2023","journal-title":"Top. Antivir. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"ofaf695.022","DOI":"10.1093\/ofid\/ofaf695.022","article-title":"549. A Phase 2a Randomized, Double-Blind, Controlled Trial of the Efficacy and Safety of an Intravenous (IV) Bacteriophage Cocktail (AP-SA02) vs. Placebo in Combination with Best Available Antibiotic Therapy (BAT) in Patients with Complicated Staphylococcus aureus Bacteremia","volume":"13","author":"Miller","year":"2026","journal-title":"Open Forum Infect. Dis."},{"key":"ref_35","unstructured":"Armata Pharmaceuticals (2026, June 24). Staphylococcus aureus Phage Product Candidate [Company Website]. Available online: https:\/\/www.armatapharma.com\/pipeline\/ap-sa02\/."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"ofaf695.086","DOI":"10.1093\/ofid\/ofaf695.086","article-title":"234. Phage Therapy with BX211 Demonstrates Positive Efficacy Results in Staphylococcus Aureus Diabetic Foot Osteomyelitis: Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"13","author":"Lipsky","year":"2026","journal-title":"Open Forum Infect. Dis."},{"key":"ref_37","unstructured":"BiomX Inc. (2026, June 24). BiomX Announces Positive FDA Feedback Supporting Next-Generation Phage Cocktail Program for Diabetic Foot Infections [Press Release]. Available online: https:\/\/ir.biomx.com\/node\/9946\/pdf."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ferry, T., Kolenda, C., Batailler, C., Gustave, C.A., Lustig, S., Malatray, M., Fevre, C., Josse, J., Petitjean, C., and Chidiac, C. (2020). Phage Therapy as Adjuvant to Conservative Surgery and Antibiotics to Salvage Patients With Relapsing S. aureus Prosthetic Knee Infection. Front. Med., 7.","DOI":"10.3389\/fmed.2020.570572"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/s41591-025-03678-8","article-title":"Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis","volume":"31","author":"Chan","year":"2025","journal-title":"Nat. Med."},{"key":"ref_40","unstructured":"Armata Pharmaceuticals (2026, June 24). Pseudomonas aeruginosa Phage Product Candidates [Company Website]. Available online: https:\/\/www.armatapharma.com\/pipeline\/ap-pa02\/."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1038\/s41467-025-60598-4","article-title":"Phage therapy with nebulized cocktail BX004-A for chronic Pseudomonas aeruginosa infections in cystic fibrosis: A randomized first-in-human trial","volume":"16","author":"Weiner","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_42","unstructured":"BiomX Inc. (2026, June 24). BiomX Provides Update on BX004 Phase 2b Trial for the Treatment of Patients with Cystic Fibrosis [Press Release]. Available online: https:\/\/ir.biomx.com\/news-releases\/news-release-details\/biomx-provides-update-bx004-phase-2b-trial-treatment-patients."},{"key":"ref_43","unstructured":"BiomX Inc. (2026, June 24). BiomX Announces Discontinuation of Phase 2b BX004 Trial Following Internal Review [Press Release]. Available online: https:\/\/www.globenewswire.com\/news-release\/2025\/12\/08\/3201429\/0\/en\/BiomX-Announces-Discontinuation-of-Phase-2b-BX004-Trial-Following-Internal-Review.html."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40560-024-00759-7","article-title":"Current status of bacteriophage therapy for severe bacterial infections","volume":"12","author":"Sawa","year":"2024","journal-title":"J. Intensive Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1186\/s13063-022-07047-5","article-title":"Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: Study protocol for a phase 1b\/2, multicenter, randomized, double-blind, placebo-controlled trial","volume":"23","author":"Tamma","year":"2022","journal-title":"Trials"},{"key":"ref_46","unstructured":"Shapiro, L. (2026, June 24). First Patient Dosed in Trial of Phage Therapy for Lung Infections: Phase 1b\/2 trial is testing investigational bacteriophage therapy WRAIR-PAM-CF1 [Press Release]. Available online: https:\/\/cysticfibrosisnewstoday.com\/news\/first-patient-dosed-phage-therapy-trial-cf-lung-infections\/."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107965","DOI":"10.1016\/j.ijid.2025.107965","article-title":"Clinical trial landscape for pneumonia: Evolving agents against bacterial pathogens","volume":"158","author":"Feng","year":"2025","journal-title":"Int. J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41587-023-01759-y","article-title":"Engineered phage with antibacterial CRISPR-Cas selectively reduce E. coli burden in mice","volume":"42","author":"Gencay","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Anastassopoulou, C., Tsakri, D., Panagiotopoulos, A.P., Saldari, C., Sagona, A.P., and Tsakris, A. (2025). Armed Phages: A New Weapon in the Battle Against Antimicrobial Resistance. Viruses, 17.","DOI":"10.3390\/v17070911"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"101257","DOI":"10.1016\/j.lanmic.2025.101257","article-title":"Safety, recovery, and pharmacodynamics of CRISPR-Cas therapeutic SNIPR001: A phase 1, randomised, double-blind, first-in-human, dose-escalation study","volume":"7","author":"Petersen","year":"2026","journal-title":"Lancet Microbe"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S1473-3099(24)00424-9","article-title":"Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): The randomised, open-label, first part of a two-part phase 2 trial","volume":"24","author":"Kim","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_52","unstructured":"SNIPR Biome (2026, June 24). SNIPR Biome Announces First Patient Dosed in its Phase 1b Clinical Trial of SNIPR001 in Patients with Hematological Cancer [Press Release]. Available online: https:\/\/lundbeckfonden.com\/business-activities\/biocapital-portfolio-news\/snipr-biome-announces-first-patient-dosed-in-its."},{"key":"ref_53","unstructured":"Locus Biosciences (2026, June 24). ELIMINATE Trial is Evaluating LBP-EC01 for Treating Urinary Tract Infections Caused by Drug-Resistant E. coli; Funding to Support Advancement into Part 2 of ELIMINATE Trial [Press Release]. Available online: https:\/\/www.locus-bio.com\/locus-biosciences-announces-23-9-million-in-funding-from-barda-to-support-first-phase-2-trial-of-crispr-engineered-bacteriophage-therapy\/."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100565","DOI":"10.1016\/j.medj.2024.11.018","article-title":"Randomized double-blind study on safety and tolerability of TP-102 phage cocktail in patients with infected and non-infected diabetic foot ulcers","volume":"6","author":"Onallah","year":"2025","journal-title":"Med"},{"key":"ref_55","unstructured":"Technophage (2026, June 24). Technophage Announces FDA Fast Track Designation Granted to TP-102 for the Treatment of Patients with Infected Diabetic Foot Ulcers Caused by Pseudomonas aeruginosa, Staphylococcus aureus and\/or Acinetobacter baumannii [Press Release]. Available online: https:\/\/technophage.pt\/technophage-announces-fda-fast-track-designation-granted-to-tp-102-for-the-treatment-of-patients-with-infected-diabetic-foot-ulcers-caused-by-pseudomonas-aeruginosa-staphylococcus-aureus-and-or\/."},{"key":"ref_56","unstructured":"Technophage (2026, June 24). TP-102 Phase 2b End of Study Marks Key Step Toward Phase 3 Development [Press Release]. Available online: https:\/\/technophage.pt\/tp-102-phase-2b-end-of-study-marks-key-step-toward-phase-3-development\/."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chen, W.H., Woolston, J., Grant-Beurmann, S., Robinson, C.K., Bansal, G., Nkeze, J., Permala-Booth, J., Fraser, C.M., Tennant, S.M., and Shriver, M.C. (2024). Safety and Tolerability of ShigActive\u2122, a Shigella spp. Targeting Bacteriophage Preparation, in a Phase 1 Randomized, Double-Blind, Controlled Clinical Trial. Antibiotics, 13.","DOI":"10.3390\/antibiotics13090858"},{"key":"ref_58","unstructured":"Havard Wyss Institute (2026, June 24). Engineered Live Biotherapeutic Product (eLBP) to Protect the Microbiome from Antibiotics [Website]. Available online: https:\/\/wyss.harvard.edu\/technology\/engineered-live-biotherapeutic-product-elbp-to-protect-the-microbiome-from-antibiotics\/."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rutter, J.W., Dekker, L., Owen, K.A., and Barnes, C.P. (2022). Microbiome engineering: Engineered live biotherapeutic products for treating human disease. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1000873"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1093\/ofid\/ofab466.130","article-title":"130. Design and Preclinical Characterization of SER-155, an Investigational Cultivated Microbiome Therapeutic to Restore Colonization Resistance and Prevent Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation","volume":"8","author":"Halvorsen","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.1200\/JCO.2025.43.16_suppl.6554","article-title":"Exploratory analyses of immune reconstitution biomarkers from a Ph1b study of an investigational, oral, live biotherapeutic, SER-155, in adult allo-HCT","volume":"43","author":"Khera","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_62","unstructured":"Seres Therapeutics (2026, June 24). Seres Therapeutics Reports SER-155 Phase 1b Placebo-Controlled Cohort 2 Study Safety and Clinical Resultsin Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT) [Press Release]. Available online: https:\/\/ir.serestherapeutics.com\/news-releases\/news-release-details\/seres-therapeutics-reports-ser-155-phase-1b-placebo-controlled."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ridelfi, M., Fonseca, V.Z.G., Sala, C., and Rappuoli, R. (Trends Immunol., 2026). Human antibodies as emerging drugs for antimicrobial resistance, Trends Immunol., in press.","DOI":"10.1016\/j.it.2026.04.003"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Rogers, J.V., Hall, V.L., and McOsker, C.C. (2022). Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance. Antibiotics, 11.","DOI":"10.3390\/antibiotics11010104"},{"key":"ref_65","unstructured":"Clarametyx Biosciences (2026, June 24). Clarametyx Biosciences Announces Positive Topline Data from Phase 2a Study Evaluating CMTX-101 in Cystic Fibrosis [Press Release]. Available online: https:\/\/clarametyx.com\/clarametyx-biosciences-announces-positive-topline-data\/."},{"key":"ref_66","unstructured":"Clarametyx Biosciences (2026, June 24). Clarametyx Biosciences Announces FDA Grant of Fast Track And Qualified Infectious Disease Product Designations For CMTX-101 [Press Release]. Available online: https:\/\/clarametyx.com\/clarametyx-biosciences-announces-fda-grant-of-fast-track-and-qualified-infectious-disease-product-designations-for-cmtx-101\/."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Burke, Z.D.C., Hart, C.M., Kelley, B.V., Mamouei, Z., Blumstein, G.W., Hamad, C., Hori, K., Cevallos, N., Villalpando, C., and Truong, N. (2023). Monoclonal Antibody Disrupts Biofilm Structure and Restores Antibiotic Susceptibility in an Orthopedic Implant Infection Model. Antibiotics, 12.","DOI":"10.3390\/antibiotics12101490"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e0065524","DOI":"10.1128\/aac.00655-24","article-title":"Phase 1 study of the pharmacokinetics and clinical proof-of-concept activity of a biofilm-disrupting human monoclonal antibody in patients with chronic prosthetic joint infection of the knee or hip","volume":"68","author":"Conway","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","first-page":"OA2783","article-title":"Late Breaking Abstract\u2014Exciting phase 1 data on RESP-X, a novel monoclonal antibody targeting a key virulence mechanism of Pseudomonas aeruginosa, with potential as a treatment to reduce exacerbations in non-CF bronchiectasis","volume":"64","author":"Leonard","year":"2024","journal-title":"Eur. Respir. J."},{"key":"ref_70","unstructured":"GlobeNewswire (2026, June 24). Infex Therapeutics Announces Positive Phase IIa Results for RESP-X in Non-Cystic Fibrosis Bronchiectasis Patients Colonised with Pseudomonas aeruginosa [Press Release]. Available online: https:\/\/firstwordpharma.com\/story\/7464035."},{"key":"ref_71","unstructured":"Aridis Pharmaceuticals (2026, June 24). AR-301: Human Anti-S. aureus mAb for Therapeutic Treatment of VAP [Company Website]. Available online: https:\/\/www.aridispharma.com\/ar-301\/."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e00710-19","DOI":"10.1128\/AAC.00710-19","article-title":"Treatment Efficacy of MEDI3902 in Pseudomonas aeruginosa Bloodstream Infection and Acute Pneumonia Rabbit Models","volume":"63","author":"Le","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s13054-022-04204-9","article-title":"Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: A randomised controlled trial","volume":"26","author":"Chastre","year":"2022","journal-title":"Crit. Care"},{"key":"ref_74","first-page":"OA2312","article-title":"A bispecific monoclonal antibody targeting Pseudomonas aeruginosa in bronchiectasis: Results from the GREAT-2 trial","volume":"66","author":"Long","year":"2025","journal-title":"Eur. Respir. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"aamag162.1285","DOI":"10.1093\/ajrccm\/aamag162.1285","article-title":"B107-14 Azd0292, a Novel Investigational Fc-engineered Humanized Monoclonal Antibody for Bronchiectasis With Chronic Pseudomonas aeruginosa Colonization: Results From a Randomized Phase I Study in Healthy Adults","volume":"212","author":"L","year":"2026","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_76","unstructured":"Chalmers, J. (2026, June 24). Trial Results Could Herald \u201cMajor Step Forward\u201d in Battle Against Hard-to-Treat Lung Infections [Press Release]. Available online: https:\/\/www.dundee.ac.uk\/press-release\/trial-results-could-herald-major-step-forward-battle-against-hard-treat-lung."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S1473-3099(18)30805-3","article-title":"CAL02, a novel antitoxin liposomal agent, in severe pneumococcal pneumonia: A first-in-human, double-blind, placebo-controlled, randomised trial","volume":"19","author":"Laterre","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1021\/acsmedchemlett.4c00308","article-title":"Facile Synthesis of FimH Antagonist and Its Analogues: Simple Entry to Complex C-Mannoside Inhibitors of E. coli Adhesion","volume":"15","author":"Zhou","year":"2024","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_79","unstructured":"Aptorum Group Limited (2022). ALS-4 Nonconfidential Overview: SMART-ACT\u2122 ALS-4 Orphan Drug Repurposing Platform [Investor Presentation], Aptorum Group Limited."},{"key":"ref_80","unstructured":"Business Wire (2026, June 24). Aptorum Group Announces Completion of Pre-IND Discussions with US FDA on its ALS-4, a First-in-Class Small Molecule Drug Targeting Methicillin Resistant Staphylococcus Aureus [Press Release]. Available online: https:\/\/www.businesswire.com\/news\/home\/20230303005009\/en\/Aptorum-Group-Announces-Completion-of-Pre-IND-Discussions-with-US-FDA-on-its-ALS-4-a-First-in-Class-Small-Molecule-Drug-Targeting-Methicillin-Resistant-Staphylococcus-Aureus."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"ofaa236","DOI":"10.1093\/ofid\/ofaa236","article-title":"Recombinant Human Plasma Gelsolin Improves Survival and Attenuates Lung Injury in a Murine Model of Multidrug-Resistant Pseudomonas aeruginosa Pneumonia","volume":"7","author":"DiNubile","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_82","unstructured":"GlobeNewswire (2026, June 24). BioAegis Therapeutics Announces Site Activation and Patient Recruitment Underway in 13 Countries in Phase 2b Clinical Trial of Gelsolin, an Immune Regulator, for the Treatment of Acute Respiratory Distress Syndrome (ARDS) [Press Release]. Available online: https:\/\/via.ritzau.dk\/pressemeddelelse\/14393449\/bioaegis-therapeutics?publisherId=90446&lang=en."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S322","DOI":"10.1093\/ofid\/ofz360.784","article-title":"716. In vitro and In vivo Nonclinical Efficacy of AR-501 (Gallium Citrate)","volume":"6","author":"Woo","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_84","unstructured":"GlobeNewswire (2026, June 24). Aridis Meets Primary and Secondary Endpoints in Phase 2a Study of AR-501 in Cystic Fibrosis Patients [Press Release]. Available online: https:\/\/www.globenewswire.com\/news-release\/2023\/03\/13\/2625673\/0\/en\/Aridis-Meets-Primary-and-Secondary-Endpoints-in-Phase-2a-Study-of-AR-501-in-Cystic-Fibrosis-Patients.html."},{"key":"ref_85","unstructured":"GlobeNewswire (2026, June 24). Aridis Provides Corporate Update [Press Release]. Available online: https:\/\/www.globenewswire.com\/news-release\/2024\/12\/20\/3000566\/0\/en\/aridis-provides-corporate-update.html."},{"key":"ref_86","unstructured":"(2026, June 24). CARB-X. Global Threat. Available online: https:\/\/carb-x.org\/about\/global-threat\/."},{"key":"ref_87","unstructured":"World Health Organization (2026, June 24). Antibacterial Products in Preclinical Development for Bacterial Priority Pathogens. Available online: https:\/\/www.who.int\/observatories\/global-observatory-on-health-research-and-development\/monitoring\/who-antibacterial-preclinical-pipeline-review."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1021\/acsinfecdis.0c00044","article-title":"The Antibacterial Research and Development Pipeline Needs Urgent Solutions","volume":"6","author":"Beyer","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e0005422","DOI":"10.1128\/aac.00054-22","article-title":"Leaks in the Pipeline: A Failure Analysis of Gram-Negative Antibiotic Development from 2010 to 2020","volume":"66","author":"Prasad","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"100512","DOI":"10.1016\/j.onehlt.2023.100512","article-title":"Antimicrobial resistance, society and environment: A glocal syndemic","volume":"16","author":"Ferrinho","year":"2023","journal-title":"One Health"},{"key":"ref_91","first-page":"e97668","article-title":"Antimicrobial Resistance: An Emerging Global Threat to Modern Medicine","volume":"17","year":"2025","journal-title":"Cureus"},{"key":"ref_92","unstructured":"Genilloud, O. (2026, June 24). How Can We Close the Early Discovery Gap and Improve our Ability to Discover New Antibiotics?\u2014By Olga Genilloud [Website]. Available online: https:\/\/revive.gardp.org\/how-can-we-close-the-early-discovery-gap-and-improve-our-ability-to-discover-new-antibiotics\/."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e01216-20","DOI":"10.1128\/mSphere.01216-20","article-title":"Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy","volume":"6","author":"Oakley","year":"2021","journal-title":"mSphere"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e0526122","DOI":"10.1128\/spectrum.05261-22","article-title":"The Lysin Exebacase Has a Low Propensity for Resistance Development in Staphylococcus aureus and Suppresses the Emergence of Resistance to Antistaphylococcal Antibiotics","volume":"11","author":"Oh","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1093\/cid\/ciae043","article-title":"Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT)","volume":"78","author":"Fowler","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Chen, H.-C., Pan, Y.-L., Chen, Y., Yang, T.-H., Hsu, E.-T., Huang, Y.-T., and Chiang, M.-H. (2024). Monoclonal Antibodies as a Therapeutic Strategy against Multidrug-Resistant Bacterial Infections in a Post-COVID-19 Era. Life, 14.","DOI":"10.3390\/life14020246"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s40258-022-00786-1","article-title":"Can the UK \u2018Netflix\u2019 Payment Model Boost the Antibacterial Pipeline?","volume":"21","author":"Leonard","year":"2023","journal-title":"Appl. Health Econ. Health Policy"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"100705","DOI":"10.1016\/j.lanepe.2023.100705","article-title":"Challenges and opportunities for incentivising antibiotic research and development in Europe","volume":"33","author":"Anderson","year":"2023","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1038\/s41467-019-12823-0","article-title":"Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei","volume":"10","author":"Boinett","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ahmed, S., Chowdhury, M.I.H., Sultana, S., Alam, S.S., Marzan, M., and Islam, M.A. (2023). Prevalence of Antibiotic-Resistant Shigella spp. in Bangladesh: A Systematic Review and Meta-Analysis of 44,519 Samples. Antibiotics, 12.","DOI":"10.3390\/antibiotics12050817"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e02588-18","DOI":"10.1128\/AAC.02588-18","article-title":"A Phase 1, Randomized, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S, an Anti-Staphylococcus aureus Thiomab Antibody-Antibiotic Conjugate, in Healthy Volunteers","volume":"63","author":"Peck","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e01379-14","DOI":"10.1128\/mBio.01379-14","article-title":"Engineered endolysin-based \u201cArtilysins\u201d to combat multidrug-resistant gram-negative pathogens","volume":"5","author":"Briers","year":"2014","journal-title":"mBio"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"100992","DOI":"10.1016\/j.lanmic.2024.100992","article-title":"Addressing urgent priorities in antibiotic development: Insights from WHO 2023 antibacterial clinical pipeline analyses","volume":"6","author":"Melchiorri","year":"2025","journal-title":"Lancet Microbe"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/899\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:40:17Z","timestamp":1789393217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/9\/899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":103,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antibiotics15090899"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15090899","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]}}}