{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:09Z","timestamp":1792789029439,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ciencia de Frontera 2023","award":["CF-2023-G-645"],"award-info":[{"award-number":["CF-2023-G-645"]}]},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","award":["1083340"],"award-info":[{"award-number":["1083340"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"crossref"}]},{"award":["1083340"],"award-info":[{"award-number":["1083340"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Antimicrobial resistance has been recognized as a major global health threat, with multidrug-resistant Acinetobacter baumannii identified as one of the most critical pathogens. To address the limitations of conventional antibiotics, phage therapy has been proposed as a complementary or alternative intervention. In this study, experimental data were integrated into a deterministic differential-equation-based model to capture phage\u2013bacteria\u2013antibiotic\u2013host immune system interactions. Methods: The model extended a previous phage\u2013host immune system synergy framework by incorporating phage\u2013antibiotic synergy and a time-dependent reduction in phage adsorption as a phenomenological representation of population-level reduction in phage susceptibility. This formulation does not explicitly model the molecular mechanisms or evolutionary emergence of resistance. In vitro observations of phage-induced resensitization to ceftazidime informed model parameterization, while remaining parameters were estimated from experimental observations or literature values. Simulations evaluated bacterial dynamics under phage-only, antibiotic-only, and immunity-only conditions, as well as combined therapeutic scenarios. Results: Model predictions indicated the greatest bacterial reduction when phages, antibiotics, and host innate immunity acted together. Phage\u2013antibiotic synergy further enhanced predicted bacterial clearance, particularly for ceftazidime-resistant populations, while a population-level reduction in phage susceptibility was predicted approximately 4 h post-infection, consistent with experimental observations. Combined scenarios involving continuous antibiotic infusion, phage plus host immunity, or low-dose antibiotic regimens predicted accelerated bacterial declines when synergistic interactions were active. Conclusions: This framework integrates experimental observations with mathematical modeling to explore therapeutic interactions and temporal changes in phage susceptibility, while assessing parameter sensitivity and guiding future experimental and preclinical studies.<\/jats:p>","DOI":"10.3390\/antibiotics15090919","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:41:35Z","timestamp":1789645295000},"page":"919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling Phage\u2013Antibiotic Synergy, Innate Immunity, and Phage Resistance in Multidrug-Resistant Acinetobacter baumannii"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-0651","authenticated-orcid":false,"given":"Alma Karen","family":"Orozco-Ochoa","sequence":"first","affiliation":[{"name":"Laboratorio Nacional para la Investigaci\u00f3n en Inocuidad Alimentaria (LANIIA), Centro de Investigaci\u00f3n en Alimentaci\u00f3n y Desarrollo, A.C. (CIAD), Carretera a Eldorado Km 5.5, Campo El Diez, Culiac\u00e1n 80110, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Jos\u00e9 Benigno","family":"Valdez-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional para la Investigaci\u00f3n en Inocuidad Alimentaria (LANIIA), Centro de Investigaci\u00f3n en Alimentaci\u00f3n y Desarrollo, A.C. (CIAD), Carretera a Eldorado Km 5.5, Campo El Diez, Culiac\u00e1n 80110, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2994-4358","authenticated-orcid":false,"given":"Jean Pierre","family":"Gonz\u00e1lez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional para la Investigaci\u00f3n en Inocuidad Alimentaria (LANIIA), Centro de Investigaci\u00f3n en Alimentaci\u00f3n y Desarrollo, A.C. (CIAD), Carretera a Eldorado Km 5.5, Campo El Diez, Culiac\u00e1n 80110, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0738-492X","authenticated-orcid":false,"given":"Nohelia","family":"Castro-del Campo","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional para la Investigaci\u00f3n en Inocuidad Alimentaria (LANIIA), Centro de Investigaci\u00f3n en Alimentaci\u00f3n y Desarrollo, A.C. (CIAD), Carretera a Eldorado Km 5.5, Campo El Diez, Culiac\u00e1n 80110, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-8270","authenticated-orcid":false,"given":"Crist\u00f3bal","family":"Chaidez-Quiroz","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional para la Investigaci\u00f3n en Inocuidad Alimentaria (LANIIA), Centro de Investigaci\u00f3n en Alimentaci\u00f3n y Desarrollo, A.C. 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