{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:51Z","timestamp":1787029311112,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR24992760"],"award-info":[{"award-number":["BR24992760"]}]},{"award":["BR24992760"],"award-info":[{"award-number":["BR24992760"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Antimicrobial resistance (AMR) is among the most pressing challenges in modern infectious medicine, driving progressive failure of standard antibacterial therapy and rising mortality from infections caused by multidrug-resistant (MDR) pathogens. Antibiotic potentiation through adjuvant compounds capable of restoring the activity of existing drugs represents a promising strategy to overcome resistance without developing fundamentally new antibacterial molecules. This study aimed to evaluate the antibiotic-potentiating activity of a dextrin\/polyvinyl alcohol\/iodine complex (D\/PVA\/I-1), developed at the Scientific Center for Anti-Infectious Drugs JSC (Almaty, Kazakhstan), against clinically relevant MDR reference strains. Methods: Nine reference strains, Staphylococcus aureus (ATCC 33591, BAA-39), Escherichia coli (ATCC BAA-196, BAA-2523), Klebsiella pneumoniae (ATCC BAA-2524, 700603), Acinetobacter baumannii (ATCC BAA-1790), Streptococcus pneumoniae (ATCC BAA-660), and Haemophilus influenzae (ATCC 33930), and two clinical isolates, P. aeruginosa SCAID PHRX1-2019 and E. coli SCAID WND1-2021, were tested. Antibiotic-potentiating activity was assessed by checkerboard assay with calculation of the fractional inhibitory concentration index (FICI); bactericidal kinetics were evaluated by time-kill analysis. The effect of D\/PVA\/I-1 on cytoplasmic membrane permeability was investigated using a crystal violet uptake assay. Results: Of 45 D\/PVA\/I-1\u2013antibiotic combinations tested across nine antibiotics, synergy (FICI \u2264 0.5) was demonstrated in 44.4% of cases, partial synergy in 48.9%, and additive effects in 6.7%; no antagonistic interactions were detected. The most pronounced potentiating effect occurred against Gram-positive pathogens, particularly MRSA strains (66.7% synergistic combinations). Time-kill analysis confirmed suppression of the regrowth phenotype characteristic of MDR strains under monotherapy and restoration of bactericidal activity against antibiotics to which strains exhibited intrinsic resistance. D\/PVA\/I-1 induced a dose- and time-dependent increase in membrane permeability in both Gram-positive and Gram-negative organisms. Conclusions: D\/PVA\/I-1 is an effective broad-spectrum antibiotic potentiator and represents a promising basis for combination therapy regimens against MDR infections.<\/jats:p>","DOI":"10.3390\/ph19081300","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:04:36Z","timestamp":1786961076000},"page":"1300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["D\/PVA\/I-1 as an Antibiotic Adjuvant: In Vitro Synergy and Membrane Permeabilization in MDR Bacteria"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8610-7321","authenticated-orcid":false,"given":"Ardak","family":"Jumagaziyeva","sequence":"first","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-3534","authenticated-orcid":false,"given":"Seitzhan","family":"Turganbay","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Kazakh National Women\u2019s Teacher Training University, Almaty 050000, Kazakhstan"},{"name":"\u201cOne Belt, One Road\u201d Petroleum Engineering, Kazakh-British Technical University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7791-3145","authenticated-orcid":false,"given":"Anar","family":"Seisembekova","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0471-0587","authenticated-orcid":false,"given":"Daniil","family":"Shepilov","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7428-0074","authenticated-orcid":false,"given":"Zhanar","family":"Iskakbayeva","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9154-1424","authenticated-orcid":false,"given":"Sabina","family":"Kenesheva","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saltanat","family":"Jumabayeva","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaukhar","family":"Askhatkyzy","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8533-3029","authenticated-orcid":false,"given":"Nurdaulet","family":"Temir","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"},{"name":"Department of Fundamental Medicine, Farabi University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3163-5730","authenticated-orcid":false,"given":"Abdurashit","family":"Khamidulin","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"},{"name":"Department of Fundamental Medicine, Farabi University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr","family":"Ilin","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_2","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. 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