Gaukhar Askhatkyzy

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–antibiotic combinations tested across nine antibiotics, synergy (FICI ≤ 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.

Iodine-based antimicrobial materials are widely considered for biomedical applications due to their broad-spectrum antimicrobial activity; however, their potential genotoxicity requires systematic evaluation prior to clinical use. The aim of this study was to assess the genotoxic potential of a dextrin–polyvinyl alcohol–iodine (D/PVA/I-1) complex in accordance with OECD guidelines. Genotoxicity was evaluated in vitro using two complementary assays: the mammalian cell micronucleus test (OECD TG 487) in L5178Y TK^+/− cells and the bacterial reverse mutation assay (Ames test, OECD TG 471) using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA, both in the presence and absence of metabolic activation (S9). In the micronucleus assay, no statistically significant increase in micronucleus frequency was observed at concentrations ranging from 0.039 to 0.625 mg/mL compared with the negative control. In the Ames test, no increase in revertant colony numbers was detected in any tested bacterial strain at concentrations up to 1250 μg/plate. At higher concentrations, pronounced cytotoxic and bactericidal effects were observed without evidence of mutagenic activity. Overall, the results demonstrate that the D/PVA/I-1 complex does not exhibit genotoxic or mutagenic potential under the tested in vitro conditions, indicating a favorable genetic safety profile and supporting further preclinical evaluation for potential biomedical applications.

Objectives: The global rise in multidrug resistance underscores the urgent need for the development of novel and effective antimicrobial agents. Semi-organic iodine-containing complexes, owing to their unique properties, low likelihood of resistance development, and stability under various conditions, represent a promising avenue for the design of new therapeutic strategies. This study describes the synthesis of semi-organic iodine-containing complexes and the in vitro evaluation of their impact on antibiotic susceptibility modulation in the multidrug-resistant pathogenic microorganisms S. aureus and E. coli. Methods: The physicochemical properties of the semiorganic compounds were characterized using UV-Vis spectroscopy, potentiometric, and titrimetric methods. Evaluation of antimicrobial activity was obtained according to CLSI protocols. The impact of semiorganic compounds on the in vitro susceptibility of MDR strains was evaluated by the disk diffusion method. Results: This study evaluated the effects of iodine-containing complexes KC-270 and KC-271 on the antibiotic susceptibility of Staphylococcus aureus BAA-39 and Escherichia coli BAA-196. The most pronounced effect was observed with KC-270 applied during the lag phase, which enhanced the activity of several antibiotics and, in some cases, restored susceptibility. KC-271 exhibited a weaker and more limited impact. The findings suggest that KC-270 has potential as a modulator of antibiotic susceptibility, particularly when administered at early stages of bacterial growth. Conclusions: The results support the ability of amino acid-based iodine coordination compounds to influence the antibiotic susceptibility of pathogenic bacteria, highlighting their potential as adjuvant agents to improve the effectiveness of current antimicrobial therapies. However, although changes in susceptibility were detected, neither compound fully eliminated resistance in the multidrug-resistant strains, indicating the necessity for further research into their mechanisms of action and possible synergistic interactions with antibiotics.