Ibrahim M Ibrahim, Ola Qadi, Osama A A Ahmed, Fatemah Kamel, Rania Magadmi, Sameer Alharthi
{"title":"Colon-targeted pH-responsive tofacitinib beads improve ulcerative colitis outcomes with lower systemic exposure.","authors":"Ibrahim M Ibrahim, Ola Qadi, Osama A A Ahmed, Fatemah Kamel, Rania Magadmi, Sameer Alharthi","doi":"10.1007/s44446-026-00076-0","DOIUrl":"10.1007/s44446-026-00076-0","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease resulting in mucosal inflammation and ulceration. Although tofacitinib, a Janus kinase inhibitor, is effective when administered systemically, its clinical use may be limited by systemic adverse effects. Thus, this study aimed to design and evaluate a colon‑targeted tofacitinib delivery system based on sodium alginate beads coated with Eudragit® S‑100 in a dextran sulfate sodium (DSS) induced colitis rat model. Tofacitinib was encapsulated within alginate beads and subsequently coated with Eudragit® S-100 for pH-dependent release. The beads were characterized for size, encapsulation efficiency, stability, and in vitro drug release. Therapeutic efficacy was evaluated in a 30-day DSS colitis model by histopathology, cytokine profiling, and drug concentrations in plasma and colon tissue. The colon-targeted beads exhibited minimal release under acidic gastric conditions and maximum release at the colonic pH. In vivo, the formulation significantly improved disease activity scores, preserved colonic architecture, and significantly reduced pro-inflammatory cytokines levels while increasing IL-10 levels. Colonic drug levels achieved with the formulated beads were substantially higher than those obtained with non‑formulated tofacitinib, accompanied by markedly reduced systemic exposure. As a conclusion, the colon-targeted tofacitinib delivery system may limit systemic exposure relative to conventional oral administration while maintaining therapeutic efficacy in experimental colitis. Nevertheless, comprehensive toxicological and long‑term safety studies are required before definitive conclusions regarding safety can be drawn.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning-guided rational engineering of ACE2-derived peptides for broad-spectrum neutralization of SARS-CoV-2 variants.","authors":"Mubarak A Alamri, Abdullah S Alawam","doi":"10.1007/s44446-026-00073-3","DOIUrl":"10.1007/s44446-026-00073-3","url":null,"abstract":"<p><p>The dynamic mutational landscape of SARS-CoV-2, especially within the spike glycoprotein's RBD, continues to undermine the effectiveness of available therapeutics. Although ACE2-derived peptides have previously been explored as spike inhibitors, their rational optimization has largely lacked systematic, data-driven selection strategies. This article describes an integrative computer-aided approach involving molecular dynamics (MD) simulations and machine learning-assisted peptide engineering to engineer potent peptide-based inhibitors targeting the RBD-ACE2 interface. Molecular dynamics simulations of wild-type and variant RBD-ACE2 complexes were first employed to identify energetically unfavorable interfacial residues, enabling the rational extraction and refinement of a 19-residue ACE2-derived peptide. A supervised regression model of the type XGBoost, trained using experimentally obtained peptide-protein affinity matrices (R<sup>2</sup> = 0.6958), estimated binding potentials for 54 synthetically designed peptide variants. The best lead, M1 (HAHTFLETFNYEAQTLSYE), exhibited improved docking energies (-257.35 kcal/mol for Omicron and -234.24 kcal/mol for wild-type) and improved free-binding energies (-35.67 kcal/mol and -21.63 kcal/mol, respectively), relative to the native peptide, with binding energies comparable to or exceeding reported RBD-hACE2 interaction benchmarks (- 13 to - 18 kcal/mol). Molecular dynamics analyses further confirmed enhanced conformational stability, sustained hydrogen bonding, and favourable energetic landscapes for the M1-RBD complexes. Collectively, this study demonstrates that integrating energetic decomposition with ML-driven peptide optimization provides a scalable and mechanistically informed strategy for developing peptide-based inhibitors against rapidly evolving viral pathogens.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liquid crystalline system for drug delivery: structural insights, preparation techniques and translational potential.","authors":"Kshitija Akarte, Drishti Panjwani, Viral Patel, Asha Patel, Nishabh Kushwaha, Shruti Patel","doi":"10.1007/s44446-026-00062-6","DOIUrl":"10.1007/s44446-026-00062-6","url":null,"abstract":"<p><p>Liquid Crystals (LCs) constitute a versatile class of soft materials whose combination of molecular order and fluidity enables the creation of nanostructured drug-delivery systems with precisely tunable properties. This review provides a unified and application-oriented evaluation of thermotropic and lyotropic liquid crystal systems, emphasizing how their self-assembly, curvature behavior, and interfacial energetics govern mesophase formation and drug-loading capacity. Particular focus is placed on the biodegradability, biocompatibility, and structural robustness of LC matrices, as these parameters critically determine safety and sustained-release performance. Key preparation strategies, including high-energy top-down dispersion, low-energy bottom-up assembly, and precursor-based methods, are examined alongside characterization tools such as polarized optical microscopy, small-angle X-ray scattering, and dynamic light scattering. The ability of LC nanocarriers to encapsulate both hydrophilic and hydrophobic drugs, minimize burst release, and deliver controlled diffusion through cubic, hexagonal, and lamellar architectures is highlighted. Their high entrapment efficiency, extended-release kinetics, and inherent colloidal stability position these systems as promising candidates for improving the delivery of poorly soluble therapeutics. The review further synthesizes insights into phase transitions, dilution responses, and stimuli-responsive behaviors that enable on-demand or site-specific release. Scalability, compatibility with low-energy processing, and stability under physiological conditions support their translational relevance. Unlike earlier reviews, this article integrates structural phase physics, formulation engineering, and translational evidence into a unified framework, contrasting cubic, hexagonal, and lamellar systems across preparation routes, stimuli responsiveness, release behavior, toxicology, and clinical progress to provide an up-to-date, application-oriented perspective for LC-based nanomedicine.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147533971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polyacetylenes as antibacterial, antibiofilm, and anti-quorum-sensing agents: Sources, chemistry, bioactivities, and <sup>13</sup>C-NMR data.","authors":"Reham M Samra, Fatma M Abdel Bar","doi":"10.1007/s44446-025-00059-7","DOIUrl":"10.1007/s44446-025-00059-7","url":null,"abstract":"<p><p>The rise of multidrug-resistant bacteria now poses significant challenges, rendering many conventional medicines ineffective and necessitating the search for new antimicrobial agents. Polyacetylenes, both natural and synthetic, possess diverse biological activities, with their remarkable antibacterial potential being particularly significant. This review offers an in-depth evaluation of the therapeutic roles of polyacetylenes as antibacterial, antibiofilm, and anti-quorum-sensing agents, summarizing the tested compounds, their natural sources, the assays employed, and the bacterial strains investigated. It also provides an overview of their biosynthesis, distribution, and pharmacokinetic properties, along with a comprehensive analysis of their chemical classification and <sup>13</sup>C-NMR data. Despite decades of research on polyacetylenes, no previous review has systematically integrated their antibacterial mechanisms, biofilm-inhibitory effects, quorum-sensing disruption, and structure-activity relationships (SAR). Our analysis revealed that antibacterial and antibiofilm activities are highly dependent on chain length, conjugation, and specific functional substituents, with halogenation, carbonyl and cinnamate incorporation, and stereochemical configuration significantly modulating potency beyond the previously assumed requirement for hydroxylation. This work fills that gap by compiling information on about 90 polyacetylenes that were reported between 1947 and January 2025. It draws attention to their dual antibacterial mechanism, involving disruption of membrane and downregulation of key QS-related genes, leading to attenuated virulence, suppressed biofilm formation, and marked decrease in bacterial burden. In conclusion, polyacetylenes represent promising antibacterial, antibiofilm, and anti-quorum-sensing candidates, offering valuable scaffolds for developing new therapies against multidrug-resistant infections.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hadeel Drweesh, Amal Alotaibi, Hussain Abdalghani Alqassim, Mohammed Mustafa Eid, Shaimaa Abdulhadi Emsaad, Mohamed Omar Saad, Alya Salah Higazy, Abdulrahman Alturaiki, Fares Almutairi, Abdulsattar Alhussain, Abdulmohsen Assiri, Hadeel Alkofide, Yazeed Alruthia, Ahmed Albassam, Abdullah Alsultan
{"title":"Comparing the pharmacokinetics of adalimumab originator and biosimilar product in patients with Inflammatory bowel disease or autoimmune disease.","authors":"Hadeel Drweesh, Amal Alotaibi, Hussain Abdalghani Alqassim, Mohammed Mustafa Eid, Shaimaa Abdulhadi Emsaad, Mohamed Omar Saad, Alya Salah Higazy, Abdulrahman Alturaiki, Fares Almutairi, Abdulsattar Alhussain, Abdulmohsen Assiri, Hadeel Alkofide, Yazeed Alruthia, Ahmed Albassam, Abdullah Alsultan","doi":"10.1007/s44446-026-00063-5","DOIUrl":"10.1007/s44446-026-00063-5","url":null,"abstract":"<p><p>Adalimumab is a monoclonal antibody approved for managing inflammatory bowel disease (IBD) and other autoimmune conditions. Biosimilars can offer a more affordable alternative to reference biologics and improve access to treatments. Despite their advantages, there are still concerns regarding physicians' adoption of biosimilar products. This study aimed to compare the clearance of originator adalimumab with its biosimilar products in patients with inflammatory bowel disease and other autoimmune diseases. This multicenter retrospective study was conducted across seven hospitals in Saudi Arabia and Qatar. The study population included adult patients who received adalimumab and underwent routine therapeutic drug monitoring. Population pharmacokinetic analysis was performed using Monolix software, and the empirical Bayesian estimate of clearance was determined for individual patients. Stepwise linear regression was then conducted to assess the effects of product type and other covariates on adalimumab clearance. This study included a total of 99 patients. Patients received various adalimumab products, including the reference biologic (Humira, 70.7%) and biosimilars (Amgevita, 16.2%; Hyrimoz, 13.1%). The average estimated clearance was 0.018 ± 0.012 L/hr. The only significant covariates in the multivariable regression were age and the presence/absence of antibodies. There was no significant difference in clearance between the originator and biosimilar products. Our study compared the clearance of adalimumab originator and its biosimilars in patients with inflammatory bowel disease and other autoimmune disorders. No significant differences in clearance were observed, suggesting comparable clearance. The adoption of biosimilars in clinical practice could improve patient access to biologic therapies while substantially reducing healthcare costs.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmad Assiri, Hussam Tariq Hakami, Abdulrahman Abdu Daghreeri, Ameera Abdulaziz Alkhamesi, Amjad Ibrahim Alrasheed
{"title":"Efficacy and safety of oral doxycycline for acne vulgaris treatment: A systematic review and meta-analysis.","authors":"Ahmad Assiri, Hussam Tariq Hakami, Abdulrahman Abdu Daghreeri, Ameera Abdulaziz Alkhamesi, Amjad Ibrahim Alrasheed","doi":"10.1007/s44446-026-00066-2","DOIUrl":"10.1007/s44446-026-00066-2","url":null,"abstract":"<p><p>Doxycycline is commonly used to manage acne vulgaris (AV), but comprehensive comparisons of its efficacy and safety against alternative treatments remain limited. This study aimed to systematically evaluate and compare the efficacy and safety of oral doxycycline with other therapeutic options for AV treatment. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. Literature searches were performed in PubMed/MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science, and Google Scholar up to March 2024, using Medical Subject Headings (MeSH) and relevant free-text terms (e.g., \"doxycycline AND acne vulgaris\"). The primary outcomes were treatment success, change in inflammatory lesion count, and Global Acne Grading System (GAGS) scores, while safety outcomes focused on the incidence of reported adverse events. The risk of bias across studies was evaluated using the Cochrane ROB-2 tool, and meta-analyses were conducted using random-effects models to account for expected heterogeneity. A total of 23 RCTs comprising 2,672 patients were included. Doxycycline showed similar efficacy to azithromycin in achieving treatment success (OR 1.28; 95% CI [0.54, 3.04], p = 0.57; I2 = 60%), with no significant difference in inflammatory lesion reduction (MD -0.71; 95% CI [-8.61, 7.19], p = 0.86; I2 = 97%). However, other treatments (e.g., isotretinoin, silymarin) demonstrated greater improvements in GAGS scores (MD 1.76; 95% CI [1.53, 2.00], p < 0.00001; I2 = 53%). More adverse events, particularly gastrointestinal and dermatological, were reported with doxycycline. While effective, its safety profile and comparative performance warrant further investigation through high-quality RCTs.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdulmueen A Alotaibi, Syed Shahid Habib, Hayam Gad, Tamadar Al Doheyan, Mubarak Aldosary, Alanoud T Aljasham, Asma F Alotaibi, Yasser A Alshawakir, Abeer AbdulMoati Al-Masri
{"title":"Improved hemodynamic and cardiorespiratory instability with vitamin D supplementation in an obstructive sleep apnea rat models.","authors":"Abdulmueen A Alotaibi, Syed Shahid Habib, Hayam Gad, Tamadar Al Doheyan, Mubarak Aldosary, Alanoud T Aljasham, Asma F Alotaibi, Yasser A Alshawakir, Abeer AbdulMoati Al-Masri","doi":"10.1007/s44446-026-00074-2","DOIUrl":"10.1007/s44446-026-00074-2","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D deficiency is linked to cardiovascular and respiratory instability, particularly during hypoxic stress, such as in obstructive sleep apnea (OSA). However, the mechanisms connecting vitamin D status to hemodynamic and cardiorespiratory responses in hypoxia remain unclear.</p><p><strong>Objective: </strong>This study aimed to assess the impact of vitamin D deficiency on hemodynamic (mean arterial pressure and heart rate) and cardiorespiratory (respiratory rate and peripheral oxygen saturation) stability in an OSA experimental model, along with the effects of dose-dependent vitamin D supplementation.</p><p><strong>Methods: </strong>Fifty-six adult male Sprague Dawley rats were divided into seven groups: control, vitamin D-deficient, vitamin D-deficient with severe intermittent hypoxia (IH) and supplementation subgroups exposed to varying levels of IH. Vitamin D deficiency was induced through a diet lacking vitamin D for three weeks, followed by oral supplementation at two doses (25 µg/kg/day and 37.5 µg/kg/day) for two weeks. Intermittent hypoxia was simulated for 14 days, and serum 25-hydroxyvitamin D (25OHD) levels were measured using Elisa. Hemodynamic and cardiorespiratory parameters were recorded, and heart, aorta tissue were analyzed.</p><p><strong>Results: </strong>Vitamin D-deficient groups exhibited significantly lower serum 25OHD levels and showed increased mean arterial pressure, heart and respiratory rates, and reduced oxygen saturation under hypoxia. High-dose supplementation improved 25OHD levels and improved physiological measures, particularly in moderate hypoxia subgroups (p = 0.001).</p><p><strong>Conclusion: </strong>Vitamin D deficiency combined with intermittent hypoxia increased mean arterial pressure, heart rate, and respiratory rate, reduced oxygen saturation, and worsened cardiovascular histology. Vitamin D supplementation improved these changes, especially at higher dose, and protected cardiovascular structures.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Adil, Sumayya Akram, Matloob Ahmad, Magdi E A Zaki
{"title":"Therapeutic potential of Aloe vera in diabetes mellitus treatment: an update.","authors":"Muhammad Adil, Sumayya Akram, Matloob Ahmad, Magdi E A Zaki","doi":"10.1007/s44446-026-00070-6","DOIUrl":"10.1007/s44446-026-00070-6","url":null,"abstract":"<p><p>Diabetes mellitus is a metabolic disease manifested by hyperglycemia, leading to critical health challenges in the kidneys, eyes, nerves, and cardiovascular system. Aloe vera (Aloe barbadensis miller), a traditionally used herbal plant for treating various diseases, contains abundant bioactive compounds like alkaloids, flavonoids, acemannans, anthraquinones, chromones, anthrones, enzymes, vitamins, and minerals. These compounds are responsible for its diverse biological activities, including antimicrobial, anticancer, antidiabetic, anti-inflammatory, antioxidant, and hypolipidemic etc. This review primarily focuses on diabetes treatment through enzyme inhibition and modulation of metabolic parameters, with additional emphasis on diabetic complications including, the wound healing efficacy of Aloe vera. This study aims to evaluate the potential of Aloe vera in managing diabetes and minimizing the chances of diabetes-related organ damage. It was done by inhibition of several enzymes, including α-glucosidase, α-amylase, dipeptidyl peptidase-4, pancreatic lipase, sucrase, and maltase enzymes, both in vivo and in vitro. The previous research revealed that administrating various doses of Aloe vera-based extracts via orally and non-orally routes in streptozotocin-induced diabetes offered metabolic regulation of signaling pathways like blood sugar, insulin, lipid profile, body weight, oxidative stress, TNF-α, and IL-6 levels. Moreover, clinical data have confirmed Aloe vera's potential in diabetic wound healing by promoting tissue regeneration mechanisms like angiogenesis, fibrinogenesis, collagen synthesis, and inflammation to reduce lesion size. These therapeutic properties highlight the hypoglycemic nature of Aloe vera, promising its potential for future clinical use as an alternative for diabetes treatment.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lan Chen, Xiaoqing Huang, Yaqian Yan, Dandan Wang, Guoping Liu, Shuwen Huang, Qingqing Li, Bin Yang, Yue Qiu
{"title":"Comparison of renal function parameters and acute kidney injury incidence between vancomycin monotherapy and vancomycin-fosfomycin combination therapy in patients: a propensity score-matched analysis.","authors":"Lan Chen, Xiaoqing Huang, Yaqian Yan, Dandan Wang, Guoping Liu, Shuwen Huang, Qingqing Li, Bin Yang, Yue Qiu","doi":"10.1007/s44446-026-00065-3","DOIUrl":"10.1007/s44446-026-00065-3","url":null,"abstract":"<p><p>Vancomycin (VAN) is a first-line agent for methicillin-resistant Staphylococcus aureus (MRSA) infections, but it poses nephrotoxicity risks. While VAN-fosfomycin (FOS) combination shows synergistic efficacy and lower mutant prevention concentrations, its renoprotective effects compared to VAN alone remain unclear. This study aims to directly compare renal function parameters and acute kidney injury incidence between VAN monotherapy and VAN + FOS combination therapy. After propensity score matching of the initial 156 patients, 76 individuals were included in the final analysis; 38 were assigned to the vancomycin monotherapy group and 38 in the VAN + FOS combination group. Renal function parameters were recorded at 48 h and 72 h post-treatment, and the incidence of acute kidney injury (AKI) was compared between the two groups. Univariate analyses were performed to identify baseline factors associated with AKI. The VAN + FOS group had a significantly lower incidence of AKI compared to the VAN-alone group (5.26% vs. 21.05%, P = 0.04). Due to the limited number of AKI cases, multivariate adjustment was not possible. Univariate analysis revealed significant associations between AKI incidence and FOS combination therapy, age, and vancomycin trough concentration (P = 0.04, P = 0.00, and P = 0.02, respectively). These findings warrant validation in larger, prospective studies. Fosfomycin adjunct therapy was associated with a lower incidence of vancomycin-induced AKI. However, these associations should be interpreted cautiously and require validation in larger cohorts.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Masaad Saeed Almutairi, Mohammed Albulaihed, Faisal Almutairi, Yasser Alsuhaibani, Mohammed Alkathlan, Faris S Alnezary, Abdulrahman Saleh Aljamhan, Afaf Ibrahim Alresheedi, Zikria Saleem, Omar A Almohammed
{"title":"Comorbidities and mortality in colistin-resistant gram-negative infections among hospitalized patients in Qassim, Saudi Arabia.","authors":"Masaad Saeed Almutairi, Mohammed Albulaihed, Faisal Almutairi, Yasser Alsuhaibani, Mohammed Alkathlan, Faris S Alnezary, Abdulrahman Saleh Aljamhan, Afaf Ibrahim Alresheedi, Zikria Saleem, Omar A Almohammed","doi":"10.1007/s44446-026-00069-z","DOIUrl":"10.1007/s44446-026-00069-z","url":null,"abstract":"<p><p>Colistin has served as a last-resort agent against multidrug-resistant Gram-negative bacilli (MDR-GNB). However, the emergence of resistance has substantially eroded its therapeutic value, particularly among hospitalized patients. Evidence regarding the clinical outcomes of colistin-resistant infections in Saudi Arabia, however, remains scarce. This study aimed at assessing the clinical characteristics and outcomes of colistin-resistant bacterial infections among hospitalized patients in the Qassim region. We conducted a single-center retrospective observational study at King Fahad Specialist Hospital, Qassim, Saudi Arabia, reviewing the records of hospitalized patients with colistin-resistant infections between 2019 to 2023. Demographic, clinical, microbiological, therapeutic, and outcome data were retrieved from both electronic and paper health records. Eighty-five patients (mean age, 65.8 years; 60% male) with eighty-five colistin-resistant isolates were identified. Enterobacterales predominated (85.9%), followed by Pseudomonas aeruginosa (9.4%) and Acinetobacter baumannii (4.7%). All isolates showed extensive colistin resistance (100% in Acinetobacter and Pseudomonas, 82.8% in Enterobacterales), acknowledging the small number of non-Enterobacterales isolates. Limited sensitivity to cephalosporins and carbapenems, underscoring the therapeutic challenge of MDR-GNB. Meropenem (39.7%) and tigecycline (15.1%) were the most frequently prescribed agents, whereas combination therapy was employed in 16.6% of cases. The overall in-hospital mortality was 54.1% (95% CI: 43.0-65.0), with substantially higher mortality among patients admitted to the ICU (70.8%, 95% CI: 55.9-83.0) compared with those managed in non-ICU settings (32.4%, 95% CI: 18.0-49.8). After adjustment for clinical indicators, ICU admission was independently associated with increased mortality. Colistin-resistant Gram-negative infections hospitalized patients were characterized by severely limited therapeutic options, substantial reliance on carbapenems and tigecycline, and high observed mortality. These observations underscore the need for strengthened antimicrobial stewardship, improved availability of rapid diagnostic tools, and expanded access to newer therapeutic agents. In the absence of such measures, the burden of colistin resistance is likely to persist in hospital settings, including patients requiring intensive care.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}