Pub Date : 2026-03-01Epub Date: 2026-01-09DOI: 10.1016/j.ijantimicag.2026.107715
Reema Singh , Yu-Wei Lin , Jinxin Zhao , Jian Li
Objectives
The global crisis of antimicrobial resistance (AMR) demands a paradigm shift in traditional drug discovery, and artificial intelligence (AI) is uniquely positioned to lead this transformation.
Methods
We highlight how AI and machine learning (ML) can accelerate the discovery of novel antimicrobials by enabling de novo drug design, virtual screening, identification of new drug targets, and elucidation of antimicrobial mechanisms.
Results
AI/ML is revolutionizing resistance prediction by integrating diverse genomic and phenotypic data for rapid diagnostics, real-time surveillance, and personalized antimicrobial therapy.
Conclusions
Despite data limitations and the ‘black-box’ challenge of model interpretability, the potential of AI to combat AMR hinges on sustained investment, data-sharing, and unprecedented interdisciplinary collaboration worldwide. The strategic deployment of AI and ML is thus a crucial element in the battle plan for the war against drug-resistant pathogens.
{"title":"Artificial intelligence and machine learning in antimicrobial discovery, resistance prediction, and precision therapy","authors":"Reema Singh , Yu-Wei Lin , Jinxin Zhao , Jian Li","doi":"10.1016/j.ijantimicag.2026.107715","DOIUrl":"10.1016/j.ijantimicag.2026.107715","url":null,"abstract":"<div><h3>Objectives</h3><div>The global crisis of antimicrobial resistance (AMR) demands a paradigm shift in traditional drug discovery, and artificial intelligence (AI) is uniquely positioned to lead this transformation.</div></div><div><h3>Methods</h3><div>We highlight how AI and machine learning (ML) can accelerate the discovery of novel antimicrobials by enabling de novo drug design, virtual screening, identification of new drug targets, and elucidation of antimicrobial mechanisms.</div></div><div><h3>Results</h3><div>AI/ML is revolutionizing resistance prediction by integrating diverse genomic and phenotypic data for rapid diagnostics, real-time surveillance, and personalized antimicrobial therapy.</div></div><div><h3>Conclusions</h3><div>Despite data limitations and the ‘black-box’ challenge of model interpretability, the potential of AI to combat AMR hinges on sustained investment, data-sharing, and unprecedented interdisciplinary collaboration worldwide. The strategic deployment of AI and ML is thus a crucial element in the battle plan for the war against drug-resistant pathogens.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107715"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.ijantimicag.2026.107720
Hongxuan Yan , Jinfeng Yuan , Shujuan Duan , Fuzhen Zhang , Zichun Ma , Weicong Ren , Shanshan Li , Yu Pang , Mengqiu Gao
Objectives
The rising prevalence of drug resistance has emerged as a major obstacle to global tuberculosis (TB) control, necessitating the development of novel host-directed strategies. This study aimed to identify compounds that enhance intracellular clearance of Mycobacterium tuberculosis (Mtb) through autophagy induction.
Methods
A cell-based screening of a G-protein-coupled receptor-related compound library was performed to identify potential autophagy inducers. Mechanistic studies were conducted in Mtb-infected macrophages to examine the effects on PI3K/AKT/mTOR signaling and ULK1 activation. In vivo efficacy was evaluated in a BALB/c mouse model of TB.
Results
Amodiaquine hydrochloride (CAS), a conventional antimalarial drug, was identified as a potent inducer of autophagic killing of intracellular Mtb. CAS reduced phosphorylation of PI3K, AKT, and mTOR in infected macrophages, promoting ULK1 activation and autophagy. In vivo, CAS treatment significantly decreased bacterial loads in the lungs of BALB/c mice.
Conclusions
CAS represents a novel host-directed therapeutic agent that enhances intracellular clearance of Mtb by triggering autophagy in macrophages, offering a potential strategy to combat drug-resistant TB.
{"title":"Amodiaquine hydrochloride facilitates mycobacterial clearance via triggering autophagy in macrophages","authors":"Hongxuan Yan , Jinfeng Yuan , Shujuan Duan , Fuzhen Zhang , Zichun Ma , Weicong Ren , Shanshan Li , Yu Pang , Mengqiu Gao","doi":"10.1016/j.ijantimicag.2026.107720","DOIUrl":"10.1016/j.ijantimicag.2026.107720","url":null,"abstract":"<div><h3>Objectives</h3><div>The rising prevalence of drug resistance has emerged as a major obstacle to global tuberculosis (TB) control, necessitating the development of novel host-directed strategies. This study aimed to identify compounds that enhance intracellular clearance of Mycobacterium tuberculosis (Mtb) through autophagy induction.</div></div><div><h3>Methods</h3><div>A cell-based screening of a G-protein-coupled receptor-related compound library was performed to identify potential autophagy inducers. Mechanistic studies were conducted in Mtb-infected macrophages to examine the effects on PI3K/AKT/mTOR signaling and ULK1 activation. In vivo efficacy was evaluated in a BALB/c mouse model of TB.</div></div><div><h3>Results</h3><div>Amodiaquine hydrochloride (CAS), a conventional antimalarial drug, was identified as a potent inducer of autophagic killing of intracellular Mtb. CAS reduced phosphorylation of PI3K, AKT, and mTOR in infected macrophages, promoting ULK1 activation and autophagy. In vivo, CAS treatment significantly decreased bacterial loads in the lungs of BALB/c mice.</div></div><div><h3>Conclusions</h3><div>CAS represents a novel host-directed therapeutic agent that enhances intracellular clearance of Mtb by triggering autophagy in macrophages, offering a potential strategy to combat drug-resistant TB.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107720"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-09DOI: 10.1016/j.ijantimicag.2026.107713
Wan-Yu Chu , Om Prakash Singh , Shyam Sundar , Krishna Pandey , Pradeep Das , Dinesh Mondal , Brima Musa Younis , Ahmed Mudawi Musa , Abhishek Kumar Singh , Deepak Kumar Verma , Rahul Chaubey , Poonam Kumari , Jaya Chakravarty , Major Madhukar , Roshan Kamal Topno , Ashish Kumar , Vinod Kumar , Md. Utba Rashid , Shomik Maruf , Prakash Ghosh , Thomas P. C Dorlo
Background
Treatment regimens and clinical outcomes for post-kala-azar dermal leishmaniasis (PKDL) vary across South Asia and Eastern Africa. We evaluated the skin target site pharmacokinetics (PK) of miltefosine, liposomal amphotericin B (LAmB) and paromomycin and associated pharmacodynamics (PD) on skin parasite reduction and lesion healing, to determine PK/PD factors driving regional differences in clinical outcomes.
Methods
In South Asia, participants (n = 126) received LAmB alone or with miltefosine. In Eastern Africa, participants (n = 110) received LAmB or paromomycin with miltefosine. Skin drug concentrations were compared to the in vitro EC50 of Leishmania donovani to assess PK target attainment, then correlated with skin parasite load and lesion score to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships.
Results
Antileishmanial drug distribution varied in skin. Miltefosine showed the highest skin-to-plasma ratio, with medians of 1.19 (IQR: 0.78–1.88) in South Asia vs. 1.58 (1.1–2.08) in Eastern Africa (P < 0.05). Combining paromomycin or LAmB with miltefosine improved PK target attainment and reduced variability. In South Asia, macular or mixed (macular and papular/nodular) lesions predominated (93%) and were associated with ≥6-fold higher baseline parasite load and lesion score versus Eastern Africa, where papular and maculopapular lesions were more common (97%). By treatment end, parasite loads dropped ≥99% in both regions, with ≤7% above the transmission threshold. Lesion scores decreased by 11% in South Asia and 93% in Eastern Africa.
Conclusions
Similar skin PK target attainment and relative parasite reduction were achieved for all regimens. Regional differences in parasite load and lesion score at baseline and lesion healing rates, suggest disease presentation is the primary factor affecting clinical outcomes.
{"title":"Skin pharmacokinetics and pharmacodynamics in patients with post-kala-azar dermal leishmaniasis","authors":"Wan-Yu Chu , Om Prakash Singh , Shyam Sundar , Krishna Pandey , Pradeep Das , Dinesh Mondal , Brima Musa Younis , Ahmed Mudawi Musa , Abhishek Kumar Singh , Deepak Kumar Verma , Rahul Chaubey , Poonam Kumari , Jaya Chakravarty , Major Madhukar , Roshan Kamal Topno , Ashish Kumar , Vinod Kumar , Md. Utba Rashid , Shomik Maruf , Prakash Ghosh , Thomas P. C Dorlo","doi":"10.1016/j.ijantimicag.2026.107713","DOIUrl":"10.1016/j.ijantimicag.2026.107713","url":null,"abstract":"<div><h3>Background</h3><div>Treatment regimens and clinical outcomes for post-kala-azar dermal leishmaniasis (PKDL) vary across South Asia and Eastern Africa. We evaluated the skin target site pharmacokinetics (PK) of miltefosine, liposomal amphotericin B (LAmB) and paromomycin and associated pharmacodynamics (PD) on skin parasite reduction and lesion healing, to determine PK/PD factors driving regional differences in clinical outcomes.</div></div><div><h3>Methods</h3><div>In South Asia, participants (<em>n</em> = 126) received LAmB alone or with miltefosine. In Eastern Africa, participants (<em>n</em> = 110) received LAmB or paromomycin with miltefosine. Skin drug concentrations were compared to the in vitro EC<sub>50</sub> of <em>Leishmania donovani</em> to assess PK target attainment, then correlated with skin parasite load and lesion score to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships.</div></div><div><h3>Results</h3><div>Antileishmanial drug distribution varied in skin. Miltefosine showed the highest skin-to-plasma ratio, with medians of 1.19 (IQR: 0.78–1.88) in South Asia vs. 1.58 (1.1–2.08) in Eastern Africa (<em>P</em> < 0.05). Combining paromomycin or LAmB with miltefosine improved PK target attainment and reduced variability. In South Asia, macular or mixed (macular and papular/nodular) lesions predominated (93%) and were associated with ≥6-fold higher baseline parasite load and lesion score versus Eastern Africa, where papular and maculopapular lesions were more common (97%). By treatment end, parasite loads dropped ≥99% in both regions, with ≤7% above the transmission threshold. Lesion scores decreased by 11% in South Asia and 93% in Eastern Africa.</div></div><div><h3>Conclusions</h3><div>Similar skin PK target attainment and relative parasite reduction were achieved for all regimens. Regional differences in parasite load and lesion score at baseline and lesion healing rates, suggest disease presentation is the primary factor affecting clinical outcomes.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107713"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The global spread of antimicrobial resistance represents a severe threat to public health, with infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) emerging as a major challenge in clinical treatment. The clinical utility of traditional antimicrobial drugs, such as sulfamethoxazole (SMZ), has become increasingly restricted by the continuous emergence of bacterial resistance. Recent advances in nanomedicine have opened up new opportunities for the "old drugs, new uses" strategy. In this study, we successfully synthesized SMZ-modified gold nanoclusters (SMZ_Au NCs) via a green one-pot method, which exhibited broad-spectrum, potent, and safe antibacterial properties. Our results showed that SMZ_Au NCs exerted potent antibacterial efficacy against various clinical MDR-GNB strains, with MIC values 8- to 16-fold lower than those of ceftriaxone. In terms of anti-biofilm activity, SMZ_Au NCs effectively inhibited biofilm formation and disrupted mature biofilm structures. Mechanistic studies indicated that SMZ_Au NCs primarily exert antibacterial effects by disrupting bacterial membrane integrity and promoting an increase in intracellular reactive oxygen species. Furthermore, SMZ_Au NCs exhibited good biocompatibility in normal cells and animal models without evident toxicity. These promising results suggest that the nanocarrier-based enhancement can provide a novel strategy for the clinical repurposing of sulfonamide antibacterial drugs, offering a promising candidate for the nanotherapeutic management of MDR-GNB infections.
{"title":"Nano-Enabling Old Drugs: Sulfamethoxazole-Modified Gold Nanoclusters Potential Application in Multi-Drug Resistant Gram-Negative Bacterial Infections.","authors":"Yiwen Xue, Yujing Wang, Congcong You, Yanlei Zheng, Qianjing Zhang, Haifeng Liu, Jianzhong Ye, Jianming Cao, Tieli Zhou","doi":"10.1016/j.ijantimicag.2026.107757","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2026.107757","url":null,"abstract":"<p><p>The global spread of antimicrobial resistance represents a severe threat to public health, with infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) emerging as a major challenge in clinical treatment. The clinical utility of traditional antimicrobial drugs, such as sulfamethoxazole (SMZ), has become increasingly restricted by the continuous emergence of bacterial resistance. Recent advances in nanomedicine have opened up new opportunities for the \"old drugs, new uses\" strategy. In this study, we successfully synthesized SMZ-modified gold nanoclusters (SMZ_Au NCs) via a green one-pot method, which exhibited broad-spectrum, potent, and safe antibacterial properties. Our results showed that SMZ_Au NCs exerted potent antibacterial efficacy against various clinical MDR-GNB strains, with MIC values 8- to 16-fold lower than those of ceftriaxone. In terms of anti-biofilm activity, SMZ_Au NCs effectively inhibited biofilm formation and disrupted mature biofilm structures. Mechanistic studies indicated that SMZ_Au NCs primarily exert antibacterial effects by disrupting bacterial membrane integrity and promoting an increase in intracellular reactive oxygen species. Furthermore, SMZ_Au NCs exhibited good biocompatibility in normal cells and animal models without evident toxicity. These promising results suggest that the nanocarrier-based enhancement can provide a novel strategy for the clinical repurposing of sulfonamide antibacterial drugs, offering a promising candidate for the nanotherapeutic management of MDR-GNB infections.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107757"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intensive care unit-acquired infections (ICU-AIs) are prevalent among critically ill patients due to multiple invasive procedures. Probiotics have emerged as a potential preventive strategy to lower infection rates in ICU settings. However, studies assessing probiotic effectiveness have reported inconsistent results, suggesting that these discrepancies are due to variations in probiotic strain, intervention duration, and dosage. Despite the growing interest and the existence of several reviews, the optimal probiotic strain, duration, and dosage for ICU patients remain uncertain.
Objectives
This review aims to assess the impact of strain specificity, intervention duration, and dosage on the effectiveness of probiotic supplementation in preventing ICU-AIs.
Methods
This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search was conducted in electronic databases for English-language interventional and observational studies published between January 2014 and August 2024. Eligible studies were those that evaluated the efficacy of probiotics in reducing ICU-AIs. Data were extracted using a standardized form that included details on strain designation, intervention duration, and dosage. Findings were synthesized descriptively using narrative text, tables, and figures.
Results
Eighteen different probiotic strains were identified. Lactobacillus acidophilus LA-5, particularly in multi-strain formulations, was commonly associated with positive outcomes. Probiotic regimens with intervention durations of 14 days or more and dosages of at least 5 × 10⁹ CFU/day demonstrated greater effectiveness in reducing ICU-AIs.
Conclusions
Strain-specificity, intervention duration, and dosage are important factors influencing probiotic effectiveness in ICU-AI prevention. Further studies are needed to confirm the efficacy of promising strains and explore the potential of new ones.
{"title":"Effect of probiotic strain, duration, and dose on preventing ICU-acquired infection: A scoping review","authors":"Aqdar Mufareh Al-Aklabi , Sara Muteb Alotaishan , Yasmin Youssuf Al-Gindan , Rabie Yousif Khattab","doi":"10.1016/j.ijantimicag.2026.107714","DOIUrl":"10.1016/j.ijantimicag.2026.107714","url":null,"abstract":"<div><h3>Background</h3><div>Intensive care unit-acquired infections (ICU-AIs) are prevalent among critically ill patients due to multiple invasive procedures. Probiotics have emerged as a potential preventive strategy to lower infection rates in ICU settings. However, studies assessing probiotic effectiveness have reported inconsistent results, suggesting that these discrepancies are due to variations in probiotic strain, intervention duration, and dosage. Despite the growing interest and the existence of several reviews, the optimal probiotic strain, duration, and dosage for ICU patients remain uncertain.</div></div><div><h3>Objectives</h3><div>This review aims to assess the impact of strain specificity, intervention duration, and dosage on the effectiveness of probiotic supplementation in preventing ICU-AIs.</div></div><div><h3>Methods</h3><div>This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search was conducted in electronic databases for English-language interventional and observational studies published between January 2014 and August 2024. Eligible studies were those that evaluated the efficacy of probiotics in reducing ICU-AIs. Data were extracted using a standardized form that included details on strain designation, intervention duration, and dosage. Findings were synthesized descriptively using narrative text, tables, and figures.</div></div><div><h3>Results</h3><div>Eighteen different probiotic strains were identified. <em>Lactobacillus acidophilus</em> LA-5, particularly in multi-strain formulations, was commonly associated with positive outcomes. Probiotic regimens with intervention durations of 14 days or more and dosages of at least 5 × 10⁹ CFU/day demonstrated greater effectiveness in reducing ICU-AIs.</div></div><div><h3>Conclusions</h3><div>Strain-specificity, intervention duration, and dosage are important factors influencing probiotic effectiveness in ICU-AI prevention. Further studies are needed to confirm the efficacy of promising strains and explore the potential of new ones.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107714"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim of this study was to develop and validate a risk score to predict the occurrence of bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) among colonised intensive care unit (ICU) patients, in order to support early clinical decision-making and antimicrobial stewardship.
Methods
Prospective observational study including adult patients admitted to ICU with CRAB colonisation at any site at the University Hospital of Pisa, Italy (June 2020-June 2023). The primary outcome measure was BSI caused by CRAB. A multivariable regression analysis was performed to identify factors independently associated with CRAB-BSI. Regression coefficients were used to develop a risk score for CRAB-BSI. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC-ROC).
Results
Among 283 colonised patients, 103/283 (36.4%) developed a BSI caused by CRAB. Median (IQR) time from colonisation to BSI was 4 days (1–8 days). On multivariable analysis, burns (OR: 8.219, 95% CI: 3.591–18.812, P < 0.001), number of colonised sites (per-site: OR: 2.197, 95% CI: 1.363–3.541, P = 0.001), respiratory tract colonisation (OR: 4.285, 95% CI: 2.179–8.426, P < 0.001), and cardiovascular disease (OR: 1.940, 95% CI: 1.068–3.524, P = 0.029) were independently associated with increased risk of BSI. The score ranged from 1 to 9 points. The AUC of the model was 0.817 (95% CI: 0.764–0.869, P < 0.001). The negative predictive value (NPV) was 97.8% in patients without septic shock and 72.2% in those who developed septic shock.
Conclusions
The rate of CRAB-BSI among colonised patients is considerable. The proposed score may be useful, after external validation, for a rational empirical use of new antibiotics.
{"title":"Risk factors for bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii in ICU patients with any site colonisation: A prospective observational study","authors":"Giusy Tiseo , Valentina Galfo , Aurelio Lepore , Manuela Pogliaghi , Lorenzo Roberto Suardi , Cesira Giordano , Alessandro Leonildi , Simona Barnini , Marco Falcone","doi":"10.1016/j.ijantimicag.2026.107717","DOIUrl":"10.1016/j.ijantimicag.2026.107717","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of this study was to develop and validate a risk score to predict the occurrence of bloodstream infections (BSI) caused by carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) among colonised intensive care unit (ICU) patients, in order to support early clinical decision-making and antimicrobial stewardship.</div></div><div><h3>Methods</h3><div>Prospective observational study including adult patients admitted to ICU with CRAB colonisation at any site at the University Hospital of Pisa, Italy (June 2020-June 2023). The primary outcome measure was BSI caused by CRAB. A multivariable regression analysis was performed to identify factors independently associated with CRAB-BSI. Regression coefficients were used to develop a risk score for CRAB-BSI. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC-ROC).</div></div><div><h3>Results</h3><div>Among 283 colonised patients, 103/283 (36.4%) developed a BSI caused by CRAB. Median (IQR) time from colonisation to BSI was 4 days (1–8 days). On multivariable analysis, burns (OR: 8.219, 95% CI: 3.591–18.812, <em>P</em> < 0.001), number of colonised sites (per-site: OR: 2.197, 95% CI: 1.363–3.541, <em>P</em> = 0.001), respiratory tract colonisation (OR: 4.285, 95% CI: 2.179–8.426, <em>P</em> < 0.001), and cardiovascular disease (OR: 1.940, 95% CI: 1.068–3.524, <em>P</em> = 0.029) were independently associated with increased risk of BSI. The score ranged from 1 to 9 points. The AUC of the model was 0.817 (95% CI: 0.764–0.869, <em>P</em> < 0.001). The negative predictive value (NPV) was 97.8% in patients without septic shock and 72.2% in those who developed septic shock.</div></div><div><h3>Conclusions</h3><div>The rate of CRAB-BSI among colonised patients is considerable. The proposed score may be useful, after external validation, for a rational empirical use of new antibiotics.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107717"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-16DOI: 10.1016/j.ijantimicag.2026.107718
Gabriele Bianco , Gherard Batisti Biffignandi , Matteo Boattini , Sara Comini , Cristina Costa , Michela Vumbaca , Paolo Gaibani
Objective
This study evaluated the in vitro activity of sulbactam/durlobactam and comparators against carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream isolates from Italy and investigated genomic mechanisms underlying resistance.
Methods
A total of 110 consecutive CRAB isolates (2021–2023) were tested for susceptibility to sulbactam/durlobactam, cefiderocol, colistin, and comparators. Whole-genome sequencing (WGS) was performed on sulbactam/durlobactam-resistant isolates to characterise β-lactamase genes, outbreak dynamics, and mutations in penicillin-binding proteins (PBPs).
Results
Sulbactam/durlobactam inhibited 87.3% of isolates (MIC₅₀ = 2 mg/L; MIC₉₀ > 64 mg/L), while 12.7% were resistant. Cefiderocol and colistin showed 91.8% and 96.4% susceptibility rates, respectively. All resistant isolates carried blaOXA-23, and three also harbored blaNDM-1. WGS revealed close clonal relationships (average nucleotide identity > 99%) among blaNDM-1 positive isolates (ST231) and among OXA-23-only isolates (ST837/ST369), indicating local outbreak dynamics. Comparative PBP analysis identified recurrent substitutions P112S and G137R (PBP1b), N392T and A515V (PBP3), and S329N (PBP5). Structural correlation suggests these mutations reduce β-lactam binding and may contribute to resistance, particularly when combined with NDM-1.
Conclusions
This study provides early evidence of sulbactam/durlobactam resistance in treatment-naïve CRAB from Italy, driven by NDM-1 co-production and PBP alterations. The coexistence of epidemic ST231 and ST837/ST369 clones highlights the need for continuous genomic surveillance and prudent antibiotic stewardship to prevent dissemination of resistant A. baumannii lineages.
{"title":"Resistance to sulbactam/durlobactam in carbapenem-resistant Acinetobacter baumannii in treatment-naive setting: In vitro data and genomic insights from Italian bloodstream isolates","authors":"Gabriele Bianco , Gherard Batisti Biffignandi , Matteo Boattini , Sara Comini , Cristina Costa , Michela Vumbaca , Paolo Gaibani","doi":"10.1016/j.ijantimicag.2026.107718","DOIUrl":"10.1016/j.ijantimicag.2026.107718","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluated the <em>in vitro</em> activity of sulbactam/durlobactam and comparators against carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) bloodstream isolates from Italy and investigated genomic mechanisms underlying resistance.</div></div><div><h3>Methods</h3><div>A total of 110 consecutive CRAB isolates (2021–2023) were tested for susceptibility to sulbactam/durlobactam, cefiderocol, colistin, and comparators. Whole-genome sequencing (WGS) was performed on sulbactam/durlobactam-resistant isolates to characterise β-lactamase genes, outbreak dynamics, and mutations in penicillin-binding proteins (PBPs).</div></div><div><h3>Results</h3><div>Sulbactam/durlobactam inhibited 87.3% of isolates (MIC₅₀ = 2 mg/L; MIC₉₀ > 64 mg/L), while 12.7% were resistant. Cefiderocol and colistin showed 91.8% and 96.4% susceptibility rates, respectively. All resistant isolates carried bla<sub>OXA-23</sub>, and three also harbored <em>bla</em><sub>NDM-1</sub>. WGS revealed close clonal relationships (average nucleotide identity > 99%) among <em>bla</em><sub>NDM-1</sub> positive isolates (ST231) and among OXA-23-only isolates (ST837/ST369), indicating local outbreak dynamics. Comparative PBP analysis identified recurrent substitutions P112S and G137R (PBP1b), N392T and A515V (PBP3), and S329N (PBP5). Structural correlation suggests these mutations reduce β-lactam binding and may contribute to resistance, particularly when combined with NDM-1.</div></div><div><h3>Conclusions</h3><div>This study provides early evidence of sulbactam/durlobactam resistance in treatment-naïve CRAB from Italy, driven by NDM-1 co-production and PBP alterations. The coexistence of epidemic ST231 and ST837/ST369 clones highlights the need for continuous genomic surveillance and prudent antibiotic stewardship to prevent dissemination of resistant <em>A. baumannii</em> lineages.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 3","pages":"Article 107718"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-22DOI: 10.1016/j.ijantimicag.2026.107721
C. Airaud , E. Demay , V. Dias Meireles , David Luque Paz , Pierre Tattevin , P. Lazaro , M. Lahouati , A. Bacle
Background
Daptomycin is increasingly used to treat Gram-positive infections, but carries a risk of muscle toxicity. Despite guideline recommendations, real-world adherence to safety monitoring remains poorly documented.
Objectives
To evaluate daptomycin prescribing practices and identify risk factors for muscle toxicity across three French university hospitals.
Methods
We conducted a retrospective multicenter study of adults (≥18 y) treated with daptomycin between June 2021 and May 2022. Data included demographics, treatment, monitoring, microbiology, and adverse events. Muscle toxicity was defined as an elevation of creatine kinase (CK) (>5 upper normal value) and/or rhabdomyolysis, identified by explicit documentation in medical records. Logistic regression identified associated factors.
Results
We collected data from 1407 patients (65.1% male; mean age 62.4 ± 16.5) treated with daptomycin during the study period, for a mean duration of 7.87 ± 7.05 d. Most patients (93.9%) received high-dose daptomycin, ≥8 mg/kg/d. Combination therapy was frequent (72%), mostly with β-lactams (91.8%). CK monitoring was reported in 34.2% of patients, muscle toxicity was reported in 4.9%, including rhabdomyolysis in 2.7%. Statins were co-prescribed without discontinuation in 15.6% of cases. In multivariate analysis, concomitant use of high-risk comedications, including statins and fibrates (OR [95% CI] = 6.68 [3.28–13.97], P < 0.001) and obesity (OR 2.25 [1.07–4.72], P = 0.03) were independently associated with muscle toxicity.
Conclusion
Despite widespread use of high-dose daptomycin, safety monitoring was inconsistent. Systematic CK testing and careful review of myotoxic co-medications are essential to mitigate adverse events in clinical practice.
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Pub Date : 2026-03-01Epub Date: 2026-02-18DOI: 10.1016/j.ijantimicag.2026.107746
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