{"title":"Access to phage therapy at Hospices Civils de Lyon in 2022: Implementation of the PHAGEinLYON Clinic program.","authors":"Tristan Ferry, Myrtille Le Bouar, Thomas Briot, Tiphaine Roussel-Gaillard, Thomas Perpoint, Sandrine Roux, Florence Ader, Florent Valour, Behrouz Kassai, Inesse Boussaha, Marietou Ndiaye, Fabien Craighero, Clément Javaux, Sébastien Lustig, Cécile Batailler","doi":"10.1016/j.ijantimicag.2024.107372","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107372","url":null,"abstract":"<p><strong>Objectives: </strong>To describe the set-up in 2022 of the PHAGEinLYON Clinic program dedicated to improve access to phage therapy in France using pharmaceutical-grade phages.</p><p><strong>Methods: </strong>We described the process, prospectively collected all phage therapy requests received during 2022 and reviewed them retrospectively to analyze the decision and also the patient care pathway (NCT05883995).</p><p><strong>Results: </strong>Among 143 phage therapy requests, the indication was confirmed by multidisciplinary team meetings for 57 (40%) of them, and 44 were infected with bacteria that could be easily targeted by phages in France. Finally, 33 patients were treated, including 26 at our institution as compassionate use or in a clinical trial. Main indications were complex bone and joint infections, endovascular infections and lung infections. To manage these patients, 172 pharmaceutic phage cocktails targeting S. aureus and/or P. aeruginosa were prepared; 57 were dedicated to local, and 99 to intravenous injections. During the follow-up, 18 (69%) patients had a favorable clinical evolution, 6 (23%) required subsequent phage therapy, with the same phages with a greater phage exposition, or with different phages from elsewhere.</p><p><strong>Conclusions: </strong>The implementation of the PHAGEinLYON Clinic program in 2022 was associated with a groundbreaking access of phage therapy in France.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567496","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}
Wenhao Wu, Shuangling Ni, Yi Zheng, Piaopiao Zhang, Yan Jiang, Xi Li, Yunsong Yu, Tingting Qu
{"title":"Hypervirulent Carbapenem-Susceptible Klebsiella pneumoniae ST412/K57 with Strong Biofilm Formation: association with gas gangrene and sepsis.","authors":"Wenhao Wu, Shuangling Ni, Yi Zheng, Piaopiao Zhang, Yan Jiang, Xi Li, Yunsong Yu, Tingting Qu","doi":"10.1016/j.ijantimicag.2024.107373","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107373","url":null,"abstract":"<p><p>Hypervirulent Klebsiella pneumoniae (hvKp) poses a serious public health threat. Gas gangrene caused by hvKp was rarely reported, potentially resulting in a poor prognosis. In this study, we described the case of a hospitalized patient with gas gangrene and sepsis by hvKP. The carbapenem-susceptible hypervirulent Klebsiella pneumoniae (CS-hvKp) strains KPLSN and KPLSX were isolated from the knee joint pus and blood specimens of the patient for further investigations. Whole genome sequencing revealed that KPLSN and KPLSX were highly homologous (SNPs<10) and belonging to ST412/K57. The minimum inhibitory concentration and minimum bactericidal concentration under biofilm values of meropenem in KPLSN and KPLSX were significantly higher than planktonic state (>128 mg/L versus 0.25 mg/L, P<0.0001). These two strains had high biofilm formation ability, and fluorescence staining experiments results showed that they were not easily killed by meropenem in the biofilm state. KPLSN and KPLSX showed high capsular production and were confirmed with high virulence through experiments with the Galleria mellonella and BALB/c mice abdominal infection model. The persistent symptoms may be due to enhanced biofilm and capsule formation. Global ST412 strains phylogenetic analysis showed their evolution towards higher virulence and resistance. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat special infections caused by these pathogens.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564411","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}
Hao Zhang, Jun Zeng, Tingting Zhu, Tao Lin, Turun Song
{"title":"Isoniazid Prophylaxis Based on Tuberculosis Risk Factors in Living Kidney Transplantation Recipients: A Retrospective Cohort Study.","authors":"Hao Zhang, Jun Zeng, Tingting Zhu, Tao Lin, Turun Song","doi":"10.1016/j.ijantimicag.2024.107375","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107375","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection (LTBI). However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain.</p><p><strong>Methods: </strong>This study included all living-donor kidney transplant recipients (KTRs) between January 2016 and December 2022. The recipients were categorized into three groups: the risk group with isoniazid (R-INH), the risk group without isoniazid (R-NINH), and the non-risk group (NR), based on the presence of TB risk factors and INH usage. The R-INH group received a 6-month INH prophylactic regimen to prevent post-transplant TB infection. The incidence of active TB among the groups was assessed.</p><p><strong>Results: </strong>A total of 1348 patients were divided into R-INH (n=108), R-NINH (n=371), and NR (n=869). Forty-seven patients (3.49%) developed TB with an incidence rate of 16.0 per 1000 person-years. Compared to NR, the TB incidence in R-INH was not statistically different (HR, 0.55, 95% CI, 0.07-4.21, P = 0.564), whereas it was significantly higher in R-NINH (HR, 5.04, 95% CI, 2.64-9.62, P < 0.001). The median time from transplantation to TB was 19 months (IQR: 6-39), and 18 patients (38.3%) were diagnosed within one year of transplantation. Ninety-four patients (87.0%) completed INH prophylaxis, with adverse events including two cases of hepatotoxicity (1.85%) and one case of peripheral neuritis (0.93%).</p><p><strong>Conclusions: </strong>A 6-month INH regimen based on TB risk factors is effective and well tolerated for preventing post-transplant TB in KTRs.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564412","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}
Le Fu, Xu Zheng, Jiawen Luo, Yiyu Zhang, Xue Gao, Li Jin, Wenting Liu, Chaoqun Zhang, Dongyu Gao, Bocheng Xu, Qingru Jiang, Shuli Chou, Liang Luo
{"title":"Machine Learning Accelerates the Discovery of Epitope-based Dual-bioactive Peptides Against Skin Infections.","authors":"Le Fu, Xu Zheng, Jiawen Luo, Yiyu Zhang, Xue Gao, Li Jin, Wenting Liu, Chaoqun Zhang, Dongyu Gao, Bocheng Xu, Qingru Jiang, Shuli Chou, Liang Luo","doi":"10.1016/j.ijantimicag.2024.107371","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107371","url":null,"abstract":"<p><p>Skin injuries and infections are an inevitable part of daily human life, particularly with chronic wounds, becoming an increasing socioeconomic burden. In treating skin infections and promoting wound healing, bioactive peptides may hold significant potential, particularly those possessing antimicrobial and anti-inflammatory properties. However, obtaining these peptides solely through traditional wet laboratory experiments is costly and time-consuming, and peptides identified by current computer-assisted predictive models largely lack validation of their effects via wet laboratory experiments. Consequently, this study aimed to integrate computer-assisted methods and traditional wet laboratory experiments to identify anti-inflammatory and antimicrobial peptides. We developed a computer-assisted mining pipeline to screen potential peptides from the epitopes of the major histocompatibility complex class II (MHC-II). The peptide AIMP1 was identified, with the ability to physically damage Escherichia coli by increasing bacterial cell membrane permeability and with the ability to inhibit inflammation by binding to endotoxin-lipopolysaccharide. Additionally, in an LPS-induced inflammation animal model, AIMP1 slightly increased levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and in a skin wound infection animal model, AIMP1 effectively accelerated healing, reduced levels of these pro-inflammatory cytokines, and showed no acute hepatotoxicity or nephrotoxicity. In conclusion, this study not only developed a computer-assisted mining pipeline for identifying anti-inflammatory and antimicrobial peptides but also successfully pinpointed the peptide AIMP1, demonstrating its therapeutic potential for skin injury treatment.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564414","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}
{"title":"Acetylshikonin reduces the spread of antibiotic resistance via plasmid conjugation.","authors":"Wei Liu, Zhiqiang Wang, Yanhu Huang, Yuan Liu, Ruichao Li, Mianzhi Wang, Haijie Zhang, Chuang Meng, Xia Xiao","doi":"10.1016/j.ijantimicag.2024.107370","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107370","url":null,"abstract":"<p><p>The plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) stands out as the primary driver behind the dissemination of antimicrobial resistance (AMR). Developing effective inhibitors that target conjugative transfer represents an efficient strategy for addressing the issue of AMR. Here, we studied the effect of acetylshikonin (ASK), a botanical derivative, on plasmid conjugation. The conjugative transfer of RP4-7 plasmid inter and intra species was notably reduced by ASK. The conjugation process of IncI2 and IncX4 plasmids harboring the mobile colistin resistance gene (mcr-1), IncX4 and IncX3 plasmids containing the carbapenem resistance gene (bla<sub>NDM-5</sub>), and IncFI and IncFII plasmids possessing the tetracycline resistance gene [tet(X4)] were also reduced by ASK. Importantly, the conjugative transfer frequency of mcr-1 positive IncI2 plasmid in mouse peritoneal conjugation model and gut conjugation model was reduced by ASK. The mechanism investigation showed that ASK disrupt the functionality of the bacterial cell membrane. Furthermore, the proton motive force (PMF) was dissipated. In addition, ASK blocked the electron transmission in bacteria's electron transport chain (ETC) through disturbing the quinone interaction, resulting in an insufficient energy supply for conjugation. Collectively, ASK is a potential conjugative transfer inhibitor, providing novel strategies to prevent the spread of AMR.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557794","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}
Sujin An, Jeein Oh, Hoh-Jeong Shon, Jaehwan Song, Youn Soo Choi, Donghyun Kim
{"title":"Co-adjuvanting Nod2-stimulating bacteria with a TLR7 agonist elicits potent protective immunity against respiratory virus infection.","authors":"Sujin An, Jeein Oh, Hoh-Jeong Shon, Jaehwan Song, Youn Soo Choi, Donghyun Kim","doi":"10.1016/j.ijantimicag.2024.107369","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107369","url":null,"abstract":"<p><p>The microbiota plays a crucial role in inducing immune responses. Our previous studies have shown that symbiotic bacterial sensing by the nucleotide-binding oligomerization-domain-containing protein 2 (Nod2) receptor is involved in the mucosal adjuvanticity of cholera toxin. However, cholera toxin's potential toxicity limits human use. Here, screening other less toxic adjuvants showed that toll-like receptor (TLR) 4 and 7 agonists synergized with the microbiota in inducing adaptive immune responses upon nasal immunization. Particularly, Imiquimod, a TLR7 agonist, exhibited synergistic effects with bacterial component MDP, a Nod2 ligand, in inducing immune responses, such as IL-12p40 and IL-6 productions in bone marrow-derived dendritic cells (BMDCs) and follicular helper T (T<sub>FH</sub>) cell differentiation and high-affinity antibody production in immunized mice. The Imiquimod-MDP combination notably elicited immune protection against influenza and SARS-CoV-2 infections. Furthermore, we isolated some bacteria from the nasal cavity of healthy donors, and their Nod2-stimulating activities were measured using a reporter cell line. Staphylococcus aureus, with notable Nod2-stimulating activity, showed higher synergy with Imiquimod than Staphylococcus epidermidis, while the synergistic effects by Imiquimod-bacteria combination disappeared in Nod2-knockout mice. Moreover, the pretreatment with S. aureus enhanced the protective effect of Imiquimod-mediated vaccination against influenza virus compared to S. epidermidis. These results imply that the Imiquimod-MDP and the Imiquimod-bacteria combinations could be novel and promising complex adjuvants in developing intranasal vaccines.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545313","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}
A Oliva, A Curtolo, A Falletta, F Sacco, F Lancellotti, M Carnevalini, G Ceccarelli, G Roma, M Bufi, G Magni, G M Raponi, M Venditti, C M Mastroianni
{"title":"Efficacy of fosfomycin-containing regimens in treating severe infections caused by KPC-producing Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii in critically ill patients.","authors":"A Oliva, A Curtolo, A Falletta, F Sacco, F Lancellotti, M Carnevalini, G Ceccarelli, G Roma, M Bufi, G Magni, G M Raponi, M Venditti, C M Mastroianni","doi":"10.1016/j.ijantimicag.2024.107365","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107365","url":null,"abstract":"<p><strong>Introduction: </strong>Fosfomycin (FOS) is gaining increasing importance as part of combination therapy for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) and KPC-producing Klebsiella pneumoniae (KPC-Kp) thanks to its in-vitro synergism with several antibiotics, high tissue distribution and good tolerability. We analyzed the effect on 30-day survival of FOS-containing regimens compared to NO-FOS in critically ill patients admitted to intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication of FOS versus NO-FOS group.</p><p><strong>Materials/methods: </strong>Monocentric retrospective observational study including SARS-Cov2-negative critically ill patients with KPC-Kp or CRAB infection treated with combination antibiotic therapy with or without FOS for ≥48h (FOS vs NO-FOS groups). Primary outcome was 30-d mortality, secondary outcomes clinical cure and microbiological eradication.</p><p><strong>Results: </strong>Of the 78 patients analyzed, 26 (33.3%) were men, median (IQR) age and Charlson Comorbidity Index (CCI) were 67 years (53-74) and 4 (2-5), respectively. Septic shock was present in 18 patients (23.1%), 37 (47.4%) were CRAB, 41 (52.6%) KPC-Kp. Compared to NO-FOS, patients receiving FOS had higher clinical cure (89.2%vs65.9%, p=0.017), early (<72h) improvement (78.4%vs52.2%, p=0.018), microbiological eradication (87.5%vs62.2%, p=0.027) and lower 7-, 14- and 30-d mortality (0%vs4.6%, p=0.027, 2.7%vs22%, p=0.016, 13.5%vs34.2%, p=0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. At multivariate analysis, receiving FOS was independently associated with survival (HR 0.29, IC95% 0.09-0.93, p=0.038), confirmed after IPTW (HR 0.501 IC95% 0.25-0.98 p=0.042).</p><p><strong>Conclusions: </strong>FOS-containing regimens exhibit higher clinical cure, higher microbiological eradication and reduced mortality than NO FOS-containing regimens in critically ill patients with CRAB and KPC-Kp infections.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567711","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}
{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2024.107360","DOIUrl":"10.1016/j.ijantimicag.2024.107360","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526905","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}
Alberto Cagigi, Rosaria Tinnirello, Gioacchin Iannolo, Bruno Douradinha
{"title":"Orthoflavivirus zikaense (Zika) vaccines: what are we waiting for?","authors":"Alberto Cagigi, Rosaria Tinnirello, Gioacchin Iannolo, Bruno Douradinha","doi":"10.1016/j.ijantimicag.2024.107367","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107367","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567895","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}