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Yang H, Kuang Y, Wang L, Ma X, Gálvez JAV, Lu J, Dai Y, Liu S, Yao J, Chen X, Cao Y. Pterostilbene attenuates intestinal barrier damage and secondary liver oxidative stress in a murine model of Clostridium difficile infection by regulating the gut microbiota. Food Funct 2025; 16:3325-3343. [PMID: 40190207 DOI: 10.1039/d4fo06413e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Clostridium difficile infection (CDI) is a significant infectious disease with limited treatment options. Pterostilbene, an active compound found in blueberries, is known for its antioxidant and anti-inflammatory properties. This study investigated the effects of pterostilbene on intestinal barrier damage and secondary liver oxidative stress induced by CDI in mice. Pathological changes in the colon and liver, the levels of anti-inflammatory cytokines and antioxidants, and the expression of related genes were evaluated. Additionally, 16S rRNA sequencing and targeted metabolomics analyses of the gut microbiota and bile acids were conducted. Pterostilbene reduced the abundance of harmful bacteria such as Enterococcus, while increasing beneficial bacteria like Lactobacillus, thereby reshaping the gut microbiota and bile acid profile and reducing the accumulation of T-βMCA. This process activated intestinal FXR signaling, which alleviated colonic inflammation and reduced intestinal permeability. The reduction in intestinal permeability prevented the translocation of bacteria and bacterial toxins into the liver via the portal vein, thereby reducing liver inflammation and oxidative stress. Pterostilbene presented a promising strategy for maintaining intestinal health through the regulation of dysbiosis and bile acid disturbances caused by CDI. When integrated into the food system, pterostilbene has the potential to improve intestinal health, mitigate the risk of CDI associated with contaminated agricultural products, and enhance public health and food safety. Additionally, we identified that regulating the intestinal bile acid profile and the FXR receptor could serve as potential therapeutic targets for CDI, thereby facilitating the development of novel treatment options and dietary strategies.
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Affiliation(s)
- Hao Yang
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Yanling Kuang
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Lamei Wang
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
| | - Xinru Ma
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Javier A Villafuerte Gálvez
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
| | - Jing Lu
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Yanfei Dai
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Shimin Liu
- Institute of Agriculture, The University of Western Australia, Perth, Australia
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Xinhua Chen
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
| | - Yangchun Cao
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
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Groenewegen B, van Lingen E, Kovynev A, van den Berg AJ, Berssenbrugge EKL, Sanders IMJG, van Prehn J, van Nood E, Goorhuis A, Kuijper EJ, Smits WK, Wiese M, Keller JJ, Ducarmon QR, Terveer EM. The presence of Clostridioides difficile in faeces before and after faecal microbiota transplantation and its relation with recurrent C. difficile infection and the gut microbiota in a Dutch cohort. Clin Microbiol Infect 2025; 31:568-574. [PMID: 39662821 DOI: 10.1016/j.cmi.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 11/19/2024] [Accepted: 12/04/2024] [Indexed: 12/13/2024]
Abstract
OBJECTIVES The objectives of this study are to investigate the presence of Clostridioides difficile in faeces of patients with recurrent C. difficile infection (rCDI) before and after faecal microbiota transplantation (FMT) and to identify risk factors for faecal C. difficile and C. difficile infection (CDI) recurrence. METHODS n = 83 faecal sample triads (pre-FMT [∼1 day], post-FMT [∼3 weeks], and a corresponding FMT donor sample), and n = 22 long-term (∼1-3 years) follow-up faecal samples were collected from FMT-treated patients. The presence of C. difficile in faeces was assessed by enrichment broth culture and PCR (tcdB gene) and associated with patient characteristics, FMT outcome, duration of pre-FMT vancomycin, FMT donor, post-FMT antibiotic use, and faecal microbiota composition (shotgun metagenomics). RESULTS The FMT cure rate for rCDI was 92.8% (77/83), with six early CDI recurrences (<2 months post-FMT). Toxigenic C. difficile was cultured in 27.7% (23/83) of all patients post-FMT, 23.4% (18/77) of patients cured 2 months post-FMT, and 13.6% (3/22) at long-term follow-up. Early CDI recurrence (n = 6) was associated with positive C. difficile culture post-FMT (21.7% [5/23] vs. 1.7% [1/60], p 0.01), post-FMT antibiotics (30.0% [3/10] vs. 4.6% [3/65], p 0.03), and a short course of pre-FMT vancomycin (median 6.0 days, IQR [5-12] vs. 18 days, IQR [10.8-29], p < 0.05). Additionally, positive C. difficile culture directly pre-FMT was associated with a short course of pre-FMT vancomycin (median 9 days IQR [5-18] vs. 17 days, IQR [10-29.2], p 0.04). Gut microbiota analyses did not reveal signatures associated with C. difficile culture result, despite statistically non-significant trends in relative abundances of the Enterobacteriaceae family, and Dorea, Roseburia, and Clostridiales species. DISCUSSION Although eradication of C. difficile is not required for clinical cure of rCDI by FMT, it is associated with reduced prevalence of early CDI recurrence, as are the full completion of pre-FMT vancomycin (at least 10 days) and avoiding post-FMT antibiotics.
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Affiliation(s)
- Bas Groenewegen
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Emilie van Lingen
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Artemiy Kovynev
- Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Alexander J van den Berg
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands
| | - Eric K L Berssenbrugge
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands
| | - Ingrid M J G Sanders
- Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Joffrey van Prehn
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Els van Nood
- Department of Medical Microbiology and Infectious Diseases and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Abraham Goorhuis
- Department of Internal Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands
| | - Ed J Kuijper
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Wiep Klaas Smits
- Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Maria Wiese
- Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands; Department of Microbiology and Systems Biology, Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
| | - Josbert J Keller
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Haaglanden Medical Center, Den Haag, The Netherlands
| | - Quinten R Ducarmon
- Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands
| | - Elisabeth M Terveer
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases Medical Microbiology and Infection Prevention, Leiden University Medical Center, Leiden, The Netherlands; Center for Microbiome Analyses and Therapeutics, Leiden University Center of Infectious Diseases Research, Leiden University Medical Center, Leiden, The Netherlands.
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Hirai J, Mori N, Hanai Y, Asai N, Hagihara M, Mikamo H. Evaluating Bezlotoxumab-Fidaxomicin Combination Therapy in Clostridioides Infection: A Single-Center Retrospective Study from Aichi Prefecture, Japan. Antibiotics (Basel) 2025; 14:228. [PMID: 40149040 PMCID: PMC11939304 DOI: 10.3390/antibiotics14030228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/13/2025] [Accepted: 02/20/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives:Clostridioides difficile infection (CDI) poses a significant healthcare challenge, with recurrence rates reaching 30%, leading to substantial morbidity and costs. Fidaxomicin (FDX) and bezlotoxumab (BEZ) have shown potential in reducing recurrence; however, real-world data on the efficacy of their combination in high-risk CDI patients remain limited. This study aimed to evaluate the efficacy and safety of FDX + BEZ compared with FDX alone in CDI patients with recurrence risk factors. Methods: CDI patients with ≥two recurrence risk factors treated with FDX alone or FDX + BEZ were analyzed. Sixteen factors were evaluated as risk factors for recurrent CDI based on findings from previous studies. Patients with FDX treatment duration <10 days or other CDI treatment prior to FDX were excluded. Outcomes included recurrence within 2 months, global and clinical cure rates, and adverse events. Univariate and multivariate analyses were performed to evaluate efficacy. Results: Among 82 patients, the FDX + BEZ group (n = 30) demonstrated significantly higher global (86.7% vs. 65.4%; p < 0.05) and clinical cure rates (90.0% vs. 69.2%; p < 0.05) compared with the FDX-alone group (n = 52), despite more severe cases in the combination group. Recurrence rates were non-significantly lower in the FDX + BEZ group (3.3% vs. 11.5%). Combination therapy also accelerated diarrhea resolution without additional adverse events. Multivariate analysis identified FDX + BEZ as significantly associated with improved clinical cure (adjusted odds ratio 4.167; 95% CI: 1.029-16.885). Conclusions: FDX + BEZ therapy offers superior efficacy and safety in CDI patients with recurrence risk factors, presenting a promising strategy for optimizing CDI management.
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Affiliation(s)
- Jun Hirai
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi 480-1195, Japan; (J.H.); (N.M.); (N.A.)
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi 480-1195, Japan
- Division of Infection Control and Prevention, Nippon Medical School Chiba Hokusoh Hospital, Chiba 270-1694, Japan
| | - Nobuaki Mori
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi 480-1195, Japan; (J.H.); (N.M.); (N.A.)
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi 480-1195, Japan
| | - Yuki Hanai
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan;
| | - Nobuhiro Asai
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi 480-1195, Japan; (J.H.); (N.M.); (N.A.)
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi 480-1195, Japan
| | - Mao Hagihara
- Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University Hospital, Aichi 480-1195, Japan;
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi 480-1195, Japan; (J.H.); (N.M.); (N.A.)
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Aichi 480-1195, Japan
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Shirinda H, Smith AM, Prinsloo B, Kock MM, Moodley M, Said M, Ehlers MM. Clostridioides difficile hypervirulent strain ST1 isolated from clinical stool specimens obtained from three Provinces in South Africa. Anaerobe 2025; 91:102926. [PMID: 39615783 DOI: 10.1016/j.anaerobe.2024.102926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/25/2024] [Accepted: 11/27/2024] [Indexed: 12/12/2024]
Abstract
OBJECTIVES Clostridioides difficile infection is a serious healthcare-associated infection linked to antimicrobial use. The severity of the disease can be associated with hypervirulent ribotypes such as RT027. The study aimed to investigate the molecular epidemiology and genomic characteristics of C. difficile isolates from private and public healthcare settings in South Africa. METHODS One hundred clinical stool specimens were cultured on cycloserine-cefoxitin-fructose agar. Conventional multiplex polymerase chain reaction (M-PCR) assays were conducted for isolate identification and detection of toxin genes. Genomic characteristics of the isolates were determined using whole genome sequencing (WGS) and data was analysed using pubMLST, EnteroBase, Pathogenwatch and CARD. RESULTS One hundred clinically presumptive C. difficile positive stool specimens were collected, of which 62 % (62/100) were confirmed as C. difficile by M-PCR assay. Among the 62 identified C. difficile isolates, 97 % (60/62) were toxigenic, with the most dominant toxin profile being A + B + CDT + according to the M-PCR assay. The results showed that 93 % (40/43) of the WGS analysed C. difficile strains clustered into clades 1 to 5. These 40 strains were categorized into 16 sequence types (STs), with ST1 (clade 2) being the most prevalent, representing 45 % (18/40), this strain is an RT027-associated strain previously epidemic hypervirulent strain. One major cluster (n = 18) comprising ST1 strains was identified in Gauteng Province and all the isolates associated with this cluster showed the same resistome (antimicrobial resistance genes and mutations: CDD-1, aac (6')-Ie-aph (2″)-Ia, PnimBG and Thr82Ile). The study also identified one strain as ST11, this strain is well known for its zoonotic potential, and two strains were identified as ST37 known as an epidemic strain. Strains from public healthcare settings exhibited genetic similarity, while those from private settings showed greater genetic diversity. CONCLUSION The study reported, for the first time, hypervirulent strains ST1 in Africa and ST11 in South Africa, with a minimum spanning tree indicating an ongoing ST1 outbreak.
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Affiliation(s)
- Hlambani Shirinda
- Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa
| | - Anthony M Smith
- Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa; Centre for Enteric Diseases, National Institute for Communicable Diseases, Johannesburg, South Africa
| | - Ben Prinsloo
- Lancet laboratories, Arcadia, Pretoria, South Africa
| | - Marleen M Kock
- Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa; National Health Laboratory Service (NHLS), Academic Division, Pretoria, South Africa
| | - Mishalan Moodley
- Sequencing Core Facility, National Institute for Communicable Diseases, Johannesburg, South Africa
| | - Mohamed Said
- Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa; National Health Laboratory Service (NHLS), Academic Division, Pretoria, South Africa
| | - Marthie M Ehlers
- Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa; National Health Laboratory Service (NHLS), Academic Division, Pretoria, South Africa.
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Zhang S, Ma W, Zhang X, Cui W, Liu Y, Tian X, Wang Q, Luo Y. Polysaccharide lyase PL3.3 possibly potentiating Clostridioides difficile clinical symptoms based on complete genome analysis of RT046/ST35 and RT012/ST54. Int Microbiol 2025:10.1007/s10123-025-00634-x. [PMID: 39833587 DOI: 10.1007/s10123-025-00634-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 12/26/2024] [Accepted: 01/10/2025] [Indexed: 01/22/2025]
Abstract
Clostridioides difficile has rapidly become a major cause of nosocomial infectious diarrhea worldwide due to the misuse of antibiotics. Our previous study confirmed that RT046/ST35 strain is associated with more severe clinical symptoms compared to RT012/ST54 strain. We conducted genome comparison of the RT046/ST35 and RT012/ST54 strains using whole-genome sequencing technology. The RT046/ST35 strain had a genome length of 7,869,254 bp with a GC content of 29.49%. The original length of the RT012/ST54 strain was 7,499,568 bp with a GC content of 29.64%. Additionally, we detected plasmid1 in the RT046/ST54 strain. We found that the RT046/ST35 strain had more genomic islands compared to the RT012/ST54 strain, and we identified polysaccharide lyase (PL) in the region around 2.2 M. Furthermore, we discovered that the increased severity of clinical symptoms in the RT046/ST35 strain compared to the RT012/ST54 strain was unrelated to virulence factors and emphasized the potential crucial role of PL in RT046/ST35. There were almost no differences in eggNOG annotation and KEGG annotation between RT046/ST35 and RT012/ST54. RT046/ST35 had more mRNA processes in GO annotation. In conclusion, our study suggests that the core factor contributing to the more serious clinical symptoms of the RT046/ST35 strain compared to the RT012/ST54 strain is possibly PL.
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Affiliation(s)
- Sen Zhang
- Department of Clinical Laboratory, Zibo Central Hospital, 54 Gongqingtuan West Road, Zhangdian District, Zibo, Shandong, 255000, P.R. China
- College of Graduate Education, Shandong Sport University, 10600 Shiji Road, Licheng Zone, Jinan, Shandong, 255300, P.R. China
| | - Wen Ma
- Department of Clinical Laboratory, Zibo Central Hospital, 54 Gongqingtuan West Road, Zhangdian District, Zibo, Shandong, 255000, P.R. China
- College of Graduate Education, Shandong Sport University, 10600 Shiji Road, Licheng Zone, Jinan, Shandong, 255300, P.R. China
| | - Xin Zhang
- Department of Clinical Laboratory, Zibo Central Hospital, 54 Gongqingtuan West Road, Zhangdian District, Zibo, Shandong, 255000, P.R. China
| | - Weitong Cui
- Key Laboratory of Biomedical Engineering & Technology of Shandong High School, Qilu Medical University, Zibo, 255300, China
| | - Youhan Liu
- College of Graduate Education, Shandong Sport University, 10600 Shiji Road, Licheng Zone, Jinan, Shandong, 255300, P.R. China
| | - Xuewen Tian
- College of Graduate Education, Shandong Sport University, 10600 Shiji Road, Licheng Zone, Jinan, Shandong, 255300, P.R. China
| | - Qinglu Wang
- College of Graduate Education, Shandong Sport University, 10600 Shiji Road, Licheng Zone, Jinan, Shandong, 255300, P.R. China.
| | - Ying Luo
- Department of Clinical Laboratory, Zibo Central Hospital, 54 Gongqingtuan West Road, Zhangdian District, Zibo, Shandong, 255000, P.R. China.
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Voziki A, Deda O, Kachrimanidou M. The Efficacy of Fecal Microbiota Transplantation in Mouse Models Infected with Clostridioides difficile from the Perspective of Metabolic Profiling: A Systematic Review. Metabolites 2024; 14:677. [PMID: 39728458 DOI: 10.3390/metabo14120677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/07/2024] [Accepted: 11/26/2024] [Indexed: 12/28/2024] Open
Abstract
Objectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes-due to factors such as immune status, treatment protocols, and donor microbiome differences-underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice.
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Affiliation(s)
- Anna Voziki
- Department of Microbiology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Olga Deda
- Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- Biomic AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center B1.4, 10th km Thessaloniki-Thermi Rd., 57001 Thessaloniki, Greece
| | - Melania Kachrimanidou
- Department of Microbiology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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Chanket W, Pipatthana M, Sangphukieo A, Harnvoravongchai P, Chankhamhaengdecha S, Janvilisri T, Phanchana M. The complete catalog of antimicrobial resistance secondary active transporters in Clostridioides difficile: evolution and drug resistance perspective. Comput Struct Biotechnol J 2024; 23:2358-2374. [PMID: 38873647 PMCID: PMC11170357 DOI: 10.1016/j.csbj.2024.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 05/01/2024] [Accepted: 05/16/2024] [Indexed: 06/15/2024] Open
Abstract
Secondary active transporters shuttle substrates across eukaryotic and prokaryotic membranes, utilizing different electrochemical gradients. They are recognized as one of the antimicrobial efflux pumps among pathogens. While primary active transporters within the genome of C. difficile 630 have been completely cataloged, the systematical study of secondary active transporters remains incomplete. Here, we not only identify secondary active transporters but also disclose their evolution and role in drug resistance in C. difficile 630. Our analysis reveals that C. difficile 630 carries 147 secondary active transporters belonging to 27 (super)families. Notably, 50 (34%) of them potentially contribute to antimicrobial resistance (AMR). AMR-secondary active transporters are structurally classified into five (super)families: the p-aminobenzoyl-glutamate transporter (AbgT), drug/metabolite transporter (DMT) superfamily, major facilitator (MFS) superfamily, multidrug and toxic compound extrusion (MATE) family, and resistance-nodulation-division (RND) family. Surprisingly, complete RND genes found in C. difficile 630 are likely an evolutionary leftover from the common ancestor with the diderm. Through protein structure comparisons, we have potentially identified six novel AMR-secondary active transporters from DMT, MATE, and MFS (super)families. Pangenome analysis revealed that half of the AMR-secondary transporters are accessory genes, which indicates an important role in adaptive AMR function rather than innate physiological homeostasis. Gene expression profile firmly supports their ability to respond to a wide spectrum of antibiotics. Our findings highlight the evolution of AMR-secondary active transporters and their integral role in antibiotic responses. This marks AMR-secondary active transporters as interesting therapeutic targets to synergize with other antibiotic activity.
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Affiliation(s)
- Wannarat Chanket
- Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Methinee Pipatthana
- Department of Microbiology, Faculty of Public Health, Mahidol University, Bangkok, Thailand
| | - Apiwat Sangphukieo
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | | | - Tavan Janvilisri
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Matthew Phanchana
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Wang S, Wang C, Shen L, Zhu M, Wu J. Microbiome modulators in the treatment of infectious diseases: insights from clinical trials. J Transl Med 2024; 22:1038. [PMID: 39558400 PMCID: PMC11575062 DOI: 10.1186/s12967-024-05884-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 11/13/2024] [Indexed: 11/20/2024] Open
Affiliation(s)
- Shidong Wang
- Department of Respiratory Medicine, Shaoxing Second Hospital, Shaoxing, Zhejiang, China
| | - Chenjuan Wang
- Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang, China
| | - Linhua Shen
- Department of Respiratory Medicine, Shaoxing Second Hospital, Shaoxing, Zhejiang, China
| | - Mengjin Zhu
- Department of Respiratory Medicine, Shaoxing Second Hospital, Shaoxing, Zhejiang, China
| | - Jiannong Wu
- Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang, China.
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Meng Y, Sun J, Zhang G. A viable remedy for overcoming resistance to anti-PD-1 immunotherapy: Fecal microbiota transplantation. Crit Rev Oncol Hematol 2024; 200:104403. [PMID: 38838927 DOI: 10.1016/j.critrevonc.2024.104403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/12/2024] [Accepted: 05/24/2024] [Indexed: 06/07/2024] Open
Abstract
Anti-PD-1 immunotherapy is a cancer therapy that focuses explicitly on the PD-1 receptor found on the surface of immune cells. This targeted therapeutic strategy is specifically designed to amplify the immune system's innate capacity to detect and subsequently eliminate cells that have become cancerous. Nevertheless, it should be noted that not all patients exhibit a favourable response to this particular therapeutic modality, necessitating the exploration of novel strategies to augment the effectiveness of immunotherapy. Previous studies have shown that fecal microbiota transplantation (FMT) can enhance the efficacy of anti-PD-1 immunotherapy in advanced melanoma patients. To investigate this intriguing possibility further, we turned to PubMed and conducted a comprehensive search for studies that analyzed the interplay between FMT and anti-PD-1 therapy in the context of tumor treatment. Our search criteria were centred around two key phrases: "fecal microbiota transplantation" and "anti-PD-1 therapy." The studies we uncovered all echo a similar sentiment. They pointed towards the potential of FMT to improve the effectiveness of immunotherapy. FMT may enhance the effectiveness of immunotherapy by altering the gut microbiota and boosting the patient's immunological response. Although promising, additional investigation is needed to improve the efficacy of FMT in the context of cancer therapy and attain a comprehensive understanding of the possible advantages and drawbacks associated with this therapeutic strategy.
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Affiliation(s)
- Yiming Meng
- Department of Central Laboratory, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, No. 44, Xiaoheyan road, Dadong district, Shenyang 110042, China.
| | - Jing Sun
- Department of Biobank, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, No. 44, Xiaoheyan road, Dadong district, Shenyang 110042, China
| | - Guirong Zhang
- Department of Central Laboratory, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, No. 44, Xiaoheyan road, Dadong district, Shenyang 110042, China
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10
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Quan M, Zhang X, Fang Q, Lv X, Wang X, Zong Z. Fighting against Clostridioides difficile infection: Current medications. Int J Antimicrob Agents 2024; 64:107198. [PMID: 38734214 DOI: 10.1016/j.ijantimicag.2024.107198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 04/18/2024] [Accepted: 05/04/2024] [Indexed: 05/13/2024]
Abstract
Clostridioides difficile (formerly Clostridium difficile) has been regarded as an 'urgent threat' and a significant global health problem, as life-threatening diarrhoea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and faecal microbiota transplantation for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g. teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g. Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g. vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g. Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarises current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation.
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Affiliation(s)
- Min Quan
- Center for Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoxia Zhang
- Center for Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Qingqing Fang
- Center for Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoju Lv
- Center for Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaohui Wang
- Center for Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China.
| | - Zhiyong Zong
- Center for Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
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11
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Ke S, Villafuerte Gálvez JA, Sun Z, Cao Y, Pollock NR, Chen X, Kelly CP, Liu YY. Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.04.30.591969. [PMID: 38746249 PMCID: PMC11092666 DOI: 10.1101/2024.04.30.591969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Clostridioides difficile infection (CDI) is one of the leading causes of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, its exact mechanisms of action and long-term safety are not fully understood. Defined consortia of clonal bacterial isolates, known as live biotherapeutic products (LBPs), have been proposed as an alternative therapeutic option. However, the rational design of LBPs remains challenging. Here, we employ a computational pipeline and three independent metagenomic datasets to systematically identify microbial strains that have the potential to inhibit CDI. We first constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) at the strain level. We then identified multiple potential protective nrMAGs that can be candidates for the design of microbial consortia targeting CDI, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these potential protective nrMAGs were found to play an important role in the success of FMT, and the majority of the top protective nrMAGs can be validated by various previously reported findings. Our results demonstrate a computational framework for the rational selection of microbial strains targeting CDI, paving the way for the computational design of microbial consortia against other enteric infections.
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Affiliation(s)
- Shanlin Ke
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
| | - Javier A Villafuerte Gálvez
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
| | - Zheng Sun
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
| | - Yangchun Cao
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China
| | - Nira R Pollock
- Division of Infectious Disease, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
- Department of Laboratory Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Xinhua Chen
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
| | - Ciarán P Kelly
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
| | - Yang-Yu Liu
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
- Center for Artificial Intelligence and Modeling, The Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Champaign, IL, USA
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12
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Tang M, Wang C, Xia Y, Tang J, Wang J, Shen L. Clostridioides difficile infection in inflammatory bowel disease: a clinical review. Expert Rev Anti Infect Ther 2024; 22:297-306. [PMID: 38676422 DOI: 10.1080/14787210.2024.2347955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 04/23/2024] [Indexed: 04/28/2024]
Abstract
INTRODUCTION Strong clinical data demonstrate that inflammatory bowel disease (IBD) is an independent risk factor for Clostridiodes difficile infection (CDI) and suggest a globally increased prevalence and severity of C. difficile coinfection in IBD patients (CDI-IBD). In addition to elderly individuals, children are also at higher risk of CDI-IBD. Rapid diagnosis is essential since the clinical manifestations of active IBD and CDI-IBD are indistinguishable. Antibiotics have been well established in the treatment of CDI-IBD, but they do not prevent recurrence. AREAS COVERED Herein, the authors focus on reviewing recent research advances on the new therapies of CDI-IBD. The novel therapies include gut microbiota restoration therapies (such as prebiotics, probiotics and FMT), immunotherapy (such as vaccines and monoclonal antibodies) and diet strategies (such as groningen anti-inflammatory diet and mediterranean diet). Future extensive prospective and placebo-controlled studies are required to evaluate their efficacy and long-term safety. EXPERT OPINION Available studies show that the prevalence of CDI-IBD is not optimistic. Currently, potential treatment options for CDI-IBD include a number of probiotics and novel antibiotics. This review updates the knowledge on the management of CDI in IBD patients, which is timely and important for GI doctors and scientists.
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Affiliation(s)
- Mengjun Tang
- Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Chunhua Wang
- Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Ying Xia
- Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Jian Tang
- Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Jiao Wang
- Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
- School of Basic Medicine, Hubei University of Arts and Science, Xiangyang, China
| | - Liang Shen
- Central Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
- Department of Clinical Laboratory, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
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13
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Nooij S, Vendrik KEW, Zwittink RD, Ducarmon QR, Keller JJ, Kuijper EJ, Terveer EM. Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection. Genome Med 2024; 16:37. [PMID: 38419010 PMCID: PMC10902993 DOI: 10.1186/s13073-024-01306-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 02/13/2024] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases. METHODS We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics. RESULTS Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years. CONCLUSIONS Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.
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Affiliation(s)
- Sam Nooij
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases (LUCID) Medical Microbiology and Infection Prevention, Leiden University Medical Center, PO Box 9600, Postzone E4-P, Leiden, 2300RC, Netherlands.
- Center for Microbiome Analyses and Therapeutics, LUCID Research, Leiden University Medical Center, Leiden, Netherlands.
| | - Karuna E W Vendrik
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases (LUCID) Medical Microbiology and Infection Prevention, Leiden University Medical Center, PO Box 9600, Postzone E4-P, Leiden, 2300RC, Netherlands
- Center for Microbiome Analyses and Therapeutics, LUCID Research, Leiden University Medical Center, Leiden, Netherlands
- Present address: Centre for Infectious Disease Control, Netherlands Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Romy D Zwittink
- Center for Microbiome Analyses and Therapeutics, LUCID Research, Leiden University Medical Center, Leiden, Netherlands
- Present address: Centre for Infectious Disease Control, Netherlands Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Quinten R Ducarmon
- Center for Microbiome Analyses and Therapeutics, LUCID Research, Leiden University Medical Center, Leiden, Netherlands
| | - Josbert J Keller
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases (LUCID) Medical Microbiology and Infection Prevention, Leiden University Medical Center, PO Box 9600, Postzone E4-P, Leiden, 2300RC, Netherlands
- Department of Gastroenterology, Haaglanden Medical Center, The Hague, Netherlands
| | - Ed J Kuijper
- Center for Microbiome Analyses and Therapeutics, LUCID Research, Leiden University Medical Center, Leiden, Netherlands
| | - Elisabeth M Terveer
- Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases (LUCID) Medical Microbiology and Infection Prevention, Leiden University Medical Center, PO Box 9600, Postzone E4-P, Leiden, 2300RC, Netherlands
- Center for Microbiome Analyses and Therapeutics, LUCID Research, Leiden University Medical Center, Leiden, Netherlands
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14
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Vitiello A, Sabbatucci M, Zovi A, Salzano A, Ponzo A, Boccellino M. Advances in Therapeutic Strategies for the Management of Clostridioides difficile Infection. J Clin Med 2024; 13:1331. [PMID: 38592194 PMCID: PMC10932341 DOI: 10.3390/jcm13051331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 02/19/2024] [Accepted: 02/23/2024] [Indexed: 04/10/2024] Open
Abstract
The infection caused by Clostridioides difficile represents one of the bacterial infections with the greatest increase in incidence among nosocomial infections in recent years. C. difficile is a Gram-positive bacterium able to produce toxins and spores. In some cases, infection results in severe diarrhoea and fulminant colitis, which cause prolonged hospitalisation and can be fatal, with repercussions also in terms of health economics. C. difficile is the most common cause of antibiotic-associated diarrhoea in the healthcare setting. The problem of bacterial forms that are increasingly resistant to common antibiotic treatments is also reflected in C. difficile infection (CDI). One of the causes of CDI is intestinal dysmicrobialism induced by prolonged antibiotic therapy. Moreover, in recent years, the emergence of increasingly virulent strains resistant to antibiotic treatment has made the picture even more complex. Evidence on preventive treatments to avoid recurrence is unclear. Current guidelines indicate the following antibiotics for the treatment of CDI: metronidazole, vancomycin, and fidaxomycin. This short narrative review provides an overview of CDI, antibiotic resistance, and emerging treatments.
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Affiliation(s)
- Antonio Vitiello
- Ministry of Health, Directorate-General for Health Prevention, Viale Giorgio Ribotta 5, 00144 Rome, Italy
| | - Michela Sabbatucci
- Department Infectious Diseases, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy
| | - Andrea Zovi
- Ministry of Health, Directorate General of Hygiene, Food Safety and Nutrition, Viale Giorgio Ribotta 5, 00144 Rome, Italy
| | - Antonio Salzano
- Ministry of Health, Directorate-General for Health Prevention, Viale Giorgio Ribotta 5, 00144 Rome, Italy
| | - Annarita Ponzo
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy
| | - Mariarosaria Boccellino
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 81100 Naples, Italy
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Ágreda Fernández M, Origüen J, Rodriguez-Goncer I, San Juan R, López-Medrano F, Parra P, Ruiz-Merlo T, Redondo N, Orellana MÁ, Aguado JM, Fernández-Ruiz M. Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection. Eur J Clin Microbiol Infect Dis 2024; 43:313-324. [PMID: 38072880 DOI: 10.1007/s10096-023-04729-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 11/28/2023] [Indexed: 01/28/2024]
Abstract
PURPOSE We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI). METHODS We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively). RESULTS We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%). CONCLUSION By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management.
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Affiliation(s)
- Mario Ágreda Fernández
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain.
| | - Julia Origüen
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
| | - Isabel Rodriguez-Goncer
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
| | - Rafael San Juan
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Patricia Parra
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
| | - Natalia Redondo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - María Ángeles Orellana
- Department of Microbiology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital, 12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
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Yakout A, Bi Y, Harris DM. Clostridioides Difficile: A Concise Review of Best Practices and Updates. J Prim Care Community Health 2024; 15:21501319241249645. [PMID: 38726585 PMCID: PMC11085020 DOI: 10.1177/21501319241249645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/05/2024] [Accepted: 04/09/2024] [Indexed: 05/12/2024] Open
Abstract
Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.
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Affiliation(s)
| | - Yan Bi
- Mayo Clinic, Jacksonville, FL, USA
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Pakeeraiah K, Mal S, Mahapatra M, Mekap SK, Sahu PK, Paidesetty SK. Schematic-portfolio of potent anti-microbial scaffolds targeting DNA gyrase: Unlocking ways to overcome resistance. Int J Biol Macromol 2024; 256:128402. [PMID: 38035955 DOI: 10.1016/j.ijbiomac.2023.128402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 11/15/2023] [Accepted: 11/22/2023] [Indexed: 12/02/2023]
Abstract
Drug development process demands validation of specific drug target impeding the Multi Drug Resistance (MDR). DNA gyrase, as a bacterial target has been in trend for developing newer antibacterial candidates due to its absence in higher eukaryotes. The fluoroquinolones are the leading molecules in the drug discovery pipeline for gyrase inhibition due to its diversity. The fluoroquinolones like levofloxacin and moxifloxacin have been listed in class A drugs for treating MDR. Gatifloxacin and ciprofloxacin also proved its efficacy against MDR TB and MDR enteric fever in adults, whereas nemonoxacin can induce anti-MDR activity of other antibiotics already suggested by studies. Though fluoroquinolones already proved its effectiveness against gyrase, other molecules viz., benzothiazinone, phenyl pyrrolamide, substituted oxadiazoles, triazolopyrimidine, arylbenzothiazole, coumarinyl amino alcohols and ciprofloxacin uracil, can inhibit the target more precisely. The structure-activity-relationships of the different scaffolds along with their synthetic strategies have been deciphered in the current review. Also, the naturally occurring compounds along with their extraction procedure have also been highlighted as potent DNA gyrase inhibitors. In addition to fluoroquinolone, the natural compounds novobiocin and simocyclinone could also inhibit the gyrase, impressively which has been designed with the gyrase structure for better understanding. Herein, ongoing clinical development of some novel drugs possessing triazaacenaphthylenes, spiropyrimidinetriones, and oxazolidinone-quinolone hybrids have been highlighted which could further assist the future generation antibiotic development corroborating gyrase as a potential target against MDR pathogens.
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Affiliation(s)
- Kakarla Pakeeraiah
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan Deemed to be University, Bhubaneswar 751003, Odisha, India
| | - Suvadeep Mal
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan Deemed to be University, Bhubaneswar 751003, Odisha, India
| | - Monalisa Mahapatra
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan Deemed to be University, Bhubaneswar 751003, Odisha, India
| | - Suman Kumar Mekap
- School of Pharmacy and Life Sciences, Centurion University of technology and management, Bhubaneswar 752050, Odisha, India
| | - Pratap Kumar Sahu
- Department of Pharmacology, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan Deemed to be University, Bhubaneswar 751003, Odisha, India
| | - Sudhir Kumar Paidesetty
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan Deemed to be University, Bhubaneswar 751003, Odisha, India.
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18
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Kravets AM, Hanneke R, Nelson RL. Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis. Tech Coloproctol 2023; 28:20. [PMID: 38112980 DOI: 10.1007/s10151-023-02878-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 11/04/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C. difficile infection (CDI): cadazolid, fidaxomicin, ridinilazole, and surotomycin. The aim of the present study was to perform a systematic review and meta-analysis of efficacy for each antibiotic. METHODS Only randomized clinical trials of patients being treated for Clostridioides disease infection were included. Studies were sought in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization clinical trials register portal (up to December 9, 2022). Sustained clinical cure was the outcome of treatment comparison, defined as the resolution of diarrhea without recurrence. Vancomycin was the standard treatment comparator. Meta-analysis was performed for each antibiotic. The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-classified as either high, moderate, low, or very low. RESULTS Fourteen eligible studies were included in the meta-analysis with 4837 patients from 773 sites. Cadazolid did not increase sustained clinical cure relative to vancomycin (risk ratio (RR) 1.04, 95% confidence intervals (CI) 0.96-1.13; moderate-certainty evidence). Fidaxomicin demonstrated a significant increase (RR 1.14, 95% CI 1.07-1.21; low-certainty evidence). In one phase 2 study, ridinilazole demonstrated a significant increase in sustained clinical cure (RR 1.71, 95% CI 1.01-2.91; very low-quality evidence). Surotomycin did not show significant improvement (RR 1.05, 95% CI 0.96-1.14; moderate-certainty evidence). CONCLUSIONS Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics.
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Affiliation(s)
- A M Kravets
- Poznan University of Medical Sciences, Poznan, Poland
| | - R Hanneke
- Library of the Health Sciences-Chicago, University of Illinois at Chicago, Chicago, IL, USA
| | - R L Nelson
- Epidemiology/Biometry Division, School of Public Health, University of Illinois, Chicago, IL, USA.
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19
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Maestri AC, Mesa D, Vasconcelos TM, Krul D, Ricieri MC, Motta FA, Dalla-Costa LM, Raboni SM, Nogueira KS. Analysis of Clostridioides difficile Infection in Children with Diarrhea in Two Hospitals in Southern Brazil. Curr Microbiol 2023; 80:390. [PMID: 37884782 DOI: 10.1007/s00284-023-03499-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 09/24/2023] [Indexed: 10/28/2023]
Abstract
Clostridioides difficile infection (CDI) has been increasingly observed in children, but there is a lack of epidemiological and molecular data on CDI in Latin America. This prospective cohort study aimed to investigate the role of CDI in children with diarrhea. It included 105 children with antimicrobial-associated diarrhea (AAD) and analyzed the molecular characteristics of strains isolated from two hospitals in southern Brazil between 2017 and 2020. Fecal samples from the participants were tested for glutamate dehydrogenase (GDH) and A/B toxins using a rapid enzyme immunoassay. GDH-positive samples underwent automated real-time polymerase chain reaction and toxigenic culture. Toxigenic C. difficile isolates were selected for whole genome sequencing. Out of the 105 patients, 14 (13.3%) met the criteria for CDI. Children with a history of previous CDI and the presence of mucus in their stool were more likely to have CDI. Metronidazole was the most used treatment (71.4%), and three patients (23.1%) experienced CDI recurrence (rCDI). Although the number of sequenced isolates was limited, a wide diversity of sequence types (ST) was observed. In addition to toxin genes (tcdA, tcdB, cdtA, and cdtB), the isolates also exhibited virulence factors involved in adhesion (cwp66, groEL, slpA, fbpA/fbp68) and immune evasion (rmlA, rmlB, rmlC, gnd, rfbA-1), along with multiple resistance factors (gyrA mutation, norA, ermB, dfrF, and vanG). These findings highlight the prevalence and recurrence of CDI among hospitalized children. Longitudinal studies are needed to better understand the characteristics of CDI-associated diarrhea and its impact on the healthcare system in this population.
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Affiliation(s)
- Adriane C Maestri
- Laboratório de Bacteriologia, Complexo Hospital de Clínicas da Universidade Federal do Paraná, Rua Padre Camargo, 280 - Alto da Glória, CEP: 80.062-240, Curitiba, Paraná, Brazil
- Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
| | - Dany Mesa
- Faculdades Pequeno Príncipe/ Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil
| | - Thais M Vasconcelos
- Faculdades Pequeno Príncipe/ Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil
| | - Damaris Krul
- Faculdades Pequeno Príncipe/ Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil
| | | | | | - Libera M Dalla-Costa
- Faculdades Pequeno Príncipe/ Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil
| | - Sonia M Raboni
- Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
- Departamento de Infectologia, Complexo Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Paraná, Brazil
| | - Keite S Nogueira
- Laboratório de Bacteriologia, Complexo Hospital de Clínicas da Universidade Federal do Paraná, Rua Padre Camargo, 280 - Alto da Glória, CEP: 80.062-240, Curitiba, Paraná, Brazil.
- Programa de Pós-Graduação em Microbiologia, Parasitologia e Patologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
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20
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Bartlett A, Montgomery A, Hammer K, Singhal S, Lo TS. Does clinician-initiated Clostridioides difficile testing improve outcomes of patients with Clostridioides Difficile infection? Am J Infect Control 2023; 51:1085-1088. [PMID: 37758340 DOI: 10.1016/j.ajic.2023.02.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 02/24/2023] [Accepted: 02/26/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Clostridioides difficile (C. difficile) is a common hospital-acquired infection which can lead to major implications for patients and our health care system. In this study, we examine a policy change at a single-site Veterans Affairs Healthcare system that allowed bedside nurses to order C. difficile testing in addition to physicians on the time to obtain test results and initiate treatment. METHODS The time to receive results and initiate treatment were analyzed before and after the policy change, and between physicians and nurses using descriptive statistics and paired student t-tests. Variables associated with lower ordering times were also analyzed using logistic regression while adjusting for patient admission location and length of inpatient hospital stay. RESULTS The difference in time to obtain the result both before and after the policy change and between ordering provider type were both statistically significant (P < .05). In unadjusted models, nurses were associated with faster test results compared to physicians (OR (95% CI) 1.72 (1.45-2.05). CONCLUSIONS Allowing bedside nurses more autonomy to order the stool sample significantly decreased the amount of time to receive the results, potentially decreasing the risk of additional infections among patients and decreasing the economic burden on the hospital.
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Affiliation(s)
- Ashley Bartlett
- Fargo VA Healthcare System, Fargo, ND; University of North Dakota, Department of Medicine, Grand Forks, ND
| | | | - Kimberly Hammer
- Fargo VA Healthcare System, Fargo, ND; University of North Dakota, Department of Medicine, Grand Forks, ND
| | - Siddharth Singhal
- Fargo VA Healthcare System, Fargo, ND; University of North Dakota, Department of Medicine, Grand Forks, ND
| | - Tze Shien Lo
- Fargo VA Healthcare System, Fargo, ND; University of North Dakota, Department of Medicine, Grand Forks, ND
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21
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Mai HTT, Espinoza JL. The Impact of COVID-19 Pandemic on ESBL-Producing Enterobacterales Infections: A Scoping Review. Antibiotics (Basel) 2023; 12:1064. [PMID: 37370383 PMCID: PMC10294973 DOI: 10.3390/antibiotics12061064] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 06/07/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
Several studies have reported an increased frequency of colonization and/or infection with antibiotic-resistant bacteria (ARB) during the COVID-19 pandemic. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) are a group of bacteria with intrinsic resistance to multiple antibiotics, including penicillins, cephalosporins, and monobactams. These pathogens are easy to spread and can cause difficult-to-treat infections. Here, we summarize the available evidence on the impact of the COVID-19 pandemic on infections caused by ESBL-PE. Using specific criteria and keywords, we searched PubMed, MEDLINE, and EMBASE for articles published up to 30 March 2023 on potential changes in the epidemiology of ESBL-E since the beginning of the COVID-19 pandemic. We identified eight studies that documented the impact of COVID-19 on ESBL-E. Five studies were focused on assessing the frequency of ESBL-PE in patient-derived specimens, and three studies investigated the epidemiological aspects of ESBL-PE infections in the context of the COVID-19 pandemic. Some of the studies that were focused on patient specimens reported a decrease in ESBL-PE positivity during the pandemic, whereas the three studies that involved patient data (1829 patients in total) reported a higher incidence of ESBL-PE infections in patients hospitalized for COVID-19 compared with those with other conditions. There are limited data on the real impact of the COVID-19 pandemic on the epidemiology of ESBL-PE infections; however, patient-derived data suggest that the pandemic has exacerbated the spread of these pathogens.
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Affiliation(s)
- Ha Thi Thao Mai
- Department of Biochemistry, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho City 900000, Vietnam
| | - J. Luis Espinoza
- Faculty of Health Sciences, Kanazawa University, Kanazawa 920-0942, Ishikawa, Japan
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22
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Yuan S, Shen DD, Bai YR, Zhang M, Zhou T, Sun C, Zhou L, Wang SQ, Liu HM. Oxazolidinone: A promising scaffold for the development of antibacterial drugs. Eur J Med Chem 2023; 250:115239. [PMID: 36893700 DOI: 10.1016/j.ejmech.2023.115239] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/16/2023] [Accepted: 02/23/2023] [Indexed: 03/06/2023]
Abstract
Due to the long-term and widespread use of antibiotics in clinic, the problem of bacterial resistance is increasingly serious, and the development of new drugs to treat drug-resistant bacteria has gradually become the mainstream direction of antibiotic research. The oxazolidinone-containing drugs linezolid, tedizolid phosphate and contezolid have been approved to the market, which are effective against a variety of Gram-positive bacterium infections. Moreover, there are also many antibiotics containing oxazolidinone fragment under clinical investigation that show good pharmacokinetic and pharmacodynamic properties with unique mechanism of action against resistant bacteria. In this review, we summarized the oxazolidinone-based antibiotics already on the market or in clinical trials and the representative bioactive molecules, and mainly focused on their structural optimizations, development strategies and structure-activity relationships in hope of insight into the reasonable design for medical chemists to develop new oxazolidinone antibiotics with highly potency and fewer side effects.
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Affiliation(s)
- Shuo Yuan
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China; School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, 450001, China.
| | - Dan-Dan Shen
- Department of Obstetrics and Gynecology, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment Zhengzhou China, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Yi-Ru Bai
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China; School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, 450001, China
| | - Miao Zhang
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China; School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, 450001, China
| | - Tian Zhou
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China; School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, 450001, China
| | - Chong Sun
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China; School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, 450001, China
| | - Li Zhou
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
| | - Sai-Qi Wang
- The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer, Zhengzhou Key Laboratory of Precision Therapy of Gastrointestinal Cancer, Zhengzhou, 450008, China.
| | - Hong-Min Liu
- School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, 450001, China.
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23
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Palenzuela Afonso B, Caparrós Nieto AB, González Cruz M, Martínez Faci C. Recurrent Clostridium difficile infection treated with bezlotoxumab. An Pediatr (Barc) 2023; 98:141-142. [PMID: 36697333 DOI: 10.1016/j.anpede.2022.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/29/2022] [Indexed: 01/25/2023] Open
Affiliation(s)
- Beatriz Palenzuela Afonso
- Oncohematología Pediátrica, Servicio de Pediatría, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
| | - Ana B Caparrós Nieto
- Oncohematología Pediátrica, Servicio de Pediatría, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
| | - Macarena González Cruz
- Oncohematología Pediátrica, Servicio de Pediatría, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
| | - Cristina Martínez Faci
- Oncohematología Pediátrica, Servicio de Pediatría, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
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24
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Lemiech-Mirowska E, Michałkiewicz M, Sierocka A, Gaszyńska E, Marczak M. The Hospital Environment as a Potential Source for Clostridioides difficile Transmission Based on Spore Detection Surveys Conducted at Paediatric Oncology and Gastroenterology Units. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1590. [PMID: 36674344 PMCID: PMC9866502 DOI: 10.3390/ijerph20021590] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/08/2023] [Accepted: 01/11/2023] [Indexed: 06/17/2023]
Abstract
Clostridioides difficile is an anaerobic, Gram-positive bacterium widely present in the hospital environment due to its ability to generate spores. The transfer of spores to patients through the hands of medical personnel is one of the most frequent paths of C. difficile transmission. In paediatric patients burdened with a serious primary illness requiring long-term hospitalisation and antibiotic therapy, C. difficile may be a significant risk factor for antibiotic-associated diarrhoea. The goal of the study was to assess the state of hospital environments as a potential source of C. difficile spores and to establish the share of hyperepidemic strains at the two paediatric units. The survey for C. difficile was conducted with a C. diff Banana BrothTM medium, used to detect spores and to recover vegetative forms of the bacteria. Environmental samples (n = 86) and swabs from the clothing of medical personnel (n = 14) were collected at two units of a paediatric hospital, where the cases of antibiotic-associated diarrhoea with a C. difficile aetiology constitute a significant clinical problem. In 17 samples, a change in the broth's colour was observed, indicating the presence of spores. Out of seven samples, C. difficile strains were cultured. The pathogenic isolates of C. difficile were obtained from swabs collected from elements of beds, a toilet, a door handle and a doctor's uniform. In our study, we indicated points of increased risk of pathogen transmission, which could constitute a source of infection. The clothing of medical personnel may be a dangerous carrier of pathogenic spores. Periodical surveys of hospital environments with the use of specialist microbiological mediums successfully indicate the direction of corrective actions to be undertaken by the medical facility in order to increase patient safety.
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Affiliation(s)
- Ewelina Lemiech-Mirowska
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Michał Michałkiewicz
- Institute of Environmental Engineering and Building Installations, Faculty of Environmental Engineering and Energy, Poznan University of Technology, 60-965 Poznan, Poland
| | - Aleksandra Sierocka
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Ewelina Gaszyńska
- Department of Nutrition and Epidemiology, Medical University of Lodz, 90-419 Lodz, Poland
| | - Michał Marczak
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
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25
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Bloom PP, Young VB. Microbiome therapeutics for the treatment of recurrent Clostridioides difficile infection. Expert Opin Biol Ther 2023; 23:89-101. [PMID: 36536532 DOI: 10.1080/14712598.2022.2154600] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The gut microbiome is implicated in Clostridioides difficile infection (CDI) and recurrent CDI (rCDI). AREAS COVERED This review covers the mechanisms by which microbiome therapeutics treat rCDI, their efficacy and safety, and clinical trial design considerations for future research. EXPERT OPINION Altering the chemical environment of the gut and reconstituting colonization resistance is a promising strategy for preventing and treating rCDI. Fecal microbiota transplant (FMT) is safe and effective for the treatment of rCDI. However, limitations of FMT have prompted investigation into alternative microbiome therapeutics. These alternative microbiome therapies require further evaluation, and adaptive trial designs should be strongly considered to more rapidly discern variables including the need for bowel preparation, timing and selection of pre-treatment antibiotics, and dose and duration of microbiome therapeutics. A broad range of adverse events must be prospectively evaluated in these controlled trials, as microbiome therapeutics have the potential for numerous effects. Future studies will lead to a greater understanding of the mechanisms by which microbiome therapies can break the cycle of rCDI, which should ultimately yield a personalized approach to rCDI treatment that restores an individual's specific deficit(s) in colonization resistance to C. difficile.
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Affiliation(s)
- Patricia P Bloom
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, USA
| | - Vincent B Young
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, USA.,Department of Microbiology and Immunology, University of Michigan, USA
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26
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Monma T, Iwamoto J, Ueda H, Tamamushi M, Kakizaki F, Konishi N, Yara S, Miyazaki T, Hirayama T, Ikegami T, Honda A. Evaluation of gut dysbiosis using serum and fecal bile acid profiles. World J Clin Cases 2022; 10:12484-12493. [PMID: 36579096 PMCID: PMC9791502 DOI: 10.12998/wjcc.v10.i34.12484] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/25/2022] [Accepted: 11/04/2022] [Indexed: 12/02/2022] Open
Abstract
Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites, and toxic substances can disrupt the barrier function of the intestinal wall, leading to the development of various diseases. Decreased levels of Clostridium subcluster XIVa (XIVa) are associated with the intestinal dysbiosis found in inflammatory bowel disease (IBD) and Clostridium difficile infection (CDI). Since XIVa is a bacterial group responsible for the conversion of primary bile acids (BAs) to secondary BAs, the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid (DCA)/[DCA + cholic acid (CA)] in feces orserum. For example, serum DCA/(DCA+CA) was significantly lower in IBD patients than in healthy controls, even in the remission period. These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation. Another report showed that a reduced serum DCA/(DCA + CA) ratio could predict susceptibility to CDI. Thus, the BA profile, particularly the ratio of secondary to primary BAs, can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.
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Affiliation(s)
- Tadakuni Monma
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Junichi Iwamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Hajime Ueda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Makoto Tamamushi
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Fumio Kakizaki
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Naoki Konishi
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Shoichiro Yara
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Teruo Miyazaki
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Takeshi Hirayama
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Tadashi Ikegami
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Akira Honda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
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27
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Kiersnowska ZM, Lemiech-Mirowska E, Michałkiewicz M, Sierocka A, Marczak M. Detection and Analysis of Clostridioides difficile Spores in a Hospital Environment. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:15670. [PMID: 36497742 PMCID: PMC9740219 DOI: 10.3390/ijerph192315670] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/19/2022] [Accepted: 11/22/2022] [Indexed: 06/17/2023]
Abstract
Clostridioides difficile, due to its long survival time in a hospital environment, is considered to be one of the most frequent factors in healthcare-associated infections. Patient care requires not only rapid and accurate diagnosis, but also knowledge of individual risk factors for infections, e.g., with C. difficile, in various clinical conditions. The goal of this study was to analyse the degree of contamination of a hospital environment with C. difficile spores. Culturing was performed using C diff Banana BrothTM medium, which enables germination of the spores of these bacteria. Samples were collected from inanimate objects within a hospital environment in a specialist hospital in Poland. The results of the study demonstrated the presence of 18 positive samples of Clostridioides spp. (15.4%). Of these, C. difficile spores were detected in six samples, Clostridioides perfringens in eight samples, Clostridioides sporogenes in two samples and Clostridioides innocuum and Clostridioides baratii in one sample each. Among the six samples of C. difficile, a total of four strains which produce the B toxin were cultured. The binary toxin related to ribotype 027 was not detected in our study. Nosocomial infection risk management is a significant problem, mainly concerning the issues of hygiene maintenance, cleaning policy and quality control, and awareness of infection risk.
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Affiliation(s)
- Zofia Maria Kiersnowska
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Ewelina Lemiech-Mirowska
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Michał Michałkiewicz
- Institute of Environmental Engineering and Building Installations, Faculty of Environmental Engineering and Energy, Poznan University of Technology, 60-965 Poznan, Poland
| | - Aleksandra Sierocka
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Michał Marczak
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
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28
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Palenzuela Afonso B, Caparrós Nieto AB, González Cruz M, Martínez Faci C. Infección recurrente por Clostridium difficile tratada con bezlotoxumab. An Pediatr (Barc) 2022. [DOI: 10.1016/j.anpedi.2022.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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29
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Azimirad M, Noori M, Azimirad F, Gholami F, Naseri K, Yadegar A, Asadzadeh Aghdaei H, Zali MR. Curcumin and capsaicin regulate apoptosis and alleviate intestinal inflammation induced by Clostridioides difficile in vitro. Ann Clin Microbiol Antimicrob 2022; 21:41. [PMID: 36155114 PMCID: PMC9511736 DOI: 10.1186/s12941-022-00533-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 09/01/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND The dramatic upsurge of Clostridioides difficile infection (CDI) by hypervirulent isolates along with the paucity of effective conventional treatment call for the development of new alternative medicines against CDI. The inhibitory effects of curcumin (CCM) and capsaicin (CAP) were investigated on the activity of toxigenic cell-free supernatants (Tox-S) of C. difficile RT 001, RT 126 and RT 084, and culture-filtrate of C. difficile ATCC 700057. METHODS Cell viability of HT-29 cells exposed to varying concentrations of CCM, CAP, C. difficile Tox-S and culture-filtrate was assessed by MTT assay. Anti-inflammatory and anti-apoptotic effects of CCM and CAP were examined by treatment of HT-29 cells with C. difficile Tox-S and culture-filtrate. Expression of BCL-2, SMAD3, NF-κB, TGF-β and TNF-α genes in stimulated HT-29 cells was measured using RT-qPCR. RESULTS C. difficile Tox-S significantly (P < 0.05) reduced the cell viability of HT-29 cells in comparison with untreated cells. Both CAP and CCM significantly (P < 0.05) downregulated the gene expression level of BCL-2, SMAD3, NF-κB and TNF-α in Tox-S treated HT-29 cells. Moreover, the gene expression of TGF-β decreased in Tox-S stimulated HT-29 cells by both CAP and CCM, although these reductions were not significantly different (P > 0.05). CONCLUSION The results of the present study highlighted that CCM and CAP can modulate the inflammatory response and apoptotic effects induced by Tox-S from different clinical C. difficile strains in vitro. Further studies are required to accurately explore the anti-toxin activity of natural components, and their probable adverse risks in clinical practice.
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Affiliation(s)
- Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Noori
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Gholami
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Naseri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Hyte ML, Arphai LJ, Vaughn CJ, Durham SH. The Role of Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infections: A Review of the Current Literature and Paradigm Shift after 2021. Antibiotics (Basel) 2022; 11:antibiotics11091211. [PMID: 36139989 PMCID: PMC9495019 DOI: 10.3390/antibiotics11091211] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/31/2022] [Accepted: 09/05/2022] [Indexed: 11/29/2022] Open
Abstract
Clostridioides difficile infections (CDIs), and particularly recurrent infections, cause a significant burden on the health-care system. Bezlotoxumab is a new agent for the prevention of recurrent CDIs that has shown strong efficacy and high tolerability in clinical trials. The purpose of this review is to evaluate the published literature for bezlotoxumab, with a focus on literature published since the release of the 2021 focused update to the CDI treatment guidelines. A Medline/PubMed search for “bezlotoxumab” was conducted, resulting in 152 articles. Seventeen studies are included in this review, after excluding non-English-language papers, phase I and II trials, and review articles. Studies published since the 2021 focused update support the recommendations in those guidelines. Furthermore, real-world studies have shown similar results to larger clinical trials. Those with more risk factors for recurrent CDI appear to benefit most from bezlotoxumab. Currently, there are no data to support the use of bezlotoxumab outside current guideline recommendations, but future trials may build on the data seen in real-world studies to further elucidate the place in therapy for bezlotoxumab.
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Affiliation(s)
- Melanie L. Hyte
- Edward Via College of Osteopathic Medicine, Auburn Campus, Auburn, AL 36832, USA
| | - Lee J. Arphai
- VA Northeast Ohio Healthcare System, Cleveland, OH 44106, USA
| | - Charles J. Vaughn
- Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA
| | - Spencer H. Durham
- Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA
- Correspondence:
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Collins DA, Riley TV. Ridinilazole: a novel, narrow-spectrum antimicrobial agent targeting Clostridium (Clostridioides) difficile. Lett Appl Microbiol 2022; 75:526-536. [PMID: 35119124 PMCID: PMC9541751 DOI: 10.1111/lam.13664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 01/12/2022] [Accepted: 01/31/2022] [Indexed: 11/26/2022]
Abstract
Clostridium (Clostridioides) difficile infection (CDI) remains an urgent threat to patients in health systems worldwide. Recurrent CDI occurs in up to 30% of cases due to sustained dysbiosis of the gut microbiota which normally protects against CDI. Associated costs of initial and recurrent episodes of CDI impose heavy financial burdens on health systems. Vancomycin and metronidazole have been the mainstay of therapy for CDI for many years; however, these agents continue to cause significant disruption to the gut microbiota and thus carry a high risk of recurrence for CDI patients. Treatment regimens are now turning towards novel narrow spectrum antimicrobial agents which target C. difficile while conserving the commensal gut microbiota, thus significantly reducing risk of recurrence. One such agent, fidaxomicin, has been in therapeutic use for several years and is now recommended as a first-line treatment for CDI, as it is superior to vancomycin in reducing risk of recurrence. Another narrow spectrum agent, ridnilazole, was recently developed and is undergoing evaluation of its potential clinical utility. This review aimed to summarize experimental reports of ridinilazole and assess its potential as a first-line agent for treatment of CDI. Reported results from in vitro assessments, and from hamster models of CDI, show potent activity against C. difficile, non-inferiority to vancomycin for clinical cure and non-susceptibility among most gut commensal bacteria. Phase I and II clinical trials have been completed with ridinilazole showing high tolerability and efficacy in treatment of CDI, and superiority over vancomycin in reducing recurrence of CDI within 30 days of treatment completion. Phase III trials are currently underway, the results of which may prove its potential to reduce recurrent CDI and lessen the heavy health and financial burden C. difficile imposes on patients and healthcare systems.
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Affiliation(s)
- Deirdre A Collins
- School of Medical and Health SciencesEdith Cowan UniversityJoondalupWesternAustralia
| | - Thomas V. Riley
- School of Medical and Health SciencesEdith Cowan UniversityJoondalupWesternAustralia
- Department of MicrobiologyPathWest Laboratory MedicineNedlandsWesternAustralia
- Medical, Molecular and Forensic SciencesMurdoch UniversityMurdochWestern AustraliaAustralia
- School of Biomedical SciencesThe University of Western AustraliaQueen Elizabeth II Medical CentreNedlandsWAAustralia
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Thandavaram A, Channar A, Purohit A, Shrestha B, Patel D, Shah H, Hanna K, Kaur H, Alazzeh MS, Mohammed L. The Efficacy of Bezlotoxumab in the Prevention of Recurrent Clostridium difficile: A Systematic Review. Cureus 2022; 14:e27979. [PMID: 36120235 PMCID: PMC9468512 DOI: 10.7759/cureus.27979] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 08/13/2022] [Indexed: 11/26/2022] Open
Abstract
Clostridium difficile infection (CDI) is the most common nosocomial infection in hospitals. Despite the fact that CDI has treatment options, recurrence is common after the treatment, recurrence will occur in approximately 20%-35% of people initially affected, with 40%-60% of these having a second recurrence. Patients are more likely to have several recurrences after the second, which can lead to antibiotic overuse, and as a result, CDI-related health care expenses, hospitalizations, and mortality are on the rise. The first treatment to receive Food and Drug Administration (FDA) approval for the prevention of C. difficile recurrence is bezlotoxumab, a novel human monoclonal antibody against C. difficile toxin B. In the present systematic review, we assessed various studies from PubMed, PubMed Central (PMC), Google Scholar, and Science direct that evaluated the efficacy of bezlotoxumab in the prevention of recurrent C. difficile (rCDI), and we also briefly discussed the pathophysiology of C. difficile and the risk factors for recurrence of C. difficile. The major MODIFY trial has proven the efficacy, pooled analysis of MODIFY 1 AND 2 trials demonstrated the following results as compared to placebo (bezlotoxumab: 129/781 [16.5] placebo:206/773 [26.6] -10.0% [95% CI -14.0 to -6.0], p<0.0001) with number needed to treat (NNT) of 10. All other observational studies also showed a positive response with bezlotoxumab in the prevention of C. difficile. In conclusion, bezlotoxumab is a great option adjunctive with standard of care CDI antibiotics for the prevention of rCDI in high-risk adults.
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Affiliation(s)
- Abhay Thandavaram
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aneeta Channar
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ansh Purohit
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Bijay Shrestha
- Family Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Deepkumar Patel
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Hriday Shah
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Kerollos Hanna
- General Physician, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Harkirat Kaur
- Family Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mohammad S Alazzeh
- Orthopedic Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lubna Mohammed
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review. J Infect 2022; 84:749-759. [PMID: 35461908 DOI: 10.1016/j.jinf.2022.04.028] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 04/10/2022] [Accepted: 04/15/2022] [Indexed: 02/06/2023]
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Ahmed UKB, Ballard JD. Autoinducing peptide-based quorum signaling systems in Clostridioides difficile. Curr Opin Microbiol 2022; 65:81-86. [PMID: 34773906 PMCID: PMC8792308 DOI: 10.1016/j.mib.2021.10.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/20/2021] [Accepted: 10/25/2021] [Indexed: 02/03/2023]
Abstract
The autoinducing peptide-based Agr system in Clostridioides difficile is involved in virulence factor expression, motility, and sporulation. This review highlights several of the recent discoveries regarding C. difficile Agr. Typical Agr systems rely on the combined activities of four proteins involved in peptide expression, peptide processing, peptide sensing, and transcriptional regulation. As emphasized in this review, at least two C. difficile Agr systems (Agr1 and Agr3) lack the set of proteins associated with this regulatory network. In line with this, recent finding indicate Agr1 can function in ways that may not depend on accumulation of extracellular peptide. Also, described are the similarities and differences in Agr systems within the pathogenic Clostridia.
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Gu Y, Zhou G, Zhou F, Li Y, Wu Q, He H, Zhang Y, Ma C, Ding J, Hua K. Gut and Vaginal Microbiomes in PCOS: Implications for Women's Health. Front Endocrinol (Lausanne) 2022; 13:808508. [PMID: 35282446 PMCID: PMC8905243 DOI: 10.3389/fendo.2022.808508] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 02/01/2022] [Indexed: 12/12/2022] Open
Abstract
PCOS is defined as a kind of endocrine and metabolic disorder which affects females at reproductive ages, is becoming much more common, nowadays. Microbiomes are known as microorganisms that inhabit the body to play a vital role in human health. In recent years, several basic and clinical studies have tried to investigate the correlation between the reproductive health/disorder and microbiomes (gut microbiomes and vaginal microbiomes). However, the mechanism is still unclear. In this review, we reviewed the relationship between PCOS and microbiomes, including gut/vaginal microbiomes compositions in PCOS, mechanism of microbiomes and PCOS, and then collectively focused on the recent findings on the influence of microbiomes on the novel insight regarding the therapeutic strategies for PCOS in the future clinical practice.
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Affiliation(s)
- Yuanyuan Gu
- Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, China
- Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Guannan Zhou
- Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Department of Gynecology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
| | - Fangyue Zhou
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yao Li
- Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
| | - Qiongwei Wu
- Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, China
| | - Hongyu He
- Department of Intensive Care Unit, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Zhang
- Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, China
| | - Chengbin Ma
- Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, China
- *Correspondence: Chengbin Ma, ; Jingxin Ding, ; Keqin Hua,
| | - Jingxin Ding
- Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Department of Gynecology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
- *Correspondence: Chengbin Ma, ; Jingxin Ding, ; Keqin Hua,
| | - Keqin Hua
- Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Department of Gynecology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
- *Correspondence: Chengbin Ma, ; Jingxin Ding, ; Keqin Hua,
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Li H, Fu ZY, Arslan ME, Cho D, Lee H. Differential diagnosis and management of immune checkpoint inhibitor-induced colitis: A comprehensive review. World J Exp Med 2021; 11:79-92. [PMID: 36246150 PMCID: PMC9553980 DOI: 10.5493/wjem.v11.i6.79] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 08/08/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs) are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4, programmed cell death 1 and programmed death-ligand 1. Checkpoint blockade by ICIs reactivates a tumor-specific T cell response. Immune-related adverse events can occur in various organs including skin, liver, and gastrointestinal tract. Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death. Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome. Unfortunately, its clinical, endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies, such as infection, medication, graft-versus-host disease and inflammatory bowel disease. Thus, a definitive diagnosis can only be rendered after these other possible etiologies are excluded. Sometimes an extensive clinical, laboratory and radiologic workup is required, making it challenging to arrive at a prompt diagnosis. Most patients experience full resolution of symptoms with corticosteroids and/or infliximab. For ICI-induced colitis that is treatment-refractory, small scale studies offer alternative strategies, such as vedolizumab and fecal microbiota transplantation. In this review, we focus on the clinical features, differential diagnosis, and management of ICI-induced colitis with special attention to emerging treatment options for treatment-refractory ICI-induced colitis.
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Affiliation(s)
- Hua Li
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Zhi-Yan Fu
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Mustafa Erdem Arslan
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
| | - Daniel Cho
- Schenectady Pathology Associates, Ellis Hospital, Schenectady, NY 12308, United States
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
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Standardisation and validation of an in-house quantitative real-time polymerase chain reaction (qPCR) assay for the diagnosis of Clostridioides difficile infection. J Microbiol Methods 2021; 193:106399. [PMID: 34958834 DOI: 10.1016/j.mimet.2021.106399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Clostridioides difficile is an emerging enteric pathogen that causes nosocomial diarrhoea in adults. The excessive cost of commercial molecular tests restricts the access of developing countries to its diagnosis. This study aimed to develop and validate in-house quantitative polymerase chain reaction (qPCR) targeting the C. difficile toxin B gene (tcdB) using two detection methodologies-SYBR Green and hydrolysis probes-for the diagnosis of C. difficile infection (CDI). METHODS Glutamate dehydrogenase (GDH) plus toxigenic culture was the standard reference diagnostic method. The SYBR Green method and hydrolysis probes were used to study 392 samples simultaneously to assess the diagnostic value of these real-time PCR assays in detecting CDI from clinical samples. RESULTS The SYBR Green and hydrolysis probe assays showed 97.9% and 87.5% sensitivity; 99.1% and 100.0% specificity; 94.0% and 100.0% positive predictive value; 99.7% and 98.3% negative predictive value; and 99.0% and 98.5% accuracy, respectively. CONCLUSIONS The two qPCR methodologies evaluated could offer an adequate tool as part of an algorithm in the laboratory diagnosis of CDI.
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van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, Krutova M, Norén T, Allerberger F, Coia JE, Goorhuis A, van Rossen TM, Ooijevaar RE, Burns K, Scharvik Olesen BR, Tschudin-Sutter S, Wilcox MH, Vehreschild MJGT, Fitzpatrick F, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect 2021; 27 Suppl 2:S1-S21. [PMID: 34678515 DOI: 10.1016/j.cmi.2021.09.038] [Citation(s) in RCA: 332] [Impact Index Per Article: 83.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/23/2021] [Accepted: 09/30/2021] [Indexed: 12/13/2022]
Abstract
SCOPE In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults. METHODS AND QUESTIONS Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure. RECOMMENDATIONS Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.
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Affiliation(s)
- Joffrey van Prehn
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Elena Reigadas
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Erik H Vogelzang
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Emilio Bouza
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Adriana Hristea
- University of Medicine and Pharmacy Carol Davila, National Institute for Infectious Diseases Prof Dr Matei Bals, Romania
| | - Benoit Guery
- Infectious Diseases Specialist, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Marcela Krutova
- Department of Medical Microbiology, Charles University in Prague and Motol University Hospital, Czech Republic
| | - Torbjorn Norén
- Faculty of Medicine and Health, Department of Laboratory Medicine, National Reference Laboratory for Clostridioides difficile, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden
| | | | - John E Coia
- Department of Clinical Microbiology, Hospital South West Jutland and Department of Regional Health Research IRS, University of Southern Denmark, Esbjerg, Denmark
| | - Abraham Goorhuis
- Department of Infectious Diseases, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, the Netherlands
| | - Tessel M van Rossen
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Rogier E Ooijevaar
- Department of Gastroenterology, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Karen Burns
- Departments of Clinical Microbiology, Beaumont Hospital & Royal College of Surgeons in Ireland, Dublin, Ireland
| | | | - Sarah Tschudin-Sutter
- Department of Infectious Diseases and Infection Control, University Hospital Basel, University Basel, Universitatsspital, Basel, Switzerland
| | - Mark H Wilcox
- Department of Microbiology, Old Medical, School Leeds General Infirmary, Leeds Teaching Hospitals & University of Leeds, Leeds, United Kingdom
| | - Maria J G T Vehreschild
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Fidelma Fitzpatrick
- Department of Clinical Microbiology, Beaumont Hospital, Dublin, Ireland; Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ed J Kuijper
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
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Sarohan AR, Kızıl M, İnkaya AÇ, Mahmud S, Akram M, Cen O. A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder. Cell Signal 2021; 87:110121. [PMID: 34438017 PMCID: PMC8380544 DOI: 10.1016/j.cellsig.2021.110121] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/18/2021] [Accepted: 08/19/2021] [Indexed: 02/08/2023]
Abstract
The SARS-CoV-2 virus has caused a worldwide COVID-19 pandemic. In less than a year and a half, more than 200 million people have been infected and more than four million have died. Despite some improvement in the treatment strategies, no definitive treatment protocol has been developed. The pathogenesis of the disease has not been clearly elucidated yet. A clear understanding of its pathogenesis will help develop effective vaccines and drugs. The immunopathogenesis of COVID-19 is characteristic with acute respiratory distress syndrome and multiorgan involvement with impaired Type I interferon response and hyperinflammation. The destructive systemic effects of COVID-19 cannot be explained simply by the viral tropism through the ACE2 and TMPRSS2 receptors. In addition, the recently identified mutations cannot fully explain the defect in all cases of Type I interferon synthesis. We hypothesize that retinol depletion and resulting impaired retinoid signaling play a central role in the COVID-19 pathogenesis that is characteristic for dysregulated immune system, defect in Type I interferon synthesis, severe inflammatory process, and destructive systemic multiorgan involvement. Viral RNA recognition mechanism through RIG-I receptors can quickly consume a large amount of the body's retinoid reserve, which causes the retinol levels to fall below the normal serum levels. This causes retinoid insufficiency and impaired retinoid signaling, which leads to interruption in Type I interferon synthesis and an excessive inflammation. Therefore, reconstitution of the retinoid signaling may prove to be a valid strategy for management of COVID-19 as well for some other chronic, degenerative, inflammatory, and autoimmune diseases.
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Affiliation(s)
- Aziz Rodan Sarohan
- Department of Obstetrics and Gynecology, Medicina Plus Medical Center, 75. Yıl Mah., İstiklal Cad. 1305 Sk., No: 16 Sultangazi, İstanbul, Turkey.
| | - Murat Kızıl
- Department of Chemistry, Faculty of Science, Dicle University. Diyarbakır, Turkey
| | - Ahmet Çağkan İnkaya
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Hacettepe University, Ankara 06230, Turkey
| | - Shokhan Mahmud
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq
| | - Muhammad Akram
- Department of Eastern Medicine Government College, University Faisalabad, Pakistan
| | - Osman Cen
- Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America; Department of Natural Sciences and Engineering, John Wood College, Quincy, IL, United States of America
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van Rossen TM, Ooijevaar RE, Vandenbroucke-Grauls CMJE, Dekkers OM, Kuijper EJ, Keller JJ, van Prehn J. Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clin Microbiol Infect 2021; 28:321-331. [PMID: 34655745 DOI: 10.1016/j.cmi.2021.09.026] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/24/2021] [Accepted: 09/25/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Clostridioides difficile infection (CDI), its subsequent recurrences (rCDIs), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices. In this systematic review we aimed to identify clinical prognostic factors associated with an increased risk of developing sCDI or rCDI. METHODS PubMed, Embase, Emcare, Web of Science and COCHRANE Library databases were searched from database inception through March, 2021. The study eligibility criteria were cohort and case-control studies. Participants were patients ≥18 years old diagnosed with CDI, in which clinical or laboratory factors were analysed to predict sCDI/rCDI. Risk of bias was assessed by using the Quality in Prognostic Research (QUIPS) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool modified for prognostic studies. Study selection was performed by two independent reviewers. Overview tables of prognostic factors were constructed to assess the number of studies and the respective effect direction and statistical significance of an association. RESULTS 136 studies were included for final analysis. Greater age and the presence of multiple comorbidities were prognostic factors for sCDI. Identified risk factors for rCDI were greater age, healthcare-associated CDI, prior hospitalization, proton pump inhibitors (PPIs) started during or after CDI diagnosis, and previous rCDI. CONCLUSIONS Prognostic factors for sCDI and rCDI could aid clinicians to make treatment decisions based on risk stratification. We suggest that future studies use standardized definitions for sCDI/rCDI and systematically collect and report the risk factors assessed in this review, to allow for meaningful meta-analysis of risk factors using data of high-quality trials.
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Affiliation(s)
- Tessel M van Rossen
- Amsterdam UMC, VU University Medical Center, Medical Microbiology & Infection Control, Amsterdam Infection & Immunity, Amsterdam, the Netherlands.
| | - Rogier E Ooijevaar
- Amsterdam UMC, VU University Medical Center, Gastroenterology & Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
| | - Christina M J E Vandenbroucke-Grauls
- Amsterdam UMC, VU University Medical Center, Medical Microbiology & Infection Control, Amsterdam Infection & Immunity, Amsterdam, the Netherlands; Aarhus University, Clinical Epidemiology, Aarhus, Denmark
| | - Olaf M Dekkers
- Leiden University Medical Center, Clinical Epidemiology, Leiden, the Netherlands
| | - Ed J Kuijper
- Leiden University Medical Center, Center for Infectious Diseases, Medical Microbiology, Leiden, the Netherlands
| | - Josbert J Keller
- Haaglanden Medical Center, Gastroenterology & Hepatology, The Hague, the Netherlands; Leiden University Medical Center, Gastroenterology & Hepatology, Leiden, the Netherlands
| | - Joffrey van Prehn
- Leiden University Medical Center, Center for Infectious Diseases, Medical Microbiology, Leiden, the Netherlands
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Sahra S, Abureesh M, Amarnath S, Alkhayyat M, Badran R, Jahangir A, Gumaste V. Clostridioides difficile infection in liver cirrhosis patients: A population-based study in United States. World J Hepatol 2021; 13:926-938. [PMID: 34552699 PMCID: PMC8422922 DOI: 10.4254/wjh.v13.i8.926] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/11/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Clostridioides (formerly Clostridium) difficile infection (CDI) is an increasingly frequent cause of morbidity and mortality in hospitalized patients. Multiple risk factors are documented in the literature that includes, but are not limited to, antibiotics use, advanced age, and gastric acid suppression. Several epidemiological studies have reported an increased incidence of CDI in advanced liver disease patients. Some have also demonstrated a higher prevalence of nosocomial infections in cirrhotic patients.
AIM To use a large nationwide database, we sought to determine CDI’s risk among liver cirrhosis patients in the United States.
METHODS We queried a commercial database (Explorys IncTM, Cleveland, OH, United States), and obtained an aggregate of electronic health record data from 26 major integrated United States healthcare systems comprising 360 hospitals in the United States from 2018 to 2021. Diagnoses were organized into the Systematized Nomenclature of Medicine Clinical Terms (SNOMED–CT) hierarchy. Statistical analysis for the multivariable model was performed using Statistical Package for Social Sciences (SPSS version 25, IBM CorpTM). For all analyses, a two-sided P value of < 0.05 was considered statistically significant.
RESULTS There were a total of 19387760 patients in the database who were above 20 years of age between the years 2018-2021. Of those, 133400 were diagnosed with liver cirrhosis. The prevalence of CDI amongst the liver cirrhosis population was 134.93 per 100.000 vs 19.06 per 100.000 in non-cirrhotic patients (P < 0.0001). The multivariate analysis model uncovered that cirrhotic patients were more likely to develop CDI (OR: 1.857; 95%CI: 1.665-2.113, P < 0.0001) compared to those without any prior history of liver cirrhosis.
CONCLUSION In this large database study, we uncovered that cirrhotic patients have a significantly higher CDI prevalence than those without cirrhosis. Liver cirrhosis may be an independent risk factor for CDI. Further prospective studies are needed to clarify this possible risk association that may lead to the implementation of screening methods in this high-risk population.
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Affiliation(s)
- Syeda Sahra
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Mohammad Abureesh
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Shivantha Amarnath
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Motasem Alkhayyat
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
| | - Rawan Badran
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Abdullah Jahangir
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY 10305, United States
| | - Vivek Gumaste
- Department of Gastroenterology, Staten Island University Hospital, Staten Island, NY 10305, United States
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Baquer F, Ali Sawan A, Auzou M, Grillon A, Jaulhac B, Join-Lambert O, Boyer PH. Broth Microdilution and Gradient Diffusion Strips vs. Reference Agar Dilution Method: First Evaluation for Clostridiales Species Antimicrobial Susceptibility Testing. Antibiotics (Basel) 2021; 10:antibiotics10080975. [PMID: 34439025 PMCID: PMC8388896 DOI: 10.3390/antibiotics10080975] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 12/05/2022] Open
Abstract
Antimicrobial susceptibility testing of anaerobes is challenging. Because MIC determination is recommended by both CLSI and EUCAST, commercial broth microdilution and diffusion strip tests have been developed. The reliability of broth microdilution methods has not been assessed yet using the agar dilution reference method. In this work, we evaluated two broth microdilution kits (MICRONAUT-S Anaerobes® MIC and Sensititre Anaerobe MIC®) and one gradient diffusion strip method (Liofilchem®) for antimicrobial susceptibility testing of 47 Clostridiales isolates (Clostridium, Clostridioides and Hungatella species) using the agar dilution method as a reference. The evaluation focused on comparing six antimicrobial molecules available in both microdilution kits. Analytical performances were evaluated according to the Food and Drug Administration (FDA) recommendations. Essential agreements (EA) and categorical agreements (CA) varied greatly according to the molecule and the evaluated method. Vancomycin had values of essential and categorical agreements above 90% for the three methods. The CA fulfilled the FDA criteria for three major molecules in the treatment of Gram-positive anaerobic infections (metronidazole, piperacillin/tazobactam and vancomycin). The highest rate of error was observed for clindamycin. Multicenter studies are needed to further validate these results.
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Affiliation(s)
- Florian Baquer
- Laboratory of Bacteriology, Strasbourg University Hospital, F-67000 Strasbourg, France; (F.B.); (A.A.S.); (A.G.); (B.J.)
| | - Asma Ali Sawan
- Laboratory of Bacteriology, Strasbourg University Hospital, F-67000 Strasbourg, France; (F.B.); (A.A.S.); (A.G.); (B.J.)
- Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Michel Auzou
- Research Group on Microbial Adaptation GRAM 2.0, Department of Microbiology and Hygiene, Caen University Hospital of Caen, UniCaen-UniRouen, F-14033 Caen, France; (M.A.); (O.J.-L.)
| | - Antoine Grillon
- Laboratory of Bacteriology, Strasbourg University Hospital, F-67000 Strasbourg, France; (F.B.); (A.A.S.); (A.G.); (B.J.)
- Institute of Bacteriology, University of Strasbourg, UR7290, ITI InnoVec, Fédération de Médecine Translationnelle de Strasbourg, 3 rue Koeberlé, F-67000 Strasbourg, France
| | - Benoît Jaulhac
- Laboratory of Bacteriology, Strasbourg University Hospital, F-67000 Strasbourg, France; (F.B.); (A.A.S.); (A.G.); (B.J.)
- Institute of Bacteriology, University of Strasbourg, UR7290, ITI InnoVec, Fédération de Médecine Translationnelle de Strasbourg, 3 rue Koeberlé, F-67000 Strasbourg, France
| | - Olivier Join-Lambert
- Research Group on Microbial Adaptation GRAM 2.0, Department of Microbiology and Hygiene, Caen University Hospital of Caen, UniCaen-UniRouen, F-14033 Caen, France; (M.A.); (O.J.-L.)
| | - Pierre H. Boyer
- Laboratory of Bacteriology, Strasbourg University Hospital, F-67000 Strasbourg, France; (F.B.); (A.A.S.); (A.G.); (B.J.)
- Institute of Bacteriology, University of Strasbourg, UR7290, ITI InnoVec, Fédération de Médecine Translationnelle de Strasbourg, 3 rue Koeberlé, F-67000 Strasbourg, France
- Correspondence:
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Boekhoud IM, Sidorov I, Nooij S, Harmanus C, Bos-Sanders IMJG, Viprey V, Spittal W, Clark E, Davies K, Freeman J, Kuijper EJ, Smits WK. Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile. J Antimicrob Chemother 2021; 76:1731-1740. [PMID: 33876817 PMCID: PMC8212768 DOI: 10.1093/jac/dkab097] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 03/02/2021] [Indexed: 01/05/2023] Open
Abstract
Background Until recently, metronidazole was the first-line treatment for Clostridioides difficile infection and it is still commonly used. Though resistance has been reported due to the plasmid pCD-METRO, this does not explain all cases. Objectives To identify factors that contribute to plasmid-independent metronidazole resistance of C. difficile. Methods Here, we investigate resistance to metronidazole in a collection of clinical isolates of C. difficile using a combination of antimicrobial susceptibility testing on different solid agar media and WGS of selected isolates. Results We find that nearly all isolates demonstrate a haem-dependent increase in the MIC of metronidazole, which in some cases leads to isolates qualifying as resistant (MIC >2 mg/L). Moreover, we find an SNP in the haem-responsive gene hsmA, which defines a metronidazole-resistant lineage of PCR ribotype 010/MLST ST15 isolates that also includes pCD-METRO-containing strains. Conclusions Our data demonstrate that haem is crucial for medium-dependent metronidazole resistance in C. difficile.
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Affiliation(s)
- Ilse M Boekhoud
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Igor Sidorov
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Sam Nooij
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.,Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
| | - Céline Harmanus
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Virginie Viprey
- Healthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK
| | - William Spittal
- Healthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK
| | - Emma Clark
- Healthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK
| | - Kerrie Davies
- Healthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK.,European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Study Group for Clostridioides difficile (ESGCD), Basel, Switzerland
| | - Jane Freeman
- Healthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK.,European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Study Group for Clostridioides difficile (ESGCD), Basel, Switzerland
| | - Ed J Kuijper
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.,European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Study Group for Clostridioides difficile (ESGCD), Basel, Switzerland.,National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Wiep Klaas Smits
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.,Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands.,European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Study Group for Clostridioides difficile (ESGCD), Basel, Switzerland
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Šamadan L, Jeličić M, Vince A, Papić N. Nonalcoholic Fatty Liver Disease-A Novel Risk Factor for Recurrent Clostridioides difficile Infection. Antibiotics (Basel) 2021; 10:antibiotics10070780. [PMID: 34198964 PMCID: PMC8300633 DOI: 10.3390/antibiotics10070780] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/23/2021] [Accepted: 06/25/2021] [Indexed: 12/17/2022] Open
Abstract
Recurrent Clostridioides difficile infections (rCDI) have a substantial impact on healthcare systems, with limited and often expensive therapeutic options. Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the adult population and is associated with metabolic syndrome, changes in gut microbiome and bile acids biosynthesis, all possibly related with rCDI. The aim of this study was to determine whether NAFLD is a risk factor associated with rCDI. A retrospective cohort study included patients ≥ 60 years hospitalized with CDI. The cohort was divided into two groups: those who were and were not readmitted with CDI within 3 months of discharge. Of the 329 patients included, 107 patients (32.5%) experienced rCDI. Patients with rCDI were older, had higher Charlson Age-Comorbidity Index (CACI) and were more frequently hospitalized within 3 months. Except for chronic kidney disease and NAFLD, which were more frequent in the rCDI group, there were no differences in other comorbidities, antibiotic classes used and duration of antimicrobial therapy. Multivariable Cox regression analysis showed that age >75 years, NAFLD, CACI >6, chronic kidney disease, statins and immobility were associated with rCDI. In conclusion, our study identified NAFLD as a possible new host-related risk factor associated with rCDI.
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Affiliation(s)
- Lara Šamadan
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.Š.); (A.V.)
| | - Mia Jeličić
- University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
| | - Adriana Vince
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.Š.); (A.V.)
- University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
| | - Neven Papić
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.Š.); (A.V.)
- University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
- Correspondence:
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Guery B, Berger P, Gauzit R, Gourdon M, Barbut F, Dafne Study Group, Bémer P, Bessède E, Camou F, Cattoir V, Couzigou C, Descamps D, Dinh A, Laurans C, Lavigne JP, Lechiche C, Leflon-Guibout V, Le Monnier A, Levast M, Mootien JY, N'Guyen Y, Piroth L, Prazuck T, Rogeaux O, Roux AL, Vachée A, Vernet Garnier V, Wallet F. A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France. J Int Med Res 2021; 49:3000605211021278. [PMID: 34162264 PMCID: PMC8236878 DOI: 10.1177/03000605211021278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. METHODS This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. RESULTS At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. CONCLUSIONS Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.
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Affiliation(s)
- Benoit Guery
- University Hospital and University of Lausanne, Lausanne, Switzerland
| | | | | | | | - Frédéric Barbut
- National Reference Laboratory for C. difficile, Saint-Antoine Hospital, Paris, France.,INSERM S-1139, Faculty of Pharmacy, University of Paris, Paris, France
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Chiu CW, Tsai PJ, Lee CC, Ko WC, Hung YP. Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents. Pathogens 2021; 10:pathogens10060649. [PMID: 34073695 PMCID: PMC8225043 DOI: 10.3390/pathogens10060649] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/02/2021] [Accepted: 05/19/2021] [Indexed: 02/07/2023] Open
Abstract
Oral vancomycin and metronidazole, though they are the therapeutic choice for Clostridioides difficile infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to C. difficile after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing Lactobacillus species, Saccharomyces boulardii, or Clostridium butyricum have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.
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Affiliation(s)
- Chun-Wei Chiu
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 700, Taiwan;
| | - Pei-Jane Tsai
- Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Medical College, Tainan 704, Taiwan;
| | - Ching-Chi Lee
- Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan;
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| | - Wen-Chien Ko
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
- Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Correspondence: (W.-C.K.); (Y.-P.H.)
| | - Yuan-Pin Hung
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 700, Taiwan;
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
- Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Correspondence: (W.-C.K.); (Y.-P.H.)
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Tortajada-Girbés M, Rivas A, Hernández M, González A, Ferrús MA, Pina-Pérez MC. Alimentary and Pharmaceutical Approach to Natural Antimicrobials against Clostridioides difficile Gastrointestinal Infection. Foods 2021; 10:foods10051124. [PMID: 34069413 PMCID: PMC8159093 DOI: 10.3390/foods10051124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/08/2021] [Accepted: 05/16/2021] [Indexed: 02/07/2023] Open
Abstract
Incidence of Clostridioides difficile infection (CDI) has been increasing in recent decades due to different factors, namely (i) extended use of broad-spectrum antibiotics, (ii) transmission within asymptomatic and susceptible patients, and (iii) unbalanced gastrointestinal microbiome and collateral diseases that favor C. difficile gastrointestinal domination and toxin production. Although antibiotic therapies have resulted in successful control of CDI in the last 20 years, the development of novel strategies is urged in order to combat the capability of C. difficile to generate and acquire resistance to conventional treatments and its consequent proliferation. In this regard, vegetable and marine bioactives have emerged as alternative and effective molecules to fight against this concerning pathogen. The present review examines the effectiveness of natural antimicrobials from vegetable and algae origin that have been used experimentally in in vitro and in vivo settings to prevent and combat CDI. The aim of the present work is to contribute to accurately describe the prospective use of emerging antimicrobials as future nutraceuticals and preventive therapies, namely (i) as dietary supplement to prevent CDI and reduce CDI recurrence by means of microbiota modulation and (ii) administering them complementarily to other treatments requiring antibiotics to prevent C. difficile gut invasion and infection progression.
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Affiliation(s)
- Miguel Tortajada-Girbés
- Department of Pediatrics, University Dr. Peset Hospital, Avda, de Gaspar Aguilar, 90, 46017 Valencia, Spain;
| | - Alejandro Rivas
- Departmento Tecnología de Alimentos, Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural (ETSIAMN), Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain;
| | - Manuel Hernández
- Departmento Biotecnología, Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural (ETSIAMN), Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain; (M.H.); (A.G.); (M.A.F.)
| | - Ana González
- Departmento Biotecnología, Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural (ETSIAMN), Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain; (M.H.); (A.G.); (M.A.F.)
| | - Maria A. Ferrús
- Departmento Biotecnología, Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural (ETSIAMN), Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain; (M.H.); (A.G.); (M.A.F.)
| | - Maria C. Pina-Pérez
- Departmento Microbiologia y Ecología, Facultad Ciencias Biológicas, Universitat de València, C/Dr. Moliner, 50, 46100 Burjassot, Spain
- Correspondence:
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Cook L, Rees WD, Wong MQ, Peters H, Levings MK, Steiner TS. Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Enhances Adaptive Immunity to C difficile Toxin B. Gastroenterology 2021; 160:2155-2158.e4. [PMID: 33444574 DOI: 10.1053/j.gastro.2021.01.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Laura Cook
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - William D Rees
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - May Q Wong
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Hannah Peters
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Megan K Levings
- BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - Theodore S Steiner
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
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Sleha R, Radochova V, Mikyska A, Houska M, Bolehovska R, Janovska S, Pejchal J, Muckova L, Cermak P, Bostik P. Strong Antimicrobial Effects of Xanthohumol and Beta-Acids from Hops against Clostridioides difficile Infection In Vivo. Antibiotics (Basel) 2021; 10:antibiotics10040392. [PMID: 33917416 PMCID: PMC8067520 DOI: 10.3390/antibiotics10040392] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 03/18/2021] [Accepted: 04/03/2021] [Indexed: 11/16/2022] Open
Abstract
Clostridioides (C.) difficile is an important causative pathogen of nosocomial gastrointestinal infections in humans with an increasing incidence, morbidity, and mortality. The available treatment options against this pathogen are limited. The standard antibiotics are expensive, can promote emerging resistance, and the recurrence rate of the infection is high. Therefore, there is an urgent need for new approaches to meet these challenges. One of the possible treatment alternatives is to use compounds available in commonly used plants. In this study, purified extracts isolated from hops-alpha and beta acids and xanthohumol-were tested in vivo for their inhibitory effect against C. difficile. A rat model of the peroral intestinal infection by C. difficile has been developed. The results show that both xanthohumol and beta acids from hops exert a notable antimicrobial effect in the C. difficile infection. The xanthohumol application showed the most pronounced antimicrobial effect together with an improvement of local inflammatory signs in the large intestine. Thus, the hops compounds represent promising antimicrobial agents for the treatment of intestinal infections caused by C. difficile.
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Affiliation(s)
- Radek Sleha
- Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, 500 03 Hradec Kralove, Czech Republic; (R.S.); (V.R.); (S.J.)
| | - Vera Radochova
- Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, 500 03 Hradec Kralove, Czech Republic; (R.S.); (V.R.); (S.J.)
| | - Alexander Mikyska
- Research Institute of Brewing and Malting, 110 00 Prague, Czech Republic;
| | - Milan Houska
- Food Research Institute, 110 00 Prague, Czech Republic;
| | - Radka Bolehovska
- Institute of Clinical Microbiology, University Hospital, 500 03 Hradec Kralove, Czech Republic;
| | - Sylva Janovska
- Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, 500 03 Hradec Kralove, Czech Republic; (R.S.); (V.R.); (S.J.)
| | - Jaroslav Pejchal
- Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, 500 03 Hradec Kralove, Czech Republic; (J.P.); (L.M.)
| | - Lubica Muckova
- Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, 500 03 Hradec Kralove, Czech Republic; (J.P.); (L.M.)
| | - Pavel Cermak
- Thomayer Hospital, 110 00 Prague, Czech Republic;
| | - Pavel Bostik
- Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, 500 03 Hradec Kralove, Czech Republic; (R.S.); (V.R.); (S.J.)
- Institute of Clinical Microbiology, University Hospital, 500 03 Hradec Kralove, Czech Republic;
- Department of Clinical Microbiology, Faculty of Medicine in Hradec Kralove, Charles University, 500 03 Hradec Kralove, Czech Republic
- Correspondence:
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Clostridoides difficile Infection Severity Assessment by Fecal Calprotectin: A Pilot Study. CURRENT HEALTH SCIENCES JOURNAL 2021; 47:204-208. [PMID: 34765239 PMCID: PMC8551903 DOI: 10.12865/chsj.47.02.09] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 06/25/2021] [Indexed: 12/21/2022]
Abstract
Clostridoides difficile infection (CDI) is the leading cause of antibiotic related diarrhea therapy and may associate high morbidity and mortality. Providing a potential biomarker to assess disease severity may help physicians in choosing the right treatment. Methods. This was a prospective, single-centre cohort study which included patients diagnosed with CDI which were assessed by fecal calprotectin (FC). Results. Patients included had a mean of 69.29 years of age, 54.23% of male gender. Patients diagnosed with mild CDI had a mean ATLAS score of 3.39 (±1.24), statistically lower (p<0.001) than patients with severe CDI who had a mean ATLAS score of 7.33 (±0.77). Fecal calprotectin concentrations were significantly higher (p<0.001) in the severe CDI patients (615.14μg/g; IQR, 403.62-784.4μg/g) than in the mild CDI patients (195.42μg/g; IQR, 131.12-298.59μg/g). We suggest a cut-off of 290.09μg/g for the predictive marker of fecal calprotectin, which permitted to identify patients with severe and mild CDI, having 100% sensitivity and 76% specificity. Conclusions. Our findings point out the potential that FC might have, as a biomarker for disease severity. However, future multicentre studies and in larger cohort need to validate the results.
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