C. Difficile: Trials, Treatments and New Guidelines

Total Page:16

File Type:pdf, Size:1020Kb

C. Difficile: Trials, Treatments and New Guidelines C. difficile: trials, treatments and new guidelines CONTENTS REVIEW: Vulnerability of long-term care facility residents to Clostridium difficile infection due to microbiome disruptions FUTURE MICROBIOLOGY Vol. 13, No. 13 INTERVIEW: The gut microbiome and the potentials of probiotics: an interview with Simon Gaisford FUTURE MICROBIOLOGY Vol. 14, No. 4 REVIEW: Clostridioides (Clostridium) difficile infection: current and alternative therapeutic strategies FUTURE MICROBIOLOGY Vol. 13, No. 4 EDITORIAL: Microbiome therapeutics – the pipeline for C. difficile infection INTERVIEW: Updates on C. difficile: from clinical trials and guidelines – an interview with Yoav Golan NEWS ARTICLE: Could common painkillers promote C. difficile infection? Review For reprint orders, please contact: [email protected] Vulnerability of long-term care facility residents to Clostridium difficile infection due to microbiome disruptions Beth Burgwyn Fuchs*,1, Nagendran Tharmalingam1 & Eleftherios Mylonakis**,1 1Rhode Island Hospital, Alpert Medical School & Brown University, Providence, Rhode Island 02903 *Author for correspondence: Tel.: +401 444 7309; Fax: +401 606 5624; Helen [email protected]; **Author for correspondence: Tel.: +401 444 7845; Fax: +401 444 8179; [email protected] Aging presents a significant risk factor for Clostridium difficile infection (CDI). A disproportionate number of CDIs affect individuals in long-term care facilities compared with the general population, likely due to the vulnerable nature of the residents and shared environment. Review of the literature cites a number of underlying medical conditions such as the use of antibiotics, proton pump inhibitors, chemotherapy, renal disease and feeding tubes as risk factors. These conditions alter the intestinal environment through direct bacterial killing, changes to pH that influence bacterial stabilities or growth, or influence nutrient availability that direct population profiles. In this review, we examine some of the contributing risk factors for elderly associated CDI and the toll they take on the microbiome. First draft submitted: 18 May 2018; Accepted for publication: 8 August 2018; Published online: 12 October 2018 Keywords: Clostridium difficile • elderly • long-term care facilities • microbiome • vulnerable population Background The intestinal environment is constantly bombarded with microbiome-altering conditions through diet, probiotic- supplemented foods, antibiotics or gastric acid altering medications to name a few [1]. At times, the flux of the microbiome can become favorable to pathogenic bacterial residents, leading to disease. As we learn more about the intestinal microbiome, we find that medical interventions associated with aging particularly contribute to intestinal bacteria imbalances. Harbored within the ranks of the intestinal milieu can be the Gram-positive, spore forming bacterium Clostridium difficile. About 5% of healthy adults have toxigenic C. difficile in their feces and are deemed carriers of the bacteria [2]. The bacteria can benignly reside or colonize the gut without generating symptoms. Conversely, patients can also newly acquire the bacteria, most typically in a healthcare setting. Once acquired, conditions can arise that ignite an active infection. In one such case, necessary therapeutic treatments for primary diseases can result in the reduction of gut flora that normally ensures a low population of C. difficile. This gut dysbiosis can lead to an active Clostridium difficile infection (CDI). Long-term care facility (LTCF) residents often experience or fall within multiple risk factor categories leaving them prone to CDI [3]. Vulnerability and incidence within the elderly population C. difficile was estimated to cause 500,000 infections in the USA in 2011; among the infected, approximately 29,000 died within 30 days of diagnosis [4]. In CDC reports provided by the Emerging Infections Program between 2012 and 2015, each year exhibit increase incidences compared with the previous year in the most advanced aged group within the study; the ≥65 years of age group was determined to have an incidence of 559.15 per 1000 persons in a 2015 annual report [5]. Within this group, there was a higher incidence of healthcare-associated CDI than community-associated CDI [4,6]. Transfer from acute care facilities to LTCF C. difficile acquisition is typically spread by healthcare workers, contact with contaminated surfaces, or by an individual shedding spores as a result of a recent infection. Among elderly patients with CDI during their hospital- 10.2217/fmb-2018-0157 C 2018 Future Medicine Ltd Future Microbiol. (2018) 13(13), 1537–1547 ISSN 1746-0913 1537 Review Fuchs, Tharmalingam & Mylonakis ization, 28% were discharged to LTCFs [7], facilitating the spread of C. difficile from the acute care setting to the LTCF community. A study of LTCF residents predicted a patient colonization rate upon admission of 8.9% [8]. Primary acquisitions at LTCFs Among LTCF residents, approximately 1 in 50 individuals ≥65 years of age was diagnosed with CDI during their stay (median resident stay was 33 days, ranging from 19 to 90 days) [9] and, for individuals housed in nursing homes with CDI, it was estimated that 8% died within 30 days of onset [10]. Between 2006 and 2012, a study that included 120 LTCFs managed by the United States Veterans Health Administration reviewed 35,754 cases of CDI, 20% were diagnosed at a LTCF [11]. Although the study of a veteran’s facility included a higher population of men compared with women, it does generate a portrait of the problem that C. difficile constitutes within a shared living environment. The question then arises whether LTCF CDI onset is the result of recent hospitalization or a new acquisition. In an investigation that included 33 LTCF conducted in Monroe County, New York, researchers found 425 onset cases of CDI within LTCF with an incidence of 2.3 cases per 10,000 resident-days in 2010. Within this study, they found that 50% of these CDI cases were more than 4 weeks after hospital discharge [3]. Infections occurring more than 4 weeks after hospitalization could possibly be attribute to a new infection. To examine this point, Ponnada and colleagues followed patients for 6 weeks after transfer to LTCFs. Among a group of 110 individuals that were followed in the study, 12 (11%) were tested positive for C. difficile atthetimeof admission (as tested by screening perirectal swabs using an enzymatic immunoassay test followed by confirmatory PCR), 4 of which developed CDI within 1 month. Among a group of 82 patients that entered the LTCF as negative for C. difficile carriership, 22 (27%) acquired the bacteria while in residence [12]. Thus, transient carriership or colonization in the LTCF is an issue. CDI burden Once colonized, patients can suffer not only from an initial onset infection, but potentially numerous reoccurrence events. A 2014 cost estimate of CDI was placed at US$5.4 billion with 68.6% of infections attributed to individuals >64 year of age within the care settings of hospitals, LTCF or long-term acute care facilities. Of the estimated 606,058 cases in the study, 25% were LTCF residents [13]. The problem is exacerbated when one considers that C. difficile can be acquired in conjunction to a primary infection and may contribute to patient morbidity and mortality. Archbald-Pannone and colleagues report that according to medical billing data, in 2008 10% (45 of 457) of all inpatient elderly deaths had a diagnosis of CDI concurrent to another disease among the Virginia hospitals included in the study [7]. To explore the risk factors associated with C. difficile acquisition in the elderly and the role played in microbiome dysbiosis, we searched PubMed from 2002 up to June, 2018 using the term: C. difficile infection, risk factors and elderly. We screened articles by title and abstract. Only manuscripts in English were reviewed. Studies were considered within the USA were preferential, but when data were lacking, we also included studies conducted outside the USA. Conference abstracts were not considered for inclusion. Additional references were obtained if further information was needed. Microbiome The human gut is a major complex ecosystem and within this ecological niche homeostasis plays a major role in preventing CDI [14,15]. Up to 30% of intestinal spore-forming bacteria represent bacterial families from Lach- nospiraceae, Ruminococcaceae, Clostridiaceae and Peptostreptococcaceae. The further populous is made up of normal intestinal microbiota such as Enterobacteriaceae, Rikenellaceae, Porphyromonadaceae, Bacteroidaceae, Coriobacteriaceae, Bifidobacteriaceae, Erysipelotrichaceae, Enterococcaceae, Bacillaceae, Lactobacillaceae and Veil- lonellaceae colonizing the gut from birth [14]. Although most of the microbiome remain consistent throughout life, structural changes can occur in the bacterial populations as individuals advance in age. Although these changes may not be reflected in altered species varieties, there can be fluctuations detectable in the viable bacteria cell counts [16]. Outside of naturally influenced fluctuations, numerous medical interventions encountered with advanced age result in dysbiosis of normal adult flora and can subsequently lead to bouts with CDI. 16S rRNA pyrosequencing analysis found a reduction in microbiota in elderly CDI patients [17]. A study by Hopkins et al. aimed to interrogate the fecal microbiota to species level in healthy young adults (aged 21–34), adults ≥67 and adults ≥67 with C.
Recommended publications
  • C. Difficile Spores Valerate + Clindamycin C
    This is an Open Access document downloaded from ORCA, Cardiff University's institutional repository: http://orca.cf.ac.uk/114080/ This is the author’s version of a work that was submitted to / accepted for publication. Citation for final published version: McDonald, Julie A.K., Mullish, Benjamin H., Pechlivanis, Alexandros, Liu, Zhigang, Brignardello, Jerusa, Kao, Dina, Holmes, Elaine, Li, Jia V., Clarke, Thomas B., Thursz, Mark R. and Marchesi, Julian R. 2018. Inhibiting growth of Clostridioides difficile by restoring valerate, produced by the intestinal microbiota. Gastroenterology 155 (5) , pp. 1495-1507. 10.1053/j.gastro.2018.07.014 file Publishers page: http://dx.doi.org/10.1053/j.gastro.2018.07.014 <http://dx.doi.org/10.1053/j.gastro.2018.07.014> Please note: Changes made as a result of publishing processes such as copy-editing, formatting and page numbers may not be reflected in this version. For the definitive version of this publication, please refer to the published source. You are advised to consult the publisher’s version if you wish to cite this paper. This version is being made available in accordance with publisher policies. See http://orca.cf.ac.uk/policies.html for usage policies. Copyright and moral rights for publications made available in ORCA are retained by the copyright holders. Accepted Manuscript Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota Julie A.K. McDonald, Benjamin H. Mullish, Alexandros Pechlivanis, Zhigang Liu, Jerusa Brignardello, Dina Kao,
    [Show full text]
  • High-Quality Draft Genome Sequences of Five Anaerobic Oral Bacteria and Description of Peptoanaerobacter Stomatis Gen
    Sizova et al. Standards in Genomic Sciences (2015) 10:37 DOI 10.1186/s40793-015-0027-8 EXTENDED GENOME REPORT Open Access High-quality draft genome sequences of five anaerobic oral bacteria and description of Peptoanaerobacter stomatis gen. nov., sp. nov., a new member of the family Peptostreptococcaceae Maria V. Sizova1, Amanda Chilaka1, Ashlee M. Earl2, Sebastian N. Doerfert1, Paul A. Muller1, Manolito Torralba3, Jamison M. McCorrison3, A. Scott Durkin3, Karen E. Nelson3 and Slava S. Epstein1* Abstract Here we report a summary classification and the features of five anaerobic oral bacteria from the family Peptostreptococcaceae. Bacterial strains were isolated from human subgingival plaque. Strains ACC19a, CM2, CM5, and OBRC8 represent the first known cultivable members of “yet uncultured” human oral taxon 081; strain AS15 belongs to “cultivable” human oral taxon 377. Based on 16S rRNA gene sequence comparisons, strains ACC19a, CM2, CM5, and OBRC8 are distantly related to Eubacterium yurii subs. yurii and Filifactor alocis, with 93.2 – 94.4 % and 85.5 % of sequence identity, respectively. The genomes of strains ACC19a, CM2, CM5, OBRC8 and AS15 are 2,541,543; 2,312,592; 2,594,242; 2,553,276; and 2,654,638 bp long. The genomes are comprised of 2277, 1973, 2325, 2277, and 2308 protein-coding genes and 54, 57, 54, 36, and 28 RNA genes, respectively. Based on the distinct characteristics presented here, we suggest that strains ACC19a, CM2, CM5, and OBRC8 represent a novel genus and species within the family Peptostreptococcaceae, for which we propose the name Peptoanaerobacter stomatis gen. nov., sp. nov. The type strain is strain ACC19aT (=HM-483T; =DSM 28705T;=ATCC BAA-2665T).
    [Show full text]
  • Mortality Following Clostridioides Difficile Infection in Europe: a Retrospective Multicenter Case-Control Study
    antibiotics Article Mortality Following Clostridioides difficile Infection in Europe: A Retrospective Multicenter Case-Control Study Jacek Czepiel 1,* , Marcela Krutova 2,3, Assaf Mizrahi 3,4,5 , Nagham Khanafer 3,6,7, David A. Enoch 8, Márta Patyi 9, Aleksander Deptuła 10, Antonella Agodi 11 , Xavier Nuvials 12 , Hanna Pituch 3,13 , Małgorzata Wójcik-Bugajska 14, Iwona Filipczak-Bryniarska 15, Bartosz Brzozowski 16, Marcin Krzanowski 17, Katarzyna Konturek 18, Marcin Fedewicz 19, Mateusz Michalak 20, Lorra Monpierre 4, Philippe Vanhems 6,7, Theodore Gouliouris 8, Artur Jurczyszyn 21, Sarah Goldman-Mazur 21, Dorota Wulta ´nska 13 , Ed J. Kuijper 3,22,23, Jan Skupie ´n 24, Grazyna˙ Biesiada 1 and Aleksander Garlicki 1 1 Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, 30-688 Krakow, Poland; [email protected] (G.B.); [email protected] (A.G.) 2 Department of Medical Microbiology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, 15006 Prague, Czech Republic; [email protected] or [email protected] 3 ESCMID Study Group for Clostridioides Difficile (ESGCD), 4001 Basel, Switzerland; [email protected] (A.M.); [email protected] (N.K.); [email protected] (H.P.); [email protected] (E.J.K.) 4 Service de Microbiologie Clinique, Groupe Hospitalier Paris Saint-Joseph, 75014 Paris, France; [email protected] 5 Institut Micalis UMR 1319, Université Paris-Saclay, INRAe, AgroParisTech, 92290 Châtenay Malabry, France 6 Unité d’Hygiène, Epidémiologie
    [Show full text]
  • Cadazolid/ACT-179811 Protocol AC-061A301
    Cadazolid/ACT-179811 Protocol AC-061A301 A multi-center, randomized, double-blind study to compare the efficacy and safety of cadazolid versus vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD) NCT Number NCT01987895 Document Version, Date Final Version 3, 22 October 2015 Document History: - Original Version 29 August 2013 - Amendment 1 11 December 2014 - Amendment 2 22 October 2015 Main reason for Amendment 1 The main analysis of the primary endpoint Clinical Cure will be conducted on two co-primary analysis sets (i.e., modified intent-to-treat [mITT] analysis set and Per-protocol analysis set [PPS]) instead of sequential analysis. Further changes include the addition of an emerging hypervirulent Clostridium difficile strain, the addition of endpoints related to susceptibility testing of C. difficile and vancomycin-resistant enterococci, and general clarifications of eligibility criteria and statistical analyses including a modification to the definition of recurrence for analyses of secondary variable sustained cure rate. Main reason for Amendment 2 To remove the interim analysis originally planned after the randomization of 67% of the subjects. Confidentiality statement Property of Actelion Pharmaceuticals Ltd. May not be used, divulged, published or otherwise disclosed without the consent of Actelion Pharmaceuticals Ltd Cadazolid/ACT-179811 EudraCT: 2013-002528-17 Clostridium difficile-associated diarrhea Doc No D-15.418 Protocol AC-061A301 Confidential Version 3 22 October 2015, page 2/138 SPONSOR CONTACT DETAILS SPONSOR ACTELION Pharmaceuticals Ltd Gewerbestrasse 16 CH-4123 Allschwil Switzerland Clinical Trial Physician MEDICAL HOTLINE Toll phone number: +41 61 227 05 63 Site-specific toll telephone numbers and toll-free numbers for the Medical Hotline can be found in the Investigator Site File.
    [Show full text]
  • Management of Adult Clostridium Difficile Digestive Contaminations: a Literature Review
    European Journal of Clinical Microbiology & Infectious Diseases (2019) 38:209–231 https://doi.org/10.1007/s10096-018-3419-z REVIEW Management of adult Clostridium difficile digestive contaminations: a literature review Fanny Mathias1 & Christophe Curti1,2 & Marc Montana1,3 & Charléric Bornet4 & Patrice Vanelle 1,2 Received: 5 October 2018 /Accepted: 30 October 2018 /Published online: 29 November 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole. Keywords Clostridiumdifficile .Fidaxomicin .Fecalmicrobiotatransplantation .Antitoxinantibodies .Surotomycin .Cadazolid Introduction (Fig.
    [Show full text]
  • Current Trends of Enterococci in Dairy Products: a Comprehensive Review of Their Multiple Roles
    foods Review Current Trends of Enterococci in Dairy Products: A Comprehensive Review of Their Multiple Roles Maria de Lurdes Enes Dapkevicius 1,2,* , Bruna Sgardioli 1,2 , Sandra P. A. Câmara 1,2, Patrícia Poeta 3,4 and Francisco Xavier Malcata 5,6,* 1 Faculty of Agricultural and Environmental Sciences, University of the Azores, 9700-042 Angra do Heroísmo, Portugal; [email protected] (B.S.); [email protected] (S.P.A.C.) 2 Institute of Agricultural and Environmental Research and Technology (IITAA), University of the Azores, 9700-042 Angra do Heroísmo, Portugal 3 Microbiology and Antibiotic Resistance Team (MicroART), Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal; [email protected] 4 Associated Laboratory for Green Chemistry (LAQV-REQUIMTE), University NOVA of Lisboa, 2829-516 Lisboa, Portugal 5 LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 420-465 Porto, Portugal 6 FEUP—Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal * Correspondence: [email protected] (M.d.L.E.D.); [email protected] (F.X.M.) Abstract: As a genus that has evolved for resistance against adverse environmental factors and that readily exchanges genetic elements, enterococci are well adapted to the cheese environment and may reach high numbers in artisanal cheeses. Their metabolites impact cheese flavor, texture, Citation: Dapkevicius, M.d.L.E.; and rheological properties, thus contributing to the development of its typical sensorial properties. Sgardioli, B.; Câmara, S.P.A.; Poeta, P.; Due to their antimicrobial activity, enterococci modulate the cheese microbiota, stimulate autoly- Malcata, F.X.
    [Show full text]
  • Oral Administration of Lactobacillus Gasseri SBT2055 Is Effective In
    www.nature.com/scientificreports OPEN Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas Received: 23 June 2015 Accepted: 7 March 2017 gingivalis-accelerated periodontal Published: xx xx xxxx disease R. Kobayashi1, T. Kobayashi2, F. Sakai3, T. Hosoya3, M. Yamamoto1 & T. Kurita-Ochiai1 Probiotics have been used to treat gastrointestinal disorders. However, the effect of orally intubated probiotics on oral disease remains unclear. We assessed the potential of oral administration of Lactobacillus gasseri SBT2055 (LG2055) for Porphyromonas gingivalis infection. LG2055 treatment significantly reduced alveolar bone loss, detachment and disorganization of the periodontal ligament, and bacterial colonization by subsequent P. gingivalis challenge. Furthermore, the expression and secretion of TNF-α and IL-6 in gingival tissue was significantly decreased in LG2055-administered mice after bacterial infection. Conversely, mouse β-defensin-14 (mBD-14) mRNA and its peptide products were significantly increased in distant mucosal components as well as the intestinal tract to which LG2055 was introduced. Moreover, IL-1β and TNF-α production from THP-1 monocytes stimulated with P. gingivalis antigen was significantly reduced by the addition of humanβ -defensin-3. These results suggest that gastrically administered LG2055 can enhance immunoregulation followed by periodontitis prevention in oral mucosa via the gut immune system; i.e., the possibility of homing in innate immunity. Porphyromonas gingivalis, a Gram-negative anaerobe, is one of the major pathogens associated with chronic periodontitis, a disease that causes the destruction of alveolar bone, and, as a consequence, tooth loss1. Recent evidence suggests that this bacterium contributes to periodontitis by functioning as a keystone pathogen2, 3.
    [Show full text]
  • Sporulation Evolution and Specialization in Bacillus
    bioRxiv preprint doi: https://doi.org/10.1101/473793; this version posted March 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Research article From root to tips: sporulation evolution and specialization in Bacillus subtilis and the intestinal pathogen Clostridioides difficile Paula Ramos-Silva1*, Mónica Serrano2, Adriano O. Henriques2 1Instituto Gulbenkian de Ciência, Oeiras, Portugal 2Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal *Corresponding author: Present address: Naturalis Biodiversity Center, Marine Biodiversity, Leiden, The Netherlands Phone: 0031 717519283 Email: [email protected] (Paula Ramos-Silva) Running title: Sporulation from root to tips Keywords: sporulation, bacterial genome evolution, horizontal gene transfer, taxon- specific genes, Bacillus subtilis, Clostridioides difficile 1 bioRxiv preprint doi: https://doi.org/10.1101/473793; this version posted March 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Abstract Bacteria of the Firmicutes phylum are able to enter a developmental pathway that culminates with the formation of a highly resistant, dormant spore. Spores allow environmental persistence, dissemination and for pathogens, are infection vehicles. In both the model Bacillus subtilis, an aerobic species, and in the intestinal pathogen Clostridioides difficile, an obligate anaerobe, sporulation mobilizes hundreds of genes.
    [Show full text]
  • Antimicrobial Resistance in Companion Animal Pathogens in Australia and Assessment of Pradofloxacin on the Gut Microbiota
    Antimicrobial resistance in companion animal pathogens in Australia and assessment of pradofloxacin on the gut microbiota Sugiyono Saputra A thesis submitted in fulfilment of the requirements of the degree of Doctor of Philosophy School of Animal and Veterinary Sciences The University of Adelaide February 2018 Table of Contents Thesis Declaration ...................................................................................................................... iii Dedication ................................................................................................................................. iv Acknowledgement ...................................................................................................................... v Preamble .................................................................................................................................... vi List of Publications ..................................................................................................................... vii Abstract .......................................................................................................................................ix Chapter 1 General Introduction ................................................................................................. 1 1.1. Antimicrobials and their consequences ............................................................................ 2 1.2. The emergence and monitoring AMR................................................................................ 2
    [Show full text]
  • WO 2018/064165 A2 (.Pdf)
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/064165 A2 05 April 2018 (05.04.2018) W !P O PCT (51) International Patent Classification: Published: A61K 35/74 (20 15.0 1) C12N 1/21 (2006 .01) — without international search report and to be republished (21) International Application Number: upon receipt of that report (Rule 48.2(g)) PCT/US2017/053717 — with sequence listing part of description (Rule 5.2(a)) (22) International Filing Date: 27 September 2017 (27.09.2017) (25) Filing Language: English (26) Publication Langi English (30) Priority Data: 62/400,372 27 September 2016 (27.09.2016) US 62/508,885 19 May 2017 (19.05.2017) US 62/557,566 12 September 2017 (12.09.2017) US (71) Applicant: BOARD OF REGENTS, THE UNIVERSI¬ TY OF TEXAS SYSTEM [US/US]; 210 West 7th St., Austin, TX 78701 (US). (72) Inventors: WARGO, Jennifer; 1814 Bissonnet St., Hous ton, TX 77005 (US). GOPALAKRISHNAN, Vanch- eswaran; 7900 Cambridge, Apt. 10-lb, Houston, TX 77054 (US). (74) Agent: BYRD, Marshall, P.; Parker Highlander PLLC, 1120 S. Capital Of Texas Highway, Bldg. One, Suite 200, Austin, TX 78746 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • Bacteriocin‐Like Inhibitory Activities of Seven Lactobacillus Delbrueckii
    Letters in Applied Microbiology ISSN 0266-8254 ORIGINAL ARTICLE Bacteriocin-like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains L. Boyanova, G. Gergova, R. Markovska, D. Yordanov and I. Mitov Department of Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria Significance and Impact of the Study: In this study, anti-Helicobacter pylori activity of seven Lactobacil- lus delbrueckii subsp. bulgaricus (GLB) strains was evaluated by four cell-free supernatant (CFS) types. The GLB strains produced heat-stable bacteriocin-like inhibitory substances (BLISs) with a strong anti-H. pylori activity and some neutralized, catalase- and heat-treated CFSs inhibited >83% of the test strains. Bacteriocin-like inhibitory substance production of GLB strains can render them valuable probiotics in the control of H. pylori infection. Keywords Abstract antibiotics, bacteriocins, Helicobacter, Lactobacillus, probiotics. The aim of the study was to detect anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains by four cell-free Correspondence supernatant (CFS) types. Activity of non-neutralized and non-heat-treated Lyudmila Boyanova, Department of Medical (CFSs1), non-neutralized and heat-treated (CFSs2), pH neutralized, catalase- Microbiology, Medical University of Sofia, treated and non-heat-treated (CFSs3), or neutralized, catalase- and heat-treated Zdrave Street 2, 1431 Sofia, Bulgaria. (CFSs4) CFSs against 18 H. pylori strains (11 of which with antibiotic E-mail: [email protected] resistance) was evaluated. All GLB strains produced bacteriocin-like inhibitory 2017/1069: received 3 June 2017, revised 27 substances (BLISs), the neutralized CFSs of two GLB strains inhibited >81% of August 2017 and accepted 25 September test strains and those of four GLB strains were active against >71% of 2017 antibiotic resistant strains.
    [Show full text]
  • Targeting Virulence Not Viability in the Search for Future Antibacterials
    Targeting Virulence not Viability in the Search for Future Antibacterials 1 Begoña Heras1#, Martin J. Scanlon2,3# and Jennifer L. Martin4#* 1La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia 2Faculty of Pharmacy and Pharmaceutical Sciences, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052 Australia 3ARC Centre of Excellence for Coherent X-ray Science, Monash University, Parkville, VIC 3052 Australia 4The University of Queensland, Institute for Molecular Bioscience, Division of Article Chemistry and Structural Biology, Brisbane, QLD 4072 Australia #Contributed equally * To whom correspondence should be addressed: Email: [email protected] Phone +61 7 3346 2016 Running Head: Antivirulence Strategies for Bacterial Infection Keywords: Antivirulence; antibacterial; bacterial infection, pilicide, quorum sensing Word Count (excluding title page, summary, references, tables, figures) 2405 Number of Tables: 1 Number of Figures: 3 This article has been accepted for publication and undergone full peer review but has not been through theAccepted copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.12356 1 This article is protected by copyright. All rights reserved. ABSTRACT New antibacterials need new approaches to overcome the problem of rapid antibiotic resistance. Here we review the development of potential new antibacterial drugs that do not kill bacteria or inhibit their growth, but combat disease instead by targeting bacterial virulence. INTRODUCTION In the ongoing battle between people and pathogens, the pendulum seems to be swingingArticle in favour of the bugs.
    [Show full text]