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Investigational Drug Therapies Currently in Early-Stage Clinical Development for the Treatment of Clostridioides (Clostridium) Difficile Infection Mai-Chi N
EXPERT OPINION ON INVESTIGATIONAL DRUGS https://doi.org/10.1080/13543784.2019.1581763 REVIEW Investigational drug therapies currently in early-stage clinical development for the treatment of clostridioides (clostridium) difficile infection Mai-Chi N. Trana,b, Ravina Kullarc and Ellie J. C. Goldsteind,e aDepartment of Pharmacy, Providence St. John’s Health Center, Santa Monica, CA, USA; bDepartment of Pharmacy, Clinica Juan Pablo Medical Group, Los Angeles, CA, USA; cDoctor Evidence, LLC, Santa Monica, CA, USA; dR M Alden Research Laboratory, Santa Monica, CA, USA; eDavid Geffen School of Medicine, Los Angeles, CA, USA ABSTRACT ARTICLE HISTORY Introduction: Clostridioides (Clostridium) difficile Infection (CDI) is an urgent global threat causing Received 16 August 2018 ~500,000 infections annually in the United States of America (USA) and is associated with a 36% 30- Accepted 8 February 2019 day attributable mortality rate. Despite the availability of three therapeutic agents, CDI recurrence KEYWORDS – – occurs in 20 40% of patients, with a 30 40% second recurrence rate in these patients. Consequently, ACX-362F; DS-2969b; there is a need for novel agents for treating CDI. LFF571; ribaxamase; Areas covered: We searched MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Register of ridinilazole; RBX 2660; Controlled Trials, and ClinicalTrials.gov for agents in early stages of clinical development. CRS3123; MCB3681/ These drugs include ACX-362E, DS-2969b, LFF 571, RBX2660, ribaxamase, ridinilazole that have MCB3837 advanced to at least phase 2 and several other drugs in phase 1 development. Expert opinion: The challenge for these new agents is three-fold: (1) to have a novel approach such as a different target/mechanism of action; (2) be ‘significantly’ better than existing agents in regard to ‘sustained clinical response’; or (3) be priced at a reasonable cost when it comes to market or perhaps all three. -
First Case of Furuncular Myiasis Due to Cordylobia Anthropophaga in A
braz j infect dis 2 0 1 8;2 2(1):70–73 The Brazilian Journal of INFECTIOUS DISEASES www.elsevi er.com/locate/bjid Case report First case of Furuncular Myiasis due to Cordylobia anthropophaga in a Latin American resident returning from Central African Republic a b a c a,∗ Jóse A. Suárez , Argentina Ying , Luis A. Orillac , Israel Cedeno˜ , Néstor Sosa a Gorgas Memorial Institute, City of Panama, Panama b Universidad de Panama, Departamento de Parasitología, City of Panama, Panama c Ministry of Health of Panama, International Health Regulations, Epidemiological Surveillance Points of Entry, City of Panama, Panama a r t i c l e i n f o a b s t r a c t 1 Article history: Myiasis is a temporary infection of the skin or other organs with fly larvae. The lar- Received 7 November 2017 vae develop into boil-like lesions. Creeping sensations and pain are usually described by Accepted 22 December 2017 patients. Following the maturation of the larvae, spontaneous exiting and healing is expe- Available online 2 February 2018 rienced. Herein we present a case of a traveler returning from Central African Republic. She does not recall insect bites. She never took off her clothing for recreational bathing, nor did Keywords: she visit any rural areas. The lesions appeared on unexposed skin. The specific diagnosis was performed by morphologic characterization of the larvae, resulting in Cordylobia anthro- Cordylobia anthropophaga Furuncular myiasis pophaga, the dominant form of myiasis in Africa. To our knowledge, this is the first reported Tumbu-fly case of C. -
WO 2015/028850 Al 5 March 2015 (05.03.2015) P O P C T
(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 2015/028850 Al 5 March 2015 (05.03.2015) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C07D 519/00 (2006.01) A61P 39/00 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, C07D 487/04 (2006.01) A61P 35/00 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61K 31/5517 (2006.01) A61P 37/00 (2006.01) HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, A61K 47/48 (2006.01) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/IB2013/058229 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (22) International Filing Date: TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, 2 September 2013 (02.09.2013) ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicant: HANGZHOU DAC BIOTECH CO., LTD UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [US/CN]; Room B2001-B2019, Building 2, No 452 Sixth TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Street, Hangzhou Economy Development Area, Hangzhou EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, City, Zhejiang 310018 (CN). -
Effect of Msa on Antibiotic Resistance and Allelic Replacement of Pkor1 in Staphylococcus Aureus
The University of Southern Mississippi The Aquila Digital Community Honors Theses Honors College Fall 12-2012 Effect of msa on Antibiotic Resistance and Allelic Replacement of pKOR1 in Staphylococcus aureus Jordan M. Towne University of Southern Mississippi Follow this and additional works at: https://aquila.usm.edu/honors_theses Recommended Citation Towne, Jordan M., "Effect of msa on Antibiotic Resistance and Allelic Replacement of pKOR1 in Staphylococcus aureus" (2012). Honors Theses. 103. https://aquila.usm.edu/honors_theses/103 This Honors College Thesis is brought to you for free and open access by the Honors College at The Aquila Digital Community. It has been accepted for inclusion in Honors Theses by an authorized administrator of The Aquila Digital Community. For more information, please contact [email protected]. The University of Southern Mississippi Effect of msa on antibiotic resistance and allelic replacement of pKOR1 in Staphylococcus aureus by Jordan Towne A Thesis Submitted to the Honors College of The University of Southern Mississippi in Partial Fulfillment of the Requirements for the Degree of Bachelor of Science in the Department of Biological Sciences December 2012 ii Approved By: ____________________________ Mohamed O. Elasri Department of Biological Sciences ____________________________ Glenmore Shearer, Chair Department of Biological Sciences ___________________________ David R. Davies, Dean Honors College iii Abstract Staphylococcus aureus is an important human pathogen that causes hospital and community-acquired infections (52). These infections are difficult to treat due to resistance to a wide range of antibiotics and spread of antibiotic-resistant strains (13, 52). S. aureus causes infection by regulation of accessory genes encoding for expression of factors contributing to virulence (9, 11, 12, 29, 34, 43, 45), including severe infection, biofilm formation, autolysis, and antibiotic resistance (4, 5, 7, 27, 56). -
Modifications to the Harmonized Tariff Schedule of the United States To
U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b). -
Prevention of Nosocomial Infections in Neonatal Intensive Care Units
81 Prevention of Nosocomial Infections in Neonatal Intensive Care Units Paolo Manzoni, MD1 Daniele De Luca, MD2 Mauro Stronati, MD3 Evelyne Jacqz-Aigrain, MD, PhD4 Giulia Ruffinazzi, MD3 Martina Luparia, MD1 Elena Tavella, MD1 Elena Boano, RN1 Elio Castagnola, MD5 Michael Mostert, MD6 Daniele Farina, MD1 1 Neonatology and NICU, “S. Anna” Hospital, Turin, Italy Address for correspondence and reprint requests Paolo Manzoni, MD, 2 Laboratory of Clinical Molecular Biology and Pediatric Intensive Care Neonatology and NICU, S. Anna Hospital, Azienda Ospedaliera Regina Unit, University Hospital “A. Gemelli,” Catholic University of the Margherita–S. Anna, C.so Spezia 60, 10126 Torino, Italy Sacred Heart, Rome, Italy (e-mail: [email protected]). 3 Neonatology, IRCCS S. Matteo, Pavia, Italy 4 Department of Paediatric Pharmacology and Pharmacogenetics, Clinical Investigation Center, Hopital “R. Debré,” Paris, France 5 Infectious Disease Unit, “G. Gaslini” Children’s Hospital, Genoa, Italy 6 Department of Paediatrics, University of Torino, Torino, Italy Am J Perinatol 2013;30:81–88. Abstract Neonatal sepsis causes a huge burden of morbidity and mortality and includes bloodstream, urine, cerebrospinal, peritoneal, and lung infections as well as infections starting from burns and wounds, or from any other usually sterile sites. It is associated with cytokine - and biomediator-induced disorders of respiratory, hemodynamic, and metabolic processes. Neonates in the neonatal intensive care unit feature many specific risk factors for bacterial and fungal sepsis. Loss of gut commensals such as Bifidobacteria and Lactobacilli spp., as occurs with prolonged antibiotic treatments, delayed enteral feeding, or nursing in incubators, translates into proliferation of pathogenic microflora and abnormal gut colonization. -
Chemical Probes to Visualize Bacterial Cell Structure and Physiology
molecules Review From Differential Stains to Next Generation Physiology: Chemical Probes to Visualize Bacterial Cell Structure and Physiology Jonathan Hira 1, Md. Jalal Uddin 1 , Marius M. Haugland 2 and Christian S. Lentz 1,* 1 Research Group for Host-Microbe Interactions, Department of Medical Biology and Centre for New Antibacterial Strategies (CANS), UiT—The Arctic University of Norway, 9019 Tromsø, Norway; [email protected] (J.H.); [email protected] (M.J.U.) 2 Department of Chemistry and Centre for New Antibacterial Strategies (CANS), UiT—The Arctic University of Norway, 9019 Tromsø, Norway; [email protected] * Correspondence: [email protected] Academic Editor: Steven Verhelst Received: 30 September 2020; Accepted: 23 October 2020; Published: 26 October 2020 Abstract: Chemical probes have been instrumental in microbiology since its birth as a discipline in the 19th century when chemical dyes were used to visualize structural features of bacterial cells for the first time. In this review article we will illustrate the evolving design of chemical probes in modern chemical biology and their diverse applications in bacterial imaging and phenotypic analysis. We will introduce and discuss a variety of different probe types including fluorogenic substrates and activity-based probes that visualize metabolic and specific enzyme activities, metabolic labeling strategies to visualize structural features of bacterial cells, antibiotic-based probes as well as fluorescent conjugates to probe biomolecular uptake pathways. Keywords: activity-based probe; antibiotic conjugate; bacterial imaging; bacterial uptake; fluorogenic substrate; metabolic labeling; phenotypic heterogeneity 1. Introduction—From 19th Century Microbiology to Modern Day Chemical Biology If chemical biology can be defined as the ‘interrogation of biological systems with chemical approaches’ [1], we must acknowledge some of the first microbiologists as chemical biologists. -
Pharmaceutical Appendix to the Tariff Schedule 2
Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9 -
Using Phage Display to Select Peptides Binding to Type 8 Capsular Polysaccharide of Staphylococcus Aureus
Using Phage Display to Select Peptides Binding to Type 8 Capsular Polysaccharide of Staphylococcus aureus by Nina M. Lenkey Submitted in Partial Fulfillment of the Requirements for the Degree of Maters of Science in the Biology Program YOUNGSTOWN STATE UNIVERSITY December, 2016 Using Phage Display to Select Peptides Binding to Type 8 Capsular Polysaccharide of Staphylococcus aureus Nina Lenkey I hereby release this thesis to the public. I understand that this thesis will be made available from the OhioLINK ETD Center and the Maag Library Circulation Desk for public access. I also authorize the University or other individuals to make copies of this thesis as needed for scholarly research. Signature: Nina Lenkey, Student Date Approvals: Dr. Diana Fagan, Thesis Advisor Date Dr. David Asch, Committee Member Date Dr. Gary Walker, Committee Member Date Dr. Salvatore A. Sanders, Dean of Graduate Studies Date Abstract S. aureus aureus (S. aureus) is a major bacterial pathogen causing an array of critical infections. Increasing the problem of S. aureus infections is the fact that forty to sixty percent of S. aureus infections have now become antibiotic resistant, making it difficult to treat. S. aureus is protected by a polysaccharide capsule, which contributes to its virulence. The goal of this project is to identify a peptide that will bind to S. aureus type 8 capsular polysaccharide using phage display technology. Phage display is a technique used to display proteins or peptides on the surface of a phage (a virus that infects a bacterium). If a peptide displayed on the phage surface binds to a molecule of interest, the DNA for that peptide can be sequenced and used to synthesize the pure peptide. -
WO 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T
(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 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A01N 43/00 (2006.01) A61K 31/33 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/US2016/028383 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 20 April 2016 (20.04.2016) 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. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/154,426 29 April 2015 (29.04.2015) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: KARDIATONOS, INC. [US/US]; 4909 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Lapeer Road, Metamora, Michigan 48455 (US). -
Cordylobia Anthropophaga in a Korean Traveler Returning from Uganda
ISSN (Print) 0023-4001 ISSN (Online) 1738-0006 Korean J Parasitol Vol. 55, No. 3: 327-331, June 2017 ▣ CASE REPORT https://doi.org/10.3347/kjp.2017.55.3.327 A Case of Furuncular Myiasis Due to Cordylobia anthropophaga in a Korean Traveler Returning from Uganda 1,3 2 1 1 3 3, Su-Min Song , Shin-Woo Kim , Youn-Kyoung Goo , Yeonchul Hong , Meesun Ock , Hee-Jae Cha *, 1, Dong-Il Chung * 1Department of Parasitology and Tropical Medicine, 2Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea; 3Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Korea Abstract: A fly larva was recovered from a boil-like lesion on the left leg of a 33-year-old male on 21 November 2016. He has worked in an endemic area of myiasis, Uganda, for 8 months and returned to Korea on 11 November 2016. The larva was identified as Cordylobia anthropophaga by morphological features, including the body shape, size, anterior end, pos- terior spiracles, and pattern of spines on the body. Subsequent 28S rRNA gene sequencing showed 99.9% similarity (916/917 bp) with the partial 28S rRNA gene of C. anthropophaga. This is the first imported case of furuncular myiasis caused by C. anthropophaga in a Korean overseas traveler. Key words: Cordylobia anthropophaga, myiasis, furuncular myiasis, molecular identification, 28S rRNA gene, Korean traveler INTRODUCTION throughout the tropical and subtropical Africa [5]. Humans can be infested through direct exposure to environments con- Myiasis is a parasitic infestation by larval stages of the flies taminated with eggs of the fly [6]. -
Identifying Targets for Potentiators in S. Aureus Using Chemical Genetic Approaches
Identifying targets for potentiators in S. aureus using chemical genetic approaches The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Rajagopal, Mithila. 2016. Identifying targets for potentiators in S. aureus using chemical genetic approaches. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:33840649 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Identifying targets for potentiators in S. aureus using chemical genetic approaches A dissertation presented by Mithila Rajagopal to The Department of Chemistry and Chemical Biology in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Chemistry Harvard University Cambridge, Massachusetts June 2016 © 2016 Mithila Rajagopal All Rights Reserved Dissertation Advisors: Dr. Suzanne Walker and Dr. Daniel Kahne Mithila Rajagopal Identifying targets for potentiators in S. aureus using chemical genetic approaches Abstract Staphylococcus aureus is a highly feared Gram-positive pathogen. The rise in antibiotic resistance has made S. aureus infections intractable. To find new ways to treat S. aureus infections, it is important to understand how this organism protects itself from antibiotics. We probed S. aureus transposon libraries with different classes of antibiotics and used Tn-Seq to identify intrinsic resistance factors that are important in withstanding antibiotics. We identified and validated the importance of a number of previously known intrinsic resistance factors such as mprF, fmtA and the graRS/vraFG multi-component sensing system, as well as a number of novel factors whose involvement in antibiotic resistance has not been previously appreciated.