WO 2013/014497 Al 31 January 2013 (31.01.2013) P O P C T

Total Page:16

File Type:pdf, Size:1020Kb

WO 2013/014497 Al 31 January 2013 (31.01.2013) 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 2013/014497 Al 31 January 2013 (31.01.2013) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/4188 (2006.01) A61K 31/431 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/424 (2006.01) A61K 45/06 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 31/43 (2006.01) A61P 31/04 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (21) Number: International Application HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, PCT/IB201 1/054352 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 4 October 201 1 (04. 10.201 1) OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (25) Filing Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: glish ( ) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 2125/MUM/201 1 26 July 201 1 (26.07.201 1) IN GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 2157/MUM/201 1 29 July 201 1 (29.07.201 1) IN UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant (for all designated States except US): WOCK- DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, HARDT LIMITED [IN/IN]; D-4, MIDC Area, Chi- LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, kalthana, Aurangabad 431210 (IN). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). (72) Inventors; and (75) Inventors/Applicants (for US only): BHAGWAT, Sachin Published: Subhash [IN/IN]; Row House No.C-2, "Nilgiris", Khiv- — with international search report (Art. 21(3)) ansara Park(E), Behind Ramayana, Cultural Hall, Ulkanagari, Aurangabad 431210 (IN). PATEL, Mahesh Vithalbhai [IN/IN]; Plot No. 157, Opposite Saint Meera School, N-3, CIDCO, Aurangabad 43 1003 (IN). (54) Title: PHARMACEUTICAL COMPOSITIONS COMPRISING BETA-LACTAM ANTIBIOTIC, SULBACTAM AND BETA- LACTAMASE INHIBITOR (57) Abstract: Pharmaceutical compositions and methods for treating or preventing bacterial infections are disclosed. The pharma ceutical compositions typically comprise pharmaceutically effective amount of: (a) at least one beta-lactam antibiotic or a pharma ceutically acceptable salt thereof, (b) sulbactam or a pharmaceutically acceptable salt thereof, and (c) at least one beta-lactamase in - hibitor or a pharmaceutically acceptable salt thereof, with the provision that the beta-lactamase inhibitor is not sulbactam. PHARMACEUTICAL COMPOSITIONS COMPRISING BETA- LACTAM ANTIBIOTIC, SULBACTAM AND BETA-LACTAMASE INHIBITOR RELATED PATENT APPLICATIONS This application claims the benefit of Indian Patent Application Nos. 2125/MUM/2011 filed on July 26, 2011, and 2157/MUM/2011 filed on July 29, 2011, the disclosures of which are incorporated herein by reference in their entirety as if fully rewritten herein. All references including patents, patent applications, and literature cited in the specification are expressly incorporated herein by reference in their entirety. FIELD OF THE INVENTION The invention relates to antibacterial compositions and methods for preventing or treating bacterial infections. BACKGROUND OF THE INVENTION Resistance to beta-lactam antibiotics is wide spread and a key concern. One of the mechanism bacteria have developed against beta-lactam antibiotics is production of several beta-lactamase enzymes, which deactivate the beta-lactam antibiotic. In general, a typical beta-lactam antibiotic alone may not be effective in treating infections caused by such beta- lactamase producing bacteria. One alternative to treating infections caused by bacteria producing beta-lactamase enzymes is by co-administration of a beta-lactamase inhibitor with the beta-lactam antibiotic. The beta-lactamase inhibitor prevents deactivation of a beta-lactam antibiotic, typically by binding with the beta-lactamase enzyme. However, even the combination therapy is also proving ineffective in treating infections caused by newer ESBL strains. Drawz et al. (Clinical Microbiology Reviews, 2010, 23(1), pages 160-201) have reviewed developments in the area of beta-lactamase inhibition and inhibitors. Drawz et al. summarize various beta-lactamase inhibitors developed to overcome bacterial resistance. Gold et al. (The New England Journal of Medicine, 1996, 335(19), pages 1445-1453) have also reviewed the subject of antimicrobial drug resistance. The widespread emergence of newer strains that do not respond to even the combination therapies, is becoming a major concern. It is estimated that, internationally the prevalence of ESBL in Klebsiella and E. coli is in the range of 30-50% depending upon the geographical location. For ESBLs, carbapenem therapy is the most widely used in the clinical settings today. Presently, all strains identified as inhibitor resistant ESBLs are treated only by carbapenems. However, some of the emerging ESBLs (e.g. those containing metallo- betalactamases, KPCs and Class D ESBLs) appear to exhibit higher degree of resistance to even carbapenems. Thus, there is a need to develop new ways to treat infections that are becoming resistant to known therapies and methods. SUMMARY OF THE INVENTION Accordingly, there are provided pharmaceutical compositions and methods for treating or preventing bacterial infections. In one general aspect, there are provided pharmaceutical compositions comprising pharmaceutically effective amount of: (a) at least one beta-lactam antibiotic or a pharmaceutically acceptable salt thereof, (b) sulbactam or a pharmaceutically acceptable salt thereof, and (c) at least one beta-lactamase inhibitor or a pharmaceutically acceptable salt thereof, with the provision that the beta-lactamase inhibitor is not sulbactam. In another general aspect, there is provided a method for preventing or treating a bacterial infection in a subject, said method comprising administering to said subject a pharmaceutically effective amount of a pharmaceutical composition comprising pharmaceutically effective amount of: (a) at least one beta-lactam antibiotic or a pharmaceutically acceptable salt thereof, (b) sulbactam or a pharmaceutically acceptable salt thereof, and (c) at least one beta-lactamase inhibitor or a pharmaceutically acceptable salt thereof, with the provision that the beta-lactamase inhibitor is not sulbactam. In another general aspect, there is provided a method for preventing or treating a bacterial infection in a subject, said infection being caused by bacteria producing one or more beta-lactamase enzymes, wherein the method comprises administering to said subject a pharmaceutically effective amount of a pharmaceutical composition comprising a pharmaceutically effective amount of: (a) at least one beta-lactam antibiotic or a pharmaceutically acceptable salt thereof, (b) sulbactam or a pharmaceutically acceptable salt thereof, and (c) at least one beta-lactamase inhibitor or a pharmaceutically acceptable salt thereof, with the provision that the beta-lactamase inhibitor is not sulbactam. In another general aspect, there is provided a method for preventing or treating a bacterial infection in a subject, said method comprising administering to said subject a pharmaceutically effective amount of: (a) at least one beta-lactam antibiotic or a pharmaceutically acceptable salt thereof, (b) sulbactam or a pharmaceutically acceptable salt thereof, and (c) at least one beta-lactamase inhibitor or a pharmaceutically acceptable salt thereof, with the provision that the beta-lactamase inhibitor is not sulbactam. In another general aspect, there is provided a method for preventing or treating a bacterial infection in a subject, said infection being caused by bacteria producing one or more beta-lactamase enzymes, said method comprising administering to said subject a pharmaceutically effective amount of: (a) at least one beta-lactam antibiotic or a pharmaceutically acceptable salt thereof, (b) sulbactam or a pharmaceutically acceptable salt thereof, and (c) at least one beta-lactamase inhibitor or a pharmaceutically acceptable salt thereof, with the provision that the beta-lactamase inhibitor is not sulbactam. In another general aspect, there is provided a method for increasing antibiotic effectiveness of a beta-lactam antibiotic in a subject, said method comprising co administering said beta-lactam antibiotic with a pharmaceutically effective amount of: (a) sulbactam or a pharmaceutically acceptable salt thereof, and (b) at least one beta-lactamase inhibitor or a pharmaceutically acceptable salt thereof, with the provision that the beta- lactamase inhibitor is not sulbactam. The details of one or more embodiments of the invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the following description including claims. DETAILED DESCRIPTION OF THE INVENTION Reference will now be made to the exemplary embodiments, and specific language will be used herein to describe the same. It should nevertheless be understood that no limitation of the scope of the invention is thereby intended. Alterations
Recommended publications
  • Jeanyoung; 617 Fairchild Center, 1212 Amsterdam Av¬ A61K 31/01 (2006.01) A61K 31/375 (2006.01) Enue, New York, NY 10027 (US)
    ) ( International Patent Classification: Jeanyoung; 617 Fairchild Center, 1212 Amsterdam Av¬ A61K 31/01 (2006.01) A61K 31/375 (2006.01) enue, New York, NY 10027 (US). A61K 31/04 2006.01) A61K 33/26 (2006.01) (74) Agent: DAVITZ, Michael, A. etal.; Leason Ellis LLP, One A61K 31/015 (2006.01) A61K 33/40 2006.01) Barker Avenue, Fifth Floor, White Plains, NY 10601 (US). A61K 31/19 (2006.01) A61K 39/104 2006.01) A61K 31/197 2006.01) A61K 45/06 (2006.01) (81) Designated States (unless otherwise indicated, for every A61K 31/198 (2006.01) kind of national protection av ailable) . AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, PCT/US2019/017233 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (22) International Filing Date: HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 08 February 2019 (08.02.2019) 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, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English 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. (30) Priority Data: 62/628,643 09 February 2018 (09.02.2018) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available) .
    [Show full text]
  • A Computational Drug Repositioning Case Study Prashant S. Kharkar1*, Ponnadurai Ramasami2, Yee S
    Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2016 Discovery of Anti-Ebola Drugs: A Computational Drug Repositioning Case Study Prashant S. Kharkar1*, Ponnadurai Ramasami2, Yee Siew Choong3, Lydia Rhyman2 and Sona Warrier1 1SPP School of Pharmacy and Technology Management, SVKM’s NMIMS, V. L. Mehta Road, Vile Parle (West), Mumbai-400 056. INDIA. 2 Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit 80837, Mauritius 3Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Malaysia Contents Sr. No. Description Page No. 1 Table 1S 1 2 Figure 1S 28 3 Figure 2S 29 4 Figure 3S 30 5 Figure 4S 31 6 Figure 5S 32 Table 1S. Top hits (#100) identified from EON screening using query 1 Estimated Sr. EON_ Shape Free Energy Drug Structure ET_pb ET_coul ET_combo Rank No. Tanimoto of Binding (kcal/mol) OH O Br N O 1 1 S -9.88 HO O O O S O O 2 Sitaxentan S 0.633 0.914 0.926 0.294 1 -14.37 HN O Cl O N O HO 3 Alitretinoina 0.66 0.91 0.906 0.246 2 -3.91 NH 2 S N N O O HN 4 Ceftriaxone S 0.606 0.937 0.823 0.217 3 -12.33 N O S N O HO O N N O H O a 5 Acitretin O 0.637 0.936 0.809 0.172 4 -3.71 OH HO NH 2 HO N N 6 Cidofovir P O 0.473 0.633 0.783 0.31 5 -4.21 HO O O N N N N 7 Telmisartan 0.601 0.908 0.775 0.174 6 -6.46 OH O 8 Nateglinidea HN 0.54 0.874 0.745 0.205 7 -3.78 OH O O H N 2 S OH N O N S O 9 Ceftizoxime N 0.557 0.88 0.735 0.178 8 -11.35 H O N O OH O 10 Treprostinil OH 0.432 0.846 0.732 0.301 9 -3.41 O HO O O S
    [Show full text]
  • WO 2015/179249 Al 26 November 2015 (26.11.2015) 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 2015/179249 Al 26 November 2015 (26.11.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12N 15/11 (2006.01) A61K 38/08 (2006.01) kind of national protection available): AE, AG, AL, AM, C12N 15/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2015/031213 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 15 May 2015 (15.05.2015) 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, (25) Filing Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/000,43 1 19 May 2014 (19.05.2014) US kind of regional protection available): ARIPO (BW, GH, 62/129,746 6 March 2015 (06.03.2015) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (72) Inventors; and TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicants : GELLER, Bruce, L.
    [Show full text]
  • Efficacy of Amoxicillin and Amoxicillin/Clavulanic Acid in the Prevention of Infection and Dry Socket After Third Molar Extraction
    Med Oral Patol Oral Cir Bucal. 2016 Jul 1;21 (4):e494-504. Amoxicillin in the prevention of infectious complications after tooth extraction Journal section: Oral Surgery doi:10.4317/medoral.21139 Publication Types: Review http://dx.doi.org/doi:10.4317/medoral.21139 Efficacy of amoxicillin and amoxicillin/clavulanic acid in the prevention of infection and dry socket after third molar extraction. A systematic review and meta-analysis María-Iciar Arteagoitia 1, Luis Barbier 2, Joseba Santamaría 3, Gorka Santamaría 4, Eva Ramos 5 1 MD, DDS, PhD, Associate Professor, Stomatology I Department, University of the Basque Country (UPV/EHU), BioCruces Health Research Institute, Spain; Consolidated research group (UPV/EHU IT821-13) 2 MD PhD, Chair Professor, Maxillofacial Surgery Department, BioCruces Health Research Institute, Cruces University Hos- pital, University of the Basque Country (UPV/EHU), Spain; Consolidated research group (UPV/EHU IT821-13) 3 MD, DDS, PhD, Professor and Chair, Maxillofacial Surgery Department, Bio Cruces Health Research Institute, Cruces University Hospital, University of the Basque Country (UPV/EHU), Bizkaia, Spain; Consolidated research group (UPV/EHU IT821-13) 4 DDS, PhD, Associate Professor, Stomatology I Department, University of the Basque Country (UPV/EHU), BioCruces Health Research Institute, Spain; Consolidated research group (UPV/EHU IT821-13) 5 PhD, Degree in Farmacy, BioCruces Health Research Institute, Cruces University Hospital. Spain Correspondence: Servicio Cirugía Maxilofacial Hospital Universitario de Cruces Plaza de Cruces s/n Arteagoitia MI, Barbier L, Santamaría J, Santamaría G, Ramos E. Ef- Barakaldo, Bizkaia, Spain ficacy of amoxicillin and amoxicillin/clavulanic acid in the prevention [email protected] of infection and dry socket after third molar extraction.
    [Show full text]
  • Download Download
    VOLUME 7 NOMOR 2 DESEMBER 2020 ISSN 2548 – 611X JURNAL BIOTEKNOLOGI & BIOSAINS INDONESIA Homepage Jurnal: http://ejurnal.bppt.go.id/index.php/JBBI IN SILICO STUDY OF CEPHALOSPORIN DERIVATIVES TO INHIBIT THE ACTIONS OF Pseudomonas aeruginosa Studi In Silico Senyawa Turunan Sefalosporin dalam Menghambat Aktivitas Bakteri Pseudomonas aeruginosa Saly Amaliacahya Aprilian*, Firdayani, Susi Kusumaningrum Pusat Teknologi Farmasi dan Medika, BPPT, Gedung LAPTIAB 610-612 Kawasan Puspiptek, Setu, Tangerang Selatan, Banten 15314 *Email: [email protected] ABSTRAK Infeksi yang diakibatkan oleh bakteri gram-negatif, seperti Pseudomonas aeruginosa telah menyebar luas di seluruh dunia. Hal ini menjadi ancaman terhadap kesehatan masyarakat karena merupakan bakteri yang multi-drug resistance dan sulit diobati. Oleh karena itu, pentingnya pengembangan agen antimikroba untuk mengobati infeksi semakin meningkat dan salah satu yang saat ini banyak dikembangkan adalah senyawa turunan sefalosporin. Penelitian ini melakukan studi mengenai interaksi tiga dimensi (3D) antara antibiotik dari senyawa turunan Sefalosporin dengan penicillin-binding proteins (PBPs) pada P. aeruginosa. Tujuan dari penelitian ini adalah untuk mengklarifikasi bahwa agen antimikroba yang berasal dari senyawa turunan sefalosporin efektif untuk menghambat aktivitas bakteri P. aeruginosa. Struktur PBPs didapatkan dari Protein Data Bank (PDB ID: 5DF9). Sketsa struktur turunan sefalosporin digambar menggunakan Marvins Sketch. Kemudian, studi mengenai interaksi antara antibiotik dan PBPs dilakukan menggunakan program Mollegro Virtual Docker 6.0. Hasil yang didapatkan yaitu nilai rerank score terendah dari kelima generasi sefalosporin, di antaranya sefalotin (-116.306), sefotetan (-133.605), sefoperazon (-160.805), sefpirom (- 144.045), dan seftarolin fosamil (-146.398). Keywords: antibiotik, penicillin-binding proteins, P. aeruginosa, sefalosporin, studi interaksi ABSTRACT Infections caused by gram-negative bacteria, such as Pseudomonas aeruginosa, have been spreading worldwide.
    [Show full text]
  • WO 2018/005606 Al 04 January 2018 (04.01.2018) W !P O PCT
    (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 2018/005606 Al 04 January 2018 (04.01.2018) W !P O PCT (51) International Patent Classification: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, A61K 38/43 (2006.01) A61K 47/36 (2006.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, A61K 38/50 (2006.01) A61K 9/S0 (2006.01) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, A61K 33/44 {2006.01) 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. (21) International Application Number: PCT/US20 17/039672 (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (22) International Filing Date: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, 28 June 2017 (28.06.2017) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (25) Filing Language: English TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (26) Publication Langi English MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (30) Priority Data: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 62/355,599 28 June 2016 (28.06.2016) US KM, ML, MR, NE, SN, TD, TG).
    [Show full text]
  • The Oral Pheneticillin Absorption Test: an Accurate Method to Identify Patients with Inadequate Oral Pheneticillin Absorption
    antibiotics Brief Report The Oral Pheneticillin Absorption Test: An Accurate Method to Identify Patients with Inadequate Oral Pheneticillin Absorption Anneke C. Dijkmans 1,*, Dinemarie M. Kweekel 2, Jaap T. van Dissel 3, Michiel J. van Esdonk 1 , Ingrid M. C. Kamerling 1 and Jacobus Burggraaf 1 1 Centre for Human Drug Research (CHDR), 2333 CL Leiden, The Netherlands 2 Department of Clinical Pharmacy, Leiden University Medical Center (LUMC), 2333 ZA LeidenLeiden, The Netherlands 3 Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands * Correspondence: [email protected] Received: 9 July 2019; Accepted: 8 August 2019; Published: 15 August 2019 Abstract: Severe streptococcal infections are commonly treated with intravenous followed by oral penicillin (pheneticillin) therapy. However, switching from iv to oral therapy is complicated by the variability in oral pheneticillin absorption. We employed an Oral Absorption Test (OAT) for pheneticillin to identify patients in whom oral pheneticillin absorption is poor. Out of 84 patients 30 patients (36%) were identified as insufficient absorbers. Treatment failure due to pheneticillin malabsorption can be avoided by performing an OAT, and these patients should be treated by another antibiotic, which is known to be absorbed well. Keywords: penicillin; oral; pheneticillin; streptococcal 1. Background In the Netherlands, patients with severe streptococcal infections are effectively treated with narrow-spectrum antibiotics, most frequently with initial intravenous (iv) penicillin G followed by oral maintenance therapy, usually with pheneticillin. The advantages of this treatment approach are the bactericidal activity of penicillin, the low costs, the possibility to switch to an oral antibiotic as soon as possible, and the lower risk of introducing resistance associated with narrow-spectrum antibiotics.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,680,136 B2 Hirst Et Al
    USOO868O136B2 (12) United States Patent (10) Patent No.: US 8,680,136 B2 Hirst et al. (45) Date of Patent: Mar. 25, 2014 (54) CYCLIC BORONIC ACID ESTER WO WOO3,O70714 8, 2003 DERVATIVES AND THERAPEUTCUSES WO WO 2004/039859 5, 2004 THEREOF WO WO 2005/033090 4/2005 WO WO 2007/095638 8, 2007 WO WO 2009/046098 A1 4, 2009 (75) Inventors: Gavin Hirst, San Diego, CA (US); Raja WO WO 2009/064413 A1 5, 2009 Reddy, San Diego, CA (US); Scott WO WO 2009/064414 A1 5.2009 Hecker, Del Mar, CA (US); Maxim WO WO 2009/140309 A2 11/2009 Totroy San Deigo, CA (US); David C. WO WO 2010/1307082010/075286 A1 11,T 2010 Griffith, San Marcos, CA (US): Olga WO WO 2011/O17125 A1 2/2011 Rodny, Mill Valley, CA (US); Michael N. Dudley, San Diego, CA (US); Serge OTHER PUBLICATIONS Boyer, San Diego, CA (US) Fanetal (2009): STN International HCAPLUS database, Columbus (73) Assignee: Rempex Pharmaceuticals, Inc., San (OH), accession No. 2009: 425839.* Diego, CA (US) Vasil'ev et al (1977): STN International HCAPLUS database, Columbus (OH), accession No. 1977: 72730.* (*) Notice: Subject to any disclaimer, the term of this Allen et al., “Ansel's Pharmaceutical Dosage Forms and Drug Deliv patent is extended or adjusted under 35 ery Systems', 8th Edition (2004). U.S.C. 154(b) by 9 days. Arya et al., “Advances in asymmetric enolate methodology'. Tetra hedron (2000) 56:917-947. (21) Appl. No.: 13/205,112 Biedrzycki et al., “Derivatives of tetrahedral boronic acids”. J. Organomet. Chem.
    [Show full text]
  • Ompf Downregulation Mediated by Sigma E Or Ompr Activation Confers
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.16.444350; this version posted May 17, 2021. 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. 1 OmpF Downregulation Mediated by Sigma E or OmpR Activation Confers 2 Cefalexin Resistance in Escherichia coli in the Absence of Acquired β- 3 Lactamases. 4 5 Maryam ALZAYN1,2, Punyawee DULYAYANGKUL1, Naphat SATAPOOMIN1, 6 Kate J. HEESOM3, Matthew B. AVISON1* 7 8 1School of Cellular & Molecular Medicine, University of Bristol, Bristol, UK 9 2Biology Department, Faculty of Science, Princess Nourah Bint Abdulrahman 10 University, Riyadh, Saudi Arabia 11 3University of Bristol Proteomics Facility, Bristol, UK 12 13 * Correspondence to: School of Cellular & Molecular Medicine, University of 14 Bristol, Bristol, United Kingdom. [email protected] 15 16 17 Running Title: OmpR and Sigma E mediated Cefalexin Resistance in E. coli 18 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.05.16.444350; this version posted May 17, 2021. 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. 19 Abstract 20 Cefalexin is a widely used 1st generation cephalosporin, and resistance in 21 Escherichia coli is caused by Extended-Spectrum (e.g. CTX-M) and AmpC β- 22 lactamase production and therefore frequently coincides with 3rd generation 23 cephalosporin resistance.
    [Show full text]
  • Antibiotic and Metal Resistance in Escherichia Coli Isolated from Pig Slaughterhouses in the United Kingdom
    antibiotics Article Antibiotic and Metal Resistance in Escherichia coli Isolated from Pig Slaughterhouses in the United Kingdom Hongyan Yang 1,2,*, Shao-Hung Wei 2,3, Jon L. Hobman 2 and Christine E. R. Dodd 2 1 College of Life Sciences, Northeast Forestry University, Harbin 150040, China 2 School of Biosciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire LE12 5RD, UK; [email protected] (S.-H.W.); [email protected] (J.L.H.); [email protected] (C.E.R.D.) 3 JHL Biotech, Zhubei City, Hsinchu County 302, Taiwan * Correspondence: [email protected] Received: 28 September 2020; Accepted: 27 October 2020; Published: 28 October 2020 Abstract: Antimicrobial resistance is currently an important concern, but there are few data on the co-presence of metal and antibiotic resistance in potentially pathogenic Escherichia coli entering the food chain from pork, which may threaten human health. We have examined the phenotypic and genotypic resistances to 18 antibiotics and 3 metals (mercury, silver, and copper) of E. coli from pig slaughterhouses in the United Kingdom. The results showed resistances to oxytetracycline, streptomycin, sulphonamide, ampicillin, chloramphenicol, trimethoprim–sulfamethoxazole, ceftiofur, amoxicillin–clavulanic acid, aztreonam, and nitrofurantoin. The top three resistances were oxytetracycline (64%), streptomycin (28%), and sulphonamide (16%). Two strains were resistant to six kinds of antibiotics. Three carried the blaTEM gene. Fifteen strains (18.75%) were resistant to 25 µg/mL mercury and five (6.25%) of these to 50 µg/mL; merA and merC genes were detected in 14 strains. Thirty-five strains (43.75%) showed resistance to silver, with 19 possessing silA, silB, and silE genes.
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 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.
    [Show full text]
  • AMEG Categorisation of Antibiotics
    12 December 2019 EMA/CVMP/CHMP/682198/2017 Committee for Medicinal Products for Veterinary use (CVMP) Committee for Medicinal Products for Human Use (CHMP) Categorisation of antibiotics in the European Union Answer to the request from the European Commission for updating the scientific advice on the impact on public health and animal health of the use of antibiotics in animals Agreed by the Antimicrobial Advice ad hoc Expert Group (AMEG) 29 October 2018 Adopted by the CVMP for release for consultation 24 January 2019 Adopted by the CHMP for release for consultation 31 January 2019 Start of public consultation 5 February 2019 End of consultation (deadline for comments) 30 April 2019 Agreed by the Antimicrobial Advice ad hoc Expert Group (AMEG) 19 November 2019 Adopted by the CVMP 5 December 2019 Adopted by the CHMP 12 December 2019 Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. Categorisation of antibiotics in the European Union Table of Contents 1. Summary assessment and recommendations .......................................... 3 2. Introduction ............................................................................................ 7 2.1. Background ........................................................................................................
    [Show full text]