Cyclic Antibiotic Peptides
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National Antibiotic Consumption for Human Use in Sierra Leone (2017–2019): a Cross-Sectional Study
Tropical Medicine and Infectious Disease Article National Antibiotic Consumption for Human Use in Sierra Leone (2017–2019): A Cross-Sectional Study Joseph Sam Kanu 1,2,* , Mohammed Khogali 3, Katrina Hann 4 , Wenjing Tao 5, Shuwary Barlatt 6,7, James Komeh 6, Joy Johnson 6, Mohamed Sesay 6, Mohamed Alex Vandi 8, Hannock Tweya 9, Collins Timire 10, Onome Thomas Abiri 6,11 , Fawzi Thomas 6, Ahmed Sankoh-Hughes 12, Bailah Molleh 4, Anna Maruta 13 and Anthony D. Harries 10,14 1 National Disease Surveillance Programme, Sierra Leone National Public Health Emergency Operations Centre, Ministry of Health and Sanitation, Cockerill, Wilkinson Road, Freetown, Sierra Leone 2 Department of Community Health, Faculty of Clinical Sciences, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone 3 Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, 1211 Geneva, Switzerland; [email protected] 4 Sustainable Health Systems, Freetown, Sierra Leone; [email protected] (K.H.); [email protected] (B.M.) 5 Unit for Antibiotics and Infection Control, Public Health Agency of Sweden, Folkhalsomyndigheten, SE-171 82 Stockholm, Sweden; [email protected] 6 Pharmacy Board of Sierra Leone, Central Medical Stores, New England Ville, Freetown, Sierra Leone; [email protected] (S.B.); [email protected] (J.K.); [email protected] (J.J.); [email protected] (M.S.); [email protected] (O.T.A.); [email protected] (F.T.) Citation: Kanu, J.S.; Khogali, M.; 7 Department of Pharmaceutics and Clinical Pharmacy & Therapeutics, Faculty of Pharmaceutical Sciences, Hann, K.; Tao, W.; Barlatt, S.; Komeh, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown 0000, Sierra Leone 8 J.; Johnson, J.; Sesay, M.; Vandi, M.A.; Directorate of Health Security & Emergencies, Ministry of Health and Sanitation, Sierra Leone National Tweya, H.; et al. -
Novel Antimicrobial Agents Inhibiting Lipid II Incorporation Into Peptidoglycan Essay MBB
27 -7-2019 Novel antimicrobial agents inhibiting lipid II incorporation into peptidoglycan Essay MBB Mark Nijland S3265978 Supervisor: Prof. Dr. Dirk-Jan Scheffers Molecular Microbiology University of Groningen Content Abstract..............................................................................................................................................2 1.0 Peptidoglycan biosynthesis of bacteria ........................................................................................3 2.0 Novel antimicrobial agents ...........................................................................................................4 2.1 Teixobactin ...............................................................................................................................4 2.2 tridecaptin A1............................................................................................................................7 2.3 Malacidins ................................................................................................................................8 2.4 Humimycins ..............................................................................................................................9 2.5 LysM ........................................................................................................................................ 10 3.0 Concluding remarks .................................................................................................................... 11 4.0 references ................................................................................................................................. -
Brilacidin First-In-Class Defensin-Mimetic Drug Candidate
Brilacidin First-in-Class Defensin-Mimetic Drug Candidate Mechanism of Action, Pre/Clinical Data and Academic Literature Supporting the Development of Brilacidin as a Potential Novel Coronavirus (COVID-19) Treatment April 20, 2020 Page # I. Brilacidin: Background Information 2 II. Brilacidin: Two Primary Mechanisms of Action 3 Membrane Disruption 4 Immunomodulatory 7 III. Brilacidin: Several Complementary Ways of Targeting COVID-19 10 Antiviral (anti-SARS-CoV-2 activity) 11 Immuno/Anti-Inflammatory 13 Antimicrobial 16 IV. Brilacidin: COVID-19 Clinical Development Pathways 18 Drug 18 Vaccine 20 Next Steps 24 V. Brilacidin: Phase 2 Clinical Trial Data in Other Indications 25 VI. AMPs/Defensins (Mimetics): Antiviral Properties 30 VII. AMPs/Defensins (Mimetics): Anti-Coronavirus Potential 33 VIII. The Broader Context: Characteristics of the COVID-19 Pandemic 36 Innovation Pharmaceuticals 301 Edgewater Place, Ste 100 Wakefield, MA 01880 978.921.4125 [email protected] Innovation Pharmaceuticals: Mechanism of Action, Pre/Clinical Data and Academic Literature Supporting the Development of Brilacidin as a Potential Novel Coronavirus (COVID-19) Treatment (April 20, 2020) Page 1 of 45 I. Brilacidin: Background Information Brilacidin (PMX-30063) is Innovation Pharmaceutical’s lead Host Defense Protein (HDP)/Defensin-Mimetic drug candidate targeting SARS-CoV-2, the virus responsible for COVID-19. Laboratory testing conducted at a U.S.-based Regional Biocontainment Laboratory (RBL) supports Brilacidin’s antiviral activity in directly inhibiting SARS-CoV-2 in cell-based assays. Additional pre-clinical and clinical data support Brilacidin’s therapeutic potential to inhibit the production of IL-6, IL-1, TNF- and other pro-inflammatory cytokines and chemokines (e.g., MCP-1), identified as central drivers in the worsening prognoses of COVID-19 patients. -
Antibiotic Assay Medium No. 3 (Assay Broth) Is Used for Microbiological Assay of Antibiotics. M042
HiMedia Laboratories Technical Data Antibiotic Assay Medium No. 3 (Assay Broth) is used for M042 microbiological assay of antibiotics. Antibiotic Assay Medium No. 3 (Assay Broth) is used for microbiological assay of antibiotics. Composition** Ingredients Gms / Litre Peptic digest of animal tissue (Peptone) 5.000 Beef extract 1.500 Yeast extract 1.500 Dextrose 1.000 Sodium chloride 3.500 Dipotassium phosphate 3.680 Potassium dihydrogen phosphate 1.320 Final pH ( at 25°C) 7.0±0.2 **Formula adjusted, standardized to suit performance parameters Directions Suspend 17.5 grams in 1000 ml distilled water. Heat if necessary to dissolve the medium completely. Sterilize by autoclaving at 15 lbs pressure (121°C) for 15 minutes. Advice:Recommended for the Microbiological assay of Amikacin, Bacitracin, Capreomycin, Chlortetracycline,Chloramphenicol,Cycloserine,Demeclocycline,Dihydrostreptomycin, Doxycycline, Gentamicin, Gramicidin, Kanamycin, Methacycline, Neomycin, Novobiocin, Oxytetracycline, Rolitetracycline, Streptomycin, Tetracycline, Tobramycin, Trolendomycin and Tylosin according to official methods . Principle And Interpretation Antibiotic Assay Medium is used in the performance of antibiotic assays. Grove and Randall have elucidated those antibiotic assays and media in their comprehensive treatise on antibiotic assays (1). Antibiotic Assay Medium No. 3 (Assay Broth) is used in the microbiological assay of different antibiotics in pharmaceutical and food products by the turbidimetric method. Ripperre et al reported that turbidimetric methods for determining the potency of antibiotics are inherently more accurate and more precise than agar diffusion procedures (2). Turbidimetric antibiotic assay is based on the change or inhibition of growth of a test microorganims in a liquid medium containing a uniform concentration of an antibiotic. After incubation of the test organism in the working dilutions of the antibiotics, the amount of growth is determined by measuring the light transmittance using spectrophotometer. -
Neomycin and Polymyxin B Sulfates and Gramicidin
NEOMYCIN AND POLYMYXIN B SULFATES AND GRAMICIDIN- neomycin sulfate, polymyxin b sulfate and gramicidin solution/ drops A-S Medication Solutions ---------- Neomycin and Polymyxin B Sulfates and Gramicidin Ophthalmic Solution, USP (Sterile) Rx only DESCRIPTION: Neomycin and Polymyxin B Sulfates and Gramicidin Ophthalmic Solution, USP is a sterile antimicrobial solution for ophthalmic use. Each mL contains: ACTIVES: Neomycin Sulfate, (equivalent to 1.75 mg neomycin base), Polymyxin B Sulfate equal to 10,000 Polymyxin B units, Gramicidin, 0.025 mg; INACTIVES: Sodium Chloride, Alcohol (0.5%), Poloxamer 188, Propylene Glycol, Purified Water. Hydrochloric Acid and/ or Ammonium Hydroxide may be added to adjust pH (4.7-6.0). PRESERVATIVE ADDED: Thimerosal 0.001%. Neomycin Sulfate is the sulfate salt of neomycin B and C, which are produced by the growth of Streptomyces fradiae Waksman (Fam. Streptomycetaceae). It has a potency equivalent of not less than 600 micrograms of neomycin base per milligram, calculated on an anhydrous basis. The structural formulae are: Polymyxin B Sulfate is the sulfate salt of polymyxin B1 and B2 which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillaceae). It has a potency of not less than 6,000 polymyxin B units per milligram, calculated on an anhydrous basis. The structural formulae are: Gramicidin (also called gramicidin D) is a mixture of three pairs of antibacterial substances (Gramicidin A, B and C) produced by the growth of Bacillus brevis Dubos (Fam. Bacillaceae). It has a potency of not less than 900 mcg of standard gramicidin per mg. The structural formulae are: CLINICAL PHARMACOLOGY: A wide range of antibacterial action is provided by the overlapping spectra of neomycin, polymyxin B sulfate, and gramicidin. -
Penicillin Allergy Guidance Document
Penicillin Allergy Guidance Document Key Points Background Careful evaluation of antibiotic allergy and prior tolerance history is essential to providing optimal treatment The true incidence of penicillin hypersensitivity amongst patients in the United States is less than 1% Alterations in antibiotic prescribing due to reported penicillin allergy has been shown to result in higher costs, increased risk of antibiotic resistance, and worse patient outcomes Cross-reactivity between truly penicillin allergic patients and later generation cephalosporins and/or carbapenems is rare Evaluation of Penicillin Allergy Obtain a detailed history of allergic reaction Classify the type and severity of the reaction paying particular attention to any IgE-mediated reactions (e.g., anaphylaxis, hives, angioedema, etc.) (Table 1) Evaluate prior tolerance of beta-lactam antibiotics utilizing patient interview or the electronic medical record Recommendations for Challenging Penicillin Allergic Patients See Figure 1 Follow-Up Document tolerance or intolerance in the patient’s allergy history Consider referring to allergy clinic for skin testing Created July 2017 by Macey Wolfe, PharmD; John Schoen, PharmD, BCPS; Scott Bergman, PharmD, BCPS; Sara May, MD; and Trevor Van Schooneveld, MD, FACP Disclaimer: This resource is intended for non-commercial educational and quality improvement purposes. Outside entities may utilize for these purposes, but must acknowledge the source. The guidance is intended to assist practitioners in managing a clinical situation but is not mandatory. The interprofessional group of authors have made considerable efforts to ensure the information upon which they are based is accurate and up to date. Any treatments have some inherent risk. Recommendations are meant to improve quality of patient care yet should not replace clinical judgment. -
Biological Function of Gramicidin: Studies on Gramicidin-Negative Mutants (Peptide Antibiotics/Sporulation/Dipicolinic Acid/Bacillus Brevis) PRANAB K
Proc. NatS. Acad. Sci. USA Vol. 74, No. 2, pp. 780-784, February 1977 Microbiology Biological function of gramicidin: Studies on gramicidin-negative mutants (peptide antibiotics/sporulation/dipicolinic acid/Bacillus brevis) PRANAB K. MUKHERJEE AND HENRY PAULUS Department of Metabolic Regulation, Boston Biomedical Research Institute, Boston, Massachusetts 02114; and Department of Biological Chemistry, Harvard Medical School, Boston, Massachusetts 02115 Communicated by Bernard D. Davis, October 28,1976 ABSTRACT By the use of a rapid radioautographic EXPERIMENTAL PROCEDURE screening rocedure, two mutants of Bacillus brevis ATCC 8185 that have lost the ability to produce gramicidin have been iso- lated. These mutants produced normal levels of tyrocidine and Bacterial Strains. Bacillus brevis ATCC 8185, the Dubos sporulated at the same frequency as the parent strain. Their strain, was obtained from the American Type Culture Collec- spores, however, were more heat-sensitive and had a reduced tion. Strain S14 is a streptomycin-resistant derivative of B. brevis 4ipicolinic acid content. Gramicidin-producing revertants oc- ATCC 8185, isolated on a streptomycin-gradient plate without curred at a relatively high frequency among tie survivors of mutagenesis. It grows well at 0.5 mg/ml of streptomycin, but prolonged heat treatment and had also regained the ability to produce heat-resistant spores. A normal spore phenotype could growth is retarded by streptomycin at 1.0 mg/ml. Strain B81 also be restored by the addition of gramicidin to cultures of the is a rifampicin-resistant derivative of strain S14, isolated on mutant strain at the end of exponential growth. On the other rifampicin-gradient plates after mutagenesis of spores with hand, the addition of dipicolinic acid could not cure the spore ethyl methanesulfonate (11). -
Topical Antibiotics for Impetigo: a Review of the Clinical Effectiveness and Guidelines
CADTH RAPID RESPONSE REPORT: SUMMARY WITH CRITICAL APPRAISAL Topical Antibiotics for Impetigo: A Review of the Clinical Effectiveness and Guidelines Service Line: Rapid Response Service Version: 1.0 Publication Date: February 21, 2017 Report Length: 23 Pages Authors: Rob Edge, Charlene Argáez Cite As: Topical antibiotics for impetigo: a review of the clinical effectiveness and guidelines. Ottawa: CADTH; 2017 Feb. (CADTH rapid response report: summary with critical appraisal). ISSN: 1922-8147 (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. -
Identification Product Identifier Product Name Neomycin Sulfate
Neomycin Sulfate & Polymyxin B Sulfates & Gramicidin Ophthalmic Solution Safety Data Sheet Section 1: Identification Product identifier Neomycin Sulfate & Polymyxin B Sulfates & Gramicidin Product Name Ophthalmic Solution Product Code AB03409; Core No. 034; NDC 24208-0790-62 Relevant identified uses of the substance or mixture and uses advised against Recommended use Finished Pharmaceutical Product; Indicated for the topical treatment of superficial infections of the external eye and its adnexa caused by susceptible bacteria. Restrictions on use Refer to the product insert and/or prescribing information for restrictions on use and contraindications. Details of the supplier of the safety data sheet Manufacturer Bausch & Lomb 1400 North Goodman Street Rochester, NY 14609 United States bausch.com Telephone (General) 1-800-553-5340 Emergency telephone number Manufacturer 1-800-535-5053 - Infotrac This safety data sheet is written to provide health, safety and environmental information for people handling this formulated product in the workplace. It is not intended to provide information relevant to consumer use of the product. Section 2: Hazard Identification UN GHS According to: UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Classification of the substance or mixture UN GHS Skin Sensitization 1B Label elements UN GHS WARNING Hazard statements May cause an allergic skin reaction Precautionary statements Preparation Date: 07/September/1994 Format: GHS Language: English (US) Revision Date: 24/April/2015 UN GHS Page 1 of 10 Neomycin Sulfate & Polymyxin B Sulfates & Gramicidin Ophthalmic Solution Prevention Wash thoroughly after handling. Response IF ON SKIN: Wash with plenty of soap and water. If skin irritation or rash occurs: Get medical advice/attention. -
Antibiotics & Common Infections ABX-2
- - Summaries: Trial SSTI Related toxicity rare - Evidence/Safety, Q&As/Extras: Nitrofurantion documents/GeriRxFiles-UTI.pdf http://www.rxfiles.ca/rxfiles/uploads/ Adults: UTIinOlder Geri-RxFiles RxFILES EXTRAS FROM lookup/59/2/e10 https://academic.oup.com/cid/article- Infections Tissue Skin &Soft IDSA2014: U.S. TISSUEINFECTIONS SKIN &SOFT assets/files/guidelines/en/1121.pdf https://www.cua.org/themes/web/ UTI Recurrent 2011: CUA 2163(16)34717-X/pdf http://www.jogc.com/article/S1701- UTI Recurrent SOGC 2010: 19April2013.pdf photos/custom/UTI%20Guidelines%20 https://saskpic.ipac-canada.org/ Settings Care UTI inContinuing 2013: SK MOH lookup/52/5/e103 https://academic.oup.com/cid/article- (UTI) Pylonephritis Cystitisand Acute Uncomplicated IDSA2010: U.S. CYSTITIS / UTI http://www.mumshealth.com MUMS Guidelines: http://www.bugsanddrugs.ca/ &Drugs: Bugs CANADIAN LINKS ABX-2 RELATED Skin Abscess: I&D +/- ABX I&D +/-ABX Skin Abscess: Clindamycin vs TMP/SMX vsTMP/SMX Clindamycin GUIDELINES/REFERENCES GUIDELINES/REFERENCES - Antibiotics & Common Infections &CommonInfections Antibiotics Stewardship, Effectiveness, Safety & Clinical Pearls-April2017 & Stewardship, Effectiveness,Safety ( Susceptibility of of Susceptibility 1) CYSTISIS UNCOMPLICATED CAUGHTOUREYE... FROMINSIDE THAT ABX-2: AFEWPEARLS Pad”. “Viral Prescription at allavailable These are friendly postersandthepatient suchasthe“GoneViral?”office/clinic extra supporttools on discussions inSaskatchewan. withproviders discussions detailing our springacademic Our tissue(SSTI)infections. and skin&soft willsupport The newchartsinthisnewsletter cystitis uncomplicated of onthetreatment topic tobringouttheABX-2 excited are We ONABX RxFILES ACADEMIC DETAILING pg9) (see Know youroptions! anaphylaxis). (e.g. allergy mediated atrueIgE will have ___ only “allergy”, penicillin 7) ALLERGY LACTAM BETA cellulitis. of treatment successful inthe essential -often 5) verywell. -
Subpart J—Certain Other Dosage Forms [Reserved] PART
Pt. 448 21 CFR Ch. I (4±1±96 Edition) (ii) Samples required: Subpart HÐRectal Dosage Forms (a) The oxytetracycline hydro- [Reserved] chloride used in making the batch: 10 packages, each containing approxi- mately 300 milligrams. Subpart IÐ[Reserved] (b) The polymyxin B sulfate used in making the batch: 10 packages, each Subpart JÐCertain Other Dosage containing approximately 300 milli- Forms [Reserved] grams. (c) The batch: A minimum of 30 tab- PART 448ÐPEPTIDE ANTIBIOTIC lets. DRUGS (b) Tests and methods of assayÐ(1) Po- tencyÐ(i) Oxytetracycline content. Pro- Subpart AÐBulk Drugs ceed as directed in § 436.106 of this chap- ter, preparing the sample for assay as Sec. 448.10 Bacitracin. follows: Place a representative number 448.10a Sterile bacitracin. of tablets into a high-speed glass blend- 448.13 Bacitracin zinc. er jar containing sufficient 0.1N hydro- 448.13a Sterile bacitracin zinc. chloric acid to obtain a stock solution 448.15a Sterile capreomycin sulfate. of convenient concentration containing 448.20a Sterile colistimethate sodium. not less than 150 micrograms of oxytet- 448.21 Colistin sulfate. racycline per milliliter (estimated). 448.23 Cyclosporine. Blend for 3 to 5 minutes. Remove an al- 448.25 Gramicidin. iquot of the stock solution and further 448.30 Polymyxin B sulfate. dilute with sterile distilled water to 448.30a Sterile polymyxin B sulfate. the reference concentration of 0.24 448.75 Tyrothricin. microgram of oxytetracycline per mil- liliter (estimated). Subpart BÐOral Dosage Forms (ii) Polymyxin B content. Proceed as 448.121 Colistin sulfate for oral suspension. directed in § 436.105 of this chapter, pre- 448.123 Cyclosporine oral dosage forms. -
Antibiotic Resistance: Nosopharm and the University of Illinois at Chicago Describe Mechanism of Action of New Class of Antibiotics in Molecular Cell
Antibiotic resistance: Nosopharm and the University of Illinois at Chicago describe mechanism of action of new class of antibiotics in Molecular Cell Newly discovered antibiotic binds to ribosome and disrupts protein synthesis Lyon, France, and Chicago (IL), United States - April 5 2018 – Nosopharm, a company dedicated to the research and development of new anti-infective drugs, and the University of Illinois at Chicago (UIC) today announce the publication of a study in Molecular Cell on the mechanism of action of odilorhabdins, a new class of antibiotics to combat antibiotic resistance. The antibiotic, first identified by Nosopharm, is unique and promising on two fronts: its unconventional source and its distinct way of killing bacteria, both of which suggest the compound may be effective at treating drug-resistant or hard to treat bacterial infections. Called odilorhabdins, or ODLs, the antibiotics are produced by symbiotic bacteria found in soil-dwelling nematode worms that colonize insects for food. The bacteria help to kill the insect and, importantly, secrete the antibiotic to keep competing bacteria away. Until now, these nematode-associated bacteria and the antibiotics they make have been largely understudied. The odilorhabdin program was launched by Nosopharm in 2011. To identify the antibiotic, Nosopharm’s researchers team screened eighty cultured strains of the bacteria for antimicrobial activity. They then isolated the active compounds, studied their chemical structures and their structure-activity relationships, investigated their pharmacology and engineered more potent derivatives. The study, published in Molecular Cell1, describes the new antibiotic and, for the first time, how it works. Nosopharm’s Maxime Gualtieri, UIC's Alexander Mankin and Yury Polikanov are corresponding authors on the study and led the research on the antibiotic's mechanism of action.