21 Cephalosporins

Total Page:16

File Type:pdf, Size:1020Kb

21 Cephalosporins Cephalosporins 21 William A. Craig and David R. Andes Although the discovery of the cephalosporin antibiotic class was Modifications at R2 often alter the pharmacology of the compound. reported in 1945, it took almost 2 decades for this class to achieve Changes in the R2 constituent may influence the ability of the com- clinical utility. Giuseppe Brotzu is widely credited for discovery of the pound to reach certain infection sites, such as the central nervous broad-spectrum inhibitory effects of sewage outflow in Sardinia, Italy.1 system, or may simply prolong the elimination half-life of the drug. Professor Brotzu subsequently isolated the mold Cephalosporin acre- The predominant changes at R1 (position C7) include the addition monium (now Acremonium chrysogenum) and demonstrated antimi- of an acyl side chain and the substitution of the hydrogen with crobial activity of culture filtrates against both gram-positive and a methoxy group.5 The R1 methoxy substitution led to the develop- gram-negative bacteria. He also demonstrated the in vivo activity of ment of the cephamycin group of compounds, including cefoxitin, these culture filtrates in animal infection models and in several patients. cefmetazole, and cefotetan. This alteration enhanced resistance The filtrate was administered both locally by injection into skin to β-lactamase produced by gram-negative anaerobic and aerobic abscesses and systemically for the treatment of brucellosis and typhoid bacteria.5,6 However, these compounds have lower affinity for the fever. penicillin-binding protein (PBP) target in gram-positive bacteria.7 The A decade after the initial discovery, the cephalosporin substances cephamycin group is structurally related to the cephalosporins but were isolated and identified as fermentation products of the mold.2 originated as a metabolite from Streptomyces lactamdurans.6 The basic Investigators at Oxford, including Florey and Abraham, systematically building block of the cephamycin group is cephamycin C. Hydrolysis studied the physical, chemical, and structural characteristics of cepha- of cephamycin C produces the 7-ACA nucleus. losporins, as they had for the penicillin class a decade earlier. Three Many modifications of the acyl side chain have been undertaken. substances—cephalosporin P, N, and C—were identified. Each of the The first compounds resulting from addition of a thienyl ring or a products possessed antimicrobial activity but only cephalosporin C tetrazole structure at R1 included the first-generation cephalosporins— demonstrated activity against both gram-negative and gram-positive cephalothin, cephaloridine, and cefazolin (Fig. 21-2). The simple sub- bacteria. In addition, it had advantageous stability in the presence of stitution of an aminobenzyl group in the C7 position is important for acid and penicillinases.2 Cephalosporin C became the foundation of oral absorption of the cephalosporins.5 Cephalexin, cephradine, cefa- subsequent drug development. clor, cefprozil, and loracarbef all have this structure or a closely related The first cephalosporin pharmaceutical, cephalothin, was intro- one (Fig. 21-3). Absorption of later-generation cephalosporins is duced for clinical use in 1964. There are more than 20 cephalosporin enhanced by the production of ester formulations. Axetil, proxetil, or antibiotics in use today (17 in the United States). The cephalosporin pivoxil esters of cefuroxime, cefpodoxime, and cefditoren are currently class is among the most widely prescribed antimicrobial classes because available. of its broad spectrum of activity, low toxicity, ease of administration, Most of the chemical modifications in cephalosporin development and favorable pharmacokinetic profile. that have resulted in changes in microbiologic spectrum are alterations CHEMISTRY Most of the available cephalosporins are semisynthetic derivatives of Cefazolin cephalosporin C. The basic structure of the cephem nucleus includes NN S C N N a β-lactam ring fused to a six-member sulfur-containing dihydrothi- N CH2 HN azine ring (Fig. 21-1). The cephem nucleus is chemically distinct from N S CH O N CH2 3 the penicillin nucleus, which contains a five-member thiazolidine ring. O S Basic structure numbering of the cephalosporin ring system begins within the dihydrothiazine ring at the sulfur moiety. The starting mate- A COOH rial used as the nucleus for current cephalosporin development is Cephalothin 7-aminocephalosporanic acid (7-ACA). Attempts to alter the physio- S O CH2 C HN chemical and biologic properties of the cephalosporins by chemical S N CH O C CH side chain modifications were based on successes with similar struc- O 2 3 tural changes at the 6-aminopenicillanic acid side chain of penicillin.3 O Chemical modifications of the basic cephem structure by substitution B COOH of constituents at positions C1, C3, and C7 led to the various cephalo- 4,5 Cefadroxil sporin compounds in use today. Alterations in position C7 and C3 S are also commonly referred to as R1 and R2, respectively. In general, HO CH C HN changes at R1 affect the microbial spectrum of activity. These modifica- N CH O 3 tions often have an impact on the stability of the compound to enzy- NH matic destruction by β-lactamases or on its affinity for the drug target. 2 O C COOH Cephalexin 1 S CH C HN 7 S R C HN 1 N CH O 3 3 R NH O N 2 2 O O D COOH - COO FIGURE 21-2 First-generation cephalosporins. A, Cefazolin. B, FIGURE 21-1 Basic cephalosporin nucleus. Cephalothin. C, Cefadroxil. D, Cephalexin. 278.
Recommended publications
  • B-Lactams: Chemical Structure, Mode of Action and Mechanisms of Resistance
    b-Lactams: chemical structure, mode of action and mechanisms of resistance Ru´ben Fernandes, Paula Amador and Cristina Prudeˆncio This synopsis summarizes the key chemical and bacteriological characteristics of b-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This review also summarizes the main resistance mechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum b-lactamases and AmpC b-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump b-lactams out of the bacterial cell. Keywords: b-lactams, chemical structure, mechanisms of resistance, mode of action Historical perspective Alexander Fleming first noticed the antibacterial nature of penicillin in 1928. When working with Antimicrobials must be understood as any kind of agent another bacteriological problem, Fleming observed with inhibitory or killing properties to a microorganism. a contaminated culture of Staphylococcus aureus with Antibiotic is a more restrictive term, which implies the the mold Penicillium notatum. Fleming remarkably saw natural source of the antimicrobial agent. Similarly, under- the potential of this unfortunate event. He dis- lying the term chemotherapeutic is the artificial origin of continued the work that he was dealing with and was an antimicrobial agent by chemical synthesis [1]. Initially, able to describe the compound around the mold antibiotics were considered as small molecular weight and isolates it. He named it penicillin and published organic molecules or metabolites used in response of his findings along with some applications of penicillin some microorganisms against others that inhabit the same [4].
    [Show full text]
  • Computational Antibiotics Book
    Andrew V DeLong, Jared C Harris, Brittany S Larcart, Chandler B Massey, Chelsie D Northcutt, Somuayiro N Nwokike, Oscar A Otieno, Harsh M Patel, Mehulkumar P Patel, Pratik Pravin Patel, Eugene I Rowell, Brandon M Rush, Marc-Edwin G Saint-Louis, Amy M Vardeman, Felicia N Woods, Giso Abadi, Thomas J. Manning Computational Antibiotics Valdosta State University is located in South Georgia. Computational Antibiotics Index • Computational Details and Website Access (p. 8) • Acknowledgements (p. 9) • Dedications (p. 11) • Antibiotic Historical Introduction (p. 13) Introduction to Antibiotic groups • Penicillin’s (p. 21) • Carbapenems (p. 22) • Oxazolidines (p. 23) • Rifamycin (p. 24) • Lincosamides (p. 25) • Quinolones (p. 26) • Polypeptides antibiotics (p. 27) • Glycopeptide Antibiotics (p. 28) • Sulfonamides (p. 29) • Lipoglycopeptides (p. 30) • First Generation Cephalosporins (p. 31) • Cephalosporin Third Generation (p. 32) • Fourth-Generation Cephalosporins (p. 33) • Fifth Generation Cephalosporin’s (p. 34) • Tetracycline antibiotics (p. 35) Computational Antibiotics Antibiotics Covered (in alphabetical order) Amikacin (p. 36) Cefempidone (p. 98) Ceftizoxime (p. 159) Amoxicillin (p. 38) Cefepime (p. 100) Ceftobiprole (p. 161) Ampicillin (p. 40) Cefetamet (p. 102) Ceftoxide (p. 163) Arsphenamine (p. 42) Cefetrizole (p. 104) Ceftriaxone (p. 165) Azithromycin (p.44) Cefivitril (p. 106) Cefuracetime (p. 167) Aziocillin (p. 46) Cefixime (p. 108) Cefuroxime (p. 169) Aztreonam (p.48) Cefmatilen ( p. 110) Cefuzonam (p. 171) Bacampicillin (p. 50) Cefmetazole (p. 112) Cefalexin (p. 173) Bacitracin (p. 52) Cefodizime (p. 114) Chloramphenicol (p.175) Balofloxacin (p. 54) Cefonicid (p. 116) Cilastatin (p. 177) Carbenicillin (p. 56) Cefoperazone (p. 118) Ciprofloxacin (p. 179) Cefacetrile (p. 58) Cefoselis (p. 120) Clarithromycin (p. 181) Cefaclor (p.
    [Show full text]
  • Cephalosporins
    Case Histories of Significant Medical Advances: Cephalosporins Amar Bhidé Srikant Datar Katherine Stebbins Working Paper 20-133 Case Histories of Significant Medical Advances: Cephalosporins Amar Bhidé Harvard Business School Srikant Datar Harvard Business School Katherine Stebbins Harvard Business School Working Paper 20-133 Copyright © 2020 by Amar Bhidé, Srikant Datar, and Katherine Stebbins. Working papers are in draft form. This working paper is distributed for purposes of comment and discussion only. It may not be reproduced without permission of the copyright holder. Copies of working papers are available from the author. Funding for this research was provided in part by Harvard Business School. Case Histories of Significant Medical Advances Cephalosporins Amar Bhidé, Harvard Business School Srikant Datar, Harvard Business School Katherine Stebbins, Harvard Business School Abstract: Our case history describes the development of three generations of cephalosporins – antibiotics that have significantly reduced hospital infections. Specifically, we chronicle how: 1) Early (pre-cephalosporin) antibiotics were developed in the first half of the 20th century. 2) Drug companies developed first-generation cephalosporins in the 1960s using foundational discoveries made by researchers in Italy and the UK in the 1940s and 1950s. 3) Continued modifications of cephalosporin molecules resulted in second and third generation of the drugs in the 1970s and 1980s. Note: Cephalosporins, like the others in this series of case-histories, are included in a list compiled by Victor Fuchs and Harold Sox (2001) of technologies produced (or significantly advanced) between 1975 and 2000 that internists in the United States said had had a major impact on patient care. The case histories focus on advances in the 20th century (i.e.
    [Show full text]
  • Development of TLC Chromatographic-Densitometric Procedure for Qualitative and Quantitative Analysis of Ceftobiprole
    processes Article Development of TLC Chromatographic-Densitometric Procedure for Qualitative and Quantitative Analysis of Ceftobiprole Zaneta˙ Binert-Kusztal, Małgorzata Starek , Joanna Zandarek˙ and Monika D ˛abrowska* Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Medical College, Jagiellonian University, 9 Medyczna St., 30-688 Kraków, Poland; [email protected] (Z.B.-K.);˙ [email protected] (M.S.); [email protected] (J.Z.)˙ * Correspondence: [email protected] Abstract: Currently, there is still a need for broad-spectrum antibiotics. The new cephalosporin antibiotics include, among others, ceftobiprole, a fifth-generation gram-positive cephalosporin, active against Staphylococcus aureus methicillin agonist (MRSA). The main focus of the work was to optimize the conditions of ceftobiprole qualitative determination and to validate the developed procedure according to ICH guidelines. As a result of the optimization process, HPTLC Cellulose chromatographic plates as a stationary phase and a mixture consisting of ethanol:2-propanol: glacial acetic acid: water (4:4:1:3, v/v/v/v) as a mobile phase were chosen. The densitometric detection was carried out at maximum absorbance of ceftobiprole (λ = 232 nm). Next, the validation process of the developed procedure was carried out. The relative standard deviation (RSD) for precision was less than 1.65%, which proves the high compatibility of the results, as well as the LOD = 0.0257 µg/spot and LOQ = 0.0779 µg/spot values, which also confirm the high sensitivity of the procedure. The Citation: Binert-Kusztal, Z.;˙ Starek, usefulness of the developed method for the stability studies of ceftobiprole was analyzed.
    [Show full text]
  • In Silico Studies of Inhibitors of Dihydrofolate Reductase And
    Archana Moon*et al. /International Journal of Pharmacy & Technology ISSN: 0975-766X CODEN: IJPTFI Available Online through Research Article www.ijptonline.com IN SILICO STUDIES OF INHIBITORS OF DIHYDROFOLATE REDUCTASE AND DIHYDROPTEROATE SYNTHASE OF E.COLI Archana Moon1, Deeba Khan2, Pranjali Gajbhiye3 & Monali Jariya4 1,2,3&4 University Department of Biochemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur -440033. Email: [email protected] Received on: 10-02-2017 Accepted on: 22-03-2017 Abstract: In the past two decades, antibiotic resistance has become an increasingly severe health problem. Bacterial infections caused by resistant strains are problematic in numerous hospitals around the world, especially in patients compromised by age, illness, and treated with immune-suppressant drugs. Antibiotics have a distinct mechanism of action capable of modifying microbial metabolism and physiological processes such as translation, DNA replication and cell wall biosynthesis. In this context, it is essential to increase the understanding of resistance mechanisms in order to develop drugs with potential activity against these pathogens. Escherichia coli is the most common causative agent of urinary tract infection (UTI), and diagnosing this infection usually relies on bacteriologic methods. Urinary tract infection (UTI) is the second most common bacterial infection after respiratory tract infection. Approximately 75-95% of UTIs are caused by Escherichia coli. Sulfonamides are competitive inhibitors of dihydropteroate synthase, the bacterial enzyme responsible for the incorporation of para-aminobenzoic acid (PABA) into dihydropteroic acid, the immediate precursor of folic acid. Trimethoprim exerts a synergistic effect with sulfonamides. It is a potent and selective competitive inhibitor of microbial dihydrofolate reductase, the enzyme that reduces dihydrofolate to tetrahydrofolate.
    [Show full text]
  • 7-Aminocephalosporanic Acid – Production and Separation
    STUDIA UBB CHEMIA, LXIV, 2,Tom I, 2019 (p. 87-99) (RECOMMENDED CITATION) DOI:10.24193/subbchem.2019.2.08 Dedicated to Professor Florin Dan Irimie on the Occasion of His 65th Anniversary 7-AMINOCEPHALOSPORANIC ACID – PRODUCTION AND SEPARATION ALEXANDRA TUCALIUCa, MĂDĂLINA POȘTARUb,*, DAN CAȘCAVALa, ANCA-IRINA GALACTIONb ABSTRACT. Cephalosporins, a large group of β-lactam antibiotics, contain a 7-aminocephalosporanic acid (7-ACA) nucleus which is derived from cephalosporin C, and substitutions of chemical groups or modifications of 7-ACA side-chains resulting in varying pharmacologic properties and antimicrobial activities, development of useful antibiotic agents, also. Cephalosporin C obtained by fungus fermentation can be transformed to 7-ACA by two-step or one step enzymatically conversion process. The most important step in 7-ACA downstream process is represented by its separation from enzymatically produced reaction mixture. Among the used methods new separation techniques have been developed and applied to bioseparations, like reactive extraction and pertraction which have considerable potential. Keywords: 7-aminocephalosporanic acid, cephalosporin C, enzymatic reaction, pertraction, reactive extraction INTRODUCTION Over the past 50 years, the industrial production of β-lactam antibiotics by fermentation is one of the outstanding examples of biotechnology. Cephalosporins are a large group of β-lactam antibiotics that are closely related to the penicillins. They are used for the treatment of infection diseases caused by gram-positive and a “Gheorghe Asachi” Technical University of Iasi, “Cristofor Simionescu” Faculty of Chemical Engineering and Environmental Protection, Dept. of Organic, Biochemical and Food Engineering, D. Mangeron 73, 700050 Iasi, Romania b “Grigore T. Popa” University of Medicine and Pharmacy of Iasi, Faculty of Medical Bioengineering, Dept.
    [Show full text]
  • Cephalosporins: Pharmacology and Chemistry
    PHARMACEUTICAL AND BIOLOGICAL EVALUATIONS December 2017; Vol. 4 (Issue 6): 234-238. www.onlinepbe.com ISSN 2394-0859 Review Article DOI: http://dx.doi.org/10.26510/2394-0859.pbe.2017.36 Cephalosporins: pharmacology and chemistry Kiran Shahbaz1,2* 1Center for health technology, Faculty of science, University of Technology Sydney, Australia 2Department of Oncology (Center for breast cancer) Perfect Health Pvt Ltd, Islamabad, Pakistan *For correspondence ABSTRACT Dr. Kiran Shahbaz, Center for health technology, Cephalosporins are the most important antibiotics having β-lactam ring Faculty of science, University and are obtained from a fungus Acremonium, also known as of Technology Sydney, cephalosporium. The wide use of cephalosporins against bacteria in Australia. various severe infections such as respiratory tract infection (RTI), skin Email: dr.kiran.shahbazz infection and urinary tract infection (UTI) has led the scientist dive into @gmail.com the detail of this antibacterial drug. The knowledge about structural activity relationship (SAR), spectrum of inhibition (SOI), chemical properties and pharmacology of cephalosporin has pivotal impact to device advanced therapeutic results. The treatment of a disease using cephalosporin has many pros and cons. If the pharmacology and chemical properties of this drug are known properly, many side effects can be diminished or minimized to a certain level. This article review some Received: 05 November 2017 pharmacological and chemical properties of cephalosporins. Revised: 28 November 2017 Keywords: Cephalosporin, Antibiotics, Pharmacology, Cefixime, β-Lactams Accepted: 30 November 2017 2 Introduction C16H15N5O7S2. Cefixime is marketed in the form of tablets and suspensions only for oral use.3 Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium Properties of cephalosporins from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu.
    [Show full text]
  • N=N` S N-Ch2-C-Hn J-Ch2-C-Hn S 11 N S-Ch2-C-Hn \\ / Ch-C-Hn H2
    gnosts.and Ivtanagenment of Infectious I)iscases i CHAPTER 20 Cephalosporins COO- DAVID R. ANDES A WILLIAM A. CRAIG FIGURE 20-1 . Basic cephalosporin nucleus . Although the discovery of the cephalosporin antibiotic class was re- duced by gram-negative anaerobic and aerobic bacteria ." These com. ported in 1945, it took nearly two decades for this class to achieve pounds, however, have lower affinity for the penicillin-binding protein clinical utility. Giuseppe Brotzu is widely credited for discovery of the (PBP) target in gram-positive bacteria .' The cephamycin group is broad-spectrum inhibitory effects of sewage outflow in Sardinia, structurally related to the cephalosporins but originated as a metabo . Italy.' Professor Brotzu subsequently isolated the mold Cephalosporin lite from Streptomyces lactamdurans .b The basic building block of the B acremonium (now Acremonium chrysogenum) and demonstrated an- cephamycin group is cephamycin C . Hydrolysis of cephamycin C, timicrobial activity of culture filtrates against both gram-positive and however, produces the 7-ACA nucleus. gram-negative bacteria . He also demonstrated the in vivo activity of Many modifications of the acyl side chain have been undertaken . these culture filtrates in both animal infection models and several pa- The first compounds resulting from addition of a thienyl ring or a tients. The filtrate was used both locally by injection into skin ab- tetrazole structure at R1 included the first-generation cephalosporins, scesses and systemically for the therapy of brucella and typhoid fever . A decade after the initial discovery', the cephalosporin substances C were isolated and identified as fermentation products of the mold .' Investigators at Oxford, including Florey and Abraham, systematically Cefazolin studied the physical, chemical, and structural characteristics of N=N` S cephalosporins as they had those of the penicillin class a decade ear- N-CH2-C-HN N-N lier.
    [Show full text]
  • Chapter 19 - Antibacterial Agents
    Chapter 19 - Antibacterial Agents 1 © Oxford University Press, 2013 Various classes of antibiotics (there are others) PENICILLINS CYCLOSERIN H CEPHALOSPORINS (tuberculosus) SULPHONAMIDES QUINOLONES H R H H N H H S R O O O R O O 2 N S S R2 F O N H NH R N N 2 1 OH O O N R R3 CO2H O 1 O R N CO2H AMINOACRIDINES R R STREPTOMYCINS CHLORAMPHENICOLS OH NH OH 2 HO OH HO HO N NH2 H2N N NH2 HO OH Cl O O NH N O MeO N NH2 O2N H Cl O H2N RIFAMYCINS O TETRACYCLINES N H O OH O O O NH2 MeO MeO O OH OH HO N O NH2 2 © Oxford University Press, 2013 A prokaryote is a single-celled organism that lacks a membrane-bound nucleus, mitochondria, or any other membrane-bound organelle. Prokaryotes can be divided into two domains, Archaea and Bacteria. Species with nuclei and organelles are placed in the domain Eukaryota. Archaea and bacteria are generally similar in size and shape, although a few archaea have very strange shapes. Despite visual similarity to bacteria, archaea possess genes and several metabolic pathways that are more closely related to those of eukaryotes, notably the enzymes involved in transcription and translation. There is no connection between the shape of a bacterium and its color in the gram staining. Prokaryotic cells have various shapes; basic shapes of bacteria are: The DNA of most bacteria is contained in a single circular molecule, called the bacterial chromosome, which sits in the cytoplasm of the bacterial cell.
    [Show full text]
  • University of Birmingham a Critical Review of Adverse Effects to the Kidney
    University of Birmingham A critical review of adverse effects to the kidney Pletz, Julia; Enoch , Steve J ; Jais , Diviya M; Mellor, Claire L ; Pawar, Gopal; Firman , James W ; Madden , Judith C ; Webb, Steven D ; Tagliati, Carlos A; Cronin, Mark.T.D DOI: 10.1080/17425255.2018.1539076 License: Other (please specify with Rights Statement) Document Version Peer reviewed version Citation for published version (Harvard): Pletz, J, Enoch , SJ, Jais , DM, Mellor, CL, Pawar, G, Firman , JW, Madden , JC, Webb, SD, Tagliati, CA & Cronin, MTD 2018, 'A critical review of adverse effects to the kidney: mechanisms, data sources, and in silico tools to assist prediction', Expert Opinion on Drug Metabolism and Toxicology, vol. 14, no. 12, pp. 1225-1253. https://doi.org/10.1080/17425255.2018.1539076 Link to publication on Research at Birmingham portal Publisher Rights Statement: This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Metabolism & Toxicology on 22/10/2018, available online: https://doi.org/10.1080/17425255.2018.1539076 General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research.
    [Show full text]
  • SAJB-55363-371.Pdf
    DOI: 10.21276/sajb Scholars Academic Journal of Biosciences (SAJB) ISSN 2321-6883 (Online) Sch. Acad. J. Biosci., 2017; 5(5):363-371 ISSN 2347-9515 (Print) ©Scholars Academic and Scientific Publisher (An International Publisher for Academic and Scientific Resources) www.saspublisher.com Review Article Production, Characterization and Clinical Applications of Third-generation Cephalosporins Hira Sundus, Kadija tul kubra, Manam Walait and Sikander Ali* Institute of Industrial Biotechnology (IIB), GC University Lahore, Pakistan *Corresponding author Sikander Ali Email: [email protected] Abstract: Cephalosporin is one of most widely used drug in world wide. Cephalosporin mechanism of action is more resistant to other agents that have infections from these agents. Its classification ranking 4th generation cephalosporin is more critical than 3rd generation cephalosporin but both are critical in WHO criteria. In human medicines and all risk management factors used cephalosporin antibiotic as one of the major factor. Its production on large scale is very important. Cephalosporin produced from Cephalosporium acremonium which immobilized in agar or other agents and cephalosporin antibiotics produced under optimum and favorable conditions. Calcium alginate and glass wool also used for immobilization and repeated batch of shake flask fermentations used for its production. It was recently improved for the treatment of community acquired pneumonia. It has also broad spectrum activity against gram positive and gram negative bacteria. It is also used for the treatment of hospitalized patients. Cephalosporin shows low resistance ratio and safety measurements. It is mostly used for the treatment of skin complicated infections. It will evaluate the pharmacological characters, efficacy, safety, antimicrobial property and its application of cephalosporin in the treatment of community acquired pneumonia.
    [Show full text]
  • THE IMPACT of PHARMACOKINETICS on the EMERGENCE of in VITRO BACTERIAL RESISTANCE to CEFOVECIN. Dr Sarah A. Robson
    THE IMPACT OF PHARMACOKINETICS ON THE EMERGENCE OF IN VITRO BACTERIAL RESISTANCE TO CEFOVECIN. Dr Sarah A. Robson BVSc(Hons) MANZCVS(pharmacology) MVS Faculty of Veterinary and Agricultural Science The University of Melbourne Student Number: 206696 2017 1 ABSTRACT Introduction Antibiotic resistance is a global issue in both human and veterinary medicine with substantial social and economic impact. Cefovecin, a third-generation cephalosporin antibiotic has a half-life of approximately 166 hours in the cat. This contrasts with the significantly shorter two-hour half-life of cephalexin, an oral first-generation cephalosporin. Sub-inhibitory antibiotic cultures were used to investigate the impact of cephalosporin antimicrobial concentration and time on the development of in vitro bacterial resistance. It was hypothesized that the long half-life of cefovecin would cause an increased emergence of bacterial resistance. Materials & Method Five clinical isolates of Escherichia coli from the U-Vet Werribee Animal Hospital laboratory collection were subjected to sub-inhibitory conditions. Escherichia coli National Collection of Type Cultures England (NCTC) 10418 and NCTC 12441 (American Type Culture Collection (ATCC) 25922) reference strains were used as controls. Minimum inhibitory concentrations (MIC) of cefovecin and cephalexin were determined by broth microdilution techniques as described by the Clinical and Laboratory Standards Institute (CLSI) standards. Antibiotic concentrations of 0 - 0.95 x MIC in Mueller-Hinton cation adjusted broth (CAMHB) were used as sub- inhibitory culture conditions. The batch-cultures were incubated on an orbital shaking platform at 37 ◦C for a total period of 144 hours. The bacteria were diluted 1:1000 into fresh antibiotic media every 24 hours.
    [Show full text]