DOCSLIB.ORG

Time-Kill Synergy Tests of Tigecycline Combined with Imipenem, Amikacin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Time-Kill Synergy Tests of Tigecycline Combined with Imipenem, Amikacin Available online at www.annclinlabsci.org Annals of Clinical & Laboratory Science, vol. 41, no. 1, 2011 39 Time-Kill Synergy Tests of Tigecycline Combined with Imipenem, Amikacin, and Ciprofloxacin against Clinical Isolates of Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli Haejun Yim,1 Heungjeong Woo,2 Wonkeun Song,3 Min-Jeong Park,3 Hyun Soo Kim,3 Kyu Man Lee,2 Jun Hur,1 and Man-Seung Park4 Departments of 1Burn Surgery, 2Internal Medicine, 3Laboratory Medicine, and 4Microbiology, Hallym University Medical Center and College of Medicine, Seoul and Chuncheon, Korea Abstract. This study evaluated the activity of tigecycline combined with imipenem, amikacin, and ciprofloxacin against clinical isolates of multidrug-resistant Klebsiella pneumoniae and Escherichia coli co-producing extended- spectrum β-lactamases and acquired AmpC β-lactamases. Broth microdilution tests were performed for cefotaxime, ceftazidime, cefepime, imipenem, amikacin, ciprofloxacin, and tigecycline. Time-kill synergy studies were tested for tigecycline plus imipenem, tigecycline plus amikacin, and tigecycline plus ciprofloxacin. Imipenem (MIC90 = 1 µg/ ml for both K. pneumoniae and E. coli) and tigecycline (MIC90 = 2 µg/ml for K. pneumoniae and 1 µg/ml for E. coli) were the most potent agents. Combination studies with tigecycline plus imipenem resulted in synergy against 18 K. pneumoniae and 3 E. coli isolates; tigecycline plus amikacin yielded synergy against 8 K. pneumoniae and 3 E. coli isolates; tigecycline plus ciprofloxacin yielded synergy against 7K. pneumoniae and 2 E. coli isolates. No antagonism was observed with any combination. In the present study, imipenem, amikacin, and ciprofloxacin led to indifferent and some synergistic effects in combination with tigecycline, and none of them demonstrated antagonistic effects. Introduction AmpCs, and isolates with reduced but may not always be effective as susceptibility to carbapenems con- monotherapy [9]. Therefore, a study β-Lactamase production is the most tinue to spread worldwide, new was designed to investigate the in common resistance mechanism to therapeutic options are needed [2-4]. vitro activities of combinations of β-lactams in Klebsiella pneumoniae Tigecycline, the first class of tigecycline and representative bac- and Escherichia coli. K. pneumoniae glycyclines, exhibits expanded- tericidal agents including imipenem, and E. coli isolates producing exten- spectrum of activity against a wide amikacin, and ciprofloxacin. Anti- ded-spectrum β-lactamases (ESBLs) variety of bacteria, including microbial combination therapy may and/or acquired AmpC β-lactamases multidrug-resistant strains such as provide clinicians an option in have been prevalent worldwide. ESBL-producing Enterobacteria- addition to imipenem for difficult ESBL-producing isolates are consid- ceae, multidrug-resistant Acineto- infections due to ESBL- or AmpC- ered resistant to all penicillins, bacter baumannii, methicillin- producing Enterobacteriaceae. cephalosporins, and aztreonam; resistant Staphylococcus aureus, and Although ESBL- and/or acquired carbapenems are the only β-lactams vancomycin-resistant enterococci AmpC-producing K. pneumoniae that remain consistently active for [5,6]. Tigecycline acts by binding to and E. coli routinely express cross- treatment in severe cases. The the 30S ribosomal subunit and resistance to other drug classes, therapeutic options for severe prevents the binding of aminoacyl synergy from combination therapy infections caused by acquired transfer RNA to the acceptor site on may achieve successful outcomes. AmpC-producing isolates are the messenger RNA-ribosome The purpose of this study was to almost restricted to carbapenems complex. Protein synthesis is evaluate the in vitro antimicrobial and cefepime [1]. Since K. pneu- inhibited, thereby exhibiting a activity of tigecycline combined moniae- and E. coli-resistant pheno- bacteriostatic effect [7]. Tigecycline with other antimicrobials against types, such as ESBLs, acquired has potentially useful activity [8] clinical isolates of multidrug- Address correspondence to Wonkeun Song, M.D., Ph.D., Department of Laboratory Medicine, Kangnam Sacred Heart Hospital, 948-1 Daelim-dong, Youngdeungpo-gu, Seoul 150-950, Republic of Korea; e-mail [email protected]. 0091-7370/11/0039-0043. $2.50. © 2011 by the Association of Clinical Scientists, Inc. 40 Annals of Clinical & Laboratory Science, vol. 41, no. 1, 2011 resistant K. pneumoniae and E. coli 5 E. coli) with tigecycline MICs of each isolates, and killing was co-producing ESBLs and acquired ≥0.125 µg/ml were chosen for time- assessed at 0, 4, 8, and 24 hr. AmpC β-lactamases. kill experiments. The combination Aliquots (0.1 ml) were removed activities of tigecycline and either from 2-ml cultures at 0, 4, 8, and 24 Materials and Methods imipenem, amikacin, or ciproflox- hr and serially diluted in 0.85% Bacterial isolates. This study acin were further evaluated in time- sterile saline. Bacterial counts were included 35 clinical isolates of K. kill experiments with concentrations determined by plating 0.1 ml of pneumoniae and 8 clinical isolates of at equal and one-fourth the MICs. appropriate dilutions to enumerate E. coli known to co-produce ESBLs Mueller-Hinton broth cultures were CFU/ml. Plating was performed in 5 and AmpCs, which were obtained inoculated with ≥5 x 10 CFU/ml of duplicate and the blood agar plates from two teaching hospitals in Korea during 2009 (Table 1). The Table 1. Bacterial isolates co-producing extended-spectrum β-lactamases and isolates were identified with the acquired AmpC β-lactamases used in this study Vitek 2 system (bioMerieux Vitek, Hazelwood, MO). Searches for Organism No. of isolates β-Lactamase genes coding for the class A ESBLs K. pneumoniae (n = 35) 23 SHV-12 plus DHA-1 were performed by PCR amplifi- 1 SHV-12 plus CMY-2 cation as described previousely [10]. 1 SHV-12 and CTX-M-12 plus DHA-1 To identify isolates with ampC 1 SHV-12 and CTX-M-15 plus DHA-1 genes, AmpC multiplex PCR was 2 CTX-M-14 plus DHA-1 performed by the method of Perez- 7 CTX-M-15 plus DHA-1 Perez and Hanson [11]. Sequencing of ampC genes with primers DHA- E. coli (n = 8) 4 SHV-12 plus DHA-1 1, CMY-1, and CMY-2 was perform- 1 CTX-M-14 plus DHA-1 ed as described previously [12]. The 1 CTX-M-15 plus CMY-1 1 CTX-M-15 plus CMY-2 PCR products were subjected to 1 CTX-M-24 plus CMY-2 direct sequencing. Both strands of each PCR product were sequenced twice with an automatic sequencer (model 3730xl; Applied Biosystems, Table 2. MICs for 43 isolates of E. coli and K. pneumoniae co-producing extended- Weiterstadt, Germany). Sequence spectrum β-lactamases and acquired AmpC β-lactamases. alignment and analysis was performed online using the BLAST Organism and Agent MIC (µg/ml) of: program (National Center for Bio- Range 50% 90% technology Information (Bethesda, K. pneumoniae (n = 35) MD; www.ncbi.nlm.nih.gov). Ceftazidime 8 – ≥ 512 ≥ 512 ≥ 512 Antimicrobial susceptibility testing. Cefotaxime 8 – ≥ 512 64 ≥ 512 Broth microdilution MIC tests were Cefepime 0.25 – ≥ 512 8 256 performed for ceftazidime (Sigma- Imipenem 0.125 – 64 0.5 1 Aldrich, St. Louis, MO), cefotaxime Amikacin ≤ 0.125 – ≥ 512 ≥ 512 ≥ 512 (Sigma-Aldrich), cefepime (Bor- Ciprofloxacin ≤ 0.125 – ≥ 512 32 ≥ 512 yung, Seoul, Korea), imipenem Tigecycline ≤ 0.125 – 4 0.5 2 (LKT Laboratories, St. Paul, MN), amikacin (Sigma-Aldrich), cipro- E. coli (n = 8) floxacin (LKT Laboratories), and tigecycline (Wyeth, Pearl River, Ceftazidime 8 – ≥ 512 ≥ 512 ≥ 512 Cefotaxime 16 – ≥ 512 256 ≥ 512 NY), according to the CLSI M7-A7 Cefepime 1 – ≥ 512 16 ≥ 512 methods [13]. For quality control, Imipenem ≤ 0.125 – 1 0.25 1 E. coli ATCC 25922 and K. Amikacin 1 – ≥ 512 4 ≥ 512 pneumoniae ATCC 700603, were Ciprofloxacin 0.25 – ≥ 512 128 ≥ 512 included in each set of tests. Tigecycline ≤ 0.125 – 1 ≤ 0.125 1 Time-kill synergy study. Thirty- three strains (28 K. pneumoniae and Tigecycline against Enterobactericeae 41 Table 3. Results of time-kill synergy for 33 isolates of E. coli and K. pneumoniae co-producing extended-spectrum β-lactamases and acquired AmpC β-lactamases at equal to one-fourth the MICs for tigecycline, imipenem, amikacin, and ciprofloxacin. Isolate MIC (µg/ml) Time-kill synergy (µg/ml) TIG IPM AMK CIP TIG+IPM TIG+AMK TIG+CIP K. pneumoniae K19 0.5 0.5 0.125 2 S(0.5+0.5) I S(0.5+2) K21 0.125 0.5 >256 16 I NT S(0.125+16) K24 0.25 32 >256 64 S(0.25+32) NT I K35 2 <0.125 32 32 NT S(2+32, 2+8, 0.5+32, I 0.5+8) K36 0.25 1 >256 1 I NT 1 K50 0.5 1 >256 2 S(0.5+1, 0.5+0.125) NT S(0.5+2, 0.5+0.5) K55 0.5 1 16 0.5 S(0.5+1, 0.5+0.125) S(0.5+16) I K56 2 0.5 >256 128 S(2+0.5) NT S(2+128) K65 1 0.5 16 >256 S(1+0.5) I NT K72 0.5 0.5 >256 2 S(0.5+0.5) NT I K75 1 64 >256 >256 I NT NT K76 0.25 <0.125 2 64 NT S(0.25+2) I K77 4 1 8 >256 S(4+1, 4+0.125, 1+1) S(4+8, 4+2) NT K86 0.25 1 >256 4 I NT I K87 0.5 0.5 2 0.25 S(0.5+0.5) S(0.5+2, 0.5+0.5) S(0.5+0.25) K89 0.5 1 >256 64 S(0.5+1) NT I K91 0.25 0.25 0.5 32 I S(0.25+0.5) S(0.25+32) K92 1 0.5 16 >256 S(1+0.5) I NT K97 2 0.5 16 >256 I I NT K102 0.25 0.5 >256 2 S(0.25+0.5) NT I K124 0.5 1 >256 128 S(0.5+1) NT I K137 1 1 8 >256 S(1+1, 1+0.125) S(1+8) NT K138 4 1 >256 >256 S(4+1, 4+0.125) NT NT K149 1 0.5 8 >256 I I NT K153 4 1 >256 16 S(4+1) NT S(4+16, 4+4, 1+16) K155 0.25 0.25 1 0.125 I I I K188 0.25 1 >256 64 S(0.25+1, 0.25+0.125) NT I K223 2 0.5 16 4 S(2+0.5) S(2+16) I E.
Load more

Recommended publications
  • Acinetobacter Baumannii Resistance: a Real Challenge for Clinicians
    antibiotics Review Acinetobacter baumannii Resistance: A Real Challenge for Clinicians Rosalino Vázquez-López 1,* , Sandra Georgina Solano-Gálvez 2, Juan José Juárez Vignon-Whaley 1 , Jorge Andrés Abello Vaamonde 1 , Luis Andrés Padró Alonzo 1, Andrés Rivera Reséndiz 1, Mauricio Muleiro Álvarez 1, Eunice Nabil Vega López 3, Giorgio Franyuti-Kelly 3 , Diego Abelardo Álvarez-Hernández 1 , Valentina Moncaleano Guzmán 1, Jorge Ernesto Juárez Bañuelos 1, José Marcos Felix 4, Juan Antonio González Barrios 5 and Tomás Barrientos Fortes 6 1 Departamento de Microbiología del Centro de Investigación en Ciencias de la Salud (CICSA), FCS, Universidad Anáhuac México Norte, Huixquilucan 52786, Mexico; [email protected] (J.J.J.V.-W.); [email protected] (J.A.A.V.); [email protected] (L.A.P.A.); [email protected] (A.R.R.); [email protected] (M.M.Á.); [email protected] (D.A.Á.-H.); [email protected] (V.M.G.); [email protected] (J.E.J.B.) 2 Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico 04510, Mexico; [email protected] 3 Medical IMPACT, Infectious Diseases Department, Mexico City 53900, Mexico; [email protected] (E.N.V.L.); [email protected] (G.F.-K.) 4 Coordinación Ciclos Clínicos Medicina, FCS, Universidad Anáhuac México Norte, Huixquilucan 52786, Mexico; [email protected] 5 Laboratorio de Medicina Genómica, Hospital Regional “1º de Octubre”, ISSSTE, Av. Instituto Politécnico Nacional 1669, Lindavista, Gustavo A. Madero, Ciudad de Mexico 07300, Mexico; [email protected] 6 Dirección Sistema Universitario de Salud de la Universidad Anáhuac México (SUSA), Huixquilucan 52786, Mexico; [email protected] * Correspondence: [email protected] or [email protected]; Tel.: +52-56-270210 (ext.
    [Show full text]
  • Acinetobacter Baumannii in a Murine Thigh-Infection Model
    RESEARCH ARTICLE Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model Bing Fan1,2☯, Jie Guan3☯, Xiumei Wang4, Yulong Cong1* 1 Clinical Laboratory of South Building, Chinese People’s Liberation Army General Hospital, Beijing 100853, a11111 China, 2 Clinical Laboratory of the Second Clinical District, the General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, China, 3 Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034, China, 4 Department of Clinical Laboratory, the General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, China ☯ These authors contributed equally to this work. * [email protected] OPEN ACCESS Citation: Fan B, Guan J, Wang X, Cong Y (2016) Abstract Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Few effective therapeutic options are available for treating severe infections caused by Sulbactam against Extensively Drug-Resistant extensively drug-resistant Acinetobacter baumannii (XDR-AB). Using a murine thigh-infec- Acinetobacter baumannii in a Murine Thigh-Infection tion model, we examined the in vivo efficacy of colistin in combination with meropenem, tige- Model. PLoS ONE 11(6): e0157757. doi:10.1371/ journal.pone.0157757 cycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial Editor: Digby F. Warner, University of Cape Town, SOUTH AFRICA counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity Received: February 13, 2016 against 91.7% of strains at 48 h post-treatment.
    [Show full text]
  • Linezolid - Tigecycline
    Linezolid - Tigecycline Paul M. Tulkens, MD, PhD Cellular and Molecular Pharmacology Louvain Drug Research Institute Catholic University of Louvain, Brussels, Belgium With the support of Wallonie-Bruxelles-International 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 1 Dong-A pharmaceuticals and tedizolid: step #1 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 2 Mode of action: • Protein synthesis inhibition: LZD binds to the 23S portion of the ribosomal 50S subunit (the centre of peptidyl transferase activity) → no initial complex 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 3 RNA interaction Karen L. Leach et al, Molecular Cell (2007) 26,393-402 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 4 Spectrum of activity No useful activity against other Gram-negative organisms because of constitutive efflux ! 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 5 Registered clinical indications Linezolid is often used off-label (endocarditis, osteomyelitis, ….) in pace of vancomycin 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 6 Linzezolid: mechanism of resistance 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 7 Can linzolid induce resistance ? 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 8 Linzolid can induce resistance… Locke et al. Antimicrob Agent Chemother 2009;53:5265-5274. 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 9 Linezolid pharmacokinetics 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 10 Linezolid human pharmacokinetics Oral therapeutic doses (600mg linezolid q12h for 21 days) Linezolid Tedizolid MIC 90 MIC90 Muñoz et al. ECCMID 2010; P1594 Flanagan SD, et al. Pharmacotherapy 2014;34(3):240–250.
    [Show full text]
  • Farrukh Javaid Malik
    I Farrukh Javaid Malik THESIS PRESENTED TO OBTAIN THE GRADE OF DOCTOR OF THE UNIVERSITY OF BORDEAUX Doctoral School, SP2: Society, Politic, Public Health Specialization Pharmacoepidemiology and Pharmacovigilance By Farrukh Javaid Malik “Analysis of the medicines panorama in Pakistan – The case of antimicrobials: market offer width and consumption.” Under the direction of Prof. Dr. Albert FIGUERAS Defense Date: 28th November 2019 Members of Jury M. Francesco SALVO, Maître de conférences des universités – praticien hospitalier, President Université de Bordeaux M. Albert FIGUERAS, Professeur des universités – praticien hospitalier, Director Université Autonome de Barcelone Mme Antonia AGUSTI, Professeure, Vall dʹHebron University Hospital Referee Mme Montserrat BOSCH, Praticienne hospitalière, Vall dʹHebron University Hospital Referee II Abstract A country’s medicines market is an indicator of its healthcare system, the epidemiological profile, and the prevalent practices therein. It is not only the first logical step to study the characteristics of medicines authorized for marketing, but also a requisite to set up a pharmacovigilance system, thus promoting rational drug utilization. The three medicines market studies presented in the present document were conducted in Pakistan with the aim of describing the characteristics of the pharmaceutical products available in the country as well as their consumption at a national level, with a special focus on antimicrobials. The most important cause of antimicrobial resistance is the inappropriate consumption of antimicrobials. The results of the researches conducted in Pakistan showed some market deficiencies which could be addressed as part of the national antimicrobial stewardship programmes. III Résumé Le marché du médicament d’un pays est un indicateur de son système de santé, de son profil épidémiologique et des pratiques [de prescription] qui y règnent.
    [Show full text]
  • Structural Basis for Potent Inhibitory Activity of the Antibiotic Tigecycline During Protein Synthesis
    Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis Lasse Jennera,b,1, Agata L. Starostac,1, Daniel S. Terryd,e, Aleksandra Mikolajkac, Liudmila Filonavaa,b,f, Marat Yusupova,b, Scott C. Blanchardd, Daniel N. Wilsonc,g,2, and Gulnara Yusupovaa,b,2 aInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, 67404 Illkirch, France; bUniversité de Strasbourg, F-67084 Strasbourg, France; cGene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany; dDepartment of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065; eTri-Institutional Training Program in Computational Biology and Medicine, New York, NY 10065; fMax Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; and gCenter for Integrated Protein Science Munich, University of Munich, 81377 Munich, Germany Edited by Rachel Green, Johns Hopkins University, Baltimore, MD, and approved January 17, 2013 (received for review September 28, 2012) + Here we present an X-ray crystallography structure of the clinically C1054 via a coordinated Mg2 ion (Fig. 1 D and E), as reported relevant tigecycline antibiotic bound to the 70S ribosome. Our previously for tetracycline (2). In addition, ring A of tigecycline + structural and biochemical analysis indicate that the enhanced coordinates a second Mg2 ion to facilitate an indirect interaction potency of tigecycline results from a stacking interaction with with the phosphate-backbone of G966 in h31 (Fig. 1 C–E). We also nucleobase C1054 within the decoding site of the ribosome.
    [Show full text]
  • Tigecycline: a Igecycline
    Molecules of the Millennium Tigecycline: A novel glycylcycline antibioticantibiotic Tetracycline antibiotics were first isolated at Lederle to occur.[5] Tigecycline is also active against organisms that Laboratories in 1945 and represented a significant display efflux-based resistance, which may be because of the advancement in the treatment of many infections. However, inability of the glycylcyclines to induce tetracycline efflux due to an increased incidence of resistance among various proteins, or because the efflux protein cannot export bacteria, the use of tetracyclines has been relegated to second tigecycline.[6] and third-line categories for most clinical indications. The two The binding site of tigecycline on the ribosome is common major mechanisms of resistance include tetracycline efflux to tetracyclines, but tigecycline binds 5-fold more strongly to and ribosomal protection, where tetracycline is prevented from the ribosome than tetracyclines and this enhanced binding is, binding to the ribosome. Research to find tetracycline probably, responsible for overcoming the ribosomal protection analogues, that circumvented these resistance mechanisms, mechanisms of tetracycline resistance.[5] The action of has led to the development of a novel group of drugs called tigecycline is bacteriostatic in nature, which is likely due to its glycylcyclines, the most promising compound being the 9-tert­ reversible interaction with the ribosome.[5] Its efficacy suggests butyl glycyclamido derivative of minocycline-tigecycline (GAR­ that traditional thinking about using bacteriostatic drugs in 936). treating serious infections needs to be revised.[7] Chemistry Antimicrobial activity The nucleus consists of four linear fused tetracyclic rings In vitro antibacterial activity of tigecycline has been and there is the addition of N, N-dimethylglycylamido (DMG) assessed against clinical isolates as a part of ongoing TEST group at C-9 position of minocycline.[1] initiative (Tigecycline Evaluation Surveillance Trial).
    [Show full text]
  • How Powerful Is It in the Fight Against Antibiotic-Resistant Bacteria?
    240 Medicina (Kaunas) 2010;46(4):240-8 Tigecycline – how powerful is it in the fight against antibiotic-resistant bacteria? Vaida Šeputienė1, Justas Povilonis1, Julija Armalytė1, 2, Kęstutis Sužiedėlis1, 2, Alvydas Pavilonis3, Edita Sužiedėlienė1 1Department of Biochemistry and Biophysics, Faculty of Natural Sciences, Vilnius University, 2Institute of Oncology, Vilnius University, 3Department of Microbiology, Kaunas University of Medicine, Lithuania Key words: tigecycline; mechanism of action; in vitro and in vivo activity; resistance. Summary. Tigecycline is a semisynthetic analogue of earlier tetracyclines and represents the first member of a novel class of antimicrobials – glycylcyclines – recently approved for clinical use. It is active against a broad range of gram-negative and gram-positive bacterial species including clinically important multidrug-resistant nosocomial and community-acquired bacterial pathogens. The exact molecular basis of tigecycline action is not clear at present, although similarly to the tetra- cyclines, it has been shown to inhibit the translation elongation step by binding to the ribosome 30S subunit and preventing aminoacylated tRNAs to accommodate in the ribosomal A site. Importantly, tigecycline overcomes the action of ribosomal protection proteins and is not a substrate for tetracy- cline efflux pumps of most bacteria – well-known and prevalent cellular mechanisms of microbial tetracycline resistance. The present review summarizes current knowledge on the molecular mecha- nism of the tigecycline action, antibacterial activity against various bacteria, clinical application, development of resistance to glycylcyclines. Introduction intra-abdominal infections (cIAIs), and communi- Use of antimicrobial drugs over the last 60 years ty-acquired bacterial pneumonia (CABP) (1–2) and in medicine and veterinary has triggered a devel- introduced during the past two decades into clinical opment of very effi cient genetic and biochemi- practice (1).
    [Show full text]
  • Trend Analysis of Antibiotics Consumption Using WHO Aware Classification in Tertiary Care Hospital
    International Journal of Basic & Clinical Pharmacology Bhardwaj A et al. Int J Basic Clin Pharmacol. 2020 Nov;9(11):1675-1680 http:// www.ijbcp.com pISSN 2319-2003 | eISSN 2279-0780 DOI: https://dx.doi.org/10.18203/2319-2003.ijbcp20204493 Original Research Article Trend analysis of antibiotics consumption using WHO AWaRe classification in tertiary care hospital Ankit Bhardwaj*, Kaveri Kapoor, Vivek Singh Saraswathi institute of Medical Sciences, Pilakhuwa, Hapur, Uttar Pradesh, India Received: 21 August 2020 Accepted: 21 September 2020 *Correspondence: Dr. Ankit Bhardwaj, Email: [email protected] Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Background: Aim of the study was to assess trend in antibiotics consumption pattern from 2016 to 2019 using AWaRe classification, ATC and Defined daily dose methodology (DDD) in a tertiary care hospital. Antibiotics are crucial for treating infectious diseases and have significantly improved the prognosis of patients with infectious diseases, reducing morbidity and mortality. The aim of the study is to classify the antibiotic based on WHO AWaRe classification and compare their four-year consumption trends. The study was conducted at a tertiary care center, Pilakhuwa, Hapur. Antibiotic procurement data for a period of 4 years (2016-2019) was collected from the Central medical store. Methods: This is a retrospective time series analysis of systemic antibiotics with no intervention at patient level. Antibiotic procurement was taken as proxy for consumption assuming that same has been used.
    [Show full text]
  • Protein Synthesis Inhibitors Lecture Outline
    Protein Synthesis Inhibitors • Macrolides - Lincosamides • Aminoglycosides • Tetracyclines • Chloramphenicol • Oxazolidinones • Streptogramins Lecture Outline • Description of protein synthesis - translation • Antibiotics – Structure - function - classification – Mechanism(s) of action – Mechanism(s) of resistance – Spectrum of activity/Indications for use – Pharmacology – Toxicity • Clinical examples 1 Overview of Translation (1) Initiation: • 30S binds RBS of mRNA • AA binds tRNA using aminoacyl-tRNA synthetase • IF2 and fmet-tRNA binds 30S at P site • 50S binds complex 70S resulilting in th e f ormati on of the initiation complex Overview of Translation (2) Initiation – tRNA + AA binds translation elongation factor – Enters ribosome and attaches at the A site 2 Overview of Translation (3) Amino Acid Transfer – Petidyltransferase on 50S ribosome attaches the next AA to the polypeptide – Met added to Leu at A site Overview of Translation (4) Elongation tRNA moved to P site by EF-G creating room at A site for next tRNA Translation termination Occurs at nonsense codon sites e.g. UAA Release factors Ribosome dissociates 3 Mechanisms of Action - Protein Synthesis Inhibitors Macrolides • Broad spectrum antibiotics • Original agent: erythromycin • Azalides: azithromycin and clarithromycin – seltdtiilected antimicrobi bildhal and pharmacoki kitinetic advantages 4 Large 14 member macrolactone ring with one or more deoxy sugars attached. Inhibits formation of 50S ribosome blocking trans- peptidation or translocation. Large 14 member lactone ring
    [Show full text]
  • Azithromycin Treatment Failure in Macrolide-Resistant Mycoplasma Pneumoniae Pneumonia
    Correspondence: M. Haschke, Division of Clinical Pharmaco- 3 George JN, Raskob GE, Shah SR, et al. Drug-induced thrombocyto- logy and Toxicology, University Hospital Basel, Petersgraben penia: a systematic review of published case reports. Ann Int Med 1998; 129: 886–890. 4, CH-4031 Basel, Switzerland. E-mail: [email protected] 4 Lee SH, Rubin LJ. Current treatment strategies for pulmonary arterial hypertension. J Intern Med 2005; 258: 199–215. Statement of Interest: None declared. 5 US Food and Drug Administration. Ventavis (iloprost) inhalation solution September 2008. MedWatch FDA Safety Information and Adverse Event Reporting Program. Date last updated: June 19, 2009. Date last accessed: December 1, 2009. REFERENCES 6 Uppsala Monitoring Centre World Health Organization collaborat- 1 Von Drygalski A, Curtis BR, Bougie DW, et al. Vancomycin- TM ing Centre for International Drug Monitoring. VigiBase Services. induced immune thrombocytopenia. N Engl J Med 2007; 356: www.umc-products.com Date last accessed: December 1, 2009. 904–910. 7 Chin KM, Channick RN, de Lemos JA, et al. Hemodynamics and 2 Documed. Product information dobutamine injection. Arzbeunuttel epoprostenol use are associated with thrombocytopenia in pulmon- Kompendium der Schweiz. [Swiss Compendium of Therapeutic ary arterial hypertension. Chest 2009; 135: 130–136. Drugs.] www.documed.ch Date last updated: 2005. Date last accessed: December 1, 2009. DOI: 10.1183/09031936.00011010 Azithromycin treatment failure in macrolide-resistant Mycoplasma pneumoniae pneumonia To the Editors: azithromycin (500 mg once daily) and oseltamivir (75 mg twice daily) were added as treatment for CAP. RT-PCR of Mycoplasma pneumoniae is one of the most common bacterial nasopharyngeal aspirate for influenza, collected 1 day before causes of community-acquired pneumonia (CAP) [1].
    [Show full text]
  • Synthesis and Antibacterial Activity of Doxycycline Neoglycosides † † ‡ § ‡ Jianjun Zhang, Larissa V
    Article pubs.acs.org/jnp Synthesis and Antibacterial Activity of Doxycycline Neoglycosides † † ‡ § ‡ Jianjun Zhang, Larissa V. Ponomareva, Karen Marchillo, Maoquan Zhou, David R. Andes, † and Jon S. Thorson*, † Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States ‡ Department of Medicine and Medical Microbiology and Immunology, University of Wisconsin−Madison, 1685 Highland Avenue, Madison, Wisconsin 53705-2281, United States § Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin−Madison, 777 Highland Avenue, Madison, Wisconsin 53705-2222, United States *S Supporting Information ABSTRACT: A set of 37 doxycycline neoglycosides were prepared, mediated via a C-9 alkoxyamino-glycyl-based spacer reminiscent of that of tigecycline. Subsequent in vitro antibacterial assays against representative drug-resistant Gram negative and Gram positive strains revealed a sugar-dependent activity profile and one doxycycline neoglycoside, the 2′- amino-α-D-glucoside conjugate, to rival that of the parent pharmacophore. In contrast, the representative tetracycline-susceptible strain E. coli 25922 was found to be relatively responsive to a range of doxycycline neoglycosides. This study also extends the use of aminosugars in the context of neoglycosylation via a simple two-step strategy anticipated to be broadly applicable for neoglycorandomization. etracyclines are broad-spectrum antibiotics that have been methods.21
    [Show full text]
  • WHO Report on Surveillance of Antibiotic Consumption: 2016-2018 Early Implementation ISBN 978-92-4-151488-0 © World Health Organization 2018 Some Rights Reserved
    WHO Report on Surveillance of Antibiotic Consumption 2016-2018 Early implementation WHO Report on Surveillance of Antibiotic Consumption 2016 - 2018 Early implementation WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation ISBN 978-92-4-151488-0 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons. org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non- commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation. Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]