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vancomycin |
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CHEBI:28001 |
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A complex glycopeptide from Streptomyces orientalis. It inhibits a specific step in the synthesis of the peptidoglycan layer in the Gram-positive bacteria Staphylococcus aureus and Clostridium difficile. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:49941, CHEBI:9931, CHEBI:27276
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No supplier information found for this compound. |
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Molfile
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SDF
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more structures >>
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call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__764850963495503__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__764850963495503__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI%3ACHEBI%3A28001","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__764850963495503__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"764850963495503","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__764850963495503__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol Marvin 05160816503D starting HoverWatcher_5 Time for openFile( Marvin 05160816503D 178187 0 0 0 0 999 V2000 -11.4870 5.7530 1.8360 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4490 4.8340 1.3030 N 0 3 0 0 0 0 0 0 0 0 0 0 -10.0280 5.1340 -0.0950 C 0 0 2 0 0 0 0 0 0 0 0 0 -11.2540 5.1310 -1.0190 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.0670 3.8210 -1.0590 C 0 0 2 0 0 0 0 0 0 0 0 0 -12.5650 3.4020 0.3240 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2120 2.7010 -1.6610 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0120 4.1020 -0.5590 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6880 3.1340 0.1250 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5050 4.3920 -1.8170 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.5180 3.5650 -2.4710 C 0 0 2 0 0 0 0 0 0 0 0 0 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0 0 0 0 58 59 4 0 0 0 0 58 65 4 0 0 0 0 59 60 4 0 0 0 0 59144 1 0 0 0 0 60 61 4 0 0 0 0 60145 1 0 0 0 0 61 62 1 0 0 0 0 61 63 4 0 0 0 0 63 64 1 0 0 0 0 63 65 4 0 0 0 0 65146 1 0 0 0 0 66 67 2 0 0 0 0 66 68 1 0 0 0 0 68 69 1 0 0 0 0 68147 1 0 0 0 0 69 70 1 0 0 0 0 69 78 1 0 0 0 0 69148 1 0 0 0 0 70 71 4 0 0 0 0 70 77 4 0 0 0 0 71 72 4 0 0 0 0 72 73 1 0 0 0 0 72 74 4 0 0 0 0 73149 1 0 0 0 0 74 75 4 0 0 0 0 74150 1 0 0 0 0 75 76 1 0 0 0 0 75 77 4 0 0 0 0 76151 1 0 0 0 0 77152 1 0 0 0 0 78 79 2 0 0 0 0 78 80 1 0 0 0 0 80153 1 0 0 0 0 81 82 1 0 0 0 0 81 89 1 0 0 0 0 81154 1 0 0 0 0 82 83 1 0 0 0 0 82 84 1 0 0 0 0 82155 1 0 0 0 0 83 92 1 0 0 0 0 84 85 1 0 0 0 0 84 86 1 0 0 0 0 84156 1 0 0 0 0 85157 1 0 0 0 0 86 87 1 0 0 0 0 86 88 1 0 0 0 0 86158 1 0 0 0 0 87159 1 0 0 0 0 88 89 1 0 0 0 0 88 90 1 0 0 0 0 88160 1 0 0 0 0 90 91 1 0 0 0 0 90161 1 0 0 0 0 90162 1 0 0 0 0 91163 1 0 0 0 0 92 93 1 0 0 0 0 92100 1 0 0 0 0 92164 1 0 0 0 0 93 94 1 0 0 0 0 93165 1 0 0 0 0 93166 1 0 0 0 0 94 95 1 0 0 0 0 94 96 1 0 0 0 0 94 97 1 0 0 0 0 95167 1 0 0 0 0 95168 1 0 0 0 0 95169 1 0 0 0 0 96170 1 0 0 0 0 96171 1 0 0 0 0 96172 1 0 0 0 0 97 98 1 0 0 0 0 97 99 1 0 0 0 0 97173 1 0 0 0 0 98174 1 0 0 0 0 99100 1 0 0 0 0 99101 1 0 0 0 0 99175 1 0 0 0 0 101176 1 0 0 0 0 101177 1 0 0 0 0 101178 1 0 0 0 0 M CHG 2 2 1 95 1 M END): 21 ms reading 178 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 178 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
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Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously (injection into a vein) to treat complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken orally (by mouth) to treat Clostridioides difficile infections. When taken orally, it is poorly absorbed.
Common side effects include pain in the area of injection and allergic reactions. Occasionally, hearing loss, low blood pressure, or bone marrow suppression occur. Safety in pregnancy is not clear, but no evidence of harm has been found, and it is likely safe for use when breastfeeding. It is a type of glycopeptide antibiotic and works by blocking the construction of a cell wall.
Vancomycin was approved for medical use in the United States in 1958. It is on the World Health Organization's List of Essential Medicines. The WHO classifies vancomycin as critically important for human medicine. It is available as a generic medication. Vancomycin is made by the soil bacterium Amycolatopsis orientalis. |
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InChI=1S/C66H75Cl2N9O24/c1-23(2)12-34(71-5)58(88)76-49-51(83)26-7-10-38(32(67)14-26)97-40-16-28-17-41(55(40)101-65-56(54(86)53(85)42(22-78)99-65)100-44-21-66(4,70)57(87)24(3)96-44)98-39-11-8-27(15-33(39)68)52(84)50-63(93)75-48(64(94)95)31-18-29(79)19-37(81)45(31)30-13-25(6-9-36(30)80)46(60(90)77-50)74-61(91)47(28)73-59(89)35(20-43(69)82)72-62(49)92/h6-11,13-19,23-24,34-35,42,44,46-54,56-57,65,71,78-81,83-87H,12,20-22,70H2,1-5H3,(H2,69,82)(H,72,92)(H,73,89)(H,74,91)(H,75,93)(H,76,88)(H,77,90)(H,94,95)/t24-,34+,35-,42+,44-,46+,47+,48-,49+,50-,51+,52+,53+,54-,56+,57+,65-,66-/m0/s1 |
MYPYJXKWCTUITO-LYRMYLQWSA-N |
CN[C@H](CC(C)C)C(=O)N[C@@H]1[C@H](O)c2ccc(Oc3cc4cc(Oc5ccc(cc5Cl)[C@@H](O)[C@@H]5NC(=O)[C@H](NC(=O)[C@@H]4NC(=O)[C@H](CC(N)=O)NC1=O)c1ccc(O)c(c1)-c1c(O)cc(O)cc1[C@H](NC5=O)C(O)=O)c3O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1)c(Cl)c2 |
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
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antibacterial drug
A drug used to treat or prevent bacterial infections.
bacterial metabolite
Any prokaryotic metabolite produced during a metabolic reaction in bacteria.
antimicrobial agent
A substance that kills or slows the growth of microorganisms, including bacteria, viruses, fungi and protozoans.
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antibacterial drug
A drug used to treat or prevent bacterial infections.
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View more via ChEBI Ontology
(3S,6R,7R,11R,23S,26S,30aS,36R,38aR)-44-[2-O-(3-amino-2,3,6-trideoxy-3-C-methyl-α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyloxy]-3-(carbamoylmethyl)-10,19-dichloro-2,3,4,5,6,7,23,25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6-(N-methyl-D-leucyl)-2,5,24,38,39-pentaoxo-1H,22H-23,36-(epiminomethano)-8,11:18,21-dietheno-13,16:31,35-di(metheno)[1,6,9]oxadiazacyclohexadecino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-26-carboxylic acid
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vancomicina
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ChemIDplus
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vancomycin
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ChemIDplus
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vancomycine
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ChemIDplus
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vancomycinum
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ChemIDplus
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(1S,2R,18R,22S,25R,28R,40S)-22-(2-amino-2-oxoethyl)-48-[2-O-(3-amino-2,3,6-trideoxy-3-methyl-α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyloxy]-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[(N-methyl-D-leucyl)amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49-pentadecaene-40-carboxylic acid
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ChEBI
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(2.2Sp,3.5Sa,2.6Sp)-O4.2,C3.4:C5.4,O4.6:C3.5,C2.7-tricyclo[N-methyl-D-leucyl-3-chloro-(R)-β-hydroxy-D-tyrosyl-L-asparaginyl-D-2-(4-{[2-O-(3-amino-2,3,6-trideoxy-3-C-methyl-α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyl]oxy}phenyl)glycyl-D-2-(4-hydroxyphenyl)glycyl-3-chloro-(R)-β-hydroxy-L-tyrosyl-L-2-(3,5-dihydroxyphenyl)glycine]
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JCBN
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vancomicin
Note: (2015-03-23) An uncommon spelling variant. |
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ChEBI
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Vancomycin
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KEGG COMPOUND
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VANCOMYCIN
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PDBeChem
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2807
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DrugCentral
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C00016052
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KNApSAcK
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C06689
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KEGG COMPOUND
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CPD-12245
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MetaCyc
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D00212
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KEGG DRUG
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DB00512
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DrugBank
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US3067099
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Patent
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VAN
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PDBeChem
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Vancomycin
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Wikipedia
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View more database links |
1404-90-6
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CAS Registry Number
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KEGG COMPOUND
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1404-90-6
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CAS Registry Number
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ChemIDplus
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3132
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Reaxys Registry Number
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Reaxys
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Hwang JH, Lee JH, Moon MK, Kim JS, Won KS, Lee CS (2012) The usefulness of arbekacin compared to vancomycin. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 31, 1663-1666 [PubMed:22124537] [show Abstract] The bacteriological efficacy response (improved, arbekacin vs. vancomycin; 71.2% vs. 79.5%) and clinical efficacy response (improved, arbekacin vs. vancomycin; 65.3% vs. 76.1%) were not statistically different between the two groups. The complication rate was significantly higher in the vancomycin group (32.9%) compared to the arbekacin group (15.1%) (p=0.019). Arbekacin was not inferior to vancomycin, and it could be a good alternative drug for vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) treatment. | Popescu M, Vialet R, Loundou A, Peyron F, Buès-Charbit M (2011) [Imprecision of vancomycin prepared for intravenous administration at the bedside in a neonatal intensive care unit]. Annales francaises d'anesthesie et de reanimation 30, 726-729 [PubMed:21719238] [show Abstract] In pediatric units, most of the intravenous medications are prepared by the attending nurse at the bedside that can be affected by an error margin, so can be imprecise. Despite the possible consequences of imprecise medications administration, published studies on the topic are scarce. The main objective of this study was to measure the difference between the prescribed vancomycine concentration and the actual concentration measured in the medication administered to the patient. The secondary objective was to determine which step in the preparation was linked to the difference in concentrations. It was a prospective study, setting in a pediatric and neonatal university hospital intensive care unit. Over a 3-month period, an aliquot from every preparation for continuous infusion of vancomycin, made at the bedside by a nurse, was collected and the modalities of the preparation noted. Vancomycin concentration was measured by high performance liquid chromatography. Sixty-four preparations, accounting for 24 patients (gestationnal age: 67 ± 75 weeks, weigh: 4.8 ± 6.5 kg) were included. Vancomycin concentrations ranged from 3.33 to 60.0mg/mL. Measured concentration were in mean 7% smaller than prescribed concentration (P<10(-3)), with a large confidence interval (75.8%-120.4% of the prescribed concentration). Imprecision the preparations was much higher than this admitted for manufactured preparation. We could not highlight any factor related to the difference in concentrations, but one third of the preparation did not respect all the ISO 7886 standards for syringes use. Bedside vancomycin preparations, like preparations for other molecules, are far more imprecise than industrial intravenous medications. Our results urge that all pediatric intravenous medications should be made only by manufacturers or pharmacists. However, it also urged clinical studies, in parallel to pharmacodynamic and pharmacokinetic studies, to make intravenous treatments as accurate as they should be. | Entenza JM, Veloso TR, Vouillamoz J, Giddey M, Moreillon P (2011) Failure of vancomycin continuous infusion against experimental endocarditis due to vancomycin-intermediate Staphylococcus aureus. Antimicrobial agents and chemotherapy 55, 385-387 [PubMed:20956604] [show Abstract] Continuous infusion of vancomycin was evaluated against experimental endocarditis due to heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA. Animals were infected with hVISA PC1 (vancomycin MIC, 2 mg/liter) or VISA PC3 (vancomycin MIC, 8 mg/liter) and treated for 5 days with constant serum levels of 20 or 40 mg/liter. Vancomycin continuous infusion was unsuccessful, as 20 mg/liter was barely active against PC1 (6 of 13 sterile vegetations) and 40 mg/liter failed against PC3 (2 of 9 sterile vegetations). | Zegbeh H, Bleyzac N, Berhoune C, Bertrand Y (2011) [Vancomycin: what dosages are needed to achieve efficacy in paediatric hematology/oncology?]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 18, 850-855 [PubMed:21664803] [show Abstract]
IntroductionIn children and infants, the determination of optimal dosages is essential from the beginning of treatments with vancomycin because of the high risk of inadequate serum concentrations and bacterial resistance. Bayesian pharmacokinetic methods can be used to adjust dosages according to serum vancomycin concentrations and the patients' physiopathological characteristics. The aim of this retrospective study was to review the effective dosages of vancomycin in paediatric hematology/oncology, using a bayesian pharmacokinetic method.Patients and methodsOne hundred and sixty-one patients in paediatric hematology/oncology units, aged from 1 month to 18 years, who were treated with vancomycin in continuous infusion, were selected between 2000 and 2010. The influence of initial vancomycin dosages on serum steady-state concentrations (S(sc)) before bayesian adaptation was studied on the basis of dosing recommendations in children and infants (i.e., 40 mg/kg/day). In addition, the S(sc) before bayesian adaptation and the effective dosages determined after bayesian adaptation (E(db)) were analysed according to the patients' age, for an identical dosage of 40 mg/kg/day (± 10%).ResultsThe percentage of patients with low S(sc) (i.e.,<10mg/L) was 28.6%, 16%, and 0 when treatment was initiated at less than 40 mg/kg/day (± 10%), at 40 mg/kg/day (± 10%), and at more than 40 mg/kg/day (± 10%), respectively. For an identical initial dosage of 40 mg/kg/day (± 10%), the S(sc) gradually increased as the patients' age increased. The S(sc) were optimal (i.e., between 15 and 20mg/L) in adolescents and children from 6 to 12 years of age, but less than 15 mg/L in children from 2 to 6 years of age and infants. The E(db) gradually increased as the patients' age decreased.Discussion and conclusionsThe choice of initial dosages of vancomycin treatment must take greater account of the patient's age in order to reduce the frequency of inadequate S(sc) before titration. In the absence of nephrotoxic cofactors, we suggest an increase in initial vancomycin dosages in continuous infusion between 40 and 45 mg/kg/day in children from 6 to 12 years old, between 45 and 50mg/kg/day in children from 2 to 6 years old, and between 50 and 55 mg/kg/day in infants, in hematology/oncology. For teenage patients, the standard dosage (i.e., 40 mg/kg/d) seems appropriate. | Schweizer ML, Furuno JP, Harris AD, Johnson JK, Shardell MD, McGregor JC, Thom KA, Cosgrove SE, Sakoulas G, Perencevich EN (2011) Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia. BMC infectious diseases 11, 279 [PubMed:22011388] [show Abstract]
BackgroundThe high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.MethodsThis retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin.Results267 patients were included; 14% (38/267) received nafcillin or cefazolin, 51% (135/267) received both vancomycin and either nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin.ConclusionsReceipt of nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of nafcillin or cefazolin in the treatment of MSSA bacteremia. | Xing B, Jiang T, Bi W, Yang Y, Li L, Ma M, Chang CK, Xu B, Yeow EK (2011) Multifunctional divalent vancomycin: the fluorescent imaging and photodynamic antimicrobial properties for drug resistant bacteria. Chemical communications (Cambridge, England) 47, 1601-1603 [PubMed:21109901] [show Abstract] A simple and specific divalent vancomycin-porphyrin has been developed. This divalent vancomycin-porphyrin conjugate indicates promising properties in fluorescent imaging and photodynamic inactivation of vancomycin-sensitive and vancomycin-resistant enterococci (VRE) bacterial strains. | Jobson S, Moise PA, Eskandarian R (2011) Retrospective observational study comparing vancomycin versus daptomycin as initial therapy for Staphylococcus aureus infections. Clinical therapeutics 33, 1391-1399 [PubMed:22015328] [show Abstract]
BackgroundData comparing alternatives to vancomycin for the treatment of Staphylococcus aureus infections with vancomycin MIC >1 are lacking.ObjectiveWe evaluated outcomes of S aureus infections based on whether daptomycin or vancomycin was used as initial therapy at a single institution, where the majority of S aureus infections had vancomycin MICs of 2 mg/L.MethodsA retrospective chart review was conducted at a 450-bed private acute care hospital. All patients >18 years of age who received initial vancomycin or daptomycin for at least 3 days to treat an S aureus infection between November 2006 and July 2008 were included. Patients with endocarditis, osteomyelitis, or a central nervous system infection and/or those being treated for an S aureus respiratory tract infection were excluded.ResultsA total of 165 patients (median age 68 years, range 24-95 years; 56% male) were included: 57 (35%) received daptomycin and 108 (65%) received vancomycin; 78% had vancomycin MIC values of 2 mg/L. The median antibiotic-related length of stay was significantly shorter with daptomycin than with vancomycin (7.5 vs 10.0 days; P = 0.035). Relapse rates in the clinically evaluable population were 25% and 23% for daptomycin and vancomycin, respectively; for the subset with S aureus bacteremia with vancomycin MICs of 2 mg/L, rates were 0% (0/9 patients) and 26% (6/23 patients) for daptomycin and vancomycin, respectively (P = 0.089). Thirty-day all-cause mortality was 6% (10/165 patients) and did not differ significantly by treatment: 7% (4/57 patients) versus 6% (6/108 patients) for daptomycin and vancomycin, respectively (P = 0.708).ConclusionIn this setting, in which the majority of S aureus infections had vancomycin MIC values of 2 mg/L, we found the median antibiotic-related length of stay to be significantly shorter with daptomycin than with vancomycin. Prospective studies are needed to determine whether daptomycin confers benefits over vancomycin in specific infection types under conditions that are unfavorable for vancomycin, such as higher vancomycin MICs. | Lazar HL, Barlam T, Cabral H (2011) The effect of topical vancomycin applied to sternotomy incisions on postoperative serum vancomycin levels. Journal of cardiac surgery 26, 461-465 [PubMed:21951032] [show Abstract]
Background and aimTopical vancomycin has been shown to reduce the incidence of sternal wound infections but concerns have been raised that persistent serum levels of vancomycin may contribute to the emergence of drug-resistant infections. This study was undertaken to determine: (1) whether serum levels of vancomycin remain elevated when applied topically to the sternum and (2) whether the use of topical vancomycin can potentiate postoperative drug-resistant infections.MethodsSerum vancomycin levels were measured on the evening of surgery and the sixth postoperative day in 36 patients in which topical vancomycin was applied to the cut edges of the sternum during their cardiac surgical procedures. Data are presented as a mean ± standard deviation and statistical significance was tested using paired t-test analyses.ResultsThere was a significant decrease in serum vancomycin levels from the night of surgery to the sixth postoperative day (11.5 ± 1.9 μg/mL to 2.12 ± 0.79 μg/mL; p <0.0001). The incidence of sternal infections was 0% and no patient developed any infection or had renal toxicity during the 12-month follow-up.ConclusionsThe use of topical vancomycin applied to the sternotomy incision does not result in persistently elevated levels of serum vancomycin following cardiac surgical procedures. Furthermore, topical vancomycin does not potentiate the emergence of drug-resistant infections or contribute to postoperative renal toxicity. | Commandeur D, Giacardi C, Danguy Des Deserts M, Huynh S, Buguet-Brown ML, Ould-Ahmed M, Drouillard I (2011) [Monitoring vancomycin in an intensive care unit: A retrospective survey on 66 patients]. Medecine et maladies infectieuses 41, 410-414 [PubMed:21458937] [show Abstract]
ObjectivesThe study objectives were to check whether recommended vancomycin doses were related to pharmacological objectives for intensive care patients: steady-state plasma concentration (SSc) and ratio SSc/MIC (Minimal Inhibiting Concentration). The authors tried to identify variability factors for vancomycin plasmatic concentrations at peak.Patients and methodsThis monocentric, observational, and retrospective survey was performed on 66 intensive care patients treated by antibiotics including vancomycin, alone or in combination, as a curative treatment for a severe infection with Gram-positive bacteria. Vancomycin was dosed at 15mg/kg during the first hour, then 40 to 60mg/kg per 24hour. Vancomycin SSc and bacteria MIC were recorded. The SSc/MIC ratio was determined and was considered efficient when superior to 8.ResultsForty-two percent of vancomycin SSc were within the effectiveness rate. Twenty-three percent of SSc/MIC ratios were superior to 8. The rate of clinical recovery was 71 %. The length of antibiotherapy was identified as positively interacting with biological effectiveness, unlike severe sepsis, a factor of negative interaction on vancomycin SSc in this study.ConclusionLess than half of the SSc and less than a quarter of the SSc/MIC ratios were at effective rates in our study. Therefore, adequacy between dosage, administration, and monitoring should be reviewed. | van Maarseveen EM, Man WH, Touw DJ, Bouma AW, van Zanten AR (2011) [Continuous and intermittent infusion of vancomycin equally effective: review of the literature]. Nederlands tijdschrift voor geneeskunde 155, A2667 [PubMed:22027450] [show Abstract]
ObjectiveTo compare the efficacy of continuous vancomycin infusion with intermittent vancomycin infusion based on clinical endpoints.DesignSystematic review of the literature.MethodSixty articles on comparative studies on continuous and intermittent vancomycin infusion were found in Pubmed. Of these, the English-language articles on studies in adults were selected. Only articles in which a comparison was made in terms of clinical endpoints were included.ResultsSix studies were included in which the differences between continuous and intermittent infusions were assessed in terms of the clinical endpoints. In the 2 prospective studies, no statistically significant differences in efficacy between the two methods of administration were found. A prospective study and retrospective study suggested that continuous infusion of high-dose vancomycin in patients with osteomyelitis may be more effective than intermittent infusion. There were no clear differences in side effects, although nephrotoxicity seemed to occur less rapidly and less often with continuous vancomycin infusion.ConclusionThe available literature showed that continuous infusion of vancomycin is as effective as intermittent administration. In addition, continuous administration is cheaper and monitoring of serum levels is simpler. This offers the possibility of discharging specific patients more quickly from hospital and facilitates home care with vancomycin. | Jelassi ML, Benlmouden A, Lefeuvre S, Mainardi JL, Billaud EM, Groupe Suivi Therapeutique Pharmacologique de la Societe Francaise de Pharmacologie et de Therapeutique (2011) [Level of evidence for therapeutic drug monitoring of vancomycin]. Therapie 66, 29-37 [PubMed:21466775] [show Abstract] Vancomycin is an antibiotic for exclusive hospital use administrated in intravenous infusion to treat systemic infections. It is mainly eliminated by kidneys and potentially nephrotoxic. Data available show that Therapeutic Drug Monitoring (TDM) of vancomycin is highly recommended. It aims to ensure efficacy and avoid resistance by maintaining trough plasma concentrations above the MIC. Secondary, vancomycine TDM may be indicated to prevent nephrotoxicity in high risk patients. TDM is often underwent at steady state (48 to 72 h after the treatment initiation) unless in case of renal impairment (24 h). While compared with intermittent administration, continuous infusion did not result in prognosis improvement; however it resulted in lower pharmacokinetic variability and better cost-efficiency. Targeted trough concentrations for intermittent infusion are between 15 and 20 mg/L (up to 25-30 mg/L for GISA). In case of continuous infusion, targets are higher (25 to 40 mg/L). | Shah RA, Musthaq A, Khardori N (2009) Vancomycin-induced thrombocytopenia in a 60-year-old man: a case report. Journal of medical case reports 3, 7290 [PubMed:19830166] [show Abstract]
IntroductionVancomycin, a glycopeptide antibiotic, is used to treat resistant gram-positive infections. There has been a 10- to 20-fold increase in its use over the past 25 years. Although ototoxicity and nephrotoxicity are well known side effects of vancomycin, it can also induce platelet reactive antibodies leading to life-threatening thrombocytopenia. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. We report a proven case of vancomycin-induced thrombocytopenia and its reversal after discontinuation of vancomycin.Case presentationA 60-year-old man with a history of hypertension, congestive heart failure and dyslipidemia was admitted for a right shoulder rotator cuff tear. He underwent right-shoulder arthroscopy and rotator cuff repair. About three weeks later, he developed pain, swelling and purulent drainage from his right shoulder. Arthroscopic irrigation and drainage was then performed. Intraoperative fluid revealed the presence of Methicillin susceptible Staphylococcus aureus, vancomycin-sensitive Enterococcus spp. and Serratia marcescens. The patient had no known allergies. After reviewing his antimicrobial susceptibility, he was started on vancomycin 1500 mgs intravenously every 12 hours (to treat both Staphylococcus aureus and Enterococcus spp) and ciprofloxacin 750 mgs by oral induction every 12 hours. The patient's condition improved following antibiotic treatment. He was discharged and allowed to go home on IV vancomycin and oral ciprofloxacin. The patient's platelet count on the day of starting vancomycin therapy was 253 x 10(3)/mm(3). At weeks one, two and three, the counts were 231 x 10(3)/mm(3), 272 x 10(3)/mm and 6 x 103/mm(3), respectively. The patient was admitted for further work-up of the thrombocytopenia. He was later shown to have vancomycin-induced platelet-reactive antibodies, causing significant thrombocytopenia, and then reversal after his vancomycin medication was discontinued.ConclusionThrombocytopenia is a potentially life-threatening condition. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. Simple laboratory testing with drug-dependent antibodies can be helpful in identifying vancomycin as a cause of thrombocytopenia. | Kaakeh Y, Phan H, DeSmet BD, Pasko DA, Glenn DK, Stevenson JG (2008) Enhanced photoemission spectroscopy for verification of high-risk i.v. medications. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 65, 49-54 [PubMed:18159039] [show Abstract]
PurposeThe sensitivity and specificity of enhanced photoemission spectroscopy (EPS) for performing an automated final check of compounded i.v. admixtures at a pediatric hospital pharmacy were studied.MethodsA tabletop EPS device was used to test samples of seven high-risk drug-diluent combinations compounded in the pharmacy; the drugs were vancomycin, lorazepam, morphine, insulin, hydromorphone, gentamicin, and epinephrine. Ten sets of samples were prepared for each drug. Typically, a sample set consisted of dilutions ranging from 10-fold above to 10-fold below the targeted concentration. Testing was performed twice weekly between November 2005 and March 2006.ResultsThe EPS device detected errors departing from the targeted concentration by 20% or more with a sensitivity of at least 95%. Specificity in distinguishing among test medications at targeted concentrations was 100%. The percentage of passing samples with intermediate concentrations varied among the drugs.ConclusionA tabletop EPS device demonstrated acceptable sensitivity and specificity for validating the identity and concentrations of selected high-risk i.v. medications compounded for pediatric patients. The device may help prevent clinically important medication errors caused by inaccurate compounding. | Yao N, Wu CY, Xiao W, Lam KS (2008) Discovery of high-affinity peptide ligands for vancomycin. Biopolymers 90, 421-432 [PubMed:18260149] [show Abstract] Vancomycin, an important antibiotic against medically relevant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus, exerts its antibacterial effects by binding with moderate affinity to the C-terminal Lys-D-Ala-D-Ala motif (Kaa) of the bacterial cell wall peptide precursor. Essential for Kaa binding to vancomcyin is the free-carboxyl group on the terminal D-Ala in Kaa. In efforts to identify other Kaa-based peptides which bind vancomycin with higher affinity, we utilized our one-bead-one-compound (OBOC) combinatorial library approach, a method which has been widely used to discover highly specific ligands against various receptors. In standard OBOC peptide libraries, the C-terminal end of the synthesized peptide is tethered to a solid-support/resin, however, this study reports development of a synthetic strategy for generating OBOC peptide libraries with a free D-Ala-D-Ala carboxyl end. We screened these "OBOC inverted" peptide libraries against vancomycin, and discovered a series of peptide ligands with strong consensus, which bind vancomycin. To further optimize these ligands, two highly focused Kaa-containing OBOC combinatorial peptidomimetic libraries were designed, synthesized, and screened against vancomycin under more stringent conditions. Peptidomimetic ligands which bind vancomycin with higher affinity than Kaa were identified. The dissociation constant of one of these ligands, Lys(Ac)-HOCit-Glu-Cha-Lys(3,5-dihydroxybenzoyl)-D-Ala-D-Ala (9), as determined by surface plasmon resonance, was 1.03 microM, roughly a 50-fold improvement in affinity compared to Kaa (K(D) = 50 microM). | Stryjewski ME, Chambers HF (2008) Skin and soft-tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 46 Suppl 5, S368-77 [PubMed:18462092] [show Abstract] Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection has become epidemic. Skin and soft-tissue infections (SSTIs) are the most frequent forms of the disease. Obtainment of culture specimens is important for documentation of the presence of MRSA and for susceptibility testing to guide therapy. Purulent lesions should be drained whenever possible. In areas where community-acquired MRSA isolates are prevalent, uncomplicated SSTI in healthy individuals may be treated empirically with clindamycin, trimethoprim-sulfamethoxazole, or long-acting tetracyclines, although specific data supporting the efficacy of these treatments are lacking. In healthy patients with small purulent lesions, drainage alone may be sufficient. In patients with complicated SSTI requiring hospitalization or intravenous therapy, vancomycin is the drug of choice because of the low cost, efficacy, and safety. Linezolid, daptomycin, and tigecycline are also effective, although published studies on the last 2 agents for the treatment of SSTI due to MRSA are more limited. Dalbavancin, telavancin, and ceftobiprole are investigational agents that may expand our therapeutic options for the treatment of SSTI caused by MRSA. | Tverdek FP, Crank CW, Segreti J (2008) Antibiotic therapy of methicillin-resistant Staphylococcus aureus in critical care. Critical care clinics 24, 249-60, vii-viii [PubMed:18361944] [show Abstract] The treatment of methicillin-resistant Staphylococcus aureus (MRSA) in the critically ill patient is challenging. Data for treatment of critically ill patients are often lacking because many such patients are excluded from industry-sponsored prospective randomized clinical trials. Infections due to MRSA are common in the critical care setting. Up to 24% of patients in intensive care units are colonized with MRSA, and 20% of all nosocomial bloodstream infections are due to MRSA. It is also one of the leading bacterial causes of ventilator- and hospital-acquired pneumonia. Vancomycin has been the drug of choice for treatment of MRSA in the critical care setting. Recent data showing vancomycin resistance, increasing numbers of MRSA isolates with higher vancomycin minumum inhibitory concentrations, and an apparent increase in vancomycin clinical failures have brought vancomycin's utility into question. A variety of treatment options for MRSA are available. Quinupristin-dalfopristin was the first alternative to vancomycin. However, its safety profile and potential for drug interactions limit its use. Linezolid has been shown to be effective in the treatment of pneumonia and skin and skin-structure infections due to MRSA. The drug's potential to cause bone marrow suppression limits its use, especially in treatment durations extending beyond 14 days. Daptomycin has been shown to be effective for the treatment of MRSA bloodstream and of MRSA skin and skin-structure infections. Tigecycline is the newest available drug with MRSA activity. It has demonstrated noninferiority to vancomycin in skin and skin-structure infections. However, its role in the treatment of ventilator- and hospital-acquired pneumonia is still unclear. | Chaudhuri A, Martinez-Martin P, Kennedy PG, Andrew Seaton R, Portegies P, Bojar M, Steiner I, EFNS Task Force (2008) EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults. European journal of neurology 15, 649-659 [PubMed:18582342] [show Abstract] Acute bacterial meningitis (ABM) is a potentially life-threatening neurological emergency. An agreed protocol for early, evidence-based and effective management of community-acquired ABM is essential for best possible outcome. A literature search of peer-reviewed articles on ABM was used to collect data on the management of ABM in older children and adults. Based on the strength of published evidence, a consensus guideline was developed for initial management, investigations, antibiotics and supportive therapy of community-acquired ABM. Patients with ABM should be rapidly hospitalized and assessed for consideration of lumbar puncture (LP) if clinically safe. Ideally, patients should have fast-track brain imaging before LP, but initiation of antibiotic therapy should not be delayed beyond 3 h after first contact of patient with health service. In every case, blood sample must be sent for culture before initiating antibiotic therapy. Laboratory examination of cerebrospinal fluid is the most definitive investigation for ABM and whenever possible, the choice of antibiotics, and the duration of therapy, should be guided by the microbiological diagnosis. Parenteral therapy with a third-generation cephalosporin is the initial antibiotics of choice in the absence of penicillin allergy and bacterial resistance; amoxicillin should be used in addition if meningitis because of Listeria monocytogenes is suspected. Vancomycin is the preferred antibiotic for penicillin-resistant pneumococcal meningitis. Dexamethasone should be administered both in adults and in children with or shortly before the first dose of antibiotic in suspected cases of Streptococcus pneumoniae and H. Influenzae meningitis. In patients presenting with rapidly evolving petechial skin rash, antibiotic therapy must be initiated immediately on suspicion of Neisseria meningitidis infection with parenteral benzyl penicillin in the absence of known history of penicillin allergy. | Zhang LF, Yang DJ, Chen HC, Sun R, Xu L, Xiong ZC, Govender T, Xiong CD (2008) An ionically crosslinked hydrogel containing vancomycin coating on a porous scaffold for drug delivery and cell culture. International journal of pharmaceutics 353, 74-87 [PubMed:18162343] [show Abstract] The aim of this study was to prepare and characterize a scaffold with an ionically crosslinked hydrogel coating layer containing a water-soluble drug, vancomycin, via a novel drug loading method for sustained drug delivery and surface modification. The poly(D,L-lactide acid) (PDLLA)/biphasic calcium phosphate (BCP) scaffold with a highly inter-connected porous structure was fabricated by a particle-leaching/thermally induced phase separation (TIPS) method. The pre-vacuumized scaffold was immersed into an alginate/vancomycin solution. Following impregnation by the solution, the scaffold was removed and immersed in a CaCl(2) solution for 30 min to allow gelation of the alginate solution. In this way, the drug was not exposed to organic solvents or detrimental temperature conditions and it could avoid loss of drug during the leaching process. The water contact angles of the scaffold surface decreased after being coated with the hydrogel. The in vitro drug release profile showed sustained release properties which were influenced by the alginate concentration and the dissolution medium. A standardized bacterial assay showed that the drug was still active after association with the scaffold by this gentle method of drug loading. The in vitro osteoblast culture experiments confirmed the biocompatibility of the scaffold for attachment and proliferation of osteoblasts. | Japoni A, Farshad S, Alborzi A, Kalani M, Rafaatpour N, Oboodi B, Pourabbas B (2008) Epidemiology and antibacterial susceptibility patterns of bloodstream infections, 2001-2004: an experience with BACTEC 9240 in Southern Iran. Pakistan journal of biological sciences : PJBS 11, 422-427 [PubMed:18817166] [show Abstract] This study was conducted to determine the prevalence of bacteria recovered from bloodstream samples by Bactec 9240 at our hospital wards and to evaluate their antibacterial susceptibility patterns. During January 2001 through December 2004, 9407 referred blood samples in Bactec bottles from admitted patients at three main wards, neonates, pediatrics and adults at Nemazee Hospital, affiliated to Shiraz University of Medical Sciences in Shiraz were processed. Positive cultures were purified and identified according to standard methods. Sensitivity of bacteria to different antibiotics was determined by Kirby-Bauer disk diffusion method. Staphylococcus aureus 132(25%), Escherichia coli 64(12.1%) and Pseudomonas aeruginosa 52(9.8%) were the most pathogenic bacteria which were recovered from the blood samples. Pathogenic microorganisms were isolated from blood samples of 305 (57.8%) at pediatrics, from 181 (34.2%) at adults and from 42 (8%) at neonates wards. The highest antibiotics activities against gram positive isolates observed for vancomycin (98.4%), chloramphenicol (86.4%) and ciprofloxacin (77.4%), while in gram negative bacteria imipenem (96.1%), ciprofloxacin (83%) and amikacin (77.9%), were effective antibiotics. Frequency of isolated bacteria at pediatrics compared to adults and neonates wards were approximately two and seven folds high, respectively which indicates special attention should be paid to pediatrics patients both in prevention and treatment aspects. Vancomycin and imipenim are the effective antibiotics and could cover majority of gram positive and negative bacteria. Therefore, combined administrations of these antibiotics seems mandatory for empirical therapy. | Khorvash F, Mostafavizadeh K, Mobasherizadeh S, Behjati M, Naeini AE, Rostami S, Abbasi S, Memarzadeh M, Khorvash FA (2008) Antimicrobial susceptibility pattern of microorganisms involved in the pathogenesis of surgical site infection (SSI); A 1 year of surveillance. Pakistan journal of biological sciences : PJBS 11, 1940-1944 [PubMed:18983037] [show Abstract] The aim of this study is to identify the antibiotic sensitivity pattern of pathogens involved in the process of surgical site infection, in surgical wards. Changes made in the pattern of antibiotic use will result in different microorganism susceptibility patterns, which needs correct determination for precise empiric antibiotic therapy. One thousand patients (62% men and 38% women, 18- 74-years-old, with mean age 43 +/- 8)) who underwent surgical treatment, in Alzahra University Hospital, Isfahan University of Medicine, Isfahan, Iran, were studied from 2005 to 2006. Surgical wound infections, based on the reported criteria, were aspirated for culturing within 1 plus gram staining of prepared smears. Minimum Inhibitory Concentrations (MICs) were determined for samples and all derived data were compared by SPSS 13 and WHO net 5 software. The prevalence of SSI was 13.3% with 150 positive cultures, totally. Of 150 bacteria, isolated from surgical site infections Staphylococcus aureus had most frequency (43%). Resistance of isolated organisms was 41.7% in amikacin, 65 and 78.6% in ceftazidime, 85.7% in ceftriaxone, 61.5% in ciprofloxacin, 78.8% in gentamicine, 6.4% in imipenem, 13% in meropenem and 70.6% in trimethoprim/sulfamethoxazole, respectively. 78.9% of Staphylococcus aureus isolates were MRSA and vancomycine was the most effective antibiotic without any resistance. Among 10 isolates of coagulase negative Staphylococcus, no vancomycine resistance was seen, but in contrast all cases were resistant to oxacillin. The most common gram negative organism was Klebsiella (18 isolates) in which 100 and 80% were sensitive to imipenem and meropenem, respectively. Seventeen cases were E. coli, in which the most sensitivity was to meropenem (80%) and imipenem (77.8%). Thirteen cases of Pseudomonas were detected, in which 16.7% were resistant to imipenem and 8.3% to meropenem. Our results demonstrated that the total antibiotic resistance is increasing among SSIs, with an up sloping pattern, which will contact with a constant empiric antibiotic therapy. So, precise up to date antibiogram tantalize us toward balancing the rate of total antibiotic resistance to SSIs. | Oldfield EC (2008) Infectious disease. Vancomycin should be the drug of choice for severe Clostridium difficile-associated diarrhea. Reviews in gastroenterological disorders 8, 270-271 [PubMed:19107100] | Radin S, Ducheyne P (2007) Controlled release of vancomycin from thin sol-gel films on titanium alloy fracture plate material. Biomaterials 28, 1721-1729 [PubMed:17184835] [show Abstract] Risk of infection is considerable in open fractures and its management is challenging, especially when fracture fixation material is used. Thus, it may be desirable to use a device from which antibiotics can be released in a controlled way. Room temperature processed silica sol-gels are novel, resorbable and biocompatible, controlled release materials. Vancomycin, a potent antibiotic used in treating osteomyelitis, can be released from silica sol-gels. Herein, we describe the synthesis of thin, resorbable, controlled release bactericidal sol-gel films on a Ti-alloy substrate and determine the effect of processing parameters on its degradation and vancomycin release. A close correlation between release and degradation rates suggests that film degradation is the main mechanism underlying the control of release. Using a multi-layer process and various concentrations of vancomycin, released concentrations exceed the minimal inhibitory concentration (MIC) of vancomycin against Staphylococcus aureus. The findings enable the tailoring of release and degradation properties of the films to therapeutic needs by controlling sol-gel processing parameters. Given the bactericidal properties of released vancomycin, and the biocompatibility of the sol-gel films, the present data suggest great promise to prevent and treat bone infections in a clinical setting. | Lodise TP, McKinnon PS (2007) Burden of methicillin-resistant Staphylococcus aureus: focus on clinical and economic outcomes. Pharmacotherapy 27, 1001-1012 [PubMed:17594206] [show Abstract] Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major public concern. Hospital-acquired MRSA rates have steadily increased over the past 25 years, and the bacterial strain is making inroads to the community. The morbidity and mortality burden of MRSA infection is compounded by delayed or inappropriate antibiotic treatment, taking a toll on health care resources that are already stretched thin. Vancomycin has historically been the drug of choice for this pathogen because its broad spectrum can address the multidrug resistance of most MRSA infections. Despite its sustained in vitro microbiologic inhibitory activity, researchers are beginning to question the continued utility of vancomycin for MRSA infections. Evidence against vancomycin is most notable with regard to nosocomial pneumonia and skin and soft tissue infections. In addition, because vancomycin must be administered intravenously, patients typically require prolonged hospitalization, which further increases the cost of MRSA treatment and exposes patients to additional nosocomial infections. Recent studies have shown that antibiotics with good bioavailability, such as linezolid, can be given orally to facilitate early hospital discharge, thus alleviating the economic burden of MRSA infections. Several agents have been developed over the past decade that have excellent in vitro activity against MRSA. Further studies are needed to determine if these drugs can better eradicate MRSA than vancomycin and remedy the adverse outcomes frequently observed with this organism. | Hong S, Valderrama E, Mattana J, Shah HH, Wagner JD, Esposito M, Singhal PC (2007) Vancomycin-induced acute granulomatous interstitial nephritis: therapeutic options. The American journal of the medical sciences 334, 296-300 [PubMed:18030187] [show Abstract] Drug-induced acute renal failure is a commonly encountered mode of renal injury in the hospitalized patient. Vancomycin is a frequently used antibiotic in patients with Gram-positive bacterial infections. In the present study, we evaluated an index case of a patient who developed severe acute granulomatous interstitial nephritis and provided a review of the reported cases of vancomycin-induced acute renal failure in the literature. A Medline search revealed a total of 11 cases of vancomycin-induced interstitial nephritis. In 2 reported cases, interstitial nephritis has been reported with associated granuloma formation. However, the role of T cells in the formation of interstitial nephritis and in the choice of therapeutic modalities in this scenario has not been evaluated in the past. In the index case, we have evaluated the effect of treatment on the basis of the type of cellular infiltrates and provided a follow-up by carrying out the repeat biopsy. | Maclayton DO, Hall RG (2007) Pharmacologic treatment options for nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus. The Annals of pharmacotherapy 41, 235-244 [PubMed:17299012] [show Abstract]
ObjectiveTo discuss current and potential treatment options for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA).Data sourcesA MEDLINE search (1966-January 2007) was conducted to identify English-language literature on pharmacotherapy of nosocomial pneumonia and the bibliographies of pertinent articles. Programs and abstracts from infectious disease meetings were also searched. Search terms included MRSA, nosocomial pneumonia, pulmonary infections, vancomycin, quinupristin/dalfopristin, linezolid, daptomycin, tigecycline, dalbavancin, oritavancin, and ceftobiprole. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all pertinent information was included in this review.Data synthesisVancomycin has been the drug of choice for MRSA infections for many years. Recent data suggest that linezolid may be superior to vancomycin in the treatment of MRSA nosocomial pneumonia. However, there are limitations to the available data. Therefore, prospective, randomized studies are needed before linezolid is recommended as the preferred first-line therapy. Other approved agents for nosocomial MRSA infections, such as quinupristin/dalfopristin and daptomycin, should not be used in the treatment of MRSA pneumonia, as they were inferior in clinical trials. Tigecycline has excellent activity against MRSA in vitro, but should not be routinely used for the treatment of MRSA pneumonia, as clinical data are lacking. In a Phase III clinical trial, an anti-MRSA cephalosporin, ceftobiprole, is being evaluated for effectiveness against nosocomial pneumonia. Investigational glycopeptides may eventually have a role in the treatment of nosocomial pneumonia, but data are currently lacking.ConclusionsVancomycin is still the drug of choice for treatment of MRSA pneumonia, and linezolid should be used as an alternative agent. Linezolid should carry strong consideration for patients with vancomycin-induced nephrotoxicity or a documented lack of response to vancomycin. Tigecycline and investigational agents with activity against MRSA may be future options for nosocomial pneumonia due to MRSA. | Kitazawa T, Ota Y, Kada N, Morisawa Y, Yoshida A, Koike K, Kimura S (2006) Successful vancomycin desensitization with a combination of rapid and slow infusion methods. Internal medicine (Tokyo, Japan) 45, 317-321 [PubMed:16596002] [show Abstract] Vancomycin, an antibiotic to which methicillin-resistant Staphylococcus aureus (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the vancomycin infusion rate and/or premedicating with antihistamine effectively reduce hypersensitivity in most cases. However, vancomycin desensitization is sometimes the only way to ensure safe use. Two types of desensitization protocols have been reported, and these utilize different infusion intervals; rapid desensitization and slow desensitization. We herein report a case of vancomycin hypersensitivity with methicillin-resistant Staphylococcus aureus infection. A combination of the two desensitization protocols, rapid desensitization followed by slow desensitization, effectively inhibited the hypersensitivity reaction during vancomycin infusion, and methicillin-resistant Staphylococcus aureus was successfully eradicated. | Kleinschmidt SL, Munckhof WJ, Nimmo GR (2006) In vitro exposure of community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains to vancomycin: does vancomycin resistance occur? International journal of antimicrobial agents 27, 168-170 [PubMed:16420976] [show Abstract] Vancomycin is the preferred parenteral antibiotic for the treatment of all methicillin-resistant Staphylococcus aureus (MRSA) infections, including the newly emerging community-associated MRSA (CA-MRSA) infections. Vancomycin-intermediate nosocomial MRSA strains have developed in vitro and in vivo after exposure to vancomycin. The aim of this study was to determine whether daily serial passage of CA-MRSA strains onto vancomycin-supplemented agar selects for the development of vancomycin resistance. Twelve clinical isolates of the six commonest Australian and US strains of CA-MRSA were serially passaged daily for 25 days onto brain-heart infusion agar plates supplemented with 4 microg/mL vancomycin and then subcultured for a further 15 days onto antibiotic-free agar to assess the stability of the resistance phenotype. Minimum inhibitory concentrations (MICs) were determined by standard Etest every 5 days from day 0 to day 40. Serial passaging resulted in increased MICs in all strains but the rises were modest, with an increase of < 2 doubling dilutions. All strains remained vancomycin susceptible throughout the experiment according to Clinical Laboratory Standards Institute criteria. | Bingen E, Mariani-Kurkdjian P, Nebbad B (2006) [Optimal vancomycin serum level in Staphylococcus aureus infections?]. Medecine et maladies infectieuses 36, 439-442 [PubMed:17027219] [show Abstract] Vancomycin is the cornerstone of therapy against methicillin-resistant Staphylococus aureus in both community and nosocomial-acquired infections. Because vancomycin is a concentration-independent or time-dependant antibiotic, most clinicians have abandoned the routine practice of determining peak serum concentrations to rely solely on monitoring serum concentrations. The so-called therapeutic range most often quoted for vancomycin was assessed for through serum concentrations of 5-10 mg/l. But prolonged exposure to serum concentration close to the MIC is associated with the emergence of resistance. More recent guidelines recommended vancomycin in concentrations of 15-20 mg/l for the treatment of severe Staphylococcus infections or in situations where vancomycin penetration is poor. However, because of the great variability of vancomycin MIC(S) (0,12-4 mg/l) of susceptible Staphylococcus strains, guidelines should recommend through serum concentrations of 5-10 times the MIC. | Cadle RM, Mansouri MD, Darouiche RO (2006) Vancomycin-induced elevation of liver enzyme levels. The Annals of pharmacotherapy 40, 1186-1189 [PubMed:16720708] [show Abstract]
ObjectiveTo report a case of oral vancomycin-induced elevation of liver enzyme levels.Case summaryA 57-year-old man with multiple medical conditions requiring systemic antibiotic therapy developed numerous Clostridium difficile-associated enterocolitis episodes. The patient did not respond adequately to oral metronidazole, as evidenced by his continuing diarrhea. He was treated with oral vancomycin on 5 separate occasions (with doses from 125 to 500 mg/day), each of which resulted in significant elevations in alanine aminotransferase (to 371 U/L) and aspartate aminotransferase (to 203 U/L) levels. The elevations resolved on each occasion with discontinuation of vancomycin.DiscussionVancomycin, a glycopeptide antibiotic, has primary activity against gram-positive bacteria. Oral vancomycin can be used for the treatment of C. difficile-associated enterocolitis in patients who fail to respond to or are intolerant to metronidazole therapy. Oral vancomycin has very poor bioavailability and, as of May 4, 2006, has not been associated with hepatic toxicity. Inflammatory bowel disease processes can result in increased absorption of oral vancomycin.ConclusionsThis is the first reported case of oral vancomycin-induced elevation of hepatic enzyme levels. Use of the Naranjo probability scale indicated that this was a probable adverse drug-associated event. | Ariano RE, Fine A, Sitar DS, Rexrode S, Zelenitsky SA (2005) Adequacy of a vancomycin dosing regimen in patients receiving high-flux hemodialysis. American journal of kidney diseases : the official journal of the National Kidney Foundation 46, 681-687 [PubMed:16183423] [show Abstract]
BackgroundSome investigators have recommended the convenient practice of administering vancomycin doses during the last hour of the hemodialysis treatment. Accepting that a greater amount of vancomycin is lost to dialysis with this recent approach, the objective of this study is to determine the pharmacokinetics of vancomycin and assess the adequacy of this dosing regimen in maintaining therapeutic predialysis concentrations.MethodsA sampling of 22 consecutive patients administered intradialytic vancomycin, 1 g, intravenously (IV) and maintenance doses of 500 mg during the last hour of high-flux dialysis sessions was studied. A population-modeling program and Bayesian pharmacokinetic analysis were used to identify all global and unique pharmacokinetic parameters of interest based on measured vancomycin predialysis concentrations.ResultsFor the 22 patients studied, this regimen achieved the targeted predialysis concentration range of 5 to 20 microg/mL for 96% of levels, whereas more narrowly within 5 to 15 microg/mL for 86% of levels. Average amount of vancomycin removed during a standardized 3- to 4-hour dialytic session ranged from 30% +/- 7% to 38% +/- 8%. Average elimination half-life of vancomycin on hemodialysis treatment was 5.4 hours (interquartile range, 5.0 to 5.9 hours). Patients showed an average predialysis plasma concentration of 11 +/- 3 microg/mL for the first 7 days of therapy.ConclusionOur results indicate that intradialytic dosing with vancomycin using a 1-g IV load and 500 mg IV with subsequent high-flux dialysis sessions conveniently maintains adequate predialysis plasma concentrations. The lack of drug accumulation with this regimen provides convincing support for a limited blood sampling approach to plasma concentration determinations. | de Macedo JL, Santos JB (2005) Bacterial and fungal colonization of burn wounds. Memorias do Instituto Oswaldo Cruz 100, 535-539 [PubMed:16184232] [show Abstract] A prospective study of fungal and bacterial flora of burn wounds was carried out from February 2004 to February 2005 at the Burns Unit of Hospital Regional da Asa Norte, Brasília, Brazil. During the period of the study, 203 patients were treated at the Burns Unit. Wound swab cultures were assessed at weekly intervals for four weeks. Three hundred and fifty four sampling procedures (surface swabs) were performed from the burn wounds. The study revealed that bacterial colonization reached 86.6% within the first week. Although the gram-negative organisms, as a group, were more predominant, Staphylococcus aureus (28.4%) was the most prevalent organism in the first week. It was however surpassed by Pseudomonas aeruginosa form third week onwards. For S. aureus and P. aeruginosa vancomycin and polymyxin were found to be the most effective drugs. Most of the isolates showed high level resistance to antimicrobial agents. Fungi were found to colonize the burn wound late during the second week postburn, with a peak incidence during the third and fourth weeks. Species identification of fungi revealed that Candida tropicalis was the most predominant, followed by Candida parapsilosis. It is crucial for every burn institution to determine the specific pattern of burn wound microbial colonization, the time-related changes in the dominant flora, and the antimicrobial sensitivity profiles. This would enable early treatment of imminent septic episodes with proper empirical systemic antibiotics, without waiting for culture results, thus improving the overall infection-related morbidity and mortality. | Samra Z, Ofer O, Shmuely H (2005) Susceptibility of methicillin-resistant Staphylococcus aureus to vancomycin, teicoplanin, linezolid, pristinamycin and other antibiotics. The Israel Medical Association journal : IMAJ 7, 148-150 [PubMed:15792257] [show Abstract]
BackgroundMethicillin-resistant Staphylococcus aureus is a major nosocomial pathogen worldwide. Vancomycin is the traditional drug of choice, but decreasing susceptibility to vancomycin and other glycopeptides has been reported since 1996.ObjectivesTo test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA isolates recovered from hospitalized patients.MethodsWe tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin) and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method.ResultsAll isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC90 was 2.0 microg/ml for vancomycin and teicoplanin (range 0.5-2.0 microg/ml and 0.125-2.0 microg/ml, respectively), and 0.5 microg/ml for pristinamycin and linezolid (range 0.125-0.75 microg/ml and 0.125-0.5 microg/ml, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ (P < 0.01) and an apparent increase in resistance to other antibiotics.ConclusionThe excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection. | Mory F, Fougnot S, Rabaud C, Schuhmacher H, Lozniewski A (2005) In vitro activities of cefotaxime, vancomycin, quinupristin/dalfopristin, linezolid and other antibiotics alone and in combination against Propionibacterium acnes isolates from central nervous system infections. The Journal of antimicrobial chemotherapy 55, 265-268 [PubMed:15590714] [show Abstract]
ObjectivesTo evaluate the antibiotic susceptibilities of Propionibacterium acnes isolates from central nervous system (CNS) infections to agents used in current treatment regimens.MethodsMICs of 16 reference antibiotics were determined by an agar dilution method for 24 consecutive strains of P. acnes isolated from individual patients with intracranial empyema or brain abscess. Bactericidal activities of antibiotics against P. acnes PAN14 were studied at 0.25-2 x MIC using a time-kill method.ResultsAll of the isolates were resistant to fosfomycin, intermediate or resistant to metronidazole and susceptible to all the other antibiotics tested, except for nine strains, which were intermediate to ofloxacin. Among antibiotics tested alone in time-kill experiments, vancomycin was the most effective drug and exhibited bactericidal activity after 24 h at 1x and 2 x MIC, whereas cefotaxime and ciprofloxacin were bactericidal after 48 h at 2 x MIC. No significant bactericidal activity could be demonstrated with the other antibiotics tested alone. The addition of cefotaxime to vancomycin resulted in bactericidal activity at lower concentrations (0.5 x MIC), whereas synergy was observed between quinupristin/dalfopristin and cefotaxime at 2 x MIC. In contrast, antagonism was observed between cefotaxime and linezolid, and ciprofloxacin and clindamycin.ConclusionOur data suggest that P. acnes isolates causing CNS infections remain highly susceptible to most antibiotics used for the treatment of such infections. Moreover, we showed that cefotaxime, vancomycin and ciprofloxacin possess good bactericidal activities against P. acnes, and that these activities may be enhanced when vancomycin is combined with cefotaxime or when cefotaxime is combined with quinupristin/dalfopristin. | Kimura T, Sunakawa K, Matsuura N, Kubo H, Shimada S, Yago K (2004) Population pharmacokinetics of arbekacin, vancomycin, and panipenem in neonates. Antimicrobial agents and chemotherapy 48, 1159-1167 [PubMed:15047516] [show Abstract] Immature renal function in neonates requires antibiotic dosage adjustment. Population pharmacokinetic studies were performed to determine the optimal dosage regimens for three types of antibiotics: an aminoglycoside, arbekacin; a glycopeptide, vancomycin; and a carbapenem, panipenem. Eighty-three neonates received arbekacin (n = 41), vancomycin (n = 19), or panipenem (n = 23). The postconceptional ages (PCAs) were 24.1 to 48.4 weeks, and the body weights (BWs) ranged from 458 to 5,200 g. A one-compartment open model with first-order elimination was applied and evaluated with a nonlinear mixed-effect model for population pharmacokinetic analysis. In the fitting process, the fixed effects significantly related to clearance (CL) were PCA, postnatal age, gestational age, BW, and serum creatinine level; and the fixed effect significantly related to the volume of distribution (V) was BW. The final formulas for the population pharmacokinetic parameters are as follows: CL(arbekacin) = 0.0238 x BW/serum creatinine level for PCAs of <33 weeks and CL(arbekacin) = 0.0367 x BW/serum creatinine level for PCAs of > or = 33 weeks, V(arbekacin) = 0.54 liters/kg, CL(vancomycin) = 0.0250 x BW/serum creatinine level for PCAs of <34 weeks and CL(vancomycin) = 0.0323 x BW/serum creatinine level for PCAs of > or = 34 weeks, V(vancomycin) = 0.66 liters/kg, CL(panipenem) = 0.0832 for PCAs of <33 weeks and CL(panipenem) = 0.179 x BW for PCAs of > or = 33 weeks, and V(panipenem) = 0.53 liters/kg. When the CL of each drug was evaluated by the nonlinear mixed-effect model, we found that the mean CL for subjects with PCAs of <33 to 34 weeks was significantly smaller than those with PCAs of > or = 33 to 34 weeks, and CL showed an exponential increase with PCA. Many antibiotics are excreted by glomerular filtration, and maturation of glomerular filtration is the most important factor for estimation of antibiotic clearance. Clinicians should consider PCA, serum creatinine level, BW, and chemical features when determining the initial antibiotic dosing regimen for neonates. | Babalola CP, Patel KB, Nightingale CH, Nicolau DP (2004) Synergistic activity of vancomycin and teicoplanin alone and in combination with streptomycin against Enterococcus faecalis strains with various vancomycin susceptibilities. International journal of antimicrobial agents 23, 343-348 [PubMed:15081082] [show Abstract] The synergy between two glycopeptides, vancomycin (Vm) and teicoplanin (Tec) and streptomycin (Sm) was studied by time-kill method. Five clinical vanB resistant Enterococcus faecalis (ENC) isolates with variable Vm-susceptibility were used. Different concentrations of Vm, Tec and Sm representing therapeutic concentrations were combined. Antibacterial activity was related to the concentrations of Vm and Sm, and Vm susceptibility to ENC. For strains with Vm MIC up to 64 mg/l, synergy was achieved with higher concentrations of Vm and Sm, while all combinations of Tec and Sm were synergistic against all strains except ENC 29. For ENC 29 with Vm MIC of 512 mg/l and Tec MIC of <1 mg/l, none of the combinations was synergistic. The significance of these in vitro results needs further investigation in vivo. | King DW, Smith MA (2004) Proliferative responses observed following vancomycin treatment in renal proximal tubule epithelial cells. Toxicology in vitro : an international journal published in association with BIBRA 18, 797-803 [PubMed:15465645] [show Abstract] Vancomycin (VAN) is a glycopeptide antibiotic used to treat gram-positive infections. Nephrotoxicity is a common side effect observed with vancomycin therapy. However, the mechanism of vancomycin-induced nephrotoxicity has not been fully characterized. In this study we examined the effect of vancomycin on cellular proliferation in renal proximal tubule cells. A dose- and time-dependent increase in cell number and total cellular protein was observed following vancomycin exposure. Vancomycin exposure also caused an increase in BrdU incorporation followed by the accumulation of renal proximal tubule cells in G(2)/M phase of the cell cycle. These effects were inhibited by pretreatment with the mitogen-activated protein kinase inhibitor, PD098059, suggesting an association between the cell proliferative effect of VAN and the induction of the mitogen-activated protein kinase signaling pathway. Mitochondrial function in renal proximal tubule cells was assessed using oxygen consumption and ATP concentrations. We observed an increase in oxygen consumption and ATP concentrations following short-term exposure to vancomycin. Together, our data suggest that vancomycin treatment produces alterations in mitochondrial function that coincide with a cell proliferative response in renal proximal tubule epithelial cells. | Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH (2003) Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 124, 1789-1797 [PubMed:14605050] [show Abstract]
ObjectiveTo assess the effect of baseline variables, including treatment, on outcome in patients with nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA).DesignRetrospective analysis of data from two prospective, randomized, double-blind studies.SettingMultinational study with 134 sites.PatientsA total of 1,019 patients with suspected Gram-positive nosocomial pneumonia, including 339 patients with documented S aureus pneumonia (S aureus subset) and 160 patients with documented MRSA pneumonia (MRSA subset).InterventionsLinezolid, 600 mg, or vancomycin, 1 g, q12h for 7 to 21 days, each with aztreonam.Measurements and resultsOutcome was measured by survival and clinical cure rates (assessed 12 to 28 days after the end of therapy). Logistic regression analysis was used to determine the effect of treatment and other baseline variables on outcome. Kaplan-Meier survival rates for linezolid vs vancomycin were 80.0% (60 of 75 patients) vs 63.5% (54 of 85 patients) for the MRSA subset (p = 0.03). Logistic regression analysis confirmed that the survival difference favoring linezolid remained significant after adjusting for baseline variables (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0 to 4.8; p = 0.05). Other baseline variables associated with significantly higher survival rates in MRSA pneumonia were serum creatinine levels less than or equal to two times the upper limit of normal and absence of cardiac comorbidities. Clinical cure rates for linezolid vs vancomycin (excluding indeterminate or missing outcomes) were 59.0% (36 of 61 patients) vs 35.5% (22 of 62 patients) for the MRSA subset (p < 0.01). Logistic regression analysis confirmed that the difference favoring linezolid remained significant after adjusting for baseline variables (OR, 3.3; 95% CI, 1.3 to 8.3; p = 0.01). Other baseline variables associated with significantly higher clinical cure rates in MRSA pneumonia were single-lobe pneumonia, absence of ventilator-associated pneumonia, and absence of oncologic and renal comorbidities.ConclusionsIn this retrospective analysis, initial therapy with linezolid was associated with significantly better survival and clinical cure rates than was vancomycin in patients with nosocomial pneumonia due to MRSA. | Pituch H, Obuch-Woszczatyński P, Glinka D, Łazińska B, Meisel-Mikołajczyk F, Łuczak M (2003) [Assessment of susceptibility to metronidazole and vancomycin of Clostridium difficile strains isolated between 1998-2002]. Medycyna doswiadczalna i mikrobiologia 55, 253-258 [PubMed:14702667] [show Abstract] The drugs of choice used to treat C. diffcile associated diarrhoea (CDAD) are metronidazole and vancomycin. C. difficile strains isolated in most laboratories are susceptible to metronidazole and vancomycin. Communication about emergence of antimicrobial resistance among C. difficile strains in some countries to metronidazole and intermediate resistance to vancomycin are alarming. This study was performed to determine the susceptibility to metronidazole and vancomycin of 140 C. difficile strains isolated from patients with CDAD hospitalised in academic hospital between 1999-2002. Resistance to metronidazole and vancomycin was not observed. | Du B, Chen DC, Liu DW (2003) [Efficacy and nephrotoxicity of vancomycin in the treatment of Gram positive infections]. Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 15, 32-34 [PubMed:12852813] [show Abstract]
ObjectiveTo evaluate the efficacy and nephrotoxicity of vancomycin in the treatment of Gram positive infections.MethodsA retrospective study of 84 patients with Gram positive infections who were treated with vancomycin in intensive care unit of Peking union medical college hospital.ResultsClinical effective rate was 90% (76/84), and bacterial eradication rate was also 90% (76/84). By univariate analysis, lower respiratory tract infection (LRTI) and longer duration of infection prior to vancomycin treatment were associated with poor clinical response, while LRTI and higher total dose of vancomycin were associated with poor bacteriologic response. The prevalence of nephrotoxicity ranged from 11% (9/84) to 14% (12/84). There was no significant difference in terms of nephrotoxicity prevalence whichever criteria of nephrotoxicity was applied. Nephrotoxicity could be reversed, either during or after treatment, in 22% to 44% of patients. The development of nephrotoxicity was associated with LRTI and poor bacteriological response.ConclusionVancomycin is a reliable and safe antibiotic in the treatment of Gram positive infections. | Blum R, Seymour JF, Toner G (2002) Significant impairment of high-dose methotrexate clearance following vancomycin administration in the absence of overt renal impairment. Annals of oncology : official journal of the European Society for Medical Oncology 13, 327-330 [PubMed:11886013] [show Abstract]
BackgroundMethotrexate is an antimetabolite cytotoxic drug which is predominantly renally excreted. Vancomycin, a glycopeptide antibiotic that is used in the febrile neutropaenic patient, can be nephrotoxic. There are no previous reports of any interactions between these two drugs.Patients and methodsWe describe two patients with osteosarcoma treated with high-dose methotrexate-containing chemotherapy who had significantly delayed methotrexate clearance several weeks following exposure to vancomycin.ResultsThese patients were treated with alternating chemotherapy consisting of 12 g/m2 methotrexate, 60 mg/m2 cisplatin, 75 mg/m2 adriamycin and 15 g/m2 ifosfamide. In both patients, serum methotrexate levels fell to below 0.2 micromol/l within 48-96 h during initial treatment cycles. However, following recent exposure to therapeutic vancomycin in the preceding 10 days and in the absence of overt renal impairment, both patients manifested markedly prolonged methotrexate clearance, requiring 170-231 h to reach serum levels of less than 0.2 microM. Subclinical renal impairment was documented by impaired glomerular filtration rates in both cases by technetium 99 m diethylene triamine penta-acetic acid scanning. Subsequent methotrexate cycles using an unmodified schedule were cleared within 72 h. Both cases had their glomerular filtration rate re-assessed, which showed marked improvement.ConclusionsRecent exposure to vancomycin, even in the absence of overt renal impairment, may adversely affect methotrexate excretion, which can subsequently lead to increased toxicity of the antimetabolite. The glomerular filtration rate should be measured in such cases so that appropriate dose modification of methotrexate can be made. | Peláez T, Alcalá L, Alonso R, Rodríguez-Créixems M, García-Lechuz JM, Bouza E (2002) Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin. Antimicrobial agents and chemotherapy 46, 1647-1650 [PubMed:12019070] [show Abstract] Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomially acquired, antibiotic-associated diarrhea. The drugs most commonly used to treat diseases associated with C. difficile are metronidazole and vancomycin. Most clinical laboratories assume that all C. difficile isolates are susceptible to metronidazole and vancomycin. We report on the antimicrobial susceptibilities of 415 C. difficile isolates to metronidazole and vancomycin over an 8-year period (1993 to 2000). The overall rate of resistance to metronidazole at the critical breakpoint (16 microg/ml) was 6.3%. Although full resistance to vancomycin was not observed, the overall rate of intermediate resistance was 3.1%. One isolate had a combination of resistance to metronidazole and intermediate resistance to vancomycin. Rates of resistance to metronidazole and vancomycin were higher among isolates from human immunodeficiency virus-infected patients. Molecular typing methods proved the absence of clonality among the isolates with decreased susceptibilities to the antimicrobials tested. | Georges B, Roche C, Archambaud M, Decun JF, Cougot P, Conil JM, Chaminade B, Andrieu P, Saivin S, Bonnet E, Chabanon G, Houin G, Samii K, Virenque C (2002) [Importance of a cefpirome-vancomycin combination on bactericidal kinetics in severe MRSA infections in intensive care]. Pathologie-biologie 50, 161-168 [PubMed:11980329] [show Abstract]
UnlabelledVancomycin is always the drug of choice for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in spite of his bactericidal kinetic.BackgroundThe aim of this study was to evaluate in vivo the improvement of bactericidal kinetic of vancomycin associated with cefpirome against MRSA infection in critically ill patients.MethodsThe prospective cross-over study was carried out in 20 patients with severe pneumonia or bacteremia. There were randomized to receive vancomycin 2 g per day (Group 1, n = 10) or vancomycin with cefpirome 2 g x 2 (Group 2, n = 10). Clinical recovery, bacteriologic parameters (bactericidal kinetic and bactericidal power in vivo at the peak and the valley), duration of ventilation and stay in ICU were comparatively explored in both groups.ResultsClinical outcome did not significantly differ between Group 1 and 2. Bactericidal kinetics were better in the Group 2 (40% vs 60% after 6 hours to the dilution for 1/8e) but the difference was not significant. However, bactericidal power in sera was also better in the Group 2 with more bactericidal dilution at 1/16e (68% vs 88.8%: NS) and overall at 1/32e (10.5% vs 50%: p < 0.05) and CRP, an inflammatory marker, was significantly lower in the Group 2 than in the Group 1 (119.5 +/- 24 mg/l vs 198.6 +/- 78 mg/l: p < 0.05) on the third day. | Martínez-Lacasa J, Cabellos C, Martos A, Fernández A, Tubau F, Viladrich PF, Liñares J, Gudiol F (2002) Experimental study of the efficacy of vancomycin, rifampicin and dexamethasone in the therapy of pneumococcal meningitis. The Journal of antimicrobial chemotherapy 49, 507-513 [PubMed:11864951] [show Abstract] The object of the study was to assess the efficacy of rifampicin and the combination of rifampicin plus vancomycin in a rabbit model of experimental penicillin-resistant pneumococcal meningitis. We also studied the effect of concomitant dexamethasone on the CSF antibiotic levels and inflammatory parameters. The rabbit model of pneumococcal meningitis was used. Groups of eight rabbits were inoculated with 106 cfu/mL of a cephalosporin-resistant pneumococcal strain (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours later they were treated with rifampicin 15 mg/kg/day, vancomycin 30 mg/kg/day or both plus minus dexamethasone (0.25 mg/kg/day) for 48 h. Serial CSF samples were withdrawn to carry out bacterial counts, antibiotic concentration and inflammatory parameters. Rifampicin and vancomycin promoted a reduction of >3 log cfu/mL at 6 and 24 h, and cfu were below the level of detection at 48 h. Combination therapy with vancomycin plus rifampicin was not synergic but it had similar efficacy to either antibiotic alone and it was able to reduce bacterial concentration below the level of detection at 48 h. Concomitant use of dexamethasone decreased vancomycin levels when it was used alone (P< 0.05), but not when it was used in combination with rifampicin. Rifampicin alone at 15 mg/kg/day produced a rapid bactericidal effect in this model of penicillin-resistant pneumococcal meningitis. The combination of vancomycin and rifampicin, although not synergic, proved to be equally effective. Using this combination in the clinical setting may allow rifampicin administration without emergence of resistance, and possibly concomitant dexamethasone administration without significant interference with CSF vancomycin levels. | Aarestrup FM, Seyfarth AM, Emborg HD, Pedersen K, Hendriksen RS, Bager F (2001) Effect of abolishment of the use of antimicrobial agents for growth promotion on occurrence of antimicrobial resistance in fecal enterococci from food animals in Denmark. Antimicrobial agents and chemotherapy 45, 2054-2059 [PubMed:11408222] [show Abstract] From 1995 to 2000, a total of 673 Enterococcus faecium and 1,088 Enterococcus faecalis isolates from pigs together with 856 E. faecium isolates from broilers were isolated and tested for susceptibility to four classes of antimicrobial agents used for growth promotion as part of the Danish program of monitoring for antimicrobial resistance. The four antimicrobials were avilamycin, erythromycin, vancomycin, and virginiamycin. Major changes in the use of antimicrobial agents for growth promotion have occurred during the last 6 years in Denmark. The government banned the use of avoparcin in 1995 and of virginiamycin in 1998. Furthermore, the producers have voluntarily stopped all use beginning in 1999. The avoparcin ban in 1995 was followed by a decrease in the occurrence of glycopeptide-resistant E. faecium (GRE) in broilers, from 72.7% in 1995 to 5.8% in 2000. The occurrence of glycopeptide resistance among isolates from pigs remained constant at around 20% from 1995 to 1997. It was shown that, in GRE from pigs, the genes encoding macrolide and glycopeptide resistance were genetically linked and that, following the decrease in the use of tylosin during 1998 and 1999, the occurrence of GRE in pigs decreased to 6.0% in 2000. From 1995 to 1997 the occurrence of erythromycin resistance among E. faecium and E. faecalis isolates from pigs was almost 90%. Use of tylosin decreased considerably during 1998 and 1999, and this decrease was followed by decreases in the occurrence of resistance to 46.7 and 28.1% among E. faecium and E. faecalis isolates from pigs, respectively. Erythromycin resistance among E. faecium isolates from broilers reached a maximum of 76.3% in 1997 but decreased to 12.7% in 2000 concomitantly with more limited use of virginiamycin. Use of virginiamycin increased from 1995 to 1997 and was followed by an increased occurrence of virginiamycin resistance among E. faecium isolates in broilers, from 27.3% in 1995 to 66.2% in 1997. In January 1998 the use of virginiamycin was banned in Denmark, and the occurrence of virginiamycin resistance decreased to 33.9% in 2000. Use of avilamycin increased from 1995 to 1996 and was followed by an increase in avilamycin resistance among E. faecium isolates from broilers, from 63.6% in 1995 to 77.4% in 1996. Since 1996 avilamycin usage has decreased, followed by a decrease in resistance to 4.8% in 2000. Our observations show that it is possible to reduce the occurrence of antimicrobial resistance in a national population of food animals when the selective pressure is removed. Cases in which resistance to vancomycin was linked to resistance to erythromycin were exceptions. In such cases resistance did not decrease until the use of both avoparcin and tylosin was limited. | Liñares J (2001) The VISA/GISA problem: therapeutic implications. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 7 Suppl 4, 8-15 [PubMed:11688538] [show Abstract] The emergence of vancomycin intermediate resistant Staphylococcus aureus (VISA) isolates in Japan, USA, France, Hong Kong and Korea among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, is of great concern. Vancomycin has been the drug of choice for the treatment of multiresistant MRSA infections in the last three decades, but the management of invasive MRSA infections will become a serious problem if VISA strains become widespread. VISA isolates reported to date have a vancomycin MIC of 8 mg/L, and were isolated from patients with underlying diseases whose long-term vancomycin treatment apparently failed. Since many VISA isolates also have been resistant to teicoplanin, the term glycopeptide-intermediate S. aureus (GISA) is more appropriate. The frequency of GISA isolates appears to be extremely low; to date, only 10 GISA infections have been reported worldwide. However, heterogeneous resistance to glycopeptides (h-GISA) have been reported in Japan, Europe and Thailand. These h-GISA strains showed vancomycin MICs ranging from 1 to 4 mg/L, but had subpopulations that could grow on agar plates containing 4-8 mg/L, which may represent the first step in the development of GISA strains. Although GISA isolates have shown resistance to many antimicrobials, all GISA isolates remain susceptible to co-trimoxazole and some of them to other common antimicrobials. Currently, there are no recommended therapy guidelines for GISA infections, although in recent studies, several new drugs have shown promising activity against GISA strains. In addition, synergy between glycopeptides and beta-lactams against GISA strains was observed in some in vivo and in vitro studies. Specific MRSA/GISA control programs, rational antibiotic policies, including the reduction of glycopeptide use, and rapid laboratory detection of GISA and h-GISA strains are the key measures in preventing the spread of these strains. | Liu F, Zhou S, Zhang S, Deng Q, Zhang L, Xu Y, Wang J (2001) [Research of drug resistance and detection of methicillin-resistant Staphylococcus aureus in chronic maxillary sinusitis]. Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology 15, 341-343 [PubMed:12541895] [show Abstract]
ObjectiveTo investigate the detection method of methicillin-resistant staphylococcus aureus (MRSA) in chronic maxillary sinusitis and the situation of drug resistance to some common antibiotics.MethodUsing multiplex polymerase chain reaction technique to detect the drug resistant gene (mecA) of MRSA and specific gene (femA) of staphylococcus aureus at the same time. Drug resistant tests were performed with disk diffusion (K-B) method.ResultfemA is a specific gene of staphylococcus aureus, the detective ratio of mecA in MRSA is 96.2% (51/53). Vancomycin is the only antibiotic which is sensitive to MRSA, while others are not.ConclusionMRSA can be rapidly and specifically identified with multiplex PCR. There are drug resistance to many antibiotic drugs for MRSA. | Moreillon P (2000) [Means of bacterial resistance]. Revue medicale de la Suisse romande 120, 641-650 [PubMed:11028184] [show Abstract] Fifty years ago, the introduction of penicillin, followed by many other antibacterial agents, represented an often underestimated medical revolution. Indeed, until that time, bacterial infections were the prime cause of mortality, especially in children and elderly patients. The discovery of numerous new substances and their development on an industrial scale confronted us with the illusion that bacterial infections were all but vanquished. However, the widespread and sometimes uncontrolled usage of these agents has led to the selection of bacteria resistant to practically all available antibiotics. Bacteria utilize three main resistance strategies: (i) decrease in drug accumulation, (ii) modification of target, and (iii) modification of the antibiotic. Bacteria can decrease drug accumulation either by becoming impermeable to antibiotics, or by actively excreting the drug accumulated in the cell. As an alternative, they can modify the structure of the antibiotic's molecular target--usually an essential metabolic enzyme of the bacteria--and thus escape the drug's toxic effect. Lastly, they can produce enzymes capable of modifying and directly inactivating the antibiotics. In addition, bacteria have evolved extremely efficient genetic transfer systems capable of exchanging and accumulating resistance genes. Some pathogens, such as methicillin-resistant Staphylococcus aureus and enterococci are now resistant to almost all available antibiotics. Vancomycin is the only non-experimental drug left to treat severe infections due to such organisms. However, vancomycin resistance has already appeared several years ago in enterococci, and was also recently described in staphylococci, in Japan, France and the United-States. Antibiotics are precious drugs which must be administered to patients who need them. On the other hand, the development of resistance must be kept under control by a better comprehension of its mechanisms and modes of transmission and by abiding by the fundamental rules of anti-infectious chemotherapy, i.e.: (i) choose the most efficient antibiotic according to clinical and local epidemiological data, (ii) target the bacteria according to the microbiological data at hand, and (iii) administer the antibiotic at an adequate dose which will leave the pathogen no chance to develop any resistance. | HIGGINS HM, HARRISON WH, WILD GM, BUNGAY HR, McCORMICK MH (1957) Vancomycin, a new antibiotic. VI. Purification and properties of vancomycin. Antibiotics annual 5, 906-914 [PubMed:13521912] | GERACI JE, HEILMAN FR, NICHOLS DR, ROSS GT, WELLMAN WE (1956) Some laboratory and clinical experiences with a new antibiotic, vancomycin. Proceedings of the staff meetings. Mayo Clinic 31, 564-582 [PubMed:13370625] |
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