41 results on '"Kiem S"'
Search Results
2. Surveillance of the Middle East respiratory syndrome (MERS) coronavirus (CoV) infection in healthcare workers after contact with confirmed MERS patients: incidence and risk factors of MERS-CoV seropositivity
- Author
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Kim, C.-J., Choi, W.S., Jung, Y., Kiem, S., Seol, H.Y., Woo, H.J., Choi, Y.H., Son, J.S., Kim, K.-H., Kim, Y.-S., Kim, E.S., Park, S.H., Yoon, J.H., Choi, S.-M., Lee, H., Oh, W.S., Choi, S.-Y., Kim, N.-J., Choi, J.-P., Park, S.Y., Kim, J., Jeong, S.J., Lee, K.S., Jang, H.C., Rhee, J.Y., Kim, B.-N., Bang, J.H., Lee, J.H., Park, S., Kim, H.Y., Choi, J.K., Wi, Y.-M., and Choi, H.J.
- Published
- 2016
- Full Text
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3. agr functionality affects clinical outcomes in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia
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Kang, C. K., Kim, Y. K., Jung, S.-I., Park, W. B., Song, K.-H., Park, K.-H., Choe, P. G., Jang, H.-C., Lee, S., Kim, Y.-S., Kwak, Y. G., Kwon, K. T., Kiem, S., Kim, C.-J., Kim, E. S., Kim, H. B., and the Korea INfectious Diseases (KIND) study group
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- 2017
- Full Text
- View/download PDF
4. Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort
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Song, K.-H., Jung, S.-I., Lee, S., Park, S., Kiem, S. M., Lee, S. H., Kwak, Y. G., Kim, Y. K., Jang, H.-C., Kim, Y.-S., Kim, H.-I., Kim, C. J., Park, K.-H., Kim, N. J., Oh, M.-D., Kim, H. B., and The Korea INfectious Diseases (KIND) study group
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- 2017
- Full Text
- View/download PDF
5. Validation of non-REM sleep stage decoding from resting state fMRI using linear support vector machines
- Author
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Altmann, A., Schröter, M. S., Spoormaker, V. I., Kiem, S. A., Jordan, D., Ilg, R., Bullmore, E. T., Greicius, M. D., Czisch, M., and Sämann, P. G.
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- 2016
- Full Text
- View/download PDF
6. Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis
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Brink, A.J., Richards, G.A., Schillack, V., Kiem, S., and Schentag, J.
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- 2009
- Full Text
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7. Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA
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McGuire D, Alexander J, Johansen O, Perkovic V, Rosenstock J, Cooper M, Wanner C, Kahn S, Toto R, Zinman B, Baanstra D, Pfarr E, Schnaidt S, Meinicke T, George J, von Eynatten M, Marx N, Aizenberg D, Fiorella A, Edgardo N, Belen C, Alonso P, Walter M, Maia K, Guillermo S, Leandro B, Constanza R, Alejandra N, Melina C, Ariel I, Rodrigo C, Alvarez C, Jorge M, Gabriel C, German S, Bartolacci I, Bolobanich G, Tale T, Meritano M, Echeverria M, Gerrini S, Alvarez M, Torrijos N, Berli M, Coggiola J, Castaneda G, Rode R, Milessi R, Roude A, Bono J, Caresani J, Arias V, Westberg J, Allende G, Liberman A, Bordonava A, Almagro S, Gerbaudo C, Schiavi L, Budassi N, Cecilia M, Buncuga M, Carlos S, Osvaldo T, Mercedes S, Calella P, Agustina V, Aljandro M, Alberto D, Fiorella M, Cantero M, Cariganano M, Anadon P, Cartasegna L, Gabriela M, Fernanda A, Alberto R, Chacon C, Jazmin F, Colombo H, Coni E, Mattausch S, Thomsenhall K, della Torre M, Morandini M, Berra F, Margarita H, Commendatore V, Tedesco J, Bolzan P, Cuneo C, Narcisa G, Caputi V, Pablo S, Sandra G, Pacora F, Tinari M, Jure H, Parody M, Toranzo A, Frechtel G, Yohena S, Lovecchio S, Muller C, Martin S, Olivera C, Breyaui M, Bianchi G, Garcia C, Luciana V, Florencia F, Ruben G, Gelersztein E, Rey G, Sanchez C, Fornasari L, Di Pierro L, Giacomi G, Miguel S, Laura T, Gonzalo C, Ramon C, Glenny J, Koretzky M, Porto A, Tiberio O, Ellenberg A, Saurral R, Igarzabal C, Vilamajo O, Matkovich J, de Lapertosa S, Villagra M, Cuzziol G, de la Cruz M, Pinchetti R, Mierez M, Lopez C, Gorosito V, Gabito A, Kleiban A, Grosembacher L, Adrian P, Paula R, Javier G, Kraft F, Andres F, Krynski F, Nicolas P, Marcelo F, Alfredo F, de la Fuente R, Natalia C, Luquez H, Recuero Y, Becchetti N, Ruiz M, Costantino M, Vazquez G, Guzman C, Pelatia P, Maffei L, Sassone S, Yantorno M, Prado G, Khron B, Maldonado N, Gustavo L, Veronica V, Marino J, Elizabeth A, Alejandra C, Oscar R, Azize G, Gallardo M, Escudero M, Vargas E, Ramos H, Lucero C, Najenson M, Crocci I, Chiesa A, Nardone L, Dominguez S, Zanini A, Manghi F, Grossman M, Giudice G, Romeo A, Piskorz D, Miguel C, Susana D, Noeli U, Rosa S, Martin V, Soledad A, Virginia M, Lorena G, Prado A, Veronica L, Eduardo H, Adolfo P, Florencia W, Rista L, Scolari C, Rojas N, Bertolio V, Zarandon R, Jair S, Orlando C, Sanabria H, Ignacio D, Viviana C, Marina R, Sarjanovich R, Scaro G, Huerta C, Mana M, Gutierrez M, Dain A, Gavicola R, Sessa H, Sacripanti J, Felman R, Vilarino P, Sicer M, Lagrutta M, Sala J, Casabella T, Cecilia H, Carlos B, Vines G, Javier R, Vico M, Lanchiotti P, Martella C, Torres L, Villarino A, Molina M, Martinez J, Farias C, Bertola S, Rojas M, Guzman P, Nisi J, Martinez D, Barrionuevo M, Vita N, Lopez A, Vottero E, Giuliano M, Paron L, Vogel D, Mele P, Imposti H, Dominguez A, Zaidman C, Fernando G, Beck M, Beltrame P, Chemello D, Junior R, Abreu A, Fernandes V, Saboia J, Rodrigues L, Carvalho M, Gurgel M, Gadelha D, Ramos C, Borba V, Golbert M, Pitthan M, Golbert L, Valentini R, Canani L, Gross J, Valenti A, Sartori C, Dutra O, Azevedo E, Azevedo A, Vaz R, Vaz H, da Costa F, da Costa L, Panarotto D, Lain F, Camazzola F, Dellomea B, Rech R, Pizzato P, Nunes C, Jaeger C, Silveira D, Wagner L, Machado L, Rea R, de Bem A, Alves J, Jonasson T, Malucelli F, Betti R, Lerario A, Lisboa H, Bem J, Tres G, Tavares C, Nardi A, Pozzatto M, Backes L, Reolao J, Scariot E, Ziguer E, Baldissera D, Griz L, Antunes D, Victor F, Freire K, Barros A, Costi B, Sa M, Carneiro A, Felicio J, Felicio K, Penha P, Ferreira J, Melo F, Alves A, Souza A, Costa L, Pinheiro D, Turatti L, Augusto G, Leanca C, Santomauro A, Forti A, Sena R, Marinho A, Facanha C, de Souza K, de Souza A, de Queiroz W, Leite S, Vieira S, Gubert L, Olsen A, Piazzetta G, Fuck A, Ferreira M, Fortes J, Brandao T, Alves F, Radice E, dos Santos J, de Almeida R, Franco D, Saporito W, Eliaschewitz F, de Siqueira K, Bona R, Genestreti P, de Castro D, Visconti G, Sampaio C, Palhares F, Konigsfeld H, Alves E, Feder C, Leao B, Saraiva J, Rodovalho S, Costa M, Pires N, Figueiredo E, Werner G, Garcia J, de Paiva I, Quirino B, Botelho R, da Silva R, Navarro A, Lourenco C, Pereira A, Arantes F, Boner D, Saad J, Falchetto E, Washizu E, Mandil A, Pimenta N, Tofani F, Fonseca T, Teixeira L, Maia L, Lemos M, Mouco O, Nakazone M, Weiand L, Bohn J, Hissa M, Araripe F, Carvalho F, Cancado G, Wang R, Chacra A, Fusaro A, de Mendonca E, Cercato C, Halpern A, Alves B, Braile M, Sestito R, Mustafa E, Ferreira V, Sbardellini B, de Almeida P, Guimaraes F, Piedade M, Bienert I, Braga J, Daher R, Hirakawa T, Terra E, Farias E, Figueiredo M, Lima L, Moraes K, Avelino I, Flato U, Plavnik F, Portes E, Moreira M, Vendramini M, Veloso R, Padilha M, Rodrigues A, Adam R, Santos S, Sayeg N, Guerrero D, Madeira M, Siqueira J, Pinheiro R, Villacorta A, Mellazi A, Braga T, Kaiser S, Paolino B, Lefterov I, Marinchev A, Angelova S, Klyuchkova N, Lybomirova Z, Kerekovski Y, Kuneva T, Penkova D, Levterov G, Videnova E, Georgieva P, Shinkov A, Borissova A, Vlahov J, Dakovska-Dekova L, Lucheva M, Luchev P, Temelkova M, Borisova K, Tsenov S, Andreeva V, Margaritov V, Arasheva G, Lozanov L, Borisov R, Gorcheva D, Henein S, Whatley S, Boutros M, Kalyniuk N, Berlingieri J, Nisker W, Hoag G, Hepburn D, Harvey M, Manjoo P, Yale J, Sherman M, Tsoukas M, Rehman W, Mason M, Santerre M, De Kock J, Barkhuizen F, Rooke C, Gill C, Kooy J, Burgoyne G, de Kock J, Degen G, Hockman L, Invik R, Roberts P, Ward K, Alasaad H, Susan A, Davies V, Gupta N, Milhalidis J, Grossman L, Agawal N, Yared Z, Rwaheed, Nouhad S, Nahla A, Khandwala H, Warwick A, Wadehra D, Manan A, Vecchiarelli J, Aslam N, Ferrao A, St-Maurice F, Collette R, Davey B, Nawaz S, Coutu B, Costi P, Greiss I, Mansour F, Raymond J, St-Phard W, Nadra I, Della Siega A, Barahona L, Klinke P, Contractor H, Fryer M, Chandra N, Conti B, Telzer L, Sorensen S, Lounsbury N, Martin E, Mitchell L, Pelzer E, Nelson S, Jones M, Cox J, Luco G, Trhoughton T, Labonte R, Chouinard G, Frechette A, Rheaume M, Cusson J, Faucher J, Dery V, Kelly A, Miranda B, Al-Kayssi N, Malette P, Rheault P, Fredette P, Dumas R, Palardy J, Belanger A, Boucher P, Doyon B, Charbonneau J, Bailey G, Odendaal M, Stephan K, Badenhorst J, Knight D, Thurgood A, Johnston M, Cooper-Rosen E, Jagger R, Green M, Weisnagel S, Gangloff A, Bergeron J, Pesant Y, Chevalier P, Woo V, Hurd C, Ruckert G, Lira J, Navarro G, Venegas M, Gonzalez P, Montecinos H, Vidal G, Fernandez M, Varas J, Fernandez C, Aguilar J, Marin R, Kindel C, Yovaniniz P, Gherman O, Aravena M, Carvajal J, Macias E, Corrado P, Lazcano M, Garrido B, Charme G, Carrasco J, Vignolo P, Saavedra S, Gajardo V, Saavedra C, Santamaria D, del Castillo B, Balda I, Zurvarra V, Fu G, Jiang D, Huang H, Wang M, Song J, Lu W, Lin Y, Lu Z, Shi Y, Zhong M, Zhao X, Chen D, Zhang G, He Y, Shi P, Chu K, Gao Q, Deng W, Zhang J, Zhang Y, Chen H, Liu E, Xie Y, Lin R, Tan W, Yuan Z, Wang Y, Ren J, Yu H, Luo M, Ma W, Shi W, Xu H, Xu M, Liu G, Dong Y, Bai B, Guo R, Liu X, Gao Y, Li S, Xu X, Liu P, Dong X, Wang S, Fu F, Jiang Q, Meng C, Yin X, Lu Y, Cui Y, Su G, Miao W, Wei F, Zhao Q, Li Z, Gao X, Lozno H, Prada W, Figueroa W, Ordonez A, Quintero E, Vallejo G, Contreras C, Escobar J, Alvaran J, Ortiz L, Marin M, Montoya C, Mendoza J, Manjarres J, Navarro B, Martinez G, Bonfanti A, Perci X, de la Hoz L, Arroyo J, Rendon C, Lopez J, Escobar N, Franco J, Lozano M, Zapata C, Ibarra L, Barrero A, Sarmiento A, Lozada H, Olitte M, Florez L, Munoz C, Quintero G, Correa G, Ruiz S, Dorado A, Causa A, Palma E, Morales A, Arteaga J, Beltran J, Granados M, Rubio A, Dada F, Bueno W, Rivera R, Corredor K, Romero V, Accini F, Palmera J, Ruiz G, Ortega M, Sanchez A, Lora Y, Cano J, Duque S, Thiriez S, Castano M, Giraldo P, Boljkovac Z, Grcic I, Balen M, Zukanovic S, Jeric M, Dvorscak D, Car S, Knezevic A, Herceg D, Franov B, Miskovic V, Bakula M, Hadak A, Superba M, Rubes J, Gornik I, Hamzic J, Ballek L, Sedlackova L, Hejlova J, Galatikova D, Huskova A, Zak P, Flekac M, Mraz M, Potuznik P, Palova S, Novak P, Okenka L, Matuska J, Rohac F, Vondrak K, Reichert P, Shamasna A, Skopek J, Lejskova M, Jiruska M, Lang P, Podoubsky R, Svobodova J, Cifkova R, Jozifova M, Krajcoviechova A, Wolfhart P, Sulc P, Silhova E, Cechakova M, Machova V, Balkova J, Peterka M, Votocek S, Prosecky R, Valis M, Barton P, Tomek J, Pumprla J, Axmannova M, Vitaskova R, Sincl F, Horanska P, Richter B, Malicherova E, Roderova E, Jenickova P, Winkelmann B, Finger C, Klausmann G, Milek K, Schwabe M, Weiss N, Mahlmann A, Werth S, Schmidt C, Schoell I, London M, Steidl E, Orban K, Taeschner H, Bonigut S, Schiefke I, Schwittay A, Kornmann O, Eich A, Franke S, Kis J, Szobota E, Danos P, Beke E, Grosz A, Csecsei G, Ferenczy J, Filo A, Ferencz I, Mihaly E, Baranyi T, Revesz K, Schlezak J, Harcsa E, Dombroczki Z, Kocsis I, Juhasz E, Literati-Nagy B, Kulcsar E, Bezzeg K, Kemeny V, Peterfai E, Buday B, Keltai K, Balo T, Somogyi A, Nagy G, Oroszlan T, Bagosi Z, Bujtor Z, Tabak A, Ferencz V, Domjan B, Tanczer T, Palinkas A, Karolyi H, Kovacs K, Csaszar I, Palhegyi E, Engelhalter G, Horthy R, Vanko E, Szabo G, Sipos G, Szigyarto M, Sebo N, Paragh G, Zsiros N, Szentimrei R, Pal D, Kobling T, Szanto I, Varadi Z, Bajnok L, Szujo S, Nemes O, Bajnok A, Mezosi E, Bodis B, Marton Z, Konyves L, Farago M, Kiss G, Kiss O, Nagy E, Takacs R, Nyitray S, Abraham G, Fehertemplomi K, Deak L, Dezso E, Karneili E, Deeb D, Zloczower M, Mahmid R, Zolotov S, Hochberg I, Elias M, Goldstein L, Poletaev V, Rock W, Koren O, Saliba W, Wolf F, Adawi F, Nimer A, Mosenzon O, Raz I, Potekhin M, Cahn A, Yulian T, Zvulunov E, Israel H, Shpitz D, Bar-Or I, Chananashvili L, Irena L, Dessau H, Halabe A, Vishlitzky V, Nabriski D, Baraf L, Itelman M, Schiff E, Willner N, Fireman-Klein E, Svistunov V, Dotan Y, Pavlichev O, Saig L, Bashkin A, Kuyantseva E, Gershkov S, Nodelman M, Arbel Y, Bogomolny N, Leshem-Rubinow E, Rofe M, Chorin E, Havkuk O, Wainstein J, Feldman D, Fujino Y, Kitamura H, Toriumi Y, Ishiguro H, Naganuma T, Shu S, Suzuki K, Hirota Y, Hayashi T, Hozawa K, Fukui T, Abe Y, Yamauchi K, Maruyama M, Matsumura S, Kozuma R, Nagai Y, Kihara Y, Maeda H, Nakanishi K, Iitsuka T, Hatori M, Shinozaki Y, Akiyama D, Kawabe M, Takei M, Sato A, Kawai Y, Kitajima K, Ide M, Sato N, Morisaki H, Nakashima K, Takayanagi H, Watanabe H, Iwahashi N, Tsujimoto M, Hibuse K, Hata T, Ueno K, Tatsuma H, Wakida Y, Ito T, Mizuno R, Fujita H, Konishi N, Kanehira T, Watanabe R, Miyaoka H, Okada T, Yamamoto M, Okita S, Murakami H, Todo Y, Umeoka F, Hori K, Shiraishi K, Tada F, Shimizu T, Tamai J, Sasaki C, Okuzima Y, Yasuda M, Iwaita Y, Tanaka K, Rha S, Na J, Cho D, Cho Y, Hwang E, Choi T, Won K, Kim H, Kim S, Oh D, Lee J, Choi H, Chung H, Park H, Suh Y, Kim Y, Kim N, Kim K, An J, Kim J, Park K, Kwak S, Kim M, Hwangbo Y, Lee D, Hong A, Kim L, Oh C, Moon S, Jung C, Jin J, Hyun B, Yang Y, Kong S, Yoon K, Yang H, Hong T, Oh J, Park J, Lee H, Choi J, Ahn J, Han S, Park W, Jo S, Suh S, An W, Park M, Lee S, Kim D, Jin H, Seo J, Chung C, Lim J, Huh J, Park I, Yu S, Sim N, Khan S, Albakari N, Sivaraman J, Manaf K, Maharuddin I, Nagendram S, Ali N, Abdul Latiff N, Othman N, Sarip S, Chew E, Mohamed S, Aziz N, Hui K, Lin L, Velaiutham S, Khir A, Lee L, Manikam S, Chooi K, Chang M, Ooi C, Anthony J, Seganathirajah M, Ng O, Ismail N, Cheah C, Ramanathan G, Mui N, Wen F, Choo T, Bin Ruhani A, Jamaludin S, Abidin S, Nor F, Abu Hassan M, Hanari N, Ahmad N, Suan M, Zainul N, Ali S, Sridhar G, Han C, Chin A, Vin L, Kadir K, Zain A, Hussain N, Pusparajah P, Lozano F, Gomez A, Zaccari E, Vigil A, Preciado C, de Leon M, Parra M, Cervantes A, Aguirre E, Orozco E, Gonzalez S, Elizondo R, Flores E, Guerrero M, Flores F, Sanchez J, Perez F, Rodriguez J, Martinez L, Marquez D, Gutierrez B, Flores M, Real M, Campos P, Garcia P, Rios M, Romero E, Perez Z, Tarabay C, Munoz L, Farias J, Gonzalez J, Palestino N, Sanchez L, Carrillo G, Ordonez N, Pech C, Andrade M, Euan J, Ortegon M, Garcia S, Orozco J, Vazquez H, Herrera R, Perez E, Arango A, Ibarra M, Gonzales L, Esperano J, Quintana L, Salazar I, Ruiz L, Barron C, Ballesteros C, Cervera L, Hercilla E, Gomez H, Mesa J, Herrera P, Rodriguez M, Ochoa R, Mora E, Charles C, Silva R, Mijangos J, Diaz C, Zavala C, Baron P, Bernal A, Martinez F, Tlapale M, Ramirez E, Basila A, Munguia R, Tello M, Martinez M, Mulder H, van der Graaff P, Nawaz A, Keller I, Schoofs M, Smak-Gregoor P, Al-Windy N, Bulut S, de Jong J, Maas A, Schaardenburgh P, Imholz B, Heijster J, Hoogenberg K, Smit C, Kooy A, Huvers F, Landewe-Cleuren S, Kars M, van Moorsel D, Wolffenbuttel B, Lutgens H, Schutte E, Gansevoort R, Idzerda N, Westerink J, Weijmans M, Berg J, van Kleef M, Slob M, Jaspers N, Hovens M, Monajemi H, Kobielusz-Gembala I, Zmuda W, Adamczyk M, Konieczny M, Strzelecka-Sosik A, Nowacka E, Krzyzagorska E, Sekulska M, CzajkowskaKaczmarek E, Kaczmarek B, Opawska K, Dabrowska M, Kus W, Wrzesien-Kus A, Piotrowski G, Hotlos L, Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, Gmytrasiewicz M, Zambrzycki J, Krysiak-Kowaluk H, Klodawska K, Klszczewski Z, Zieleniewski J, Opadczuk P, Urbanska K, Faran-Grabowska K, Szczepanik T, Siegel A, Kleczek A, Kincel K, Nowak D, Slowik-Gomulka L, Watemborska-Matuszyk G, Lampart J, Strozik-Krecichwost A, Dziewit T, Broncel M, Wojcik-Odyniec J, Jakubczyk E, Wierzbicka K, Witowicz A, Jedrych B, Korczyk P, Socik-Pojawa M, Monteiro P, Monteiro S, Mendes P, Soares F, Mendes S, Leite L, Vicente J, Santos M, Ferreira A, Alves P, Rosario F, Garrao A, Duarte L, Rogado C, Duarte R, Laginha T, Matos P, Raposo J, Mariz J, Teixeira J, Capela C, Leitao A, Cardiga R, Alface M, Augusto S, Basto L, Cunha A, Rei D, Dantas J, Verdasca I, Andrade L, Silva A, Suarez M, Dias V, Silva J, Pereira N, Goncalves M, Goncalves A, Silveira A, Sampaio A, Dias A, Diogo M, Vilaca C, Cif A, Calin T, Elena S, Crisan C, Adina S, Ramona S, Anghel V, Simona C, Turcu L, Mihaela V, Cosma D, Cristina H, Marius-Calin H, Negrisanu G, Andreea-Andrada M, Maria-Mihaela V, Camelia T, Oana P, Monia A, Onaca A, Mircea O, Mot A, Stolea V, Elena N, Barbonta D, Cristian B, Oana S, Popescu A, Madalina M, Coman A, Anca C, Constantinescu S, Mircea C, Diaconu-Sotropa M, Ene D, Pintilei E, Mihai G, Delia R, Toarba I, Simona H, Negru D, Flaminzeanu F, Iulian C, Maria-Cristina C, Doros R, Cleo S, Sorin B, Demian L, Mihai S, Raul B, Ioana A, Nicolau A, Cosmin P, Isabela G, Elena C, Ileana T, Valuyskikh E, Miroshnichenko E, Klementyeva N, Zelman O, Chumakova G, Vigel A, Leonova N, Pergaeva Y, Stefanovskaya O, Pushkareva S, Antoshkina L, Zheleznova N, Iveitsman, Barbarash O, Zvereva T, Zhuravleva E, Zavyrylina I, Usoltceva E, Savostyanova Y, Kupriyanova T, Krivoshapova K, Kondyukova N, Inozemceva A, Argunova Y, Tsyba L, Belenky D, Mariich O, Terekhova A, Tsygankova O, Kuznetsova E, Nagibovich G, Ivchenko Y, Dobronravov V, Dobronravov A, Bush M, Trofimenko I, Vishnevsky A, Zikov V, Kositsyn D, Palzman Z, Spiridonova T, Rodina N, Polozhentsev S, Mamedova L, Panov A, 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Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
- Subjects
cardiovascular disease ,type 2 diabetes mellitus ,heart failure ,chronic kidney diseases - Abstract
Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease. Methods: Participants in 27 countries with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease were randomized 1:1 to receive once daily oral linagliptin 5 mg or placebo, on top of standard of care. All hospitalization for HF (hHF), cardiovascular outcomes, and deaths were prospectively captured and centrally adjudicated. In prespecified and post hoc analyses of HF and related events, Cox proportional hazards models adjusting for region and baseline history of HF were used. Recurrent hHF events were analyzed using a negative binomial model. In a subset of participants with left ventricular ejection fraction captured within the year before randomization, HF-related outcomes were assessed in subgroups stratified by left ventricular ejection fraction > or 50%. Results: CARMELINA enrolled 6979 participants (mean age, 65.9 years; estimated glomerular filtration rate, mL/min per 1.73m(2); hemoglobin A1c, 8.0%; 62.9% men; diabetes mellitus duration, 14.8 years), including 1873 (26.8%) with a history of HF at baseline. Median follow-up was 2.2 years. Linagliptin versus placebo did not affect the incidence of hHF (209/3494 [6.0%] versus 226/3485 [6.5%], respectively; hazard ratio [HR], 0.90; 95% CI, 0.74-1.08), the composite of cardiovascular death/hHF (HR, 0.94; 95% CI, 0.82-1.08), or risk for recurrent hHF events (326 versus 359 events, respectively; rate ratio, 0.94; 95% CI, 0.75-1.20). There was no heterogeneity of linagliptin effects on hHF by history of HF at baseline, baseline estimated glomerular filtration rate or urine albumin-creatinine ratio, or prerandomization left ventricular ejection fraction. Conclusions: In a large, international cardiovascular outcome trial in participants with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease, linagliptin did not affect the risk of hHF or other selected HF-related outcomes, including among participants with and without a history of HF, across the spectrum of kidney disease, and independent of previous left ventricular ejection fraction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01897532.
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- 2019
8. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk The CARMELINA Randomized Clinical Trial
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S, Park W, Jo S, Suh S, An W, Park M, Lee S, Kim D, Jin H, Seo J, Chung C, Lim J, Huh J, Park I, Yu S, Sim N, Khan S, Albakari N, Sivaraman J, Manaf K, Maharuddin I, Nagendram S, Ali N, Abdul Latiff N, Othman N, Sarip S, Chew E, Mohamed S, Aziz N, Hui K, Lin L, Velaiutham S, Khir A, Lee L, Manikam S, Chooi K, Chang M, Ooi C, Anthony J, Seganathirajah M, Ng O, Ismail N, Cheah C, Ramanathan G, Mui N, Wen F, Choo T, Bin Ruhani A, Jamaludin S, Abidin S, Nor F, Abu Hassan M, Hanari N, Ahmad N, Suan M, Zainul N, Ali S, Sridhar G, Han C, Chin A, Vin L, Kadir K, Zain A, Hussain N, Pusparajah P, Lozano F, Gomez A, Zaccari E, Vigil A, Preciado C, de Leon M, Parra M, Cervantes A, Aguirre E, Orozco E, Gonzalez S, Elizondo R, Flores E, Guerrero M, Flores F, Sanchez J, Perez F, Rodriguez J, Martinez L, Marquez D, Gutierrez B, Flores M, Real M, Campos P, Garcia P, Rios M, Romero E, Perez Z, Tarabay C, Munoz L, Farias J, Gonzalez J, Palestino N, Sanchez L, Carrillo G, Ordonez N, Pech C, Andrade M, 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L, Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, 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Abesadze I, Alugishvili M, Ivashkin V, Drapkina O, Korneeva O, Zyatenkova E, Glinkina I, Poluboyarinova I, Gurova O, Raykhman A, Vertkin A, Rodykova I, Shamaeva K, Petrovskaya T, Uzueva E, Milovanov Y, Milovanova S, Milovanova L, Markina M, Dobrosmyslov I, Markov V, Afanasiev S, Babich E, Belokopytova N, Demyanov S, Maximov A, Maximov I, Rebrova T, Shtatolkina M, Masin A, Demko A, Chuyko O, Pronina A, Charf G, Akatova E, Urlaeva I, Nikolin O, Khovaeva Y, Ermachkova L, Burdina E, Shvalb P, Suchkov I, Pshennikov A, Gryaznov S, Rymar O, Dolinskaya Y, Bahareva Y, Mustafina S, Sherbakova L, Ovsyannikova A, Bolshakova O, Polunicheva E, Dora S, Agafyina A, Yashina A, Vasilieva I, Yakhontova P, Selivanova S, Kargapoltseva O, Shilina N, Bayramova G, Sorokin I, Astamirova K, Kuchuk P, Koniushenko D, Malykh N, Dvorkin M, Krovelets T, Konovalova K, Seeber M, van Niekerk F, Siebert H, Steenkamp W, Wiid S, Noeth M, Siebert R, Breedt J, Bouwer J, Kapp C, Venter T, Rayner B, Trinder Y, Rheeder P, Delport E, Mathijs S, Soma P, van Zyl D, Strydom M, Marais A, Badat A, Hansa S, Fourie D, Walton T, Engelbrecht J, Jansen J, Roos J, du Toit S, Lehloenya K, van Zyl L, van Zyl F, Naude M, Mookadam M, van der Merwe A, Trokis J, Lombard L, Coetzee K, Ismail S, Bruning H, Latiff G, Yasmin O, Pillay T, Mohamed Z, Dawood S, Stapelberg A, Abrahams P, Jurgens J, van Heerden P, Swart E, Botha C, Meeding J, Hemus A, Oosthuysen W, Visagie G, Fourie N, Hutton P, van der Merwe N, Chelin N, Everton T, Duki M, Ghila N, Joshi M, Hira M, Madueno F, Martinez B, Sebastian N, Mercadal L, Isbert S, Gonzalez I, Asencio J, Figueras M, Rivas M, Garcia H, Fusalba A, Geat D, Cambra G, Sastre J, Castro F, Mas A, Portillo C, Serrano I, Hernandez S, Fajardo F, Juan C, Ferrer J, Peralta F, Padin C, Mauricio D, Madorell B, San Miguel F, Pedrol N, Trescoli C, Montanana C, Gonzalo M, Capellan J, Estrella A, Martinez C, Montesinos I, Loscos A, Coronado J, Perez J, Castillo B, Alonso C, Quesada V, Teruel J, Perez S, Lama M, del Rio E, Zlova T, Ponomarenko K, Karpenko O, Bezuglova S, Mitskevych L, Kizim S, Nevolina I, Katerenchuk V, Liudmyla B, Ivan K, Rudyk I, Olena M, Anna I, Ganna B, Topchii I, Semenovykh P, Yulia Y, Mykhalchyshyn G, Kirienko D, Kobiliak N, Bodnar, Mykhalchyshyn, Pertseva N, Olena G, Tomashkevych H, Korpachev V, Prybyla O, Kovalchuk A, Kushnarova N, Zinych O, Tseluyko V, Andriy Z, Olga R, Mankovskyy B, Zherdova N, Lykhoshapko O, Logoida P, Godlevska O, Olena V, Olga C, Gyrina O, Alifer O, Dozhuk K, Pekhenko V, Gorobets N, Korneichuk A, Makarenko E, Martynyuk L, Martynuyk O, Stanislavchuk M, Larysa P, Natalia S, Botsyurko V, Kostitska I, Dzeman O, Ablitsov Y, Ivaseiko S, Konovart O, Sandurska S, Vendzilovych Y, Samoylov O, Iryna C, Rozhkivska L, Ulyanchenko I, Kateryna V, Orlenko V, Ivaskina K, Tronko M, Tronko K, Pashkovska N, Stankova N, Vynnychenko L, Bolotnikova N, Demokhova N, Reshotko D, Popova A, Dr Bogdana, Tetiana S, Svitlana D, Oksana R, Vlasenko M, Litvinova S, Semenyuk I, Fishchuk O, Mostovoy Y, Tkachenko T, Ovcharuk M, Rasputina L, Vakaliuk I, Tymochko N, Drapchak I, Petrovska L, Lai W, Yen H, Voon W, Lin T, Cheng K, Chiu C, Chu C, Hsu P, Chiang C, Li Y, Kuo C, Lin S, Chao T, Yu W, Sung S, Wang K, Lu T, Shih K, Wu C, Chiang F, Hwang J, Tsai C, Juang J, Jeng J, Tang S, Lai C, Cheng C, Hsieh I, Hsieh M, Chen C, Lee C, Pai P, Ko P, Wang T, Chen T, Wu H, Chang S, Chen K, Hsieh L, Chou C, Jiang J, Lee M, Huang J, Chen J, Chiu K, Tsai L, Chen P, Saxena M, Collier D, Vaidya B, Harman S, Ramell M, Davies M, Chatterjee S, Meakin L, Quinn M, Bain S, Mallipedhi A, Min T, Bashir J, Blagden M, Ali J, McCrimmon R, Brennan G, Malcolm E, McDonald D, Pearson E, Illsley G, Darzy K, Winocour P, Hanif W, Cockwell P, Charlton M, Thekkepat S, Howat I, Devers M, Patrick J, Wyatt N, Smith C, Singh B, Nicholas J, Gillani S, Green F, Bell E, Boyle J, MacKin S, Livingstone R, Arif A, Syed M, Hammoud J, Sparks J, Anderson M, Tumey R, Condit J, Reddy M, Abalos-Galito M, Rebecca J, Barker T, Seaton B, Campbell E, Kompanik H, Jayson L, Huffman C, Bialow M, McDonnell G, McCaffrey J, Manis C, DeLuca E, Levins J, Bartlett M, Anorga K, Franco M, Gentry P, Hodge D, Pohil R, Rschultz, Leggett R, Blair L, Gisler J, Niegos F, Osburn M, Parma K, Schendel S, Stines L, Winnie M, Wu P, Canales J, Yu J, Cornett G, Beavins J, Hyde D, Zapinski D, Johnson T, Levinson D, Ahmed A, Kenny B, Kuehl A, Bates C, Jantzi C, Ananthula P, Shafer J, Louthan J, Bays A, Stapleton A, Staton P, Strum D, Taylor P, Smith A, Rapp R, Bao S, Randolph C, MacGillivray B, Schuster R, Harden T, Barnella C, Dunnam T, Whiles R, Bolick C, Brockmyre A, Plucker S, Marshall C, Poteet C, Morin D, Tavel E, Averill N, McFann A, Purcell D, Dixon T, Corey E, Goss J, Drescher R, Irfan M, Naeem M, Egelhof R, Mehta P, Koehler T, Walia J, Fernandez J, Bedel G, Preet R, Bhuchar S, Ahmed F, Onyema D, Benchabbat A, Kohanbash L, Miller P, Lalinde M, Carrithers E, Patterson R, Raube-Miceli A, Martinez A, Harris B, Levy R, Siev E, Berlin H, DiMattia M, Sugimoto D, Dugas J, Benson M, Stegemoller R, Schmoll M, Kinnaman S, O'Connor T, Powel T, Rudolph L, Lewiecki M, Best E, Chavez J, Garcia M, Cohen R, Colman D, Ocampo M, Heaney L, Rappley G, Quezada I, Santos V, Nikfarjam A, Reyes M, Rodriguez R, Josephs L, Hernandez R, Flores P, Espinoza L, Mejia W, Pedraza Z, Castaneda R, Laguerre J, Cook R, Patel R, Werner H, Blank R, Small S, Andersen J, Holmes D, Farmer M, Wiener V, Pharr W, Bray B, Beekman J, Anderson A, Andrawis N, Gabra N, Moche T, Marty S, Galvez O, Reyes R, Garcia R, Lerma G, Pliquin B, Mayfield R, Durham N, Phillips R, Baran A, Kondo N, Dempsey S, Kufs W, Laddis T, Zimmer K, Van Depol M, Dweck L, Kestler M, Werner N, Ashraf M, Quick A, Schallert G, Sligh T, Trueba P, Batista J, Martinez T, Moya J, Amarales V, Santos E, Torres P, Diaz T, Diaz J, Hodish I, Else T, Buras E, Moratis A, Valika S, Rahman A, Malalis W, Box E, Box P, Kerwood B, Nagaeva J, Metz C, Hinnant J, Griswell D, Philbeck A, Dukkipati R, Shaarawy R, Patak R, Kaye W, Steinsapir J, Horowitz B, Denenberg M, Reynolds C, Jenkinsdr M, Adlakha A, Hicklin H, Peelman J, Lerman S, Lamkin S, Smith S, Gould G, Cheung D, Stephen Z, Leigh T, Norwood P, Chelsea F, Trejo R, Neolms K, Bache R, Dinnerstein A, Sachson R, Aronoff S, Mendez A, Brooks S, Jones L, Dorfman S, Schill J, Leuck, Miklius A, Maw K, Hahn J, Gamarra L, Buynak R, Smith M, Ames J, Volom P, Anderson R, Desouza C, Shivaswamy V, Lefebvre G, Schweppe L, Berenguer R, Nelson R, Mas L, Gonzalez N, Palacio J, Bartkowiak A, Dilling J, Jordan T, Geishauser J, Jordan R, Arias E, Griffin C, Fisher M, Bryant C, Schnitz W, Kipgen W, Kasper J, Lopez R, Wright E, Thomas J, Weinstein D, Emerick G, Mendelson R, Aqua K, Lafaille J, Seco G, Garcia G, Cubillas M, de Souza J, Schneider A, Tjaden J, Goswami G, Schubart U, Kishore P, Bravo W, Guerrero J, Bertoli-Avella M, Reyes C, Dominguez M, Ramos S, Columbie A, Ares-Romero P, Hechavarria J, Villaverde M, Doyle N, Sherrod T, Krishnaswamy K, Aamir S, Giddaluri P, Guevara S, Kazmi P, Thomas P, Popeil L, Albright D, Pimentel S, Mould E, Cox M, Alderson T, Conrow J, Sandberg J, Raam S, Suresh B, Lafave J, Lorenz T, Johnston J, Fereidouni S, Mahadevan A, West R, Nelson A, Scott K, Ansari S, Khan B, Rastogi A, Saumell F, Gonzalez G, Torres E, Elias R, Hart T, Lozano J, Gudavilla G, Savin V, Khan A, Wiegmann T, Goel A, Gomes M, Fernandez-Gonzalez M, Gustavo F, Ivan C, Chiong R, Llerena S, Jimenez M, Oram D, George D, Lewis J, Kiefer J, Dollman A, Edje L, Pastor F, Kandath D, Lorch D, Graves A, Powell R, Hooker T, Shah S, Gomez N, Miranda F, Rosales J, Bayona I, Gomez Y, Guedes R, Rodriguez Y, Wahlen J, Jonathan W, Spencer H, Michael W, Kumar U, Govindariju K, Ordonez S, Aguirre H, Sulur P, Agarwal N, Peters L, Kaviani B, Fomenko O, Firek A, Loreen W, Ronald F, Olha F, Parrillo J, Janovitz R, Hutchinson R, Delgado E, Ashley A, Robinson S, Barbel-Johnson K, Timothy L, William C, Al-Karadsheh A, Hooper L, Suarez J, Perez D, Guerrero V, Tung D, Loo C, Sodolak K, Michaelis C, Jackson R, Covington D, Wise J, Tran T, Messina T, Torres D, Falcone J, Barettella M, Patel K, Ribo A, Mattews T, Amendolare D, McGeehan J, Corder C, Black C, Hearne S, Bounds C, Cinderella J, Etherton J, Kiem S, Treuth M, Burke B, Tivikaran V, Howard S, Miller C, Neff H, Giullian J, Mcrae J, Surratt D, Phillips J, Kretchmar J, Valdes M, Cruz J, Navarro E, Zewail A, Tai-Chi-Kwo, Stevens J, Diane S, Kim T, Gregory L, Neal S, William S, Sangrigoli R, Gejer E, Stoller S, Jeffrey D, Colar S, Kenneth W, Farris N, Mooney S, Jamal A, Nitin B, Syed R, Andrew Y, Christopher W, Abid R, Claudio G, Mojtaba M, Amna R, Michael B, Vincent T, Cherlin R, Ashton R, Pudi K, Julian W, Stephen K, Ronald A, Frias J, Kelly S, Hsia S, Clemens P, Cara H, Farley B, Raible L, Oliveros O, Hafeez H, Pecci P, Bagga-Malhotra S, Reza R, Jamal M, Mulgado M, Guevara A, Vela M, Ochoa H, Melliza T, Pena G, Awua-Larbi S, Shafi M, Alausa T, Polster S, Earl J, McNeill R, Farrington C, Carr K, Nabat M, Matthew S, Yvette E, Handelsman Y, Delkhah S, Ismail Y, Janna C, Akhtar A, Neiman A, Blumenthal S, Colleen V, Schmidt D, Ashraf E, Bhargava A, Khoo T, Langel C, Theuma P, Wright D, Fitzgerald K, Hitchcock J, Capasso-Gulve E, Wolff E, Umpierrez G, Priyathama V, Francisco P, Dawn S, Quraishi A, Kahn B, Ferro F, Hertz B, Phelps J, Campbell A, Downing J, Pangtay D, Pangatay S, Villagran-Solis K, Haseeb M, Rettig K, Kwan R, Cox R, Slimak V, So A, Schmedtje J, Chang A, Douglas Z, McGarity W, Jestel J, Kanade P, Julie J, Asher R, Canaan Y, Perez A, Alonso I, Cutchin R, Koser A, Adeola Y, Brito S, Stocks J, Frandsen B, Weigelt M, Stehouwer E, Ince C, Stephen P, Shadi B, Jeffrey C, Thethi T, Carpio G, McDuffie R, Moreau C, Stell C, Katalenich B, McKendall-Lewis C, Htun W, Conroy K, Lovre D, Galagan R, Olmeda C, Sihota A, Barton A, Beasley R, Nankivel P, Aberle M, Machin I, Porras J, Rodriguez D, Albornoz A, Haidar A, Lopez-Santini R, Rivero G, Robins G, Colyar L, Hutchins C, Sturm D, Hart K, Phillips T, Montgomery C, Albrecht W, Fehlis K, Overman D, Box M, Villarreal-Martinez D, David-Svatek D, Ajani D, Shaikh Z, Wheeler K, Brown M, Ghosh C, Bandukwala I, Kleber S, Madden J, Bishara M, Perry K, Paoli-Bruno J, Abreu E, Espiritu R, Zmeili O, Christensen T, Grubb S, Beloff S, Caugh A, van Dijk C, Yalavarthy R, DeGraauw J, Fabian S, Gillum D, Corrigan G, Singh H, Jensen K, DeMore S, Montague T, Zieve F, Levy J, Fredrickson S, Tarkington P, Chapla P, Salacata A, Walls U, Iyer R, Nguyen K, Lettman J, Appleman B, Safavie F, Scaliem L, Eder F, Maklad S, Schlaen B, Molstead J, Hartwell J, Hubish D, Little R, Rando K, Kelly R, Drury M, Young P, Wininger S, Harman A, Daza R, Robbin S, Sanchez M, Rivera I, Garcia-Estrada M, Iglesias N, Dobs A, Andrade A, Falkowski S, Parrott T, Koon A, Wood T, Burkett E, Chavous K, Gupta A, Estes C, Loud D, Rhodes S, Chen M, Bromley L, Palma R, Kattan D, Kirk U, Tatu H, Stamatin R, Lupea S, Frasie M, Colfer H, Kane L, Teklinski A, Gadowski G, Levanovich P, Saba F, Confident L, Hossain S, Steinberg B, Philippe B, Choroenthkongtrakal S, Boccalano F, Anand R, Syam V, Manohar A, Suresh P, Madhusudhan P, Patel P, Cambier P, Klonaris J, Cheng W, Fisher S, Schelle M, Reese L, McLean S, Poock J, Hoens J, Rosie A, Welshons R, Dean J, Kuhlman P, Luke R, Lohrbauer L, Cunningham M, Buday P, Lehmann M, Chrzanowski K, Fletcher A, Hargrove J, Harris F, Debs-Perez G, Maiquez A, Cordoves L, Georgescu M, Tayoun H, Munoz F, Ortiz D, Munoz G, Hamzeh I, Misra A, Zhang L, Forgosh L, Loria K, Roncari C, Hommerding J, Morris G, Lebron C, Blake K, LaVenture K, Lange C, Levinson L, Baungarten T, Edevante S, Shawley S, Moyer H, Elliott K, Iachini K, Rajan R, Davis C, Shattuck A, Simon W, Lakin G, Secrist N, Buth D, Steere D, Talbot K, Singh N, Mascolo R, Sloan S, Kmetzo J, Brown J, Carter L, Lawrence M, Arauz-Pacheco C, Lender D, Kozlow W, Cavanaugh L, Wilson J, Gujja P, Akhter F, Khan M, Mohammed A, Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
- Abstract
IMPORTANCE Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. OBJECTIVE To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A(1c) of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] > 200mg/g), and high renal risk (reduced eGFR and micro-or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. INTERVENTIONS Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. MAIN OUTCOMES AND MEASURES Primary outcomewas time to first occurrence of the composite of CV death, nonfatalmyocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. RESULTS Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73m2; 80.1% with UACR > 30mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI,-0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P
- Published
- 2019
9. fMRT-Ruhenetzwerke gesunder Probanden
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Kiem, S.
- Abstract
Die Hypothalamus-Hypophysen-Nebennierenrinden-Achse (HPA-Achse) ist ein hierarchisch organisiertes, neuroendokrines System, das unter anderem die Freisetzung des Nebennierenrindenhormons Kortisol, dem zentralen Hormon der Stressantwort und der Homöostase des Organismus in Bezug auf die Anpassung an Umweltanforderungen, regelt. Die HPA-Achse ist in ein komplexes System von Regulationsnetzwerken eingebunden, über die der Organismus die Anpassung an ständig wechselnde Anforderungen erfasst und steuert. Fehlanpassungen der HPA-Achse sind hierbei von großer klinischer Bedeutung, da sie zu psychiatrischen Erkrankungen führen können. Ziel der vorliegenden Arbeit war es daher, HPA-Achsen-regulierende kortikale Netzwerke mithilfe der funktionalen Magnetresonanztomographie (fMRT) in verschiedenen Versuchansätzen zu identifizieren. Der Stand der bisherigen Forschungsergebnisse deutet darauf hin, dass es grundsätzlich einen mit der Methode der fMRT messbaren Zusammenhang zwischen diesen kortikalen Netzwerken im Gehirn und der neuroendokrinologischen Stressregulationsachse (HPA-Achse) gibt. Wichtige Knotenpunkte solcher kortikaler Netzwerke sind dabei insbesondere Kerne der Amygdala, Teile des Hippokampus und des Hypothalamus sowie Bereiche des präfrontalen Kortex. Diese Regionen üben zum einen Einfluss auf die Freisetzung des Corticotropin-releasing-Hormons (CRH) im Hypothalamus aus, zum anderen werden sie durch Kortisol rekursiv in ihrer Funktion durch ein negatives Feedback beeinflusst. Diese beiden Aspekte wurden im Rahmen dieser Arbeit in separaten Analysen bearbeitet: Es wurde zunächst untersucht, ob die Aktivität der kortikalen Netzwerke des Gehirns in Ruhe das Ergebnis des kombinierten Dexamethason-Suppressions-CRH-Stimulations-Tests (Dex/CRH-Test) als sensitiven endokrinologischen Stresstest vorhersagen kann. Ferner wurde untersucht, ob sich die Aktivität der Ruhenetzwerke durch eine experimentelle Modulation des Kortisolspiegels signifikant verändert, wobei sowohl der Effekt einer intravenösen Applikation von Kortisol im Vergleich zu Placebo als auch der Effekt einer durch Dexamethason herbeigeführten Suppression von Kortisol untersucht wurde. Bei der hierfür durchgeführten Studie handelt es sich um ein placebo-kontrolliertes, endokrinologisches fMRT-Experiment im Cross-Over-Design mit kombinierter EEG. Zusätzlich zu den EEG/fMRT-Ruhe-Messungen wurde ein Dex/CRH-Test außerhalb des MRT aufgenommen, um die Funktionalität der HPA-Achse in den Probanden zu quantifizieren. Es wurden 20 gesunde männliche Probanden untersucht. An den Messtagen 1 und 3 wurde je eine knapp einstündige kombinierte EEG/fMRT-Messung durchgeführt, wobei einmal 20 mg Kortisol, gelöst in 10 ml Kochsalzlösung, und einmal 0,9%-ige Kochsalzlösung (10 ml) während der Messung durch eine Bolusinjektion verabreicht wurden. Am Messtag 2 wurden die EEG/fMRT-Ruhe-Daten (̑exttt{˛har126}} 15 Minuten) im Status der Kortisolsuppression durch Dexamethason aufgenommen. Die kombinierte EEG-Messung diente hier vor allem der Vigilanzüberwachung der Probanden, da aus verschiedenen Studien bekannt ist, dass sich die Ruhenetzwerke des Gehirns in Abhängigkeit des Vigilanzstatus verändern. An einem zusätzlichen 4. Messtag wurde außerhalb des MRT an einer Teilgruppe der Probanden die Wirkung einer Kortisolbolusinjektion (20 mg) auf Blutdruck, Puls und Sauerstoffsättigung bestimmt und zusätzlich auch die Wirksamkeit des extern zugeführten Kortisols auf die HPA-Achse ermittelt. Die fMRT-Ruhe-Daten wurden mit komplementären Methoden aus dem Bereich der Konnektivitätsanalysen untersucht. Dabei wurden sowohl hypothesengeleitete Analysen von Ruhenetzwerken über die Seed-Methode als auch Kreuzkor-relationsanalysen definierter Regionen, oder - im explorativen Ansatz - des gesamten Gehirns einschließlich voxelbasierter Verfahren, angewandt. Die Analysen zur Modulierung des Kortisolmilieus insgesamt betrachtet lassen den Schluss zu, dass sich die funktionelle Konnektivität des Gehirns in Ruhe durch die Änderung des Kortisolmilieus ändert, sei es durch direkte exogene Kortisolgabe, oder indirekten Kortisolentzug durch die Dexamethasonsuppression. Der Schwerpunkt dieser kortisolabhängigen Modulation lag dabei in präfrontal basierten Ruhenetzwerken. In den Analysen, in denen die drei Zustände der Kortisolmilieuänderungen (Kortisol, Placebo, Kortisolsuppression) verglichen wurden, zeigten sich stärkere Effekte durch die Kortisolsuppression als durch das exogen zugeführte Kortisol. Diese Effekte hatten ihren regionalen Schwerpunkt für die hypothesenbasierte Seedanalyse im medialen präfrontalen Kortex/anterioren cingulären Kortex (ACC), und in der explorativen Analyse im dorsolateralen präfrontalen Kortex. Effekte auf den Hippokampus und die Amygdala waren dabei relativ schwach ausgeprägt. Die Analysen der dynamischen Änderung nach Kortisolgabe im Vergleich zu Placebo zeigten Effekte im subcallosalen/ subgenualen ACC und im dorsalen ACC, sowohl im hypothesengesteuerten als auch im explorativen Ansatz. Da der Analyseschwerpunkt bisheriger Arbeiten auf der Hippokampus/Amygdala-Region lag wird neu postuliert, dass Akuteffekte nach 20 mg Kortisol möglicherweise auf ACC-Regionen stärker wirken als auf den Hippokampus. Ebenfalls hergestellt werden konnte ein prädiktiver Zusammenhang zwischen der Stärke der funktionellen Konnektivität in limbischen und paralimbischen Regionen in Ruhe, insbesondere hippokampaler Netzwerke, und dem Ergebnis des Dex/CRH-Tests. Da der Dex/CRH-Test das gesamte zerebrale Feedbacksystem belastet, kann hieraus abgeleitet werden, dass spezifische Netzwerke in beiden Korrelationsrichtungen einen Einfluss auf das Ergebnis des Dex/CRH-Tests haben. Damit wurde erstmals indirekt das Regulationssystem sichtbar gemacht, das durch den Dex/CRH-Test belastet wird. In zukünftigen Studien können die konzentrations- und zeitabhängige Sensitivität der Ruhenetzwerke gegenüber Kortisol, zusammen mit der funktionellen Konnektivität, die die individuelle Regulation der HPA-Achse vorhersagt, als Grundlage zur Etablierung eines Stressbiomarkes verwendet werden.
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- 2013
10. Impact of Organism Species on Microbial Eradication and Development of Resistance in Severe Gram-Negative Pneumonia
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Kiem, S., primary and Schentag, J.J., additional
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- 2010
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11. Active and passive material response of urinary bladder smooth muscle tissue in uniaxial and biaxial tensile testing.
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Geldner J, Papenkort S, Kiem S, Böl M, and Siebert T
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- Animals, Swine, Sus scrofa, Materials Testing, Biomechanical Phenomena, Urinary Bladder physiology, Muscle, Smooth physiology, Tensile Strength, Stress, Mechanical
- Abstract
The urinary bladder is a hollow organ that undergoes significant deformation as it receives, stores, and releases urine. To understand the organ mechanics, it is necessary to obtain information about the material properties of the tissues involved. In displacement-controlled tensile tests, tissue samples are mounted on a device that applies stretches to the tissue in one or more directions, resulting in a specific stress response. For this study, we performed uniaxial and biaxial stretch experiments on tissue samples (n = 36) from the body region of the porcine urinary bladder. We analyzed the stress-relaxation, activation dynamics, and passive and active stretch-stress response. Main findings of our experiments are: (1) For uniaxial and biaxial stretching, the time constants for stress-relaxation depend on the stretch amplitude, (2) biaxially stretched samples experienced slower activation with τ
act increasing by +63% compared to uniaxial stretching, (3) biaxial tests are characterized by reduced optimum stretches λopt by -18%, and (4) biaxial and uniaxial tests showed no significant difference in maximum active stresses σopt . To interpret the results, we present a continuum mechanical model based on a viscoelastic, isotropic solid extended by a set of active muscle fibers. Model predictions show that results (3) and (4) can be explained by a uniform distribution of fiber orientations and a specific shape of the active fiber stress-stretch relationship. This study highlights how deformation modes during tensile testing affects smooth muscle mechanics, proving insights for interpreting experimental data and improving organ modeling. STATEMENT OF SIGNIFICANCE: In this study, we examined the mechanical properties of porcine bladder smooth muscle using uniaxial and equibiaxial tensile tests. To our knowledge, this is the first instance where the active stress-stretch relationships of smooth muscle tissue have been analysed under equibiaxial stretch. The data collected offer a detailed understanding of the connection between deformation and active stress production, surpassing the insights provided by existing uniaxial tests in the literature. These findings are crucial for comprehending the physiology of smooth muscle tissue and for developing constitutive muscle models that can make more accurate predictions about the functionality of hollow organs in both health and disease. Additionally, our findings on smooth muscle active stress could aid in the creation of biomaterials that interact with or even replace natural muscle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2025
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12. Regional differences in stomach stretch during organ filling and their implications on the mechanical stress response.
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Papenkort S, Borsdorf M, Kiem S, Böl M, and Siebert T
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- Animals, Swine, Tensile Strength physiology, Biomechanical Phenomena, Models, Biological, Stomach physiology, Stress, Mechanical
- Abstract
As part of the digestive system, the stomach plays a crucial role in the health and well-being of an organism. It produces acids and performs contractions that initiate the digestive process and begin the break-up of ingested food. Therefore, its mechanical properties are of interest. This study includes a detailed investigation of strains in the porcine stomach wall during passive organ filling. In addition, the observed strains were applied to tissue samples subjected to biaxial tensile tests. The results show inhomogeneous strains during filling, which tend to be higher in the circumferential direction (antrum: 13.2%, corpus: 22.0%, fundus: 67.8%), compared to the longitudinal direction (antrum: 4.8%, corpus: 24.7%, fundus: 50.0%) at a maximum filling of 3500 ml. Consequently, the fundus region experienced the greatest strain. In the biaxial tensile experiments, the corpus region appeared to be the stiffest, reaching nominal stress values above 400 kPa in the circumferential direction, whereas the other regions only reached stress levels of below 50 kPa in both directions for the investigated stretch range. Our findings gain new insight into stomach mechanics and provide valuable data for the development and validation of computational stomach models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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13. Diffusion tensor imaging: Influence of segmentation on fiber tracking in the supraspinatus muscle-An inter-operator reliability analysis.
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Vetter S, Köhler HP, Hepp P, Steinke H, Schleifenbaum S, Theopold J, Kiem S, Witt M, Henkelmann J, and Roth C
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- Humans, Reproducibility of Results, Anisotropy, Benchmarking, Rotator Cuff, Diffusion Tensor Imaging
- Abstract
The ability of muscle to generate force depends on its architecture and health condition. MR-based diffusion tensor imaging of muscle (mDTI) is an innovative approach for showing the fiber arrangement for the whole muscle volume. For accurate calculations of fiber metrics, muscle segmentation prior to tractography is regarded as necessary. Since segmentation is known to be operator dependent, it is important to understand how segmentation affects tractography. The aim of this study was to compare the results of deterministic fiber tracking based on muscle models generated by two independent operators. In addition, this study compares the results with a segmentation-free approach. Fifteen subjects underwent mDTI of the right shoulder. The results showed that mDTI can be successfully applied to complex joints such as the human shoulder. Furthermore, operator segmentation did not influence the results of fiber tracking and fascicle length (FL), fiber volume (FV), fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) showed excellent intraclass correlation estimates (≥ 0.975). As an exploratory approach, the segmentation-free fiber tracking showed significant differences in terms of mean fascicle length. Based on these findings, we conclude that tractography is not sensitive to small deviations in muscle segmentation. Furthermore, it implies that mDTI and automatic segmentation approaches or even a segmentation-free analysis can be considered for evaluation of muscle architecture., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vetter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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14. Guidelines on Implementing Antimicrobial Stewardship Programs in Korea.
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Yoon YK, Kwon KT, Jeong SJ, Moon C, Kim B, Kiem S, Kim HS, Heo E, and Kim SW
- Abstract
These guidelines were developed as a part of the 2021 Academic R&D Service Project of the Korea Disease Control and Prevention Agency in response to requests from healthcare professionals in clinical practice for guidance on developing antimicrobial stewardship programs (ASPs). These guidelines were developed by means of a systematic literature review and a summary of recent literature, in which evidence-based intervention methods were used to address key questions about the appropriate use of antimicrobial agents and ASP expansion. These guidelines also provide evidence of the effectiveness of ASPs and describe intervention methods applicable in Korea., Competing Interests: No conflicts of interest, (Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)
- Published
- 2021
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15. Infection, dissemination, and transmission efficiencies of Zika virus in Aedes aegypti after serial passage in mosquito or mammalian cell lines or alternating passage in both cell types.
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Talavera-Aguilar LG, Murrieta RA, Kiem S, Cetina-Trejo RC, Baak-Baak CM, Ebel GD, Blitvich BJ, and Machain-Williams C
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- Animals, Cell Line, Chlorocebus aethiops, Disease Vectors, Genetic Fitness, Insecta cytology, Salivary Glands virology, Vero Cells, Viral Load, Aedes virology, Mosquito Vectors virology, Serial Passage methods, Zika Virus genetics, Zika Virus physiology, Zika Virus Infection transmission
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Background: Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) with an urban transmission cycle that primarily involves humans and Aedes aegypti. Evidence suggests that the evolution of some arboviruses is constrained by their dependency on alternating between disparate (vertebrate and invertebrate) hosts. The goals of this study are to compare the genetic changes that occur in ZIKV after serial passaging in mosquito or vertebrate cell lines or alternate passaging in both cell types and to compare the replication, dissemination, and transmission efficiencies of the cell culture-derived viruses in Ae. aegypti., Methods: An isolate of ZIKV originally acquired from a febrile patient in Yucatan, Mexico, was serially passaged six times in African green monkey kidney (Vero) cells or Aedes albopictus (C6/36) cells or both cell types by alternating passage. A colony of Ae. aegypti from Yucatan was established, and mosquitoes were challenged with the cell-adapted viruses. Midguts, Malpighian tubules, ovaries, salivary glands, wings/legs and saliva were collected at various times after challenge and tested for evidence of virus infection., Results: Genome sequencing revealed the presence of two non-synonymous substitutions in the premembrane and NS1 regions of the mosquito cell-adapted virus and two non-synonymous substitutions in the capsid and NS2A regions of both the vertebrate cell-adapted and alternate-passaged viruses. Additional genetic changes were identified by intrahost variant frequency analysis. Virus maintained by continuous C6/36 cell passage was significantly more infectious in Ae. aegypti than viruses maintained by alternating passage and consecutive Vero cell passage., Conclusions: Mosquito cell-adapted ZIKV displayed greater in vivo fitness in Ae. aegypti compared to the other viruses, indicating that obligate cycling between disparate hosts carries a fitness cost. These data increase our understanding of the factors that drive ZIKV adaptation and evolution and underscore the important need to consider the in vivo passage histories of flaviviruses to be evaluated in vector competence studies.
- Published
- 2021
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16. Development of Antibiotic Classification for Measuring Antibiotic Usage in Korean Hospitals Using a Modified Delphi Method.
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Kim B, Yoon YK, Kim DS, Jeong SJ, Ahn SV, Park SH, Kwon KT, Kim HB, Park YS, Kim SW, Kiem S, and Choi JY
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- Adult, Community-Acquired Infections drug therapy, Cross Infection drug therapy, Drug Resistance, Bacterial, Humans, Anti-Bacterial Agents classification, Anti-Bacterial Agents therapeutic use, Delphi Technique
- Abstract
In 2019, a project designed to develop a system for measuring and comparing antibiotic usage in hospitals was launched in Korea. As part of this project, we developed a means to classify antibiotic usage in Korean hospitals using a modified Delphi method. In results, the following categories of antibiotic classification were accepted for use in Korean hospitals: 1) broad-spectrum antibacterial agents predominantly used for hospital-onset infections in adults, 2) broad-spectrum antibacterial agents predominantly used for community-acquired infections in adults, 3) antibacterial agents predominantly used for resistant gram-positive infections in adults, 4) narrow-spectrum beta-lactam agents in adults, 5) antibacterial agents predominantly used for extensive antibiotic resistant gram-negative bacteria in adults, and 6) total antibacterial agents., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)
- Published
- 2020
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17. Self-Assessment Questionnaire for Efficient and Safe Evaluation of Patients with Mild COVID-19.
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Jeong H, Lee J, Kim J, Choen S, Sohn KM, Kim YS, and Kiem S
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As the outbreak of coronavirus disease 2019 continues and the number of confirmed cases requiring isolation increases, there is a need for a safe and efficient system to assess patients' condition. We developed and evaluated a self-assessment questionnaire consisting of 23 symptoms with linear-scale scores from 0 to 10. Patients were asked to indicate their worst score for each symptom daily, and medical personnel assessed clinical improvement or deterioration based on the changes in scores. Focused communication on severity of specific symptoms was the primary advantage for the clinicians, and a thorough check for their symptoms was helpful for patients., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)
- Published
- 2020
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18. A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.
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Kang CK, Song KH, Kim SE, Kim ES, Park WB, Park KH, Chun SH, Lee S, Cho CR, Kang SJ, Oh MD, Kim YS, Lee SH, Kwak YG, Jang HC, Kim CJ, Kim YK, Bang JH, Kiem S, Kwon KT, Jung Y, Kang YM, Jung SI, and Kim HB
- Subjects
- Anti-Bacterial Agents pharmacology, Humans, Methicillin Resistance, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus pathogenicity, Phenotype, Prospective Studies, Republic of Korea, Risk Factors, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Bacteremia microbiology, Staphylococcus aureus drug effects
- Abstract
The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n = 995) than in patients with methicillin-susceptible SAB (MSSAB; n = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P < 0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P < 0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality., (Copyright © 2019 American Society for Microbiology.)
- Published
- 2019
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19. A new population pharmacokinetic model for vancomycin in patients with variable renal function: Therapeutic drug monitoring based on extended covariate model using CKD-EPI estimation.
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Kim DJ, Lee DH, Ahn S, Jung J, Kiem S, Kim SW, and Shin JG
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- Drug Monitoring methods, Female, Humans, Kidney Function Tests methods, Male, Middle Aged, Vancomycin administration & dosage, Glomerular Filtration Rate drug effects, Renal Insufficiency, Chronic chemically induced, Vancomycin adverse effects, Vancomycin pharmacokinetics
- Abstract
WHAT IS KNOWN AND OBJECTIVE: Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high-strength and long-term vancomycin therapy might have unstable and time-varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (PK) modeling and model-based estimation of vancomycin pharmacokinetics. While Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for renal function estimation has been widely integrated into clinical practice, a population PK model including CKD-EPI has not been established. The study was aimed at developing a new population PK model for optimal vancomycin prediction in patients with time-varying and variable renal function to evaluate the interchangeability of estimation methods. METHODS: The most suitable population PK model was explored and evaluated using non-linear mixed-effect modelling for the best fit of vancomycin concentrations from patients who needed to maintain high trough vancomycin concentrations of >10 mg/L or >15 mg/L. Renal function was estimated using the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations. NONMEM 7.4 was used to develop the population PK model. RESULTS: A total of 328 vancomycin concentrations in 99 patients were used to develop the population PK model. Vancomycin pharmacokinetics was best described by a two-compartment model. The CKD-EPI equation for vancomycin clearance was included in the final model among the estimation methods of renal function. A new covariate model, including extended covariate parameters that explain changes in renal function from the population-predicted value and individual dosing time, provided the best explanation for vancomycin pharmacokinetics among the various models tested. WHAT IS NEW AND CONCLUSION: A new extended covariate model for vancomycin using the CKD-EPI method may afford suitable dose adjustment for high-strength and long-term vancomycin therapy that results in unstable renal function., (© 2019 John Wiley & Sons Ltd.)
- Published
- 2019
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20. Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics.
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Song KH, Jung SI, Lee S, Park S, Kim ES, Park KH, Park WB, Choe PG, Kim YK, Kwak YG, Kim YS, Jang HC, Kiem S, Kim HI, and Kim HB
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- Bacteremia drug therapy, Bacteremia microbiology, Bacteremia mortality, Humans, Korea, Microbial Sensitivity Tests, Staphylococcus aureus enzymology, Staphylococcus aureus genetics, beta-Lactamases genetics, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Staphylococcal Infections mortality, Staphylococcus aureus drug effects, beta-Lactams pharmacology, beta-Lactams therapeutic use
- Abstract
Scarce information concerning the inoculum effect (InE) of methicillin-susceptible Staphylococcus aureus (MSSA) against broad-spectrum β-lactam antibiotics is available. We investigated the InE of MSSA against ceftriaxone, cefepime, meropenem, ampicillin/sulbactam and piperacillin/tazobactam. The bacteraemic MSSA isolates were collected at ten Korean general hospitals from Sep 2013 to Mar 2015. The InE was defined if MICs of antibiotics at high inoculum (HI, ~5 × 10
7 CFU/ml) increased beyond the susceptible range compared to those at standard inoculum (SI, ~5 × 105 CFU/ml). All isolates were sequenced for blaZ gene typing. Among 302 MSSA isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of all tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p < 0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p < 0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively. About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p < 0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p < 0.001). A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.- Published
- 2019
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21. Rapidly Fatal Emphysematous Osteomyelitis with Multiple Septic Emboli and Liver Abscess Caused by Klebsiella pneumoniae .
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Kim YK, Jo KM, Jang JH, Heo CM, Lee JH, Park JH, Kim S, Jang HJ, Kim HK, and Kiem S
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Emphysematous osteomyelitis, characterized by intraosseous gas, is a rare but potentially fatal condition that requires prompt diagnosis and aggressive therapy. Causative organisms are members of the bacterial family Enterobacteriaceae or anaerobes in most cases and significant comorbidities such as diabetes mellitus and malignancy, may predispose an individual to the development of emphysematous osteomyelitis. We report a case of extensive emphysematous osteomyelitis via hematogenous spread from Klebsiella pneumoniae liver abscess, complicated by gas-containing abscesses in adjacent soft tissues and epidural space, and multiple systemic septic emboli in a diabetic patient., Competing Interests: No conflicts of interest., (Copyright © 2018 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy.)
- Published
- 2018
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22. Population Pharmacokinetic Analysis of Meropenem After Intravenous Infusion in Korean Patients With Acute Infections.
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Kim YK, Lee DH, Jeon J, Jang HJ, Kim HK, Jin K, Lim SN, Lee SS, Park BS, Kim YW, Shin JG, and Kiem S
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- Aged, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents blood, Bacterial Infections drug therapy, Body Weight, Female, Humans, Infusions, Intravenous, Kidney Function Tests, Male, Mathematical Concepts, Meropenem administration & dosage, Meropenem blood, Middle Aged, Monte Carlo Method, Republic of Korea, Anti-Bacterial Agents pharmacokinetics, Creatinine blood, Meropenem pharmacokinetics
- Abstract
Purpose: The aim of this study was to investigate the population pharmacokinetic (PK) profile of meropenem in Korean patients with acute infections., Methods: The study included 37 patients with a creatinine clearance ≤50 or >50 mL/min who received a 500- or 1000-mg dose of meropenem, respectively, infused intravenously over 1 hour every 8 hours. Blood samples were collected before and at 1, 1.5, and 5 hours after the start of the fourth infusion. The population PK analysis was conducted by using nonlinear mixed effect modeling software (NONMEM). Monte-Carlo simulations were performed to identify optimal dosing regimens., Findings: Thirty-seven subjects completed the study. Meropenem PK variables were well described by using a one-compartment model. The typical values (relative SE) for weight-normalized clearance (CL) and V
d were 0.266 L/h/kg (12.29%) and 0.489 L/kg (11.01%), respectively. Meropenem CL was significantly influenced by the serum creatinine level, which explained 11% of the interindividual CK variability. The proposed equation to estimate meropenem CL in Korean patients was as follows: CL (L/h) = 0.266 × weight × [serum creatinine/0.74]-1.017 . The simulation results indicate that the current meropenem dosing regimen may be suboptimal in patients infected with normal or augmented renal function., Implications: Prolonged infusions of meropenem over at least 2 hours should be considered, especially in patients with augmented renal function and those infected with pathogens for which the minimum inhibitory meropenem concentration is >1 μg/mL. Our results suggest an individualized meropenem dosing regimen for patients with abnormal renal function and those infected with pathogens with decreased in vitro susceptibility., (Copyright © 2018. Published by Elsevier Inc.)- Published
- 2018
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23. Guideline for Antibiotic Use in Adults with Community-acquired Pneumonia.
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Lee MS, Oh JY, Kang CI, Kim ES, Park S, Rhee CK, Jung JY, Jo KW, Heo EY, Park DA, Suh GY, and Kiem S
- Abstract
Community-acquired pneumonia is common and important infectious disease in adults. This work represents an update to 2009 treatment guideline for community-acquired pneumonia in Korea. The present clinical practice guideline provides revised recommendations on the appropriate diagnosis, treatment, and prevention of community-acquired pneumonia in adults aged 19 years or older, taking into account the current situation regarding community-acquired pneumonia in Korea. This guideline may help reduce the difference in the level of treatment between medical institutions and medical staff, and enable efficient treatment. It may also reduce antibiotic resistance by preventing antibiotic misuse against acute lower respiratory tract infection in Korea., Competing Interests: No conflicts of interest., (Copyright © 2018 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy.)
- Published
- 2018
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24. Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea.
- Author
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Lee S, Song KH, Jung SI, Park WB, Lee SH, Kim YS, Kwak YG, Kim YK, Kiem SM, Kim HI, Kim ES, Park KH, Kim NJ, Jang HC, and Kim HB
- Subjects
- Aged, Anti-Bacterial Agents administration & dosage, Bacteremia microbiology, Cefazolin administration & dosage, Drug Therapy, Combination, Female, Humans, Male, Methicillin therapeutic use, Middle Aged, Nafcillin administration & dosage, Prospective Studies, Republic of Korea, Staphylococcal Infections microbiology, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Cefazolin therapeutic use, Nafcillin therapeutic use, Staphylococcal Infections drug therapy
- Abstract
Objectives: No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia., Methods: A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics., Results: Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group., Conclusions: Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
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25. Maternal, Fetal, and Neonatal Outcomes in Pregnant Dengue Patients in Mexico.
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Machain-Williams C, Raga E, Baak-Baak CM, Kiem S, Blitvich BJ, and Ramos C
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- Abortion, Spontaneous diagnosis, Abortion, Spontaneous mortality, Adult, Female, Humans, Infant, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Live Birth, Maternal Mortality, Mexico epidemiology, Pregnancy, Dengue diagnosis, Dengue mortality, Infant Mortality, Pregnancy Complications, Infectious diagnosis, Pregnancy Complications, Infectious mortality
- Abstract
To increase our understanding of the consequences of dengue virus infection during pregnancy, a retrospective analysis was performed on the medical records of all completed pregnancies (live births and pregnancy losses) at nine public hospitals in the Gulf of Mexico from January to October 2013. Eighty-two patients developed clinical, laboratory-confirmed dengue virus infections while pregnant. Of these, 54 (65.9%) patients were diagnosed with dengue without warning signs, 15 (18.3%) patients were diagnosed with dengue with warning signs, and 13 (15.9%) patients had severe dengue. Five (38.5%) patients with severe dengue experienced fetal distress and underwent emergency cesarean sections. Four patients delivered apparently healthy infants of normal birthweight while the remaining patient delivered a premature infant of low birthweight. Patients died of multiple organ failure during or within 10 days of the procedure. Severe dengue was also associated with obstetric hemorrhage (30.8%, four cases), preeclampsia (15.4%, two cases), and eclampsia (7.7%, one case). These complications were less common or absent in patients in the other two disease categories. Additionally, nonsevere dengue was not associated with maternal mortality, fetal distress, or adverse neonatal outcomes. In summary, the study provides evidence that severe dengue during pregnancy is associated with a high rate of fetal distress, cesarean delivery, and maternal mortality.
- Published
- 2018
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26. Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections.
- Author
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Lee DH, Kim YK, Jin K, Kang MJ, Joo YD, Kim YW, Moon YS, Shin JG, and Kiem S
- Subjects
- Aged, Anti-Bacterial Agents adverse effects, Carbapenems adverse effects, Creatinine blood, Doripenem, Female, Glomerular Filtration Rate physiology, Humans, Infusions, Intravenous, Male, Microbial Sensitivity Tests, Middle Aged, Models, Biological, Monte Carlo Method, Republic of Korea, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents therapeutic use, Bacterial Infections drug therapy, Carbapenems pharmacokinetics, Carbapenems therapeutic use
- Abstract
We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients ( n = 37) with a creatinine clearance (CL
CR ) of 20 to 50 ml/min or >50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution ( V /WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CLCR The proposed equation to estimate doripenem CL in Korean patients was CL/WT = 0.109 × WT × (CLCR /57)0.688 , where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was ≤1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility., (Copyright © 2017 American Society for Microbiology.)- Published
- 2017
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27. Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii .
- Author
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Kim YK, Lee JH, Lee HK, Chung BC, Yu SJ, Lee HY, Park JH, Kim S, Kim HK, Kiem S, and Jang HJ
- Abstract
Background: Although there have been studies regarding the role of nebulized colistin as adjunctive therapy of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB), a paucity of information on the efficacy of nebulized colistin as monotherapy is available., Methods: We retrospectively reviewed 219 patients with VAP caused by CRAB treated with either intravenous (n=93) or nebulized colistin (n=126), from March 2010 to November 2015. Factors related to clinical failure was assessed using propensity-score-matched analysis., Results: Of 219 patients, 39 patients from each group (n=78) were matched after covariate adjustment using propensity score. There were no significant differences in baseline characteristics as well as the rates of clinical failure between the propensity-score-matched groups [Odds ratio (OR), 0.48; 95% confidence interval (CI), 0.19-1.19; P=0.11], while a significantly lower rate of acute kidney injury (AKI) during colistin therapy (18% vs. 49%, P=0.004) was observed in nebulized colistin group. In addition, multivariable analysis revealed that nebulized colistin did not significantly alter the rate of clinical failure [adjusted odds ratio (aOR), 0.36; 95% CI, 0.12-1.09; P=0.070]. Instead, medical intensive care unit (ICU) admission (aOR, 7.14; 95% CI, 1.60-32.00; P=0.010), and septic shock (aOR, 3.93; 95% CI, 1.27-12.17; P=0.018) were independent risk factors for clinical failure., Conclusions: Our findings suggest that nebulized colistin-based therapy, even without concurrent administration of intravenous colistin, may be an effective and safe treatment option for VAP caused by CRAB., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
- Published
- 2017
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28. Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections.
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Kim YK, Jung JA, Choi HK, Bae IG, Choi WS, Hur J, Jin SJ, Kim SW, Kwon KT, Lee SR, Shin JG, and Kiem S
- Abstract
Background: For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients' characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections., Materials and Methods: At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CL(cr)) ≤50 ml/min or CL(cr) >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P < 0.05 for selection and P < 0.01 for elimination., Results: Both piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CL(cr) /47 for piperacillin and CL = 1.76 + 4.81 × CL(cr) /47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam., Conclusion: The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance., Competing Interests: The study drug was provided by the Kuhnil Pharmaceutical Company.
- Published
- 2016
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29. Population pharmacokinetics of levofloxacin in Korean patients.
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Kiem S, Ryu SM, Lee YM, Schentag JJ, Kim YW, Kim HK, Jang HJ, Joo YD, Jin K, Shin JG, and Ghim JL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents blood, Area Under Curve, Female, Humans, Levofloxacin blood, Male, Middle Aged, Republic of Korea, Young Adult, Anti-Bacterial Agents pharmacokinetics, Levofloxacin pharmacokinetics
- Abstract
Levofloxacin (LVFX) has different effects depending on the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio. While AUC can be expressed as dose/clearance (CL), we measured serial concentrations of LVFX in Koreans and tried to set a Korean-specific equation, estimating the CL of the antibiotic. In total, 38 patients, aged 18-87 years, received once daily intravenous LVFX doses of 500 mg or 250 mg, depending on their renal function. Four plasma samples were obtained according to a D optimal sampling design. The population pharmacokinetic (PK) parameters of LVFX were estimated using non-linear mixed-effect modeling (NONMEM, ver. 7.2). The CL of LVFX was dependent on creatinine clearance (CLCR) as a covariate. The mean population PK parameters of LVFX in Koreans were as follows: CL (l/hour) = 6.19 × (CLCR/75)(1.32). The CL of LVFX in Koreans is expected to be lower than that in Western people.
- Published
- 2016
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30. Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against Methicillin Resistant Staphylococcus aureus.
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Kiem S and Schentag JJ
- Abstract
Although antibiotics whose epithelial lining fluid (ELF) concentrations are reported high tend to be preferred in treatment of pneumonia, measurement of ELF concentrations of antibiotics could be misled by contamination from lysis of ELF cells and technical errors of bronchoalveolar lavage (BAL). In this review, ELF concentrations of anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics were interpreted considering above confounding factors. An equation used to explain antibiotic diffusion into CSF (cerebrospinal fluid) was adopted: ELF/free serum concentration ratio = 0.96 + 0.091 × ln (partition coefficient / molecular weight(1/2)). Seven anti-MRSA antibiotics with reported ELF concentrations were fitted to this equation to see if their ELF concentrations were explainable by the penetration capacity only. Then, outliers were modeled under the assumption of varying contamination from lysed ELF cells (test range 0-10% of ELF volume). ELF concentrations of oritavancin, telavancin, tigecycline, and vancomycin were well described by the diffusion equation, with or without additional impact from cell lysis. For modestly high ELF/free serum concentration ratio of linezolid, technical errors of BAL should be excluded. Although teicoplanin and iclaprim showed high ELF/free serum ratios also, their protein binding levels need to be cleared for proper interpretation. At the moment, it appears very premature to use ELF concentrations of anti-MRSA antibiotics as a relevant guide for treatment of lung infections by MRSA.
- Published
- 2014
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31. The burden of nosocomial staphylococcus aureus bloodstream infection in South Korea: a prospective hospital-based nationwide study.
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Kim CJ, Kim HB, Oh MD, Kim Y, Kim A, Oh SH, Song KH, Kim E, Cho Y, Choi Y, Park J, Kim BN, Kim NJ, Kim KH, Lee E, Jun JB, Kim Y, Kiem S, Choi H, Choo E, Sohn KM, Lee S, Chang H, Bang J, Lee S, Lee J, Park S, Jeon M, and Yun N
- Subjects
- Aged, Case-Control Studies, Cost of Illness, Databases, Factual, Female, Hospitals, Humans, Incidence, Male, Methicillin Resistance, Prospective Studies, Republic of Korea epidemiology, Staphylococcus aureus drug effects, Bacteremia epidemiology, Cross Infection epidemiology, Staphylococcal Infections epidemiology, Staphylococcus aureus isolation & purification
- Abstract
Background: We estimated the nationwide burden of nosocomial S. aureus bloodstream infection (SA-BSI), a major cause of nosocomial infection, in South Korea., Methods: To evaluate the nationwide incidence of nosocomial SA-BSI, cases of SA-BSI were prospectively collected from 22 hospitals with over 500 beds over 4?months. Data on patient-days were obtained from a national health insurance database containing the claims data for all healthcare facilities in South Korea. The additional cost of SA-BSI was estimated through a matched case?control study. The economic burden was calculated from the sum of the medical costs, the costs of caregiving and loss of productivity., Results: Three hundred and thirty nine cases of nosocomial SA-BSI were included in the study: 254 cases of methicillin-resistant SA-BSI (MRSA-BSI) and 85 cases of methicillin-susceptible SA-BSI (MSSA-BSI). Death related to BSI occurred in 81 cases (31.9%) of MRSA-BSI and 12 cases (14.1%) of MSSA-BSI. The estimated incidence of nosocomial MRSA-BSI was 0.12/1,000 patient-days and that of nosocomial MSSA-BSI, 0.04/1,000 patient-days. The estimated annual cases of nosocomial BSI were 2,946 for MRSA and 986 for MSSA in South Korea. The additional economic burden per case of nosocomial SA-BSI was US $20,494 for MRSA-BSI and $6,914 for MSSA-BSI. Total additional annual cost of nosocomial SA-BSI was $67,192,559., Conclusion: In view of the burden of nosocomial SA-BSI, a national strategy for reducing nosocomial SA-BSI is urgently needed in South Korea.
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- 2014
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32. Attraction, recruitment and distribution of health professionals in rural and remote Australia: early results of the Rural Health Professionals Program.
- Author
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Morell AL, Kiem S, Millsteed MA, and Pollice A
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- Adult, Australia, Career Choice, Female, Humans, Male, Workforce, Young Adult, Allied Health Personnel, Medically Underserved Area, Nurses, Personnel Selection, Rural Health Services, Rural Population
- Abstract
Background: Australians living in rural and remote communities experience relatively poor health status in comparison to the wider Australian population (Med J Aust 185:37-38, 2006). This can be attributed in part to issues of access to health services arising from difficulties in recruiting and retaining health professionals in these areas. The Rural Health Professionals Program is an initiative designed to increase the number of allied health and nursing professionals in rural and remote Australia by providing case managed recruitment and retention support services. This paper reports on early analysis of available programme data to build knowledge of factors related to the recruitment and distribution of health professionals in rural and remote Australia., Methods: Administrative programme data were collected monthly from 349 health professionals over the first 13 months of programme operation. These data were collated and quantitative analysis was conducted using SPSS software., Results: Sixty-nine percent of recruits were women, and recruits had a mean age of 32.85 (SD = 10.92). Sixty percent of recruits were domestically trained, and the top two professions recruited were nurses (29%) and physiotherapists (21%). Eighty-seven percent were recruited to regional areas, with the remaining 13% recruited to remote areas. Among reasons for interest in the programme, financial support factors were most commonly cited by recruits (51%). Recruitment to a remote location was associated with being domestically trained, having previously lived in a rural or remote location, being a nurse (as opposed to an allied health professional) and older age., Discussion: The findings provide early support for a case managed recruitment programme to improve distribution of health professionals, and some directions for future marketing and promotion of the programme. It is recommended that an outcome evaluation be conducted to determine the impact of the programme on recruitment and distribution outcomes., Conclusion: The findings herein begin to address gaps in the literature relating to the effectiveness of interventions to improve the distribution of health professionals. While this provides some preliminary indication that case managed recruitment and retention programmes have capacity to improve distribution, further research and evaluation is required to confirm the impact of the programme on retention.
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- 2014
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33. Correlations between Microbiological Outcomes and Clinical Responses in Patients with Severe Pneumonia.
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Kiem S and Schentag JJ
- Abstract
Background: In treatment of pneumonia, microorganisms sometimes persist, appear or reappear despite good clinical responses. On the other hand, recent increasing antibiotic resistance emphases the goal of rapid eradication of pathogen in severe infection. This study was planned to evaluate the correlations between microbiological outcomes and clinical responses in severe pneumonia., Materials and Methods: Data was gathered from 3 clinical trials regarding severe pneumonia. Microbiological outcomes, determined by serial culture of respiratory tract samples,were compared with clinical outcomes., Results: In total, 146 bacterial strains from 76 patients were analyzed. While clinical success was generally related to total or partial eradication of isolated organisms, Acinetobacter, Enterobacter, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia were often not eradicated and yet were observed in 56% of cases considered clinically successful at the end of antibiotic treatment. Most of the non-eradicated strains (71%) already had or developed resistance against the antibiotics used for treatment. Ten patients relapsed during the follow-up period; 7 of these relapses were associated with 10 non-eradicated organisms., Conclusions: These data raise concern about the pathogenicity of bacteria that persist in the respiratory tract even though good clinical outcomes of pneumonia are achieved, especially when Acinetobacter, Enterobacter, P. aeruginosa, or S. maltophilia were involved. Thus, clinical relapse and development of drug resistance by non-eradicated organisms may be raised.
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- 2013
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34. Interpretation of antibiotic concentration ratios measured in epithelial lining fluid.
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Kiem S and Schentag JJ
- Subjects
- Anti-Bacterial Agents chemistry, Anti-Bacterial Agents classification, Bronchoalveolar Lavage Fluid cytology, Confounding Factors, Epidemiologic, Humans, Macrophages, Alveolar metabolism, Anti-Bacterial Agents pharmacokinetics, Bronchoalveolar Lavage Fluid chemistry, Epithelium metabolism
- Published
- 2008
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35. Synergy of arbekacin-based combinations against vancomycin hetero-intermediate Staphylococcus aureus.
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Lee JY, Oh WS, Ko KS, Heo ST, Moon CS, Ki HK, Kiem S, Peck KR, and Song JH
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- Ampicillin administration & dosage, Dibekacin administration & dosage, Drug Resistance, Bacterial, Drug Synergism, Humans, In Vitro Techniques, Methicillin Resistance, Microbial Sensitivity Tests, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Staphylococcus aureus isolation & purification, Sulbactam administration & dosage, Teicoplanin administration & dosage, Virginiamycin administration & dosage, Aminoglycosides administration & dosage, Anti-Bacterial Agents administration & dosage, Dibekacin analogs & derivatives, Staphylococcus aureus drug effects, Vancomycin administration & dosage
- Abstract
This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinupristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillin-sulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.
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- 2006
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36. Relationship of minimal inhibitory concentration and bactericidal activity to efficacy of antibiotics for treatment of ventilator-associated pneumonia.
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Kiem S and Schentag JJ
- Subjects
- Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents pharmacology, Area Under Curve, Cross Infection drug therapy, Drug Therapy, Combination, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Humans, Pneumonia, Bacterial etiology, Pneumonia, Bacterial microbiology, Serum Bactericidal Test, Anti-Bacterial Agents therapeutic use, Drug Resistance, Bacterial physiology, Microbial Sensitivity Tests, Pneumonia, Bacterial drug therapy, Ventilators, Mechanical adverse effects
- Abstract
Although minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) have been used as the most popular prediction tools for antimicrobial action, they have shortcomings. The MIC and MBC do not consider time-related antimicrobial effects, such as killing rate and postantibiotic effect. In this regard, the concept of pharmacokinetic and pharmacodynamic (PK/PD) modeling has been introduced to help interpret determinations of susceptibility breakpoints. Although area under the inhibitory concentration-time curve (AUIC) can be used as a universal PK/PD parameter, target magnitudes of the parameter have to be high enough to exert rapid bactericidal activity (> 250) and to prevent selection and induction of resistance (> 100). For vancomycin used in treatment of methicillin-resistant Staphylococcus aureus pneumonia, a much higher AUIC (400) is suggested to avoid treatment failure. For resistant gram-negative bacteria, such as Pseudomonas aeruginosa, the usual dosage of fourth-generation cephalosporins, carbapenems, and fluoroquinolones cannot achieve the target AUICs. Either combination therapy or higher dosage should be administered to achieve target AUICs and prevent the potential for failure. Unresolved issues, such as influence of protein binding, PK/PD at tissue sites versus blood, the impact of the immune system, should be addressed to refine the applicability of PK/PD in antibiotic treatment.
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- 2006
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37. Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin.
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Song JH, Hiramatsu K, Suh JY, Ko KS, Ito T, Kapi M, Kiem S, Kim YS, Oh WS, Peck KR, and Lee NY
- Subjects
- Asia epidemiology, Methicillin Resistance, Microbial Sensitivity Tests, Population, Staphylococcal Infections epidemiology, Staphylococcus aureus drug effects, Vancomycin Resistance
- Abstract
To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates were found among MRSA isolates from Asian countries in this survey.
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- 2004
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38. Phase variation of biofilm formation in Staphylococcus aureus by IS 256 insertion and its impact on the capacity adhering to polyurethane surface.
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Kiem S, Oh WS, Peck KR, Lee NY, Lee JY, Song JH, Hwang ES, Kim EC, Cha CY, and Choe KW
- Subjects
- Cell Adhesion Molecules genetics, Equipment Contamination prevention & control, Mutagenesis, Insertional methods, Mutagenesis, Site-Directed genetics, Phase Transition, Polysaccharides, Bacterial genetics, Species Specificity, Staphylococcus aureus cytology, Structure-Activity Relationship, Bacterial Adhesion physiology, Biofilms growth & development, Cell Adhesion Molecules metabolism, Polysaccharides, Bacterial metabolism, Polyurethanes, Staphylococcus aureus physiology
- Abstract
While ica gene of Staphylococcus epidermidis is known to undergo phase variation by insertion of IS256, the phenomenon in Staphylococcus aureus has not been evaluated. Six biofilm-positive strains were tested for the presence of biofilm-negative phase-variant strains by Congo red agar test. For potential phase-variant strains, pulsed-field gel electrophoresis was done to exclude the possibility of contamination. To investigate the mechanism of the biofilm-negative phase variation, PCR for each ica genes were done. Changes of ica genes detected by PCR were confirmed by southern hybridization, and their nucleotides were analyzed by DNA sequencing. Influence of ica genes and biofilm formation on capacity for adherence to biomedical material was evaluated by comparing the ability of adhering to polyurethane surface among a biofilm-negative phase-variant strain and its parent strain. A biofilm-negative phase-variant S. aureus strain was detected from 6 strains tested. icaC gene of the phase-variant strain was found to be inactivated by insertion of additional gene segment, IS256. The biofilm-negative phase-variant strain showed lower adhering capacity to polyurethane than its parent strain. This study shows that phase variation of ica gene occurs in S. aureus by insertion of IS256 also, and this biofilm-negative phase variation reduces adhering capacity of the bacteria.
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- 2004
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39. Evaluation of a triple-drug combination for treatment of experimental multidrug-resistant pneumococcal meningitis.
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Lee H, Song JH, Kim SW, Oh WS, Jung SI, Kiem S, Peck KR, and Lee NY
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- Animals, Ceftriaxone administration & dosage, Ceftriaxone pharmacokinetics, Colony Count, Microbial, Dexamethasone administration & dosage, Drug Evaluation, Preclinical, Drug Therapy, Combination pharmacokinetics, Meningitis, Pneumococcal metabolism, Meningitis, Pneumococcal microbiology, Rabbits, Rifampin administration & dosage, Rifampin pharmacokinetics, Streptococcus pneumoniae drug effects, Streptococcus pneumoniae isolation & purification, Vancomycin administration & dosage, Vancomycin pharmacokinetics, Drug Therapy, Combination administration & dosage, Meningitis, Pneumococcal drug therapy
- Abstract
To evaluate the therapeutic efficacy of ceftriaxone + vancomycin + rifampicin (CVR) in the treatment of pneumococcal meningitis caused by a multidrug-resistant strain, single-drug regimens (ceftriaxone 100 mg/kg, rifampicin 15 mg/kg, or vancomycin 20 mg/kg), double-drug regimens (ceftriaxone + vancomycin [CV] and ceftriaxone + rifampicin [CR]) and a triple-drug combination (CVR) with or without dexamethasone were compared in a rabbit meningitis model. Meningitis was induced by a highly penicillin-resistant (MIC 2 mg/l) and ceftriaxone-resistant (MIC 4 mg/l) pneumococcal strain. Final therapeutic efficacy was evaluated by the bacterial concentration at 24 h, and the bacterial killing rate was also evaluated. All combination regimens were superior to ceftriaxone or vancomycin single-drug regimens with regard to sterilisation of CSF and bacterial killing rate. Rifampicin was as effective as combination regimens. Regardless of dexamethasone, therapeutic efficacy of CVR and CR were superior to that of CV. CVR showed comparable therapeutic efficacy to CR. Data suggested that CVR would not have additional therapeutic benefit over CR during the initial 24 h of treatment.
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- 2004
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- View/download PDF
40. Efficacy of vancomycin-beta-lactam combinations against heterogeneously vancomycin-resistant Staphylococcus aureus (hetero-VRSA).
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Kim YS, Kiem S, Yun HJ, Jung SI, Oh WS, Kim SW, Peck KR, Lee NY, and Song JH
- Subjects
- Cefotaxime pharmacology, Drug Synergism, Humans, In Vitro Techniques, Microbial Sensitivity Tests, Vancomycin Resistance, beta-Lactam Resistance, Anti-Bacterial Agents pharmacology, Oxacillin pharmacology, Staphylococcus aureus drug effects, Vancomycin pharmacology
- Abstract
There have been conflicting data about the interactions between vancomycin and beta-lactam agents against Staphylococcus aureus strains with heterogeneous resistance to vancomycin. We evaluated the efficacy of these combinations against Mu 3 and heterogeneously vancomycin-resistant S. aureus (hetero-VRSA) strains which were isolated from Korean patients using a population analysis method. Antagonistic effects were observed when less than 1 g/mL of beta-lactam antibiotics was combined with vancomycin, whereas synergistic effects were noticed with more than 4 microgram/mL of beta-lactam antibiotics. The antagonistic effects at low concentrations of beta-lactams were most prominent at 2 microgram/mL of vancomycin, which were the vancomycin MICs of tested hetero-VRSA strains. This study showed the variable effects of vancomycin- beta-lactam combinations depending on the concentrations of beta-lactam antibiotics and this property could be used to develop screening methods for hetero-VRSA strains.
- Published
- 2003
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41. One-point population analysis and effect of osmolarity on detection of hetero-vancomycin-resistant Staphylococcus aureus.
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Jung SI, Kiem S, Lee NY, Kim YS, Oh WS, Cho HL, Peck KR, and Song JH
- Subjects
- Anti-Bacterial Agents pharmacology, Humans, Methicillin Resistance, Microbial Sensitivity Tests methods, Osmolar Concentration, Staphylococcal Infections microbiology, Vancomycin pharmacology, Sodium Chloride pharmacology, Staphylococcus aureus drug effects, Staphylococcus aureus growth & development, Vancomycin Resistance
- Abstract
The original screening test and one-point population analysis (OPPA) were compared for the detection of hetero-vancomycin-resistant Staphylococcus aureus, and the influence of osmolarity on those tests was evaluated. The positivity rates and the reproducibilities were similar for both tests. The addition of NaCl increased the MIC as well as the positivity rates for both tests and the reproducibility of OPPA.
- Published
- 2002
- Full Text
- View/download PDF
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