The short story is a comparatively modern phenomenon in Kuwait; the first appeared in 1929. There have been two distinct periods in the history of the short story in Kuwait. The first was from 1947 to 1959, the second was from 1962 to 1985. During the first period, it was more of a vehicle for didactic and predicative than for literary purposes. Characterisation was elementary, plot was negatory and structure was primitive. The second period witnessed a considerable development in the genre; the short story became, in all respects, more recognisable as such. Today, the art of short story writing is practised in Kuwait in a manner indistinguishable from that of any other Arab country.

So far, textual hetero-representations of the Romani people (usually called `Gypsies' by the non-Roma) have focused on their foreignness and alleged `non-conformity' to the dominant order. Such depictions, conflating history and myth, art and reality, promote the perception of an unbridgeable divide between the `primitive', `illiterate' Roma and the `civilized' society. In this respect, the forging of a fictional `Gypsy' identity can be seen as an ethnic strategy aimed at endorsing harsh policies of oppression and social marginalization of the Roma. The recent rise of *a Romani written literature has shown that, contrary to common belief, the Roma cannot simply be defined as people `without writing'. This thesis aims to highlight the complex features of their literature, characterized by an irreducible plurality of voices and styles which is in striking contrast with the rigid, monolithic structure of the conventional images of the 'Gypsy'. The intertextual, hybrid features of Romani literature seem to suggest alternative ways of looking at Romani identity which substantially undermine the rigid binarism of ethnocentric definitions of the 'Gypsy'. More specifically, the study of Romani literature enables us to view Romani textual hetero- and auto-representations not as irreconcilable, mutually exclusive terms, but in the light of their interconnections and mutual influences. The adoption of a dynamic, intercultural approach is a crucial factor in our understanding of the complex features of Romani identity, and may ultimately contribute to a profound (and long due) reassessment of the troubled Roma/Gağe relationship.

This book examines the questions of how Gypsy ethnicity, identity and history are interlinked in the context of examining various contested narratives or origins and migration. The text is itself a series of narratives and counter-narratives that engage in a self-critical, deconstructive analysis of the underlying assumptions hitherto presented in many, if not most of the previous scholarship regarding the origins and identity of the Gypsies, with particular focus on the contextual and radically contingent nature of all such texts. As such, the primary examination is an historiographical and theoretical consideration of the questions surrounding Gypsy ethnicity and identity. The dissertation also considers to what extent the production of historical knowledge is affected by those who produce it from within and without the Gypsy community or communities themselves. Most especially, this survey examines the production of literatures in Turkish scholarship, as related to the underlying conception of the book arguing for a re-examination of Romanī historiography from east to west, rather than the ‘traditional’ Orientalist and Europe-centric perspectives deployed by much of the previous scholarship. Moreover, the dissertation focuses upon the Turkish lands to argue that the historical experiences of Gypsies in this region are of critical importance in understanding the development of both European Romanī histories and in acknowledging the flawed basis for the universalist conceptions of European Roma identity and political mobilisation, as they are now articulated. The importance of Islam in the origins and history of the Gypsies is stressed. This theoretical framework underlies the interweaving narratives that make up the latter sections of the text, a reconsideration of the sources for early Gypsy history that posits an alternative narrative.

Bibliographische Beschreibung Pharmakokinetisch/pharmakodynamische Untersuchung zur in vitro Aktivtität von Levofloxacin und Moxifloxacin gegenüber B. fragilis und E. coli in Mono- und Mischkultur Universität Leipzig, Dissertation 92 S., 190 Lit., 25 Abb., 20 Tab., 3 Anlagen Referat: Bei intraabdominellen Infektionen findet sich häufig ein polymikrobielles Erregerspektrum aus fakultativ und obligat anaeroben Bakterien. Natürliches Habitat der dabei am häufigsten isolierten Erreger E. coli und B. fragilis ist der gastrointestinale Trakt. Durch Störungen der Darmwandintegrität und nachfolgendem Eindringen der Bakterien in eine sterile Umgebung, wie beispielsweise der Peritonealhöhle, kann es zur Infektion kommen. Die häufigste Form der intraabdominellen Infektionen ist die sekundäre Peritonitis. Die Therapie erfolgt chirurgisch, begleitet von einer antibiotischen Therapie. Dabei sind Kenntnisse über Wirksamkeit und Empfindlichkeit der Erreger gegenüber den verwendeten Antibiotika von entscheidender Bedeutung. In dieser Arbeit wurden die MHK-Werte von vier B. fragilis und vier E. coli Stämmen für Levofloxacin und Moxifloxacin bestimmt, wobei ein B. fragilis und drei E. coli Stämme resistent gegenüber Levofloxacin und Moxifloxacin waren. Anschließend wurden mit einem in vitro PK/PD-Modell die pharmakodynamischen Effekte von Levofloxacin und Moxifloxacin in Mono- und Mischkulturen von B. fragilis und E. coli untersucht. Die Monokulturversuche mit E. coli Stämmen wurden sowohl unter aeroben als auch anaeroben Bedingungen durchgeführt. Durch die Untersuchung von Aktivität und Wirksamkeit von Levofloxacin und Moxifloxacin in vitro können Aussagen über eine mögliche Verwendung bei intraabdominellen Infektionen getroffen werden. Levofloxacin wirkte auf den sensiblen E. coli Stamm nur unter aeroben Bedingungen bakterizid, nicht jedoch unter anaeroben Bedingungen. Hingegen wirkte Moxifloxacin in aerober und anaerober Umgebung bakterizid auf diesen E. coli Stamm. In den Mischkulturen zeigte Moxifloxacin eine bessere in vitro Aktivität als Levofloxacin, wobei Moxifloxacin allerdings auch nur eine moderate Aktivität hatte. Aufgrund der Ergebnisse könnte Moxifloxacin dennoch eine theraupeutische Option bei der Behandlung intraabdomineller Infektionen bieten. Der Einsatz dieser Substanzen sollte jedoch nicht unkritisch erfolgen.

In the last three decades, Speech Act Theory has been displaced from the spotlight of pragmatic research and relegated to the back seat of this field. This has been the case despite the potential this theory still has to serve pragmatic research. This study is an attempt to revive and develop speech act theory by means of applying it to interactive naturally-occurring discourse proposing a number of different types of speech act and incorporating into analysis a wider range of pragmatic IFIDs. The main purpose of the study is to: (1) investigate speech acts in interaction and find out which 'illocutionary force indicating devices (IFIDs) are used to identify speech acts in an interactive context, and (2) compare the investigated speech acts and IFIDs cross-culturally between English and Arabic. Regarding data, the study investigated 12 English and Arabic short news interviews (six each). Some of these were video-recorded live from BBC and Sky news channels (English dataset) and Al-Arabiya, Sky news Arabia and Al-Wataniya channels (Arabic dataset). Other interviews were downloaded from YouTube. Two topics were the focus of these interviews: (1) the immigration crisis in 2015 (six English and Arabic interviews), and (2) the Iranian nuclear deal in 2015 (six English and Arabic interviews). The study investigated the two datasets to find which speech acts are used in short news interviews and what interactional IFIDs are used to identify them. Results show that many different speech acts are used in news interviews — the study counted 48 individual speech acts in the analysed interviews. However, it was found that a mere itemizing and classification of speech acts in the classical sense (Austin‘s and Searle‘s classifications) was not enough. In addition, the study identifies various new types of speech acts according to the role they play in the ongoing discourse. The first type is termed turn speech acts‘. These are speech acts which have special status in the turn they occur in and are of two subtypes: 'main act' and 'overall speech act'. The second type is 'interactional acts'. These are speech acts which are named in relation to other speech acts in the same exchange. The third type is ̳superior speech acts‘. These are superordinate speech acts with the performance of which other subordinate (inferior) speech acts are performed as well. The study also found three different types of utterances vis-à-vis the speech acts they perform. These are 'single utterance' (which performs a single speech act only), 'double-edged utterance' (which performs two speech acts concurrently) and 'Fala utterance' (which performs three speech acts together). As for IFIDs, the study found that several already-established pragmatic concepts can help identify speech acts in interaction. These are Adjacency Pair, Activity Type, Cooperative Principle, Politeness Principle, Facework, Context (Co-utterance and Pragmalinguistic cues). These devices are new additions to Searle‘s original list of IFIDs. Furthermore, they are expanding this concept as they include a type of IFID different from the original ones. Finally, the study has found no significant differences between English and Arabic news interviews as regards speech acts (types), utterance types and the analysed IFIDs. The study attracts attention to Speech Act Theory and encourages further involvement of this theory in other genres of interactive discourse (e.g., long interviews, chat shows, written internet chat, etc.). It also encourages further exploration of the different types of speech acts and utterances discussed in this study as well as probing the currently-investigated and other IFIDs. It is hoped that by returning to the core insight of SAT (i.e., that language-in-use does things) and at the same time freeing it from its pragmalinguistic shackles, its value can be seen more clearly.

Uppsatsen undersöker genom retoriseringsanalys förändringar kring begreppet ”identitetspolitik” i svensk debatt under år 2014 och 2015, med fokus på ”den stora identitetspolitiska debatten” under senhösten 2014.

Le MTX est un agent anticancéreux utilisé à hautes doses pour le traitement des hémopathies malignes et de certaines tumeurs solides. Il présente une importante variabilité pharmacocinétique (PK) traduite par des surexpositions à l'origine de toxicités très sévères, surtout lors d'une administration à haute dose. Les retards d'élimination du MTX surviennent encore de manière inattendue et il n'existe à ce jour aucun biomarqueur qui permette un diagnostic précoce du risque de surexposition. Nos travaux ont focalisé sur les déterminants de l'élimination rénale du MTX, et en particulier le rôle du transporteur MRP2/ABCC2 dans ce processus. Ce travail s'inscrit donc (1) dans la recherche de biomarqueurs métabolomiques urinaires prédictifs de la PK du MTX et (2) dans l'identification de substrats endogènes de MRP2 parmi un panel de 217 acides organiques urinaires analysés par chromatographie gazeuse couplée à la spectrométrie de masse. Nos analyses ont abouti à un profil de 28 anions organiques endogènes, prédictifs de la CL MTX. L'outil était en revanche mal adapté à la prédiction des retards d'élimination. Pour la 2eme partie, nos résultats tendent à montrer que 8 métabolites urinaires sont des bio-marqueurs potentiels de l'activité de MRP2. Leur utilisation en clinique nécessite encore des études confirmatoires. / MTX is an anticancer agent used at high doses for the treatment of malignant haemopathies and some solid tumors. It presents an important pharmacokinetic variability (PK), manifested by overexposures causing very severe toxicities, especially when administered at high doses. Delayed elimination of MTX still occurs unexpectedly and there is currently no biomarker that allows early diagnosis of the risk of overexposure. Our work focused on the determinants of renal elimination of MTX, and particularly on the role of MRP2 / ABCC2 in this process. This work is therefore devoted to (1) the search for metabolomic biomarkers predictive of MTX PK and (2) the identification of endogenous substrates of MRP2, from a panel of 217 urinary organic acids analyzed by gas chromatography-mass spectrometry. Our analyses resulted in a profile of 28 endogenous organic anions, predictive of CL MTX. The tool was, on the other hand, poorly adapted to the prediction of delayed elimination. For the second part, our results tend to show that 8 urinary metabolites are potential biomarkers of MRP2 activity. Their clinical use still requires confirmatory studies.

Bibliographische Beschreibung Pharmakokinetisch/pharmakodynamische Untersuchung zur in vitro Aktivtität von Levofloxacin und Moxifloxacin gegenüber B. fragilis und E. coli in Mono- und Mischkultur Universität Leipzig, Dissertation 92 S., 190 Lit., 25 Abb., 20 Tab., 3 Anlagen Referat: Bei intraabdominellen Infektionen findet sich häufig ein polymikrobielles Erregerspektrum aus fakultativ und obligat anaeroben Bakterien. Natürliches Habitat der dabei am häufigsten isolierten Erreger E. coli und B. fragilis ist der gastrointestinale Trakt. Durch Störungen der Darmwandintegrität und nachfolgendem Eindringen der Bakterien in eine sterile Umgebung, wie beispielsweise der Peritonealhöhle, kann es zur Infektion kommen. Die häufigste Form der intraabdominellen Infektionen ist die sekundäre Peritonitis. Die Therapie erfolgt chirurgisch, begleitet von einer antibiotischen Therapie. Dabei sind Kenntnisse über Wirksamkeit und Empfindlichkeit der Erreger gegenüber den verwendeten Antibiotika von entscheidender Bedeutung. In dieser Arbeit wurden die MHK-Werte von vier B. fragilis und vier E. coli Stämmen für Levofloxacin und Moxifloxacin bestimmt, wobei ein B. fragilis und drei E. coli Stämme resistent gegenüber Levofloxacin und Moxifloxacin waren. Anschließend wurden mit einem in vitro PK/PD-Modell die pharmakodynamischen Effekte von Levofloxacin und Moxifloxacin in Mono- und Mischkulturen von B. fragilis und E. coli untersucht. Die Monokulturversuche mit E. coli Stämmen wurden sowohl unter aeroben als auch anaeroben Bedingungen durchgeführt. Durch die Untersuchung von Aktivität und Wirksamkeit von Levofloxacin und Moxifloxacin in vitro können Aussagen über eine mögliche Verwendung bei intraabdominellen Infektionen getroffen werden. Levofloxacin wirkte auf den sensiblen E. coli Stamm nur unter aeroben Bedingungen bakterizid, nicht jedoch unter anaeroben Bedingungen. Hingegen wirkte Moxifloxacin in aerober und anaerober Umgebung bakterizid auf diesen E. coli Stamm. In den Mischkulturen zeigte Moxifloxacin eine bessere in vitro Aktivität als Levofloxacin, wobei Moxifloxacin allerdings auch nur eine moderate Aktivität hatte. Aufgrund der Ergebnisse könnte Moxifloxacin dennoch eine theraupeutische Option bei der Behandlung intraabdomineller Infektionen bieten. Der Einsatz dieser Substanzen sollte jedoch nicht unkritisch erfolgen.

INTRODUÇÃO - OBJETIVO: A vancomicina é um glicopeptídeo de primeira escolha largamente prescrito aos pacientes críticos no tratamento de infecções graves causadas por patógenos nosocomiais Gram-positivos susceptíveis. Os pacientes grandes queimados são considerados pacientes críticos pelas condições metabólicas e importantes alterações fisiopatológicas decorrentes do choque séptico que modificam a farmacocinética da vancomicina. Destaca-se, entretanto que nos pacientes críticos queimados pediátricos essa alteração ocorre em diferente proporção quando comparada aquela reportada para pacientes adultos. Assim sendo, a efetividade desse antimicrobiano é um desafio para a equipe clínica da terapia intensiva, uma vez que a dose empírica nesses pacientes tem fornecido concentrações inferiores às recomendadas, resultando em falha terapêutica pela falta de cobertura do antimicrobiano contra patógenos susceptíveis, CIM ≥1mg/L. O objetivo foi realizar o monitoramento das concentrações plasmáticas de vancomicina seguido da abordagem farmacocinética-farmacodinâmica (PK/PD) a fim de se avaliar a efetividade do regime empírico recomendado ao paciente crítico pediátrico e se realizar o ajuste de dose para erradicação dos patógenos. CASUÍSTICA E MÉTODOS: Incluíram-se 20 pacientes (14M/6F), função renal normal com média de idade 5,95 (4,5-7,4) anos, peso 25,2 (20,5-30)kg, superfície de área queimada total 31,1(25-37)%. Os acidentes foram causados pelo fogo/ combustão por álcool; registrou-se lesão inalatória (12/20) e uso de drogas vasoativas e ventilação mecânica em 13/20 pacientes. Os exames de rotina laboratorial foram realizados diariamente; antes do início da terapia antimicrobiana, colheram-se amostras de sangue no D0 para cultura e realização do teste de susceptibilidade. Os pacientes foram investigados em diferentes seguimentos durante o choque séptico; o regime de dose empírica recomendada pelo CCIH foi prescrito e 3-4 amostras seriadas de sangue (1,5 mL/cada) foram coletadas do CVC no intervalo de dose após a dose diária empírica recomendada e após a individualização da terapia medicamentosa. A quantificação de vancomicina plasmática foi realizada através da cromatografia líquida. Na modelagem PK utilizou-se o programa PK Solutions Noncompartmental Data Analysis versão 2.0. Na abordagem PK/PD e no tratamento estatístico aplicou-se o programa GraphPad Prisma v.5.0. Empregou-se a razão da área sob a curva (ASCss0-24) e concentração inibitória mínima superior a 400 (ASCss0-24/CIM>400) como índice preditivo de efetividade recomendada para o antimicrobiano. Aplicou-se estatística paramétrica com relação aos dados demográficos e laboratoriais, e estatística não paramétrica com relação à dose, concentração plasmática, área sob a curva, constantes farmacocinéticas e efetividade do antimicrobiano. Aplicaram-se nesse estudo os testes paramétricos (ANOVA e Teste T de Student) e não paramétricos (Wilcoxon e Mann Whitney) no programa GraphPad Prisma v.5.0., e o nível de alfa igual ou inferior a 0,05 (P<0,05) foi considerado na significância estatística. RESULTADOS: A dose empírica de vancomicina foi 50 (44-51) mg/kg dia, mediana (quartis, IQ25-75) mostrou que o alvo foi atingido para 85% (17/20) dos pacientes apenas contra cepas sensíveis (CIM&≤1mg/L), ficando desta forma todos os pacientes desprotegidos contra cepas CIM >1mg/L (CIM: 2-4 mg/L). Então, registrou-se alteração de conduta médica relativa à prescrição com aumento da dose diária de vancomicina 94 (85-104) mg/Kg. Esse aumento se mostrou significativo com relação a dose inicial empírica, p<0,05. Após nova estabilização pela terapia dose ajustada, e coletas de sangue no platô, o alvo PK/PD foi alcançado para todos os pacientes, contra patógenos CIM 1mg/L. Entretanto, apenas 5/20 pacientes alcançaram o alvo PK/PD contra cepas susceptíveis CIM: 2mg/L, sendo que nenhum paciente se mostrou coberto contra cepas CIM 4mg/L. CONCLUSÃO: O regime empírico de dose recomendado para a vancomicina não se mostrou efetivo contra os patógenos sensíveis isolados. Concluindo, o controle terapêutico, estudo da farmacocinética e abordagem PK/PD realizado em tempo real possibilitou a alteração precoce de prescrição da vancomicina nos pacientes pediátricos grandes queimados de forma a otimizar a terapia antimicrobiana e o controle das infecções causadas por patógenos hospitalares susceptíveis (CIM ≥1mg/L). / INTRODUCTION- OBJECTIVE: Vancomycin is a first choice glycopeptide largely prescribed to critically ill adult or pediatric patients under therapy of severe infections caused by gram-positive susceptible nosocomial strains. Burn patients have metabolic conditions that change the pharmacokinetics of vancomycin in the treatment of severe infections. Pediatric patients are even more complicated because pharmacokinetic changes are quite different compared to adults, then effective vancomycin dose regimen is a challenge to clinic staff, once the initial dose recommended cannot reach the target against MIC ≥ 1 mg/L strains. Then therapeutic fail with impact on desired outcome. Therefore the rational of study was to apply therapeutic drug plasma monitoring (TDM) in order to identify the pharmacokinetic changes that occur in paediatric burns through PK/PD approach to perform in a real time the dose adjustment required. METHODS - CASUISTRY: Twenty septic burn pediatric patients was investigated after the admission in the Intensive Care Unit of Burns (ICBU) Plastic Surgery Division of HCFMUSP. Vancomycin empiric dose regimen recommended was prescribed 500mg every 6 hours, and patients received one hour drug infusion. Blood sampling was performed after drug infusion at time dose interval (1.5 mL/tube, sodium EDTA): 2nd or 3rd h, 4th, and before the next dose. Vancomycin was quantified by liquid chromatography (LC). Pharmacokinetics was investigated on the basis on one compartment open model by Noncompartmental Data Analysis PK Solutions v 2.0, software. PK/PD approach was based on the ratio of area under the plasma concentration - time curve (AUCss0-24) and the minimum inhibitory concentration (MIC) performed by GraphPad Prism v 5.0 software. The predictive index of drug effectiveness recommended was ASCss0-24/CIM>400. Statistics also was performed through by GraphPad Prism v 5.0 software by application of parametric tests to demographic data and also to laboratorial data (ANOVA, Student T test). Nonparametric statistics was applied related to dose, drug plasma measurements and AUC, kinetic data, data related to drug effectiveness (Mann Whitney). Statistical significant difference was considered, alpha lower than 0,05 (P<0,05). RESULTS -CONCLUSION: It was shown that the therapeutic target was reached to 85% (17/20) patients with the empiric daily dose of vancomycin (44-51) mg/kg, median (quartiles, IQ25-75) only for susceptible strains (MIC≤1mg/L). Then, changes of the prescription occurred in a real time and the daily dose was increased to 94 (85-104) mg/kg, p<0.05. New blood sampling was done at the steady state for TDM, PK and PK/PD approach and the target was reached for all patients MIC 1 mg/L strains; while the target was reached only 5/20 patients against MIC: 2mg/L susceptible strains, and none patient reached the target against MIC 4mg/L strains. It was shown that the drug effectiveness wasn\'t guaranteed by the vancomycin dose regimen recommended for the treatment of sepsis caused by nosocomial MIC≥1mg/L strains. In conclusion, TDM, pharmacokinetic study and PK/PD approach must be considered important tools do change vancomycin prescription in a real time in order to optimize the antimicrobial treatment of septic shock caused by nosocomial pathogens.

INTRODUÇÃO - OBJETIVO: A vancomicina é um glicopeptídeo de primeira escolha largamente prescrito aos pacientes críticos no tratamento de infecções graves causadas por patógenos nosocomiais Gram-positivos susceptíveis. Os pacientes grandes queimados são considerados pacientes críticos pelas condições metabólicas e importantes alterações fisiopatológicas decorrentes do choque séptico que modificam a farmacocinética da vancomicina. Destaca-se, entretanto que nos pacientes críticos queimados pediátricos essa alteração ocorre em diferente proporção quando comparada aquela reportada para pacientes adultos. Assim sendo, a efetividade desse antimicrobiano é um desafio para a equipe clínica da terapia intensiva, uma vez que a dose empírica nesses pacientes tem fornecido concentrações inferiores às recomendadas, resultando em falha terapêutica pela falta de cobertura do antimicrobiano contra patógenos susceptíveis, CIM ≥1mg/L. O objetivo foi realizar o monitoramento das concentrações plasmáticas de vancomicina seguido da abordagem farmacocinética-farmacodinâmica (PK/PD) a fim de se avaliar a efetividade do regime empírico recomendado ao paciente crítico pediátrico e se realizar o ajuste de dose para erradicação dos patógenos. CASUÍSTICA E MÉTODOS: Incluíram-se 20 pacientes (14M/6F), função renal normal com média de idade 5,95 (4,5-7,4) anos, peso 25,2 (20,5-30)kg, superfície de área queimada total 31,1(25-37)%. Os acidentes foram causados pelo fogo/ combustão por álcool; registrou-se lesão inalatória (12/20) e uso de drogas vasoativas e ventilação mecânica em 13/20 pacientes. Os exames de rotina laboratorial foram realizados diariamente; antes do início da terapia antimicrobiana, colheram-se amostras de sangue no D0 para cultura e realização do teste de susceptibilidade. Os pacientes foram investigados em diferentes seguimentos durante o choque séptico; o regime de dose empírica recomendada pelo CCIH foi prescrito e 3-4 amostras seriadas de sangue (1,5 mL/cada) foram coletadas do CVC no intervalo de dose após a dose diária empírica recomendada e após a individualização da terapia medicamentosa. A quantificação de vancomicina plasmática foi realizada através da cromatografia líquida. Na modelagem PK utilizou-se o programa PK Solutions Noncompartmental Data Analysis versão 2.0. Na abordagem PK/PD e no tratamento estatístico aplicou-se o programa GraphPad Prisma v.5.0. Empregou-se a razão da área sob a curva (ASCss0-24) e concentração inibitória mínima superior a 400 (ASCss0-24/CIM>400) como índice preditivo de efetividade recomendada para o antimicrobiano. Aplicou-se estatística paramétrica com relação aos dados demográficos e laboratoriais, e estatística não paramétrica com relação à dose, concentração plasmática, área sob a curva, constantes farmacocinéticas e efetividade do antimicrobiano. Aplicaram-se nesse estudo os testes paramétricos (ANOVA e Teste T de Student) e não paramétricos (Wilcoxon e Mann Whitney) no programa GraphPad Prisma v.5.0., e o nível de alfa igual ou inferior a 0,05 (P<0,05) foi considerado na significância estatística. RESULTADOS: A dose empírica de vancomicina foi 50 (44-51) mg/kg dia, mediana (quartis, IQ25-75) mostrou que o alvo foi atingido para 85% (17/20) dos pacientes apenas contra cepas sensíveis (CIM&≤1mg/L), ficando desta forma todos os pacientes desprotegidos contra cepas CIM >1mg/L (CIM: 2-4 mg/L). Então, registrou-se alteração de conduta médica relativa à prescrição com aumento da dose diária de vancomicina 94 (85-104) mg/Kg. Esse aumento se mostrou significativo com relação a dose inicial empírica, p<0,05. Após nova estabilização pela terapia dose ajustada, e coletas de sangue no platô, o alvo PK/PD foi alcançado para todos os pacientes, contra patógenos CIM 1mg/L. Entretanto, apenas 5/20 pacientes alcançaram o alvo PK/PD contra cepas susceptíveis CIM: 2mg/L, sendo que nenhum paciente se mostrou coberto contra cepas CIM 4mg/L. CONCLUSÃO: O regime empírico de dose recomendado para a vancomicina não se mostrou efetivo contra os patógenos sensíveis isolados. Concluindo, o controle terapêutico, estudo da farmacocinética e abordagem PK/PD realizado em tempo real possibilitou a alteração precoce de prescrição da vancomicina nos pacientes pediátricos grandes queimados de forma a otimizar a terapia antimicrobiana e o controle das infecções causadas por patógenos hospitalares susceptíveis (CIM ≥1mg/L). / INTRODUCTION- OBJECTIVE: Vancomycin is a first choice glycopeptide largely prescribed to critically ill adult or pediatric patients under therapy of severe infections caused by gram-positive susceptible nosocomial strains. Burn patients have metabolic conditions that change the pharmacokinetics of vancomycin in the treatment of severe infections. Pediatric patients are even more complicated because pharmacokinetic changes are quite different compared to adults, then effective vancomycin dose regimen is a challenge to clinic staff, once the initial dose recommended cannot reach the target against MIC ≥ 1 mg/L strains. Then therapeutic fail with impact on desired outcome. Therefore the rational of study was to apply therapeutic drug plasma monitoring (TDM) in order to identify the pharmacokinetic changes that occur in paediatric burns through PK/PD approach to perform in a real time the dose adjustment required. METHODS - CASUISTRY: Twenty septic burn pediatric patients was investigated after the admission in the Intensive Care Unit of Burns (ICBU) Plastic Surgery Division of HCFMUSP. Vancomycin empiric dose regimen recommended was prescribed 500mg every 6 hours, and patients received one hour drug infusion. Blood sampling was performed after drug infusion at time dose interval (1.5 mL/tube, sodium EDTA): 2nd or 3rd h, 4th, and before the next dose. Vancomycin was quantified by liquid chromatography (LC). Pharmacokinetics was investigated on the basis on one compartment open model by Noncompartmental Data Analysis PK Solutions v 2.0, software. PK/PD approach was based on the ratio of area under the plasma concentration - time curve (AUCss0-24) and the minimum inhibitory concentration (MIC) performed by GraphPad Prism v 5.0 software. The predictive index of drug effectiveness recommended was ASCss0-24/CIM>400. Statistics also was performed through by GraphPad Prism v 5.0 software by application of parametric tests to demographic data and also to laboratorial data (ANOVA, Student T test). Nonparametric statistics was applied related to dose, drug plasma measurements and AUC, kinetic data, data related to drug effectiveness (Mann Whitney). Statistical significant difference was considered, alpha lower than 0,05 (P<0,05). RESULTS -CONCLUSION: It was shown that the therapeutic target was reached to 85% (17/20) patients with the empiric daily dose of vancomycin (44-51) mg/kg, median (quartiles, IQ25-75) only for susceptible strains (MIC≤1mg/L). Then, changes of the prescription occurred in a real time and the daily dose was increased to 94 (85-104) mg/kg, p<0.05. New blood sampling was done at the steady state for TDM, PK and PK/PD approach and the target was reached for all patients MIC 1 mg/L strains; while the target was reached only 5/20 patients against MIC: 2mg/L susceptible strains, and none patient reached the target against MIC 4mg/L strains. It was shown that the drug effectiveness wasn\'t guaranteed by the vancomycin dose regimen recommended for the treatment of sepsis caused by nosocomial MIC≥1mg/L strains. In conclusion, TDM, pharmacokinetic study and PK/PD approach must be considered important tools do change vancomycin prescription in a real time in order to optimize the antimicrobial treatment of septic shock caused by nosocomial pathogens.