<p>Cilj ove disertacije je da se ispita uticaj aplikacije niacina na metabolizam lipida u peripartalnom periodu, da se utvrdi dali aplikacija niacina utiče na insulinsku rezistenciju, vezu između metaboličkih parametara i lipolize i ketogeneze i uticaj aplikacije niacina na koncetracije NAD i NADP. NAD i NADP predstavljaju adekvatne pokazatelje statusa niacina kod krava u ranoj laktaciji, a njihova vrednost je značajno vi&scaron;a kod krava koje su primale ovaj vitamin. NED i NADP pokazuju pozitivnu korelaciju. Pored ovoga izvedene vrednosti kao &scaron;to je NAD:NADP indeks i povr&scaron;ina ispod krive koju prave ovi vitameri posle teljnja zavise od aplikacije niacina. Aplikacija niacina dovodi do smanjenja koncentracije NEFA, BHB i MDA, a do povećanja koncentracije triglicerida i holesterola u krvi krava. Aplikacija niacina dovodi do porasta koncentracije insulina i glukoze kod krava posle teljenja. Uticaj niacina na insulinsku rezistenciju se mora dvojako posmatrati. Krave koje primaju niacin imaju nižu vrednost indeksa glukoza:insulin, &scaron;to znači da se po jedinici insulina neutrali&scaron;e manje glukoze. Ovakvo stanje nastaje jer sa porastom koncentracije insulina opada njegova efikasnost i životinje ulaze u insulinsku rezustenciju. Međutim, RQUICKIBHB indeks insulinske rezistencije je pokazao da su krave koje su primale niacin mnogo osetljivije na insulin, &scaron;to se može pripisati povećanoj insulinskoj senzitivnosti masnog tkiva. Kod krava koje su primale niacin nađena je niža koncentracija bilirubina i aktivnost AST, ALP i GGT. Nađena je vi&scaron;a koncentracija albumina i vi&scaron;a koncentracija uree i niža koncentracija fosfora. Rezultati pokazuju da aplikacija niacina pozitivno utiče na status hepatocita, a može uticati i na metabolizam proteina u organizmu zbog promena u vrednosti uree. Promena metaboličkih parametara posle teljenja i&scaron;la je u istom pravcu u oglednoj i kontrolnog grupu, samo se menjao intenzitet promena u funkciji aplikacije niacina. Parcijalna korelacija pokazuje da vitameri niacina mogu objasniti određeni deo korelacije koji postoji između lipolize, ketogeneze i metaboličkim parametrima. Stopa promene veze između<br />142<br />&nbsp;<br />metaboličkih parametara sa NEFA i BHB zavisi od stope promene statusa niacina u organizmu krava u ranoj laktaciji. Naknadnim istraživanjima treba odrediti kauzalnu prirodu ovih veza. Krave koje su primale niacina pokazivale su tendenciju povećane proizvodnje mleka do 30. dana laktacije. Ovakav uticaj niacina se izgubio prilikom merenja u 60. danu laktacije. Krave sa boljim statusom niacina (vi&scaron;a vrednost NAD i NADP) pokazuju manji stepen zama&scaron;ćenja i bolju vitalnost hepatocita, a nađen je i veći dijametar adipocita u potkožnom&nbsp; masnom&nbsp; tkivu, &scaron;to se može pripisati antilipoliznom efektu niacina.</p> / <p>AB&nbsp;<br />The aim of this dissertation is to examine the effect of niacin on lipid metabolism in perpaturient period, to determine does application of niacin have effects on insulin resistance, relationship between metabolic parameters and lipolysis and ketogenesis and effects of application of niacin on NAD and NADP concentration in plasma. NAD and NADP present the adequate indicator of the status of niacin in cows in early lactation, and concentration of NAD and NADP is significant increase in cows that were treated with niacin. NAD and NADP demonstrate positive correlation. Despite this, the derived values like NAD:NADP ratio and area under the curve depends of the application of niacin. Application of niacin leads to decreased NEFA, BHB and MDA plasma concentration, and increased triglyceride and cholesterol concentration in plasma in cows. Application of niacin leads to increased concentration of insulin and glucose in plasma after partum. The effect of niacin on insulin resistance may have two sides. Cows that received niacin had lower value of&nbsp; glucose:insulin ratio, that means that one unit of insulin metabolized less glucose. This state became because with increased insulin concentration decreased its efficiency and animals obtained insulin resistance. On the other hand index RQUICKIBHB for insulin resistance showed that cows that received niacin were much more sensitive to insulin, and that may be as a result of increased insulin sensitivity in adipose tissue.&nbsp; Cows that have received niacin bilirubin concentration and activity of AST, ALP and GGT were decrease. Albumin concentration was increased, urea and phosphor concentration was decreased in group that had received niacin. Results indicate that application of niacin have positive impact on status hepatocytes, and may have influence on protein metabolism in organism because of alteration on value in urea. In control and niacin group alteration on metabolic parameters after partum went on the same direction, but intensity of changing was in function of application of niacin. Partial correlation indicates that niacin vitamers may explain certain part of correlation that exists between lipolysis, ketogenesis, and metabolic parameters.&nbsp; Rate changes of the relationship between metabolic parameters with NEFA&nbsp; and BHB depends of the rate changes of the niacin status in cows in early lactation. Subsequent research should determinate the causal nature of this relationship. Cows that have received niacin were demonstrating tendency of increased milk production until 30.day lactation. This impact of niacin was lost in 60.day of lactation. Cows with better status niacin (greater value of NAD and NADP) manifest smaller grade of hepatic lipidosis and better vitality of hepatocytes, and was found bigger<br />145<br />&nbsp;<br />diameter on subcutaneous adipocytes, which can be as a result of antilipolitic effects of niacin.</p>

Dabartiniame jaunimo subkultūrų žemėlapyje pastebima dešimtys skirtingų subkultūrų. Dalis jų egzistuoja kaip tam tikra jaunimo laisvalaikio forma ar individualaus identiteto konstravimo įrankis, kurio pagrindas yra tam tikras muzikos ir mados stilius. Kita dalis subkultūrinių grupių gali būti apibūdinamos kaip turinčios tam tikrą subkultūrinę „filosofiją“, kuriai išreikšti pasitelkiamos specifinės praktikos. Vienos subkultūros labiau leidžiasi būti konstruojamos masinių medijų ir pasyviai perima jų teikiamas idėjas, o kitos siekia atsiriboti nuo jų įtakos, kad išlaikytų savitą subkultūrinį tapatumą. Šiame darbe nagrinėjama problematika siekia atskleisti kokiu būdu šiandien yra įmanoma subkultūrinė rezistencija ir kaip ji išreiškiama subkultūroje. Darbe koncentruojamasi į pankų subkultūrą, kuri daugelio Lietuvos ir užsienio autorių vertinama kaip klasikinis subkultūrinės rezistencijos pavyzdys. Pirmojoje darbo dalyje nagrinėjama moderniųjų ir postmoderniųjų subkultūrinių teorijų specifika, ribotumai ir kritika. Taip pat nagrinėjama subkultūros sąvokos problematika bei modernių ir postmodernių subkultūrų bruožai aptinkami ankstyvosios ir vėlyvosios Birmingemo mokyklos atstovų darbuose. Pankų subkultūra darbe vertinama pagal tris pagrindinius subkultūros egzistavimo komponentus, padedančius atskirti konfliktuojančias nuo labiau atvirų populiariosios kultūros įtakai subkultūrų. Minėtus aspektus sudaro subkultūros erdvė, nurodanti subkultūrinės veiklos pobūdį (uždaras... [toliau žr. visą tekstą] / There are tens of subcultures in the present-day subcultural map. Some of them exist as a particular form of leisure or as an identity building tool that is based on some fashion or musical style. Other subcultures can be described as having certain subcultural „philosophy“ which is expressed through specific praxis. Some subcultures are more passive and less resistant to the influence of mass media and its attempts to generate ideas for the subcultures themselves. Other youth cultural groups tries to protect their subcultural identity by avoiding external impact. This work tries to reveal how subcultural resistance is possible in nowadays and how it is expressed in particular subculture. This paper is based on punk subculture which is conserned as an classic example of subcultural resistance by many foreign and Lithuanian authors. In the first part of the work the particularity, limitations and criticisms of modern and postmodern subcultural theories are examined. The problematic and features of subcultural concept, which is found in modern and postmodern theories of early and late Birmingham school members, is also analysed. Punk subculture analysis is based on three main components, that hepls to separate conflict subcultures from these that are more open to the influence of popular culture. These components are subcultural space, that indicates manner of subcultural activity (underground or overground); subcultural content, that includes ideological and practical... [to full text]

Šiame darbe, pasitelkus hermeutinę įžvalgą ir atidųjį skaitymą, stengiamasi atskleisti A. Miškinio poziciją aptariant jo kolaboravimą ar pasipriešinimą sovietinės okupacijos metais. Analizuojant poeto kūrybą istoriniame – kultūriniame kontekste, prieita prie išvados, kad A. Miškinio kūriniai, atspindintys istoriją ir atskleidžiantys autoriaus vidinius išgyvenimus, derinant istorinį objektyvumą ir individualias patirtis, yra verti dėmesio ir reikalauja istorinio suvokimo, vertinant autoriaus poziciją. / The basic aim of this work is to identify a position of A. Miškinis regarding his collaboration or resistance in the time of Soviet occupation. It is done with the help of hermeneutic insight and attentive reading. Analysis of poet‘s works in istorical – cultural context enables to draw a conclusion that these works of A. Miškinis which reflect history and reveal intimate emotions, tie in a historical objectivity and personal experiences are worth attention and demand historical perception in evaluation of author‘s position.

Darbe analizuojama intelektualo geba ir būtinybė kritiškai mąstyti disciplinarinės valdžios salygomis. Šios valdžios objektas yra visuomenės gyvenimas, populiacija, žmonių kūnai suprantami kaip vertingi ištekliai. Disciplinarinės valdžios uždavinys yra versti visuomenę augti tam tikra kryptimi, klasifikuoti, kategorizuoti individus taip, kad užtikrinti reguliarų išteklių atsinaujinimą; kai reikia – atsikratyti pertekliaus ir kontroliuoti jų augimą. Populiacija, suvokiama kaip resursai – žmogiškieji resursai, atsinaujinantys resursai – reikia prižiūrėt, kad jie nenunyktų, neišsivaikščiotų. Intelektualo funkcija šiuose procesuose yra nuolat konfrontuoti galios procesams, juos atpažinti, o atpažinus traukyti saitus. Foucault supranta, kad galios santykiai yra neišvengiami ir įvardina intelektualo laikyseną kaip stiprų pesimistinį aktyvizmą. Rezistencija svarbi kaip kritinio klausinėjimo kelias, kuris atveria suvokimą, kad visuomenės negalima aiškinti vien tik pasitelkus techninius galios apibrėžimus. Šis nuolatinės konfrontacijos kelias yra vienintelis, kuris lieka tikrąjam intelektualui. / This work analyzes the possibility and necessity to think critically in the condition of disciplinary government. The object of this kind of government is living in society, it’s population, bodies of people are understood as valuable resources. The aim of disciplinary government is to force society grow in certain direction, to classify and categorize individuals in such form, which can ensure renewal of regular resources. When we understand population as resources - human resources, renewal of resources – it is necessary supervise that these resources wouldn’t vanish. Intellectual’s function in these processes is to recognize and confront to these processes of power, to damage it’s bonds. Foucault understands the manifestations of modern disciplines in terms of power-knowledge relationship. These relationships of power are inevitable and designates intellectual’s attitude as strong pessimistic activism. Resistance is significant as the way of critical questioning, which opens perception, that we can’t treat society only in definitions of technical power. The ongoing confrontation is the only path that remains to the true intellectual.

<p>U radu je ispitana zastupljenost influenca A virusa, njihova antigenska i genetička svojstva i osetljivost na antivirotik oseltamivir.</p><p>Ispitivanje je sprovedeno u toku četiri uzastopne sezone, od 2010/2011 do 2013/2014 &nbsp;i obuhvatilo je 887 briseva nosa i grla pacijenata sa simptomima gripa, sa teritorije Južnobačkog okruga. Svi uzorci su&nbsp;testirani na prisustvo influenca A(H1N1)pdm09, A(H3N2), A(H1N1), A(H5) i A(H7) i influenca B virusa, real-time RT PCR testom. Pozitivni uzorci iz sezona 2012/2013 i 2013/2014, podvrgnuti su izolaciji na MDCK ćelijskim kulturama, a zatim je izvr&scaron;eno ispitivanje sposobnosti dobijenih izolata da aglutiniraju eritrocite koko&scaron;ke, čoveka i zamorca u reakciji virusne hemaglutinacije. Antigenska svojstva izolata sa hemaglutinacionim titrom &ge;40, ispitana su reakcijom inhibicije hemaglutinacije. Genetičkoj karakterizaciji, sekvenciranjem hemaglutinin i neuraminidaza gena, podvrgnuti su reprezentativni izolati iz sezona 2012/2013 i 2013/2014. Za ispitivanje osetljivosti odabranih izolata virusa na oseltamivir upotrebljen je hemiluminiscentni test inhibicije aktivnosti neuraminidaze.</p><p>Ukupno 46,3% (411/887) uzoraka bilo je influenca pozitivno, od čega je 73% (300/411) bilo influenca A pozitivno, a 27% (111/411)influenca B pozitivno (p&lt;0,0001). &nbsp;Influenca A(H1N1)pdm09 podtip je detektovan u 48% (144/300), a A(H3N2) podtip u&nbsp;52% (156/300) influenca Apozitivnih uzoraka. Najveći procenat influencaA pozitivnih zabeležen je u uzrastnoj grupi 5-14 godina (48,2%, 77/160) i kod pacijenata sa lak&scaron;im kliničkim manifestacijama gripa (43,7%, 153/350).</p><p>Influenca A(H1N1)pdm09 podtip preovladavao je u uzrastnoj grupi 15-29 godina (66%, 31/47, p=0,0400) i 30-64 godina (55,9%,71/127, p=0,0215), kao i kod pacijenata sa te&scaron;kom akutnom respiratornom bole&scaron;ću (63,5%, 80/126, p&lt;0,0001), fatalnih slučajeva (100%,9/9, p=0,0039) i pacijenata sa hroničnim bolestima i stanjima (68,8%, 84/122, p&lt;0,0001).&nbsp;</p><p>Influenca A(H3N2) podtip dominirao je kod dece uzrasta do 4 godine (72,2%,13/18, p=0,0381) i 5-14 godina (75,3%, 58/77, p&lt;0,0001), kod pacijenata sa lak&scaron;im oblikom bolesti (69,3%,106/153, p&lt;0,0001) i bez hroničnih bolesti ili stanja (66,3%, 118/178,&nbsp;p&lt;0,0001).</p><p>Najznačajniji predikcioni faktori komplikacija influence bili su: prisustvo hroničnih bolesti ili stanja i uzrast &ge;15 godina. Prisustvo hroničnih bolesti ili stanja nosilo je 34 puta, a uzrast &ge;15 godina 10 puta veći rizik od nastanka te&scaron;kih oblika bolesti.</p><p>Izolacija influenca virusa na MDCK ćelijskim kulturama, bila je uspe&scaron;na u 34,3% (70/204) slučajeva, pri čemu je u grupi uzoraka sa real-time RT-PCR Ct vrednostima &lt;30 ona iznosila 80,5% (62/77), kod uzoraka sa Ct vrednostima 30-34 svega 8,7% (8/92), a izolacija iz uzoraka sa Ct vrednostima &gt;34 nije bila moguća. U reakciji hemaglutinacije, najbolji rezultati su postignuti sa eritrocitima zamorca, koje je u titru &ge;40 aglutiniralo 56% (14/25) A(H1N1)pdm09 virusa i 62,5% (15/24) A(H3N2) virusa. Sa humanim eritrocitima dobar titar dalo je 16% (4/25) influenca A(H1N1)pdm09 i 8,3% (2/24) A(H3N2) virusa, a sa koko&scaron;ijim eritrocitima 8% (2/25) A(H1N1)pdm09 virusa i nijedan virus A(H3N2) podtipa.</p><p>Rezultati antigenske karakterizacije pokazali su da je svih 23 influenca virusa A(H1N1)pdm09 podtipa, iz sezona 2012/2013 i 2013/2014, antigenski bilo slično referentnom, vakcinalnom virusu A/California/7/2009. Nasuprot tome, samo 1 od 7 ispitanih A(H3N2) virusa iz sezone 2012/2013, antigenski je bio sličan vakcinalnom virusu A/Victoria/361/2011, a samo 2 od 20 iz sezone 2013/2014 antigenski je bilo slično vakcinalnom A/Texas /50/2012 virusu.</p><p>Filogenetska analiza hemaglutinin gena influenca A(H1N1)pdm09 virusa iz sezone 2012/2013, pokazala je da su u na&scaron;oj sredini, bili prisutni virusi iz dve različite genogrupe, 6C i 7, dok su naredne sezone svi analizirani virusi pripadali genogrupi 6B. Virusi iz na&scaron;e sredine bili su filogenetski srodni A(H1N1)pdm09 virusima iz drugih evropskih zemalja. Svi ispitani A(H3N2) virusi iz sezone 2012/2013 i2013/2014, pripadali su genetičkoj grupi&nbsp; 3C.3.Filogenetski su bili srodni sa virusima iz drugih gografskih regiona Evrope.</p><p>Svih 20 izolata influenca A(H1N1)pdm09 podtipa i 23 A(H3N2) podtipa pokazali su normalnu inhibiciju aktivnosti neuraminidaze pod dejstvom oseltamivira.ekvenciranje neuraminidaza gena jednog A(H3N2) virusa, koji je imao 8 puta redukovanu inhibiciju aktivnosti neuraminidaze oseltamivirom, ukazalo jena prisustvo retke mutacije Q391H, povezane sa rezistencijom na inhibitore neuraminidaze.</p><p>Rezultati ovog rada ukazali su na značaj influenca A virusa kao etiolo&scaron;kih uzročnika akutnih respiratornih obolenja u na&scaron;oj sredini, naročito za osobe sa hroničnim bolestima koje su pod povećanim rizikom od razvoja te&scaron;kih oblika gripa. U ovom istraživanju stečena su i saznanja koja imaju praktičnu primenu u postupku antigenske karakterizacije influenca A virusa, koja je jedna od ključnih faza u procesu pripreme vakcine protiv gripa. Značajna antigenska razlika A(H3N2) virusa koji su cirkulisali u sezonama 2012/2013 i 2013/2014 u odnosu na viruse koji su bili u sastavu vakcina u datim sezonama, ukazala je na neophodnost unapređenja proizvodnje vakcine protiv gripa. Dobijeni su i prvipodaci orezistenciji na antivirotik oseltamivir, kao i o filogenetskim odnosima i genetičkim grupama virusa koji su&nbsp; cirkulisali u na&scaron;oj sredini.</p> / <p>In this study we investigated the representation, antigenic and genetic properties, and sensitivity to antiviral drug oseltamivir of influenza A viruses. The study was conducted&nbsp; during 4 consecutiveseasons 2010/2011 - 2013/2014, and included 887 nasal and throat swabs taken from patients with influenza-like symptoms from South&nbsp; Backa district. All samples were tested for influenza A(H1N1)pdm09, A(H3N2), A(H1N1), A(H5), A(H7) and influenza B viruses, by real-time RT-PCR. Isolation on MDCK cell culture was performed with positive samples from seasons 2012/2013 and 2013/2014, and virus isolates were tested for ability&nbsp; to agglutinate guinea pig, chicken and human red blood cells in reaction of virus hemagglutination. Antigenic properties of isolates with hemagglutination titre &ge;40, were investigated using reaction&nbsp; of hemagglutination inhibition. Genetic characterization was performed by sequencing of neuraminidase and hemagglutination genes of representative isolates from seasons 2012/2013 and 2013/2014. Testing for sensitivity to oseltamivir was done with chemiluminescent neuraminidase inhibition assay.</p><p>Total of 46,3% (411/887) of samples were influenza positive, out of which 73% (300/411) were influenza A positive and 27% (111/4111, p&lt;0,0001) were influenza&nbsp; B positive. Influenza A(H1N1)pdm09 subtype was detected in 48% (144/300), and A(H3N2) subtype in 52% (156/300) of influenza A positive samples. The highest proportion of influenza A positive samples wasfound in age group 5-14&nbsp; years (48,2%,&nbsp; 77/160) and among patients with uncomplicated influenza (43,7%, 153/350).</p><p>Influenza A(H1N1)pdm09 subtype predominated in age group 15-29 years (66%, 31/47, p=0,0400) and 30-64 years (55,9%,71/127, p=0,0215), in patients with severe acute respiratory illness (63,5%, 80/126, p&lt;0,0001), in fatal cases (100%, 9/9, p=0,0039), and among patients with underlying chronic diseases and conditions (68,8%,84/122, p&lt;0,0001).</p><p>Influenza A(H3N2) subtype predominated in age group &le;4 years (72,2%, 13/18, p=0,0381) and 5-14 years (75,3%,58/77, p&lt;0,0001), in patients with mild form of influenza (69,3%,106/153, p&lt;0,0001), and in group of patients without chronic diseases and conditions (66,3%,60/478, p&lt;0,0001).</p><p>The most significant risk factors for severe influenza were: the presence of underlying diseases and conditions and age &ge;15 years. Patients with chronic illnesses and conditions had 34 times higher and patients &ge;15 years of age 10 times higher risk from severe influenza.</p><p>Isolation rate of influenza A viruses in MDCK cell cultures was 34,3% (70/204). For samples with real time RT-PCR Ct values &lt;30 isolation rate was 80,5% (62/77), for samples with Ct values 30-34 it was 8,7% (8/92), while isolation of viruses from samples with Ct values &gt;34 was not successful. In the reaction of virus hemagglutination, the best results were achieved with guinea pig red blood cells which agglutinated in titre &ge;40, 56% (14/25) of influenza A(H1N1)pdm09 viruses and&nbsp; 62,5% (15/24) of A(H3N2) viruses. With human erythrocytes, good titre gave 16% (4/25) of influenza A(H1N1)pdm09 and 8,3% (2/24)of A(H3N2) viruses and with chicken erythrocytes 8% (2/25) A(H1N1)pdm09 viruses and none of the A(H3N2) viruses.</p><p>Results of the antigenic characterization of 23 influenza A(H1N1)pdm09 viruses, showed that they were antigenically similarto referent, vaccine virus A/California/7/2009. On the contrary, only 1 out of 7 influenza A(H3N2) viruses from season 2012/2013,was antigenically similar to A/Victoria/361/2011 vaccine virus, and only 2 out of 20 from season 2013/2014 were antigenically similar to A/Texas/50/2012&nbsp; vaccine virus.</p><p>Filogenetic analysis of hemagglutinin genes indicated co-circulation of 2 distinct genetic groups, 6C and 7, of A(H1N1)pdm09 viruses during the season 2012/2013, while during the season 2013/2014 all tested viruses were from genetic group 6B. Influenza A(H1N1)pdm09 viruses from our region, were closely related to viruses from other European countries. All influenza A(H3N2) viruses from season 2012/2013 and 2013/2014 belonged to genetic clade 3C.3 and were closely related to viruses from different European countries.</p><p>Total of 20 A(H1N1)pdm09 isolates and 23 A(H3N2) isolates were tested for sensitivity to oseltamivir, and all of them showed normal inhibition of neuraminidase activity with oseltamivir. Sequencing of&nbsp; neuraminidase gene of one A(H3N2) virus with 8-fold reduced inhibition by oseltamivir, revealed rare mutation Q391H associated with antiviral resistance.</p><p>Results of this study indicate the significance of influenza A viruses as etiological factors of acute respiratory diseases in our area, especially for persons with chronic medical conditions who are at higher risk for severe influenza. Data gathered during&nbsp;the process of virus isolation and investigation of hemagglutination abilities of&nbsp; isolated viruses, have practical application in antigenic testing of influenza A viruses which is one of the key points of process of anti-flu vaccine production. Significant &nbsp;antigenic difference between influenza A(H3N2) viruses from seasons 2012/2013 and&nbsp; 2013/2014 and vaccine viruses, emphasis the importance of vaccine production improvement. During this study, the first data about antiviral resistance, filogenetic relationships and genetic groups of influenza viruses from our region, were obtained.</p>

<p>Salmonele su najče&scaron;ći prouzrokovači.crevnih<br />infekcija kod ljudi i životinja &Scaron;iroko su<br />rasprostranjene u prirodi a mogu kolonizovati<br />različite domaćine Poebno su značajne one<br />životinje čije se meso koristi za ishranu ljudi, a<br />koje su i glavni izvor infekcije ljudi. Inficirane<br />životinje ne ispoljavaju simptome i terapija se<br />sprovodi nalazom salmonela prilikom rutinske<br />kontrole zdravstvenog stanja. Posebno, kod ljudi i<br />životinja salmoneloze su značajne i zbog<br />klicono&scaron;tva koje može trajati veoma dugo zavisno<br />od starosti inficiranog organizma. Čest su uzrok<br />alimentarnih toksiinfekcija kod ljudi. Duž čitavog<br />lanca ishrane moguća je i sekundarna<br />kontaminacija salmonelama. Pored rutinskih<br />mikrobiolo&scaron;kih analiza u otkrivanju izvora i<br />puteva &scaron;irenja infekcije koriste se i molekularne<br />metode koje daju precizne podatke o klonalnom<br />poreklu bakterija izolovanih iz obolelih ljudi,<br />namirnica i životinja. Međunarodnom trgovinom<br />hrane isti tipovi bakterija mogu se pojaviti na<br />geografski udaljenim lokacijama. Molekularna<br />karakterizacija Salmonella je značajna zbog<br />određivanja raznolikosti sojeva. Potrebno je da se<br />izolati tipiziraju ne samo do nivoa vrste i serotipa<br />nego i preciznije. Tipizacija je bitna za utvrđivanje<br />epidemiolo&scaron;ke povezanosti izolata, a<br />genotipizacija podrazumeva direktnu analizu<br />DNK. Geni rezistencije koji se od saprofita mogu<br />preneti na patogene vrste imaju važnu ulogu u<br />pojavljivanju rezistentnih i multirezistentnih<br />sojeva. Međusobni odnos gena rezistencije i<br />upotrebe antimikrobnih sredstava određuje<br />jednačinu rezistencije na antimikrobna sredstva.<br />Rezistencija predstavlja problem iako je<br />salmoneloza samolimitirajuća infekcija zbog čega<br />se terapija antibioticima primenjuje samo kod<br />dece, starijih ljudi i u slučajevima sistemskih<br />infekcija. Navedena problematika je aktuelna i u<br />Crnoj Gori jer ne postoji stalan monitoring<br />primene antimikrobnih sredstava kod domaćih<br />životinja. Iz navedenih razloga cilj ove doktorske<br />disertacije bilo je utvrđivanje prisustva Salmonella<br />vrsta na farmama živine sa tri lokaliteta u Crnoj<br />Gori, izolacija i identifikacija primenom standardnih<br />mikrobiolo&scaron;kih metoda, serotipizacija pomoću<br />aglutinacije na predmetnom staklu (slide<br />agglutination) uz primenu anti-O i anti-H seruma<br />.(Staten Serum Institute, Danska). Primenom<br />standardnih mikrobiolo&scaron;kih metoda utvrđeno je<br />prisustvo serovarijeteta Salmonella Enteritidis i<br />Salmonella Tiphymurium. Serovarijeteti<br />Salmonella .Gallinarum biotip Gallinarum i<br />Salmonella Gallinarum biotip Pullorum nisu bile<br />serolo&scaron;ki tipizirane. Identifikacija navedenih<br />serovarijeteta je potvrđena metodom multipleks<br />PCR detekcijom amplifikovanih DNK fragmenata<br />u agaroznom gelu.. Nakon digestije 50 izolata<br />Salmonella enterica podvrste enterica odabranih<br />prema lokalitetima i zastupljenosti pomoću SpeI<br />restrikcionog enzma i njihovom analizom<br />primenom PFGE utvrđeno je 5 različitih SpeI<br />pulsotipova. Kod 10% ispitivanih sojeva<br />ustanovljena je rezistencija na tetraciklin i<br />streptomicin. Svi ispitivani serovarijeteti<br />salmonela bili su osetljivi na amoksicilin sa<br />klavulanskom kiselinom, enrofloksacin,<br />ciprofloksacin, sulfametoksazol-trimetoprim,<br />cefuroksim, ceftriakson i norfloksacin. Vrednosti<br />MIK (minimalnih inhibitornih koncentracija)<br />određenih antibiotika za odabrane sojeve<br />serovarijeteta Salmonella Enteritidis primenom<br />aparata VITEK 2 iznosile su za: piperacilin &le; 4 &ndash;<br />64 &mu;g/ml (S &ndash; R) , cefuroksim 4 &ndash; 32 &mu;g/ml (S -<br />R), cefuroksim aksetil 4 &ndash;32 &mu;g/ml (S&ndash; R),<br />cefiksim &le; 0,25 &ndash; 2 &mu;g/ml (S - I), ceftriakson &le; 1 &ndash;<br />2 &mu;g/ml (S - I) i minociklin &le; 1 &ndash; 4 &mu;g/ml (S),<br />tetraciklin &le; 1 &mu;g/ml (S), tigeciklin &le; 0,5 &ndash; 1 &mu;g/ml<br />(S), hloramfenikol &le; 2 &ndash; 8 &mu;g/ml (S), kolistin &le;<br />0,5&ndash;1 &mu;g/ml (S) i sulfametoksazol/trimetoprim &le;<br />0,5 &mu;g/ml (S).</p> / <p>Salmonella is the most common cause of alimentary<br />toxic infections among humans. They have been<br />adapted to a number of warm-blooded animals. The<br />infected animals do not exhibit symptoms and the<br />treatment performs by finding of salmonella in routine<br />health check. The secondary contamination by<br />salmonella ois possible in during entire food chain.<br />Apart from the routine microbiological analysis in<br />detection of sources and pathways of spreading the<br />infection, there are also used the molecular methods<br />that provide accurate information about the clonal<br />origin of bacteria isolated from diseased humans, food<br />and animals. During international trade of food, the<br />same types of bacteria can occur in geographically<br />remote locations. Molecular characterization of<br />Salmonella is important in determination of diversity of<br />strains. It is necessary isolates to be typified not only to<br />the level of species and serotypes but also more<br />precisely. Typification is essential to determine the<br />epidemiological connection of isolates. Genotyping<br />includes a direct analysis of DNA. The resistance genes<br />that can be transferred from saprophytes to pathogenic<br />microorganisms play an important role in the<br />emergence of resistant and multiresistant strains. The<br />above mentoned is also a current issue in our country<br />because there is a constant monitoring of using of<br />antimicrobials drugs to farm animals. For these reasons,<br />the aim of this dissertation is to examine the serovars of<br />Salmonella in Montenegro, their molecular<br />characterization using biomolecular methods based on<br />isolation of DNA and subsequent amplification of<br />serovar-specific genes.(multiplex PCR method and<br />PFGE), and testing sensitivity, or resistance to<br />antimicrobial drugs used in clinic vet practice.</p>

<p>U skladu sa postavljenim ciljevima rada formirana je kolekcija&nbsp;<br />fenotipski i genotipski okarakterisanih multiplo rezistentnih&nbsp;<br />kultura genomske vrste <em>Acinetobacter baumannii</em>. Za sojeve iz&nbsp;<br />kolekcije kultura utvrđen je anti-<em>A. baumannii</em> efekat etarskih&nbsp;<br />ulja, biljnih ekstrakata i njihovih bioaktivnih komponenti, kao&nbsp;<br />nekonvencionalnih antimikrobnih agensa. Takođe, osim njihovog&nbsp;<br />pojedinačnog efekta utvrđen je i kombinovani efekat&nbsp;<br />konvencionalnih i nekonvencionalnih antimikrobnih agenasa, koji&nbsp;<br />je dovedo do redukcije minimalnih ihnibitronih koncentracija oba&nbsp;<br />agensa u kombinaciji. Kombinacije etarskih ulja i njihovih&nbsp;<br />bioaktivnih komponenti sa trenutno dostupnim konvencionalnim&nbsp;<br />antibioticima, čija je efikasnost smanjena kada se primenjuju&nbsp;<br />pojedinačno, predstavljaju novu perspektivnu strategiju u terapiji&nbsp;<br />infekcija multiplo rezistentnim sojevima vrste <em>A. baumannii</em>.</p> / <p>In accordance to the aims of the work the collection of phenotypic and<br />genotypic characterized multidrug-resistant cultures of genomic species<br /><em>Acinetobacter baumannii</em> was formed. For the strains from the culture<br />collection an anti-<em>A. baumannii </em>effect of the essential oils, plant extracts<br />and their bioactive components, as non-conventional antimicrobial<br />agents, was determined. Also, in addition to their individual effect the<br />combined effect of conventional and non-conventional antimicrobial<br />agents was determined, which lead to a reduction of the minimal<br />inhibitroy cocnentrations of both agents in combination. Combinations<br />of the essential oils and their bioactive components with the currently<br />available conventional antibiotics, whose efficiency reduced when<br />administered individually, represent a promising new strategy for the<br />treatment of infections caused by multidrug-resistant <em>A. baumannii.</em></p>

<p>Uvod: Febrilna neutropenija, kao prvi znak infekcije, je česta komplikacija u fazi postterapijske aplazije kostne srži u obolelih od akutne nelimfoblastne leukemije. Klinička slika febrilne neutropenije može biti suptilna, a progresija u stanje septičnog &scaron;oka znatno brža nego kod imunokompetentnih bolesnika. Rana predikcija rizika od komplikacija febrilne neutropenije i uvođenje empirijske antibiotske terapije može da pobolj&scaron;a prognozu bolesnika. Insulinska rezistencija, dislipidemija i inflamacija masnog tkiva se javljaju u sklopu sistemske inflamacije. Njihova uloga i značaj kao potencijalnih faktora predikcije toka i ishoda febrilne neutropenije nisu ispitani. Ciljevi istraživanja: Ustanoviti promene pokazatelja stepena insulinske senzitivnosti, ukupnog holesterola, triglicerida, HDL - holesterola, LDL - holesterola, apolipoproteina A-I, lipoproteina (a) i adiponektina pre i u fazi febrilne neutropenije kod bolesnika sa akutnom nelimfoblastnom leukemijom. Uporediti vrednosti pokazatelja stepena insulinske senzitivnosti, ukupnog holesterola, triglicerida, HDL - holesterola, LDL - holesterola, apolipoproteina A-I, lipoproteina (a) i adiponektina bolesnika sa akutnom nelimfoblastnom leukemijom pre početka febrilne neutropenije i kontrolne grupe gojaznih. Uporediti vrednosti pokazatelja stepena insulinske senzitivnosti, ukupnog holesterola, triglicerida, HDL - holesterola, LDL - holesterola, apolipoproteina A-I, lipoproteina (a) i adiponektina bolesnika sa akutnom nelimfoblastnom leukemijom u fazi febrilne neutropenije i kontrolne grupe gojaznih. Utvrditi da li su pokazatelj stepena insulinske senzitivnosti, ukupni serumski holesterol, trigliceridi, HDL - holesterol, LDL - holesterol, apolipoprotein A-I, lipoprotein (a) i adiponektin bolesnika sa akutnom nelimfoblastnom leukemijom u fazi febrilne neutropenije u korelaciji sa vrednostima parametara inflamacije, njenim tokom i ishodom. Materijal i metode: Istraživanje je sprovedeno u Klinici za hematologiju i Klinici za endokrinologiju, dijabetes i bolesti metabolizma. Obuhvatilo je 60 ispitanika, od kojih je 30 ispitanika obolelo od akutne nelimfoblastne leukemije, a 30 ispitanika je činilo kontrolnu grupu gojaznih. Nakon uključivanja u istraživanje, ispitanicima su urađeni predviđeni pregledi i laboratorijske analize u cilju procene insulinske senzitivnosti, metaboličkog statusa i serumskog adiponektina. Navedena merenja su urađena pre hemioterapije i u febrilnoj neutropeniji. Zdravstveno stanje ispitanika je praćeno do kraja prve hospitalizacije. Statistička obrada je izvr&scaron;ena uz pomoć statističkog paketa Statistica. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost je odreĎivana na nivou p &lt; 0.05. Rezultati: U febrilnoj neutropeniji bolesnika sa akutnom leukemijom je do&scaron;lo do razvoja insulinske rezistencije (t = - 2.43, p = 0.021), dislipidemije sa značajnim sniţenjem ukupnog holesterola (t = 3.59, p = 0.0012), LDL &ndash; holesterola (t = 3.56, p = 0.0013) i apoA &ndash; I (t = 2.27, p = 0.03). Oboleli od akutne nelimfoblastne leukemije u febrilnoj neutropeniji su razvili metaboličke promene viđene kod gojaznih osoba sa insulinskom rezistencijom. Nastanak i progresija insulinske rezistencije je bila u pozitivnoj korelaciji sa fibrinogenom kao pokazateljem težine inflamacije (r = 0.59, p &lt; 0.05) dok je apoA - I negativno korelirao sa CRP (r = - 0.37, p &lt; 0.05). Ispitanici sa nižom insulinemijom i vrednostima HDL - holesterola pre hemoterapije su imali značajno bolji tok febrilne neutropenije (t = -2.38, p = 0.024 vs. t = - 2.87, p = 0.007). Ispitanici sa većim indeksom telesne mase (BMI) i obimom struka imali su povoljniji ishod febrilne neutropenije (r = - 0.47, p &lt; 0.05 vs. r = - 0.40, p &lt; 0.05). Drugi pokazatelji insulinske senzitivnosti, metaboličkog statusa i adiponektin nisu značajno uticali na tok i ishod febrilne neutropenije. Normalna telesna masa pre hemioterapije, a u febrilnoj neutropeniji temperatura u trajanju dužem od 7 dana, niže vrednosti MASCC indeksa rizika, vi&scaron;e vrednosti CRP, vi&scaron;e vrednosti adiponektina, niže vrednosti Lp(a) i komplikovan tok febrilne neutropenije su bili prediktori lo&scaron;ije prognoze febrilne neutropenije. Zaključak: Pored klasičnih hematolo&scaron;kih parametara potrebno je uzeti u obzir antropometrijske karakteristike, redistribuciju masne mase, disfunkcionalnost masne mase, insulinsku rezistenciju i metaboličke parametre u cilju praćenja i predviđanja mogućih komplikacija i komorbiditeta.</p> / <p>Introduction: Febrile neutropenia is a common complication in posttreatment aplasia in patients with acute nonlymphoblastic leukemia. Its clinical manifestation can be subtle. However, it can progress to septic shock more quickly than in immunocompetent patients. Early prediction of complications and recognition of risk factors can improve outcome. Systemic inflammation is characterized by insulin resistance, dyslipidemia and adipocyte dysfunction. However, their importance in predicting complications and outcome of febrile neutropenia is not entirely known.<br />Aims: To determine changes in HOMA-IR, total cholesterol, triglycerides, HDL - cholesterol, LDL - cholesterol, apolipoprotein A-I, lipoprotein (a) and adiponectin in patients before chemotherapy and during febrile neutropenia. To compare HOMA-IR, total cholesterol, triglycerides, HDL - cholesterol, LDL - cholesterol, apolipoprotein A-I, lipoprotein (a) and adiponectin in patients before chemotherapy and the obese. To compare HOMA-IR, total cholesterol, triglycerides, HDL - cholesterol, LDL - cholesterol, apolipoprotein A-I, lipoprotein (a) and adiponectin in patients during febrile neutropenia and the obese. To determine whether HOMA-IR, total cholesterol, triglycerides, HDL - cholesterol, LDL - cholesterol, apolipoprotein A-I, lipoprotein (a) and adiponectin in febrile neutropenia are in correlation with the severity of the infection, appearance of complications and outcome. Materials and methods: The study was conducted at the Clinic for hematology and Clinic for endocrinology, diabetes, and metabolic disorders. 60 patients who fulfilled the inclusion criteria were included in the study. 30 patients had acute leukemia, and 30 were obese. Clinical and laboratory examination to assess insulin sensitivity, metabolic disorders and adiponectin was done before chemotherapy and during febrile neutropenia. Patients were followed up until the end of the first hospitalization. Data were analyzed with Statistica software and presented in tables and graphs. Statistical significance was set at p&lt;0.05. Results: During febrile neutropenia, patients with acute leukemia developed insulin resistance (t = - 2.43, p = 0.021), alongside significant decline of total cholesterol (t = 3.59, p = 0.0012), LDL &ndash; cholesterol (t = 3.56, p = 0.0013) and apoA &ndash; I (t = 2.27, p = 0.03). In acute inflammation, metabolic changes in patients with acute leukemia resembled those in the obese with insulin resistance. HOMA-IR values were in positive correlation with fibrinogen (r = 0.59, p &lt; 0.05) whereas apoA-I was in negative correlation to CRP (r = - 0.37, p &lt; 0.05). Patients with higher body mass index and waist circumference had better course and outcome of febrile neutropenia (r = - 0.47, p &lt; 0.05 vs. r = - 0.40, p &lt; 0.05). Patients with lower insulin levels and HDL - cholesterol prior to chemotherapy had a significantly better course of febrile neutropenia (t = -2.38, p = 0.024 vs. t = - 2.87, p = 0.007). Other parameters of insulin sensitivity, metabolic status, and adiponectin did not influence the course and outcome of inflammation significantly. Normal body weight, duration of febrile neutropenia for longer than 7 days, lower MASCC risk index, higher CRP and adiponectin, low Lp(a) in febrile neutropenia and a complicated course od febrile neutropenia were predictors of a worse outcome. Conclusion: Besides known hematological risk factors for complications in febrile neutropenia, anthropometric characteristics, fat mass distribution and disfunction, insulin resistance and metabolic parameters are useful predictors of the course and outcome of febrile neutropenia.</p>

<p>Uvod: U na&scaron;oj zemlji nema smernica za lečenje bakterijskih infekcija u tercijarnim zdravstvenim ustanovama. Odabir antibakterijskih lekova je empirijski, &scaron;to nije uvek u skladu sa preporučenom terapijom prema međunarodnim smernicama. Zbog toga su na Klinici za infektivne bolesti Kliničkog centra Vojvodine u januaru 2013. godine usvojeni međunarodni protokoli i primenjivani za lečenje infektivnih bolesti bakterijske etiologije. Cilj istraživanja bio je da se ispita i uporedi efikasnost lečenja pojedinih antibiotskih tretmana za lečenja infektivnih bolesti bakterijske etiologije prema kliničkom iskustvu ordinirajućeg lekara, prema međunarodno prihvaćenim protokolima i prema modifikovanim međunarodnim protokolima na osnovu stanja lokalne rezistencije. Materijal i metode: Ispitivanje je bilo retrospektivno-prospektivno u trajanju od tri godine od&nbsp; 01.01.2012-31.12.2014.godine, sprovedeno je na Klinici za infektivne bolesti Kliničkog centra Vojvodine. U studiju je uključeno 1147 pacijenata sa dijagnozom infektivne bolesti bakterijske etiologije (sepsa, infekcija urinarnog trakta, bakterijski meningitis, infekcije kože i mekih tkiva, bakterijski tonzilofaringitisi, pneumonija, febrilni gastroenteritis i spondilodiscitis). U retrospektivnom delu, tokom 2012. godine ustanovljena je efikasnost lečenja prema kliničkom iskustvu ordinirajućeg lekara, kod 459 pacijenata. U drugom delu ispitivanja koje je bilo prospektivno, tokom 2013. godine, kod 487 pacijenata, ustanovljena je efikasnost lečenja prema međunarodnim protokolima i upoređena sa lečenjem prema kliničkom iskustvu ordinirajućeg lekara. Tokom 2012. i 2013. godine, ustanovljena je struktura uzročnika i rezistencija na antimikrobne lekove, i prema stanju lokalne rezistencija modifikovani su međunarodni protkoli i primenjivani su tokom 2014. godine. U trećem delu ispitivanja koje je bilo prospektivno, tokom 2014. godine, kod 201 pacijenta ustanovljena je efikasnost lečenja prema modifikovanim međunarodnim protokolima i upoređena sa lečenjem prema usvojenim međunarodnim protokolima. Efikasnost lečenja praćena je na osnovu vrednosti telesne temperature i na osnovu laboratorijskih parametara (leukocita, C reaktivnog proteina, fibrinogena, sedimentacije eritrocita i prokalcitonina), prvog i sedmog dana hospitalizacije. Za upoređivanje efikasnosti terapijskih režima napravljen je sistem skorovanja telesne temperature i laboratorijskih parametara. Za statističku obradu podataka kori&scaron;ćen je programski paket Statistical Package for Social Sciences - SPSS 21. Statistički značajnim se smatraju vrednosti nivoa značajnosti p&lt;0.05. Rezultati: Praćenjem rezistencija bakterija u na&scaron;oj sredini modifikovani su međunarodni protokoli za lečenje infekcija izazvanih E.coli i S aureus-om. Rezistencija E. coli iz urinokultura tokom 2012. i 2013. godine na ciprofloksacin (koji je preporučen prema međunarodnim protokolima za lečenje infekcija urinarnog trakta) je bila u 2012. godini 38,8% i u 2013. godini 57,1%, a na levofloksacin 27,7% u 2012. godini i u 2013. godini 28,6%. Rezistencija S. aureus-a izolovanog iz brisa rana na cefazolin (koji je preporučen prema međunarodnim protokolima za lečenje infekcija kože i mekih tkiva) u prve dve godine ispitivanja bila je 25% a na klindamicin nije zabeležena rezistencija. Rezistencija S. aureus-a na cefazolin (koji je preporučen prema međunarodnim protokolima za lečenje bakterijskih tonzilofaringitisa) iz brisa grla bila je u 2012. godini 18,1%, u 2013. godini 14,2% a na klindamicin u ovom periodu nije zabeležena rezistencija. Tako da je preporuka u modifikovanom kliničkom protokolu za lečenje infekcija urinarnog trakta levofloksacin, za lečenje bakterijskih tonzilofaringitisa i lečenje infekcija kože i mekih tkiva izazvanih S aureus-om klindamicin.Poredeći ukupan skor kliničkih i laboratorijskih parametara, lečenje pacijenata prema usvojenim međunarodnim protokolima, statistički značajno je efikasnije u odnosu na lečenje prema kliničkom iskustvu lekara kod lečenja pacijenata sa infekcijom urinarnog trakta (p=0,034) i infekcijom kože i mekih tkiva (p=0,032). U lečenju ostalih ispitivanih bakterijskih infekcija prema kliničkom iskustvu lekara i usvojenim međunarodnim protokolima nema statički značajne razlike (p&gt;0,05). Lečenje pacijenata sa infekcijom urinarnog trakta, prema modifikovanim međunarodnim protokolima je statistički značajno efikasnije u odnosu na efikasnost lečenja prema usvojenim međunarodnim protokolima (p=0,025) poredeći ukupan skor kliničkih i laboratorijskih parametara. Lečenje pacijenata sa tonzilofaringitisima i infekcijama kože i mekih tkiva prema modifikovanim međunarodnim protokolima podjednako je efikasno u odnosu na lečenje prema usvojenim međunarodnim protokolima (p=0,100) poredeći ukupan skor kliničkih i laboratorijskih parametara. Zaključak: Upoređivanjem dobijenih rezultata, omogućeno je određivanje najoptimalnijeg načina lečenja bolesti bakterijske etiologije, uvažavajući preporuke prema međunarodnim smernicama. Dobijeni rezultati ukazuju na to da je praćenjem lokalne strukture uzročnika i stanja lokalne rezistencije omogućeno određivanje optimalnijeg načina lečenja infekcija urinarnog trakta i infekcije kože i mekih tkiva, uvažavajući međunarodne preporuke i modifikaciju međunarodnih smernica prema stanju rezistencija bakterija na antimikrobne lekove u na&scaron;oj sredini</p> / <p>Introduction:In our country,there are noguidelines for the treatment of bacterial infections in tertiary health institutions. The choice of antibiotic is empirical and it does not always comply with the recommended treatment according to international guidelines. For this reason, international protocols were adopted at the Clinic for infectious diseases of the Clinical Center of Vojvodinain January 2013. and implemented in therapy of infectious diseases caused by bacteria. The aim of the study was to compare different regimens and to evaluate their effectiveness in therapy of the bacterial infections: one based on the clinical experience of the prescribing physician, another based on international guidelines and the third, modified international protocoladapted to comply with the local antibacterial resistance. Material and methods: Thisretrospective-prospective study was conducted at the Clinic for Infectious Diseases of the Clinical Center of Vojvodina and it covered the period of three years, from 01.01.2012.-31.12.2014. 1,147 patients diagnosed with infectious diseases of bacterial etiology (sepsis, urinary tract infections, bacterial meningitis, skin and soft tissue infections, bacterial tonsillopharyngitis, pneumonia, febrile gastroenteritis and spondylodiscitis) were included in the study. In the first, retrospective part of the study, the efficacy of therapy based on the clinical experience of the prescribing physician was analyzed from medical records of 459 patients treated in 2012. In 2013, during the second, prospective part of the study, the efficacy of treatment according to the international guidelines was evaluated in 487 patients and the results were compared to the data obtained from the patients treated according to the clinical experience of the prescribing physician. The types of organism isolated in 2012/2013 were analyzed as well as their resistance to antimicrobials, the international protocols were subsequently modified according to the state of local resistance and implemented during 2014. In 2014, during the third, prospective part of the study, the efficacy of therapy according to modified international protocols was established in 201 patients, and the results were compared to the ones obtained by therapy according to original international protocols. The efficacy of the treatment was estimated by body temperature measurements and laboratory parameters (leukocytes, C-reactive protein, fibrinogen, erythrocyte sedimentation rate and procalcitonin) on day 1 and day 7 of hospitalization. The scoring system for body temperature and laboratory parameters was designed to compare therapeutic regimes efficiency. For statistical analysis, we used a software package Statistical Package for Social Sciences- SPSS 21. The values of p&lt;0.05were considered statistically significant. Results.Monitoring of antibiotic resistance patterns in our community led to modification international protocols for treating infections caused by E. coli and S aureus. Resistance of E.coli to ciprofloxacin (recommended for the treatment of urinary tract infectionsby international protocols) from urine culture in 2012 and 2013 was 38.8% and 57.1% respectively, while resistance to levofloxacin in 2012 and 2013 was 27.7% and 28.6%, respectively. Resistance of S. aureus to cefazolin (recommended by international protocols for the treatment of the skin and soft tissue infections) from wound cultures in 2012 and 2013 was 25% while the resistance to&nbsp; clindamycin was not present. Resistance to cefazolin (recommended for the treatment of bacterial tonsillopharyngitisby international protocols) from throat culture in 2012 and 2013 was 18,1% and 14,2%, respectively,and the resistance to clindamycin was not present in the same period. Accordingly, clinical therapeutic protocols were modified, levofloxacin was recommended for urinary tract infections and clindamycin was recommended for treatment of tonsillopharyngitis and skin and soft tissues infections caused by S. aureus. Comparing the total score of clinical and laboratory parameters, the treatment of patients according to the adopted international protocols was statistically significantly more effective compared to the one based on clinical experience of physicianin urinary tract infections (p = 0.034) and skin and soft tissue infections(p = 0.032). No statically significant difference (p&gt;0.05) was observed in efficiency of treatment options for other studied bacterial infections. In therapy of urinary tract infections, modified international protocols proved to be significantly more efficient than the adopted international protocols (p = 0.025) when the total score of clinical and laboratory parameters was compared.&nbsp; Comparing the total score of clinical and laboratory parameters, both adopted international protocols and modified international protocols proved to be equally efficient (p=0,100) in therapy of bacterial tonsillopharyngitis and skin and soft tissue infections. Conclusion:Comparison of the obtained results made possible to develop the optimal way of treating diseases of bacterial etiology, taking into account recommendations by international guidelines.The results suggest that the monitoring of the local structure of pathogens and their resistance pattern enabled the determination of optimal treatment options for urinary tract infections and skin and soft tissue infections, respecting international recommendations and modifying the international guidelines to match bacterial resistance pattern in our community.</p>

<p><em>Streptococcus pneumoniae</em> (pneumokok) je&nbsp; jedan&nbsp; od&nbsp; vodećih&nbsp; uzroka morbiditeta i mortaliteta &scaron;irom sveta, kada su u pitanju infektivne bolesti. Pretežno izaziva infekcije gornjih respiratornih puteva (sinuzitis, otitis) i konjunktivitis. Vodeći je uzročnih vanbolničkih pneumonija, bakterijskog meningitisa i sepse. Lekovi izbora u terapiji pneumokoknih bolesti su beta laktamski antibiotici i makrolidi. Iako se makrolidni antibiotici uveliko koriste u lečenju pneumokoknih infekcija &scaron;irom sveta, porast rezistencije na makrolide&nbsp; bi&nbsp; mogao&nbsp; da&nbsp; kompromituje&nbsp; njihovu&nbsp; upotrebu. Rezistencija pneumokoka na makrolide je posredovana putem dva glavna mehanizma: modifikacija ciljnog mesta delovanja leka&nbsp; i aktivni efluks leka. Metilaciju 23S ribozomalne ribonukleinske kiseline (rRNK) obavlja enzim metilaza, čiju sintezu kodira<em> ermB</em> gen. Kod ovog tipa rezistencije dolazi do ukr&scaron;tene rezistencije na makrolide (M), linkozamide (L) i streptogramine B (Sb). Ovakav vid rezistencije se ispoljava kao MLS_b - fenotip i karakteri&scaron;e ga visok nivo rezistencije. Može se javiti kao konstitutivni (cMLS) i inducibilni (iMLS). Drugi mehanizam rezistencije na makrolide je aktivni efluks leka, kodiran od strane <em>mefA</em>&nbsp; gena. Efluks antibiotik a determini&scaron;e rezistenciju samo na 14-člane i 15-člane makrolide, bez ukr&scaron;tene rezistencije. Ispoljava se kao M-fenotip, a karakteri&scaron;e ga niži stepen rezistencije. Cilj ove studije je bio&nbsp; da&nbsp; se&nbsp; odredi u čestalost&nbsp; makrolidne&nbsp; rezistencije <em>Streptococcus pneumoniae</em> među invazivnim i neinvazivnim izolatima kod dece i odraslih, da se odrediti u čestalost korezistencije i multiple rezistencije kod makrolid rezistentnih sojeva&nbsp; <em>Streptococcus pneumoniae</em>, da se fenotipski odredi tip rezistencije na makrolide i da se ispita genska osnova makrolidne rezistencije (detektovati prisustvo <em>ermB</em> i <em>mefA</em> gena). Analizirani su podaci o 326 sojeva <em>Streptococcus pneumoniae</em> rezistentnih na makrolide (MRSP) sakupljenih &scaron;irom&nbsp; Srbije&nbsp; u&nbsp; periodu&nbsp; od&nbsp; januara&nbsp; 2010.&nbsp; do&nbsp; decembra&nbsp; 2012.&nbsp; godine. Sakupljeni&nbsp; MRSP&nbsp; izolati&nbsp; su&nbsp; transportovani&nbsp; u&nbsp; Nacionalnu&nbsp; referentnu laboratoriju za streptokok radi daljih ispitivanja. Identifikacija je vr&scaron;ena na osnovu mikroskopskih, kulturelnih i biohemijskih osobina. Konzervacija je vr&scaron;ena u moždano-srčanom bujonu sa 10% sadržajem glicerola na -80&deg;C. Dvostruki&nbsp; disk&nbsp; difuzioni&nbsp; test,&nbsp; kombinovani&nbsp; difuzion odilucioni&nbsp; test&nbsp; i automatizovani VITEK 2 sistem su kori&scaron;ćeni za određivanje fenotipova rezistencije na makrolide. Geni koji kodiraju rezistenciju na makrolide su detektovani PCR metodom. Ukupna rezistencija sojeva <em>S.pneumoniae</em> na makrolide u Srbiji je iznosila 34%. Sojevi <em>S.pneumoniae</em> rezistentni na makrolide su če&scaron;će bili izolovani kod dece (36%) u odnosu na odrasle (29%) osobe, i če&scaron;će su izolovani iz neinvazivnih (35,5%) u odnosu na invazivne (27,4%) materijale. Dominantan fenotip rezistencije na makrolide je bio MLS_b fenotip (78,5%). Konstitutivan MLS fenotip je bio zastupljen kod 73,9%, a inducibilan MLS kod 4,6% MRSP izolata. Potvrđena je udruženost <em>mefA</em>&nbsp; gena i M fenotipa; <em>ermB</em> gena i iMLS fenotipa, kao i <em>ermB</em> gena i cMLS fenotipa. Prisustvo oba ermB i mefA gena rezistencije je potvrđeno kod 43,9 % izolata. Svi izolati sa koji su imali oba gena rezistencije su ispoljili&nbsp; MLS_b fenotip.&nbsp; Istovremena&nbsp; neosetljivost&nbsp; na&nbsp; penicilin&nbsp; je bila zastupljena kod 16% MRSP sojeva. Visok nivo rezistencije na penicilin je imalo svega 5,8% MRSP izolata. Među MRSP sojevima je bio prisutan visok nivo&nbsp; rezistencije&nbsp; na&nbsp; tetraciklin&nbsp; (81,3%)&nbsp; i&nbsp; trimetoprim-sulfametoksazol (74,3%). Multirezistenti sojevi, koji su bili rezistentni na tetracikline i trimetoprim-sulfametoksazol su predstavljali dve trećine (66,1%) MRSP izolata.&nbsp; Zastupljenost&nbsp; udružene&nbsp; rezistencije&nbsp; MRSP&nbsp; na&nbsp; tetraciklin i trimetoprim-sulfametoksazol je bila veća kod sojeva sa MLS fenotipom (73,1%)&nbsp; u&nbsp; odnosu&nbsp; na&nbsp; sojeve&nbsp; sa&nbsp; M&nbsp; fenotipom&nbsp; (36,7%). Zastupljenost istovremene rezistencije na makrolide i druge antibiotike među kojima su penicilin, amoksicilin, cefotaksim, tetraciklin, trimetoprim-sulfametoksazol, kao&nbsp; i&nbsp; multirezistentnih&nbsp; sojeva&nbsp; je&nbsp; bila&nbsp; veća&nbsp; kod pedijatrijskih&nbsp; izolata pneumokoka&nbsp; u&nbsp; odnosu&nbsp; na&nbsp; sojeve&nbsp; dobijene&nbsp; kod&nbsp; odraslih.&nbsp; U čestalost istovremene rezistencije na makrolide i druge antibiotike među kojima su tetraciklin i ofloksacin je bila vi&scaron;e prisutna među neinvazivnim u odnosu na invazivne MRSP izolate. Invazivni MRSP izolati iz likvora su pokazivali veću rezistenciju na beta laktamske antibiotike u odnosu neinvazivne sojeve. MRSP sojevi su pokazali veoma visok nivo osetljivosti na levofloksacin (99,6), telitromicin (98,4%), cefotaksim (93,5%), i mipenem (97,3%). MRSP sojevi su u potpunosti bili osetljivi na vankomicin, linezolid, moksifloksacin, sparfloksacin, rifampicin&nbsp; i&nbsp; pristinamicin.&nbsp; Među&nbsp; invazivnim&nbsp; sojevima <em>S.pneumoniae</em> rezistentnim na makrolide je nađeno 12 različitih serotipova. Polovina izolata je pripadala serotipovima 19F (25%) i 14 (23%), dok su sledeći po učestalosti bili 6A (10,4%) i 23F (8,3%). Istovremena rezistencija na makrolide, penicilin, tetracikline i trimetoprim-sulfametoksazol je nađena kod serotipova 19F, 14 i 23F, dok su serotpovi 12F i 31 bili neosetljivi samo na makrolide. Na&scaron;e istraživanje predstavlja prvu detaljnu analizu fenotipskih i&nbsp; genotipskih&nbsp; osobina&nbsp; sojeva&nbsp; pneumokoka&nbsp; rezistentnih&nbsp; na&nbsp; makrolidne antibiotike u Srbiji. Dobijeni rezultati ukazuju na&nbsp; potrebu za aktivnim nadzorom nad pneumokoknim infekcijama u Srbiji.</p> / <p><em>Streptococcus pneumoniae</em> (pneumococcus) is one of the leading morbidity and&nbsp; mortality&nbsp; causes&nbsp; all&nbsp; over&nbsp; the&nbsp; world&nbsp; with&nbsp; respect&nbsp; to&nbsp; infectious&nbsp; diseases. <em>Streptococcus&nbsp; pneumoniae</em> is&nbsp; a&nbsp; leading&nbsp; cause&nbsp; of upper&nbsp; respiratory&nbsp; tract infections&nbsp; (&nbsp; sinusitis,&nbsp; otitis)&nbsp; and&nbsp; conjunctivitis. It&nbsp; is&nbsp; also&nbsp; the&nbsp; most&nbsp; common cause&nbsp; of&nbsp; community-acquired&nbsp; pneumonia, bacterial&nbsp; meningitis&nbsp; and&nbsp; sepsis. Beta lactam and&nbsp; macrolide antibiotics remained a first choice for empirical treatment of pneumococcal infections. Although macrolides are widely used for&nbsp;&nbsp; treatment&nbsp;&nbsp; of&nbsp;&nbsp; pneumococcal&nbsp;&nbsp; infections, an&nbsp;&nbsp; increase&nbsp;&nbsp; in&nbsp;&nbsp; macrolide resistance&nbsp; might compromise&nbsp; their use. Pneumococcal&nbsp; macrolide resistance is&nbsp; mediated&nbsp; by&nbsp; two&nbsp; major&nbsp; mechanisms:&nbsp; target&nbsp; site&nbsp; modification&nbsp; and&nbsp; active drug&nbsp; efflux.&nbsp; Methylation&nbsp; of&nbsp; the&nbsp; 23S&nbsp; ribosomal&nbsp; ribonucleic&nbsp; acid&nbsp; (rRNA)&nbsp; is performed&nbsp;&nbsp; by&nbsp;&nbsp; the&nbsp;&nbsp; enzyme&nbsp;&nbsp; methylase,&nbsp;&nbsp; encoded&nbsp;&nbsp; by&nbsp;&nbsp; the<em> ermB </em>gene. Modification&nbsp; of&nbsp; ribosomal&nbsp; targets&nbsp; leads&nbsp; to&nbsp; cross-resistance to&nbsp; macrolides (M),&nbsp; lincosamides&nbsp; (L)&nbsp; and&nbsp; streptogramins&nbsp; B&nbsp; (Sb). It&nbsp; is&nbsp; expressed&nbsp; as&nbsp; the MLS_b &ndash;phenotype,&nbsp; which&nbsp; confers&nbsp; a&nbsp; high-level&nbsp; resistance. This&nbsp; phenotype&nbsp; can&nbsp;&nbsp; be&nbsp;&nbsp; either&nbsp;&nbsp; constitutively&nbsp;&nbsp; (cMLS)&nbsp;&nbsp; or&nbsp;&nbsp; inducibly&nbsp;&nbsp; (iMLS). expressed. Another macrolide resistance mechanism is the active drug efflux, encoded by&nbsp; the <em>mefA&nbsp;</em> gene.&nbsp; The&nbsp; drug&nbsp; efflux&nbsp; confers&nbsp; resistance&nbsp; to&nbsp; 14-&nbsp; and&nbsp; 15-membered&nbsp; macrolides&nbsp; only,&nbsp; with&nbsp; no&nbsp; cross-resistance.&nbsp; It&nbsp; is&nbsp; expressed&nbsp; as&nbsp; the M-phenotype,&nbsp; which&nbsp; confers&nbsp; low-level&nbsp; resistance.&nbsp; The&nbsp; objective of&nbsp; this study&nbsp;&nbsp; was&nbsp;&nbsp; :&nbsp;&nbsp; 1) to&nbsp;&nbsp; examine&nbsp;&nbsp; the&nbsp;&nbsp; prevalence of&nbsp;&nbsp; macrolide&nbsp;&nbsp; resistant <em>Streptococcus&nbsp;&nbsp; pneumoniae </em>(MRSP) among&nbsp;&nbsp; invasive&nbsp;&nbsp; and&nbsp;&nbsp; noninvasive isolates in children and adults, 2) to examine the prevalence of coresistance and multiple-resistance among MRSP strains, 3) to examine the prevalence of&nbsp; macrolide&nbsp; resistant&nbsp; phenotypes,&nbsp; and&nbsp; 4)&nbsp; to&nbsp; examine&nbsp; the&nbsp; prevalence&nbsp; of macrolide&nbsp; resistant&nbsp; genotypes&nbsp; (detect&nbsp; the&nbsp; presence of&nbsp; the <em>ermB</em>&nbsp;&nbsp; and <em>mefA</em> gene).&nbsp; A&nbsp; total&nbsp; of&nbsp;&nbsp; 326&nbsp; MRSP&nbsp; strains&nbsp; were&nbsp; analyzed,&nbsp; which&nbsp; were&nbsp; collecte dall&nbsp; over&nbsp; Serbia&nbsp; in&nbsp; the&nbsp; period&nbsp; from&nbsp; January,&nbsp; 2010&nbsp; - December,&nbsp; 2012.&nbsp; The collected&nbsp;&nbsp; MRSP&nbsp;&nbsp; isolates&nbsp;&nbsp; were&nbsp;&nbsp; referred&nbsp;&nbsp; to&nbsp;&nbsp; the&nbsp;&nbsp; National&nbsp; Reference Laboratory&nbsp; for&nbsp; streptococci&nbsp; and&nbsp; pneumococci for&nbsp; further&nbsp; investigation. Identification based on microscopic, culture and biochemical features of the isolates. Conservation was performed in the brain-heart infusion broth with a&nbsp; 10%&nbsp; glycerol&nbsp; content&nbsp; at&nbsp; -80&deg;C.&nbsp; Macrolide&nbsp; resistance&nbsp; phenotypes&nbsp; were determined by a double disc diffusion test, combine d diffusion-dilution test and&nbsp;&nbsp; automatized&nbsp;&nbsp; VITEK&nbsp; 2 system. Macrolide&nbsp;&nbsp; resistance&nbsp;&nbsp; genes&nbsp;&nbsp; were&nbsp; determined by PCR. Overall, macrolide nonsusceptibility rate in Serbia was 34%.&nbsp; MRSP&nbsp; isolates&nbsp; were&nbsp; more&nbsp; prevale nt&nbsp; among&nbsp; children&nbsp; (36%)&nbsp; than adults&nbsp; (29%),&nbsp; and&nbsp; were&nbsp; more&nbsp; prevalent&nbsp; among&nbsp;&nbsp; noninvasive&nbsp; (35.5%)&nbsp; than invasive&nbsp; (27.4%)&nbsp; samples.&nbsp; Predominant&nbsp; macrolide&nbsp; resistance&nbsp; phenotype was&nbsp; the&nbsp; MLS b&nbsp; phenotype&nbsp; (78.5%),&nbsp; from&nbsp; which&nbsp; 73.9 %&nbsp; belonged&nbsp; to&nbsp; cMLS and&nbsp; 4.6%&nbsp; to&nbsp; iMLS&nbsp; phenotype.&nbsp; All&nbsp; the&nbsp; strains&nbsp; assigne d&nbsp; to&nbsp; the&nbsp; MLS_b phenotype harbored<em> ermB</em> gene, while all the strains with M phenotype had the mefA gene.&nbsp; The&nbsp; presence&nbsp; of&nbsp; both ermB and mefA resistance&nbsp; genes&nbsp; was confirmed&nbsp; in&nbsp; 43.9&nbsp; %&nbsp; of&nbsp; isolates. All&nbsp; the&nbsp; isolates&nbsp; which&nbsp; harbored&nbsp; both resistance genes expressed the MLS_b phenotype. Among macrolide resistant strains,&nbsp; penicillin&nbsp; nonsusceptiblility&nbsp; was&nbsp; observed&nbsp;&nbsp; in&nbsp; 16% .&nbsp; A&nbsp; high&nbsp; level resistance was confirmed in 5. 8% of MRSP isolates. MRSP strains showed high&nbsp; resistance rates to tetracyclin&nbsp; (81.3%) and&nbsp; trimethoprim-sulfamethoxazole&nbsp; (74.3%).&nbsp; Multiresistant&nbsp; strains,&nbsp; resistant&nbsp; to&nbsp; tetracyclines and&nbsp; trimethoprim-sulfamethoxazole,&nbsp; made&nbsp; two&nbsp; thirds&nbsp; (66.1&nbsp; %)&nbsp; of&nbsp; MRSP isolates.&nbsp; Among&nbsp; MRSP,&nbsp; co-resistance&nbsp; to&nbsp; tetracycline&nbsp; and&nbsp; trimethoprim-sulfamethoxazole&nbsp; was&nbsp; more&nbsp; prevalent&nbsp; among&nbsp; MLS&nbsp; phenotypes&nbsp; (73.1%) than&nbsp; M&nbsp; phenotypes&nbsp; (36.7%).&nbsp; Co-resistance&nbsp; strains&nbsp; to&nbsp; macrolides&nbsp; and&nbsp; other antibiotics including&nbsp;&nbsp;&nbsp; penicillin,&nbsp;&nbsp; amoxicillin,&nbsp;&nbsp;&nbsp; cefotaxime,&nbsp; tetracyclin, trimethoprim-sulfamethoxazole and multiresistant&nbsp; strains&nbsp; were more prevalent among children than adult. Coresistance to macrolides and other antibiotics&nbsp; including&nbsp; tetracycline&nbsp; and&nbsp; ofloxacin&nbsp; was&nbsp; more&nbsp; prevalent&nbsp; among noninvasive&nbsp;&nbsp; than&nbsp;&nbsp; invasive&nbsp;&nbsp; strains.&nbsp;&nbsp; Invasive&nbsp;&nbsp; MRSP&nbsp;&nbsp; isolates&nbsp;&nbsp; from&nbsp;&nbsp; the cerebrospinal fluid showed a higher resistance rate to beta lactam antibiotics than&nbsp; noninvasive&nbsp; strains.&nbsp; MRSP&nbsp; strains&nbsp; had&nbsp; a&nbsp; high&nbsp; susceptibility&nbsp; rates&nbsp; to levofloxacin&nbsp;&nbsp; (99.6),&nbsp;&nbsp; telithromycin&nbsp;&nbsp; (98.4%),&nbsp;&nbsp; cefotak sime&nbsp;&nbsp; (93.5%)&nbsp;&nbsp; and imipenem&nbsp; (97.3%).&nbsp; MRSP&nbsp; strains&nbsp; were&nbsp; fully&nbsp; susceptible&nbsp; to&nbsp; vancomycin, linezolid, moxifloxacin, sparfloxacin, rifampicin a nd pristinamycin. Among macrolide&nbsp;&nbsp; resistant <em>S.pneumoniae</em> strains,&nbsp;&nbsp; 12 different&nbsp;&nbsp; serotypes&nbsp;&nbsp; were identified.&nbsp; One&nbsp; half&nbsp; of&nbsp; these&nbsp; isolates&nbsp; belonged&nbsp; to the&nbsp; 19F&nbsp; (27.1%)&nbsp; and&nbsp; 14 (22.&nbsp; 9%)&nbsp; serotype,&nbsp; followed&nbsp; in&nbsp; frequency&nbsp; by&nbsp; the&nbsp; 6A&nbsp; (10.41%)&nbsp; and&nbsp; 23F (8.3%)&nbsp; serotype .&nbsp; Multiresistant&nbsp; strains&nbsp; (macrolides,&nbsp; penicillin,&nbsp; tetracyclines and&nbsp; trimethoprim-sulfamethoxazole)&nbsp; belonged&nbsp; to&nbsp; serotypes 19F,&nbsp; 14&nbsp; and 23F, while the 12F and 31 serotype were resistant to macrolides only. This in vestigation&nbsp;&nbsp; represents&nbsp;&nbsp; the&nbsp;&nbsp; first&nbsp;&nbsp; detailed&nbsp;&nbsp; analysis of&nbsp;&nbsp; phenotypes&nbsp;&nbsp; and genotypes&nbsp; of&nbsp; macrolide&nbsp; resistant&nbsp; pneumococcal&nbsp; strains&nbsp; in&nbsp; Serbia.&nbsp; The obtained&nbsp; results suggest&nbsp; the need for an active surveillance&nbsp; of pneumococcal infections in Serbia.</p>