20.500.12556/RUL-71216 Ugotavljanje odpornosti na antibiotike pri okužbah z E.coli, ki izločajo beta laktamazo z razširjenim spektrom delovanja diplomska naloga Assessment of resistance to antibiotics regarding infections with E.coli which secrete extended-spectrum beta-lactamases Bakterija Escherichia coli je ena izmed gramnegativnih bakterij iz družine Enterobacteriaceae. Spada med bakterije normalne črevesne flore, vendar nekateri sevi nosijo take faktorje virulence, s pomočjo katerih povzročajo zunajčrevesne okužbe, najpogosteje okužbe sečil. Ena izmed mehanizmov odpornosti proti protimikrobnim zdravilom je nastanek encimov, ki hidrolizirajo betalaktamske antibiotike. Nastali encimi, ki imajo dodatno sposobnost prenosa bakterijske odpornosti proti penicilinom, cefalosporinom prve, druge in tretje generacije ter proti aztreonamu, se imenujejo betalaktamaze z razširjenim spektrom delovanja. Povzročajo tako bolnišnične kot zunajbolnišnične okužbe. V zvezi s tem so raziskovali tudi dejavnike tveganja za pridobitev okužb s temi organizmi. Enterobakterije, ki izločajo betalaktamazo z razširjenim spektrom, so velik svetovni problem. V Pomurju so povečano pojavljanje takih bakterij opazili leta 2005. Zaradi obrambnih ukrepov se je obseg problema sicer zmanjšal do leta 2008, vendar se je leta 2009 število izolatov E. coli, ki izloča betalaktamazo razširjenega spektra, drastično povečalo. Večina izolatov je bila izolirana iz urina. V retrospektivno študijo smo z različnih akutnih oddelkov Splošne bolnišnice Murska Sobota vključili 49 bolnikov, ki so jim iz urina izolirali bakterijo E. coli, ki izloča betalaktamazo razširjenega spektra. 71,4 % bolnikov je bila ženskega spola, povprečna starost skupine pa je bila 70,6 let. Pri vsakem bolniku smo za vsako protimikrobno zdravilo preverili skladnost odmerjanja in trajanja zdravljenja s smernicami in s povzetki glavnih značilnosti zdravila. Večjo skladnost smo opazili pri odmerjanju glede obeh priporočil. Skladnost trajanja zdravljena je bila večinoma neskladna glede na smernice, glede na povzetke glavnih značilnosti zdravila pa trajanja večinoma nismo mogli oceniti. Ker vsi bolniki niso dobili protimikrobne terapije zaradi okužbe sečil, nismo mogli preveriti skladnosti terapije glede na mikrobiološki izvid pri vseh bolnikih. Za dobljeno empirično terapijo je bila bakterija občutljiva le v 16,7 %. Prehod je bil narejen v 45,8 %, v 16,7 % pa niso zamenjali učinkovine, proti kateri je bila bakterija odporna. Če je odpornost proti določenemu kemoterapevtiku višja od 10 % do 20 %, je empirično zdravljenje vprašljivo. Ko signifikanten delež gramnegativnih bakterij na določeni enoti izloča betalaktamazo razširjenega spektra, se empirična terapija obrne proti uporabi karbapenema, kinolona ali kombinacije betalaktama in zaviralca betalaktamaze. Ob pregledu občutljivosti smo ugotovili, da je bakterija E. coli, ki izloča betalaktamaze razširjenega spektra, povsem odporna proti penicilinom ter cefalosporinom prve, II druge in tretje generacije, visoko odporna proti fluorokinolonom in gentamicinu. Občutljiva je za karbapeneme, vendar se že pojavlja odpornost proti ertapenemu. Pri pregledu morebitnih dejavnikov tveganja za pridobitev teh okužb so izstopali: ženski spol, visoka starost, nepokretnost, inkontinenca, kardiovaskularne bolezni, prisotnost urinskega katetra, hospitalizacija v zadnjem letu, predhodna protimikrobna terapija. Večina bolnikov je bila odpuščenih domov, smrtnih izidov je bilo 20,4 %, med temi so zaradi okužbe sečil z odpornimi bakterijami in/ali urosepse umrli trije bolniki, kar predstavlja 6,1 % celotne skupine. Escherichia coli is one of the Gram negative bacterium from the family Enterobacteriaceae. It is a member of the normal intestinal flora but some strains carry virulence factors, which cause extraintestinal infections, infections of the urinary tract in particular. One of the mechanisms of the antimicrobial resistance is the production of enzymes, which hydrolyze beta-lactam antibiotics. Enzymes capable of transmitting bacterial resistance to penicillins, first-, second-, and thirdgeneration cephalosporins, and aztreonam have arisen called extended-spectrum betalactamases (ESBL). They cause hospital- and community-acquired infections. Due to this, studies were conducted on risk factors concerning infections with these organisms. ESBL-producing Enterobacteriacea are a major global problem. The studies found an increased occurrence of these bacteria in the Pomurje region in 2005. The extent of the problem lessened by the year 2008 because of defensive measures, but the number of ESBL-producing E. coli has dramatically increased in 2009. Most isolates were isolated from urine. Forty-nine patients were included in the retrospective study. Patients were from different acute wards from the General Hospital of Murska Sobota, ESBL-producing E. coli from urine was isolated in all of them. 71.4 % of the patients were female; the average age of the group was 70.6 years. We have observed accordance of dosage and the length of therapy for every antimicrobial drug with guidelines and Summary of Product Characteristics for every patient. We have observed higher accordance of dosage with regard to both references. Accordance of the therapy length was mostly inappropriate according to guidelines, and we could not assess therapy length regarding to Summary of Product Characteristics in most cases. Not every patient received antimicrobial therapy because of urinary tract infections, hence we were unable to assess therapy in accordance to the microbiological tests. The bacteria were sensitive on the empirical therapy in 16.7 % of the cases. Antimicrobial therapy was changed in 45.8 % of the cases, and they have not changed the antimicrobial drug on which were resistant bacteria in 16.7 %. If the resistance to certain chemotherapeutic agent is higher than 10-20 %, empirical treatment is problematic. When a significant portion of Gram negative bacteria in a particular unit produce ESBL, empirical therapy turns toward the use of carbapenems, quinolones or combination of beta-lactams and beta-lactamase inhibitors. When we examined the sensitivity, we observed that ESBL-producing E. coli is completely resistant to penicillins, first-, second-, and third-generation cephalosporins, highly resistant to fluoroquinolones and gentamicin. It is sensitive to carbapenems but resistance is already apparent to ertapenem. Most probable of the potential risk factors include: female gender, advanced age, immobility, cardiovascular diseases, presence of urinary catheter, hospitalization in the last year, prior antimicrobial therapy. Most of the patients returned home, the portion of fatal outcomes was 20.4 %, three patients died because of urinary tract infections with resistant bacteria and/or urosepsis among them; that amounts to 6.1 % of the observed group. E. coli betalaktamaze epidemiologija encimov ESBL laboratorijska diagnostika zdravljenje okužb protimikrobne terapije true false false [E. Balaskó] Slovenski jezik Angleški jezik Diplomsko delo 2015-07-10 22:03:18 2015-07-10 22:03:18 2022-08-01 14:11:59 0000-00-00 00:00:00 2011 0 Ljubljana 2011 Ljubljana VII, 109 f. 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61+615.2 3057265 UNI_Balasko_Eniko_2011.pdf UNI_Balasko_Eniko_2011.pdf 1 0404E7BBA3A2ABA94307971615D5C050 5713f299338062ed408e313d6a6760f9cf069c2be7794c6d0db0f9928af602a1 3e464c7c-a1ba-11eb-a523-00155dcfd717 20.500.12556/rul/c927825a-3d7c-48b9-96da-8dd253aa54e6 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=136041 Fakulteta za farmacijo 0 0 0