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The objective of the study was to analyze antibiotic consumption and determine bacterial resistance rates as an indicator of the rational utilization of this drug group at the urology department in the Health Centre “Studenica” Kraljevo. Over a two-year period, the average antibiotic consumption was 104.55 DDD/100BD. Of the total financial assets used for medical treatment, the antibiotic group JO1 had a share of 49.52% in 2011 and 47.53% in 2012. Antibacterial drugs from a group of β-lactamic antibiotics were consumed most commonly, at 54.02% (2011) and 43.44% (2012). First-generation cephalosporins, quinolones and aminoglycosides were the most frequently used drug groups, while cephalexin was the antibiotic with the highest individual consumption. E. coli was the most frequently isolated bacterium in 2011, while in 2012, Klebsiella pneumoniae was the most frequently isolated bacterium. The total bacterial resistance both in 2011 and 2012 was above 50%. Gram-negative bacteria showed a higher resistance rate (2011, 59.3%; 2012, 58.9%) than Gram-positive bacteria (2011, 44.4%; 2012, 40.6%). Klebsiella pneumoniae was the bacterium with the highest resistance (75.3%) in 2011, while in 2012, there was a resistance increase in Pseudomonas aeruginosa (71.4%), especially to carbapenems. A correlation was determined between the consumption of individual antibiotics and bacterial strain resistance in 2011 (r=0.433, p=0.044) and in 2012 (r=0.478, p=0.024). The high resistance rate shown in the bacterial strains, which was correlated with antibiotic consumption, as well as the great financial assets used for this group of drugs suggest the necessity for the rationalization of their utilization. Empirical therapy with Gram-negative bacteria should be based on carbapenems utilization, except with Pseudomonas aeruginosa, where piperacillin/tazobactam should be used.

Uvod: U našoj zemlji nema smernica za lečenje bakterijskih infekcija u tercijarnim zdravstvenim ustanovama. Odabir antibakterijskih lekova je empirijski, što 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 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 korišćen je programski paket Statistical Package for Social Sciences - SPSS 21. Statistički značajnim se smatraju vrednosti nivoa značajnosti p0,05). 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 našoj sredini, 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 p0.05) 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. 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.

In the past decades most infective microorganisms have shown increasing resistance to standard available antibiotics. In pediatrics, the increase in the rate of development of antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae is of great concern, because these bacteria are the major etiologic agents causing serious pediatric infections such as meningitis and septicemia. Antibiotic resistance among Gram-negative bacteria has reached critical level. The rise of carbapenem resistance in Enterobacteriaceae carrying additional resistance genes to multiple antibiotic classes has created a generation of organisms nearly resistant to all available therapy. Inappropriate use of antibiotics, especially for viral respiratory infections, has favoured the development and spread of antibiotic-resistant microorganisms. U poslednjih nekoliko decenija kod većine patogenih mikroorganizama registrovan je razvoj rezistencije na standardne antibiotike. U pedijatrijskoj praksi porast broja rezistentnih sojeva Streptococcus pneumoniae i Haemophilus influenzae je zabrinjavajući, jer su ove bakterije česti uzročnici ozbiljnih infekcija kao što su meningitis i septikemija. Rezistencija gram-negativnih bakterija na antibiotike dostigla je kritičan nivo. Sojevi enterobakterija koji su rezistentni na karbapeneme istovremeno nose gene rezistencije na više različitih grupa antibiotika, što praktično znači da se radi o bakterijama koje su otporne na skoro sve trenutno dostupne antimikrobne lekove. Neopravdana primena antibiotika, naročito u slučajevima virusnih infekcija gornjih respiratornih puteva, jedan je od faktora koji su doprineli razvoju i širenju rezistentnih sojeva mikroorganizama.