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Acinetobacter baumannii has emerged as one of the most common nosocomial pathogens worldwide. This organism mostly targets the susceptible immunocompromised patients in ICUs where natural barriers are breached by trauma, surgery or mechanical support ventilation. MDR clinical isolates represent a major problem in the epidemiological and therapeutic sense and challenge for clinicians. Surveillance of carbapenem resistant isolates (which are also multiresistant) of A. baumannii in Croatia is continually monitored since in the last decade the percentage of carbepenem resistant isolates reached 97%. In addition to Croatia, Bosnia and Herzegovina and Serbia also recorded a significant increase in the incidence and prevalence in carbapenem resistant clinically relevant isolates of A. baumannii. The aim of this pilot study was to compare the genotype resemblance and resistance mechanism of 12 isolates of carbapenem resistant A. baumannii collected from three different hospitals in neighbouring countries in region of south-eastern Europe. First results of pilot study were presented on 12th Symposium on the biology of Acinetobacter in Frankfurt during September 2019.

Uvod: Procenjuje se da se skoro svaki četvrti slučaj maligne bolesti u svetu može dovesti u vezu sa infektivnim agensom od kojih je približno svaki treći uzrokovan HPV. Karcinom grlića materice uzrokovan perzistentnom infekcijom visokorizičnim genotipovima HPV je drugi vodeći uzrok smrti kod žena uzrasta od 15 do 44 godine. Testovi zasnovani na molekularno biološkim metodama koji se danas uobičajeno koriste u dijagnostici HPV infekcija omogućavaju dokazivanje prisustva genoma i određivanje pojedinačnih tipova HPV u uzorcima cervikalnih briseva. Međutim, ovaj dijagnostički pristup ne pruža uvid u vrstu infekcije (tranzijentna ili perzistentna) i procenu rizika od nastanka cervikalnog karcinoma. Poslednjih godina brojna istraživanja se bave unapređenjem primarnog testa u cilju pronalaženja odgovarajuće dijagnostičke metode, kojom bi se stekao uvid u tip infekcije. Ciljevi istraživanja su bili usmereni na utvrđivanje i međusobno poređenje onkogene aktivnosti najčešće dijagnostikovanih visokorizičnih HPV u uzorcima cervikalnih briseva primenom iRNK testa, kao i poređenje u odnosu na stepen težine cervikalne intraepitelne lezije. Materijal i metode: Istraživanjem je bilo obuhvaćeno 365 uzoraka cervikalnih briseva pacijentkinja starijih od 18 godina, upućenih od strane ginekologa u Centar za virusologiju, Instituta za javno zdravlje Vojvodine u periodu od 2017–2021. godine. Uzorci su bili grupisani prema stepenu težine cervikalne intraepitelne lezije po 2014 Bethesda System klasifikaciji (NILM, ASCUS, LSIL, HSIL). U svakoj grupi se nalazilo najmanje 25 uzoraka cervikalnih briseva u kojima je dokazano prisustvo HPV DNK. Evidentirani su demografski podaci i faktori rizika koji doprinose sticanju i perzistiranju HPV infekcije cervikalnog epitela. Primenom kvalitativnog real time PCR testa je izvršeno dokazivanje i genotipizacija HPV DNK u uzorcima cervikalnih briseva, dok je metodom reverzne transkripcije i amplifikacije ciljne sekvence dokazano prisustvo iRNK onkogena E6/E7, odnosno onkogena aktivnost ispitanih HPV. Statistička analiza izvršena je primenom parametarskih i neparametarskih testova, kao i korelacione, univarijantne i multivarijantne logističke regresione analize. Rezultati ukazuju da su najzastupljeniji genotipovi u populaciji žena Južnobačkog okruga HPV 16, 31, 33 i 51. U 84,3% analiziranih uzoraka dokazana je infekcija izazvana pojedinačnim genotipom, dok je u 15,7% slučajeva prisutna udružena infekcija. Utvrđena je statistički značajna razlika u zastupljenosti broja pozitivnih nalaza HPV 16 (p = 0,035) i HPV 31 (p = 0,017) u zavisnosti od stepena težine citološkog nalaza, što nije utvrđeno za HPV 33 i 51. Prisustvo HPV 16 podjednako je zastupljeno u svim uzrasnim kategorijama, detekcija HPV 31 i 33 genotipova se smanjuje sa godinama života, dok se HPV 51 povećava. Onkogena aktivnost je dokazana kod 64,5% HPV pozitivnih pacijentkinja. Statistički značajna razlika je utvrđena u broju pozitivnih nalaza iRNK E6/E7 HPV 16 u odnosu na citološki status (p = 0,000) i uzrasne kategorije (p = 0,026). Približno svaki drugi HPV 16 genotip je onkogeno eksprimiran (48,6%) i najzastupljeniji je u grupi pacijentkinja sa HSIL citološkim nalazom (64,2%), dok je prisustvo iRNK E6/E7 HPV 31 najmanje detektovano u HSIL (7,5%). Distribucija onkogene aktivnosti preostalih genotipova je približno ista kroz različite citološke grupe i zadržava se na niskom nivou (2,2% – 11,4%). Komparacija testova za detekciju HPV i njihove onkogene aktivnosti u cilju procene progresije cervikalne intraepitelne lezije ukazala je da je statistički značajno veća specifičnost (89,1%) i pozitivna prediktivna vrednost (69,8% – 78,7%) iskazana za iRNK E6/E7 test, dok se značajno veća senzitivnost beleži pri upotrebi HPV DNK testa (67,6% – 88%). Rezultati ROC krive determinišu veću verovatnoću detekcije HPV infekcije za 7% koju pruža iRNK test. U konačnom delu rezultata definisan je statistički značajan finalni model, pri čemu su kao najjači prediktori za nastanak prekanceroznih lezija imenovani onkogena aktivnosti HPV 16 i uzrasna kategorija HPV pozitivnih pacijentkinja. Analiza parametara posmatranih demografskih faktora i faktora rizika HR HPV pozitivnih ispitanica ukazala je na određene razlike u odnosu na stepen težine cervikalne lezije. Zaključci: Najveći udeo inficiranih žena Južnobačkog okruga izazvan je visokorizičnim genotipovima HPV 16, 31, 33, 51 koji su u više od polovine ispitanih slučajeva onkogeno aktivni. Ukupna onkogena aktivnost ispitanih genotipova HPV raste sa porastom stepena težine cervikalne intraepitelne lezije, pri čemu se onkogeno aktivan HPV 16 najčešće detektuje u visokostepenim cervikalnim lezijama. Nasuprot tome, zastupljenost onkogeno aktivnog HPV 31 se najmanje detektuje u visokostepenim lezijama, dok je zastupljenost HR HPV 33 i 51 niska i nije srazmerna stepenu težine cervikalne lezije. Zastupljenost HPV infekcije je obrnuto proporcionalna uzrastu pacijentkinja Južnobačkog okruga što ukazuje da je regresija infekcije dominantan proces koji je u skladu sa adekvatnim imunskim odgovorom organizma. Veća specifičnost i pozitivna prediktivna vrednost iRNK testa u odnosu na HPV DNK test ukazuje na veću verovatnoću detekcije perzistentne HPV infekcije prilikom njegove upotrebe. Onkogena aktivnost najčešće detektovanih visokorizičnih HPV ima prediktivni potencijal u proceni nastanka visokostepene lezije cervikalnog epitela. Biomarkeri sa najjačim prediktivnim vrednostima za nastanak ovih lezija su onkogena aktivnost HPV 16 i uzrast pacijentkinja. Introduction: It is estimated that almost one-quarter of worldwide malignancy can be associated with infectious agents, of which approximately one third is caused by HPV. Cervical cancer caused by persistent infection with high-risk HPV genotypes is the second leading cause of death in women aged 15 to 44. Tests based on molecular biological methods commonly used today in diagnosing HPV infections enable genome detection and determination of individual HPV genotypes in cervical smear samples. However, this diagnostic approach does not provide insight into the type of infection and assessment of the risk of cervical cancer. In recent years, numerous studies have focused on improving the primary test to find an appropriate diagnostic method to provide insight into the type of infection. The study's objectives were to determine the oncogenic activity of the most commonly diagnosed high-risk HPVs in cervical smear samples using the mRNA test and compare the results according to the severity of the cervical intraepithelial lesion. Material and methods: The study included 365 samples of cervical swabs of women older than 18 years, referred by gynecologists to the Center for Virology, Institute of Public Health of Vojvodina from 2017 to 2021. According to the Bethesda classification, samples were grouped according to the severity of the cervical intraepithelial lesion (NILM, ASCUS, LSIL, HSIL). There were at least 25 samples of cervical smears in each group in which the presence of HPV DNA was proven. Demographic data and risk factors that contribute to the acquisition and persistence of HPV infection of the cervical epithelium were recorded. Using a qualitative real time PCR test, HPV DNA was detected and genotyped in cervical smear samples, while the reverse transcription and amplification method proved the presence of mRNA oncogenes E6 and E7, the oncogenic activity of tested HPV. Statistical analysis was performed using parametric and nonparametric tests, correlation, univariate, and multivariate logistic regression analysis. The results indicate that the most common genotypes in the female population of South Bačka District are HPV 16, 31, 33, and 51. In 84.3% of the analysed samples, the infection caused by a single genotype was proven, while in 15.7% of cases, a co-infection is present. A statistically significant difference was found for HPV 16 (p = 0.035) and HPV 31 (p = 0.017) depending on the severity of the cytological results, which did not determine for HPV 33 and 51. The presence of HPV 16 is equally present in all age categories. The detection of HPV 31 and 33 genotypes decreases with years of life, while HPV 51 increases. The oncogenic activity was demonstrated in 64.5% of HPV-positive women. A statistically significant difference was found in the number of positive mRNA E6/E7 HPV 16 results concerning cytological status (p = 0.000) and age categories (p = 0.026). Approximately every other HPV 16 genotype was oncogenically active (48.6%). It was most prevalent in women with HSIL cytological results (64.2%), while the presence of mRNA E6/E7 HPV 31 was minimally detected in HSIL (7.5%). The distribution of oncogenic activity of the remaining genotypes is approximately the same through different cytological groups and remains at low level (2.2% – 11.4%). A comparison of tests for the detection of HPV and their oncogenic activity to assess the progression of cervical intraepithelial lesion indicated that statistically significantly higher specificity (89.1%) and positive predictive value (69.8% – 78.7%) were expressed for mRNA E6/E7 test, while significantly higher sensitivity is recorded when using the HPV DNA test (67.6% – 88%). The results of the ROC curve determine the higher probability of detecting HPV infection by 7% provided by the mRNA test. A statistically significant final model was defined. The oncogenic activity of HPV 16 and the age category of HPV-positive women were named as the strongest predictors for the development of precancerous lesions. Analysis of the parameters of the observed demographic factors and risk factors of HR HPV-positive subjects showed a difference concerning the severity of the cervical lesion. Conclusions: The largest number of infected women in the South Bačka District is caused by high-risk genotypes HPV 16, 31, 33, 51, which are oncogenic in more than half of the examined cases. The total oncogenic activity increases with increasing severity of the cervical intraepithelial lesion, with oncogenic active HPV 16 being most commonly detected in high-grade cervical lesions. In contrast, the prevalence of oncogenic active HPV 31 is minimally detected in high-grade lesions, while the prevalence of HR HPV 33 and 51 is low and not proportional to the severity of the cervical lesion. The prevalence of HPV infection is inversely proportional to the age of women in the South Bačka District, which indicates that regression of infection is the dominant process following the adequate immune response. The higher specificity and positive predictive value of the mRNA test than the HPV DNA test indicate a higher probability of detecting persistent HPV infection. The oncogenic activity of the most commonly detected high-risk HPVs has a predictive potential in assessing the occurrence of high-grade cervical epithelial lesions. The oncogenic activity of HPV 16 and age were the biomarkers with the strongest predictive values for the development of these lesions.

Uvod: Procenjuje se da se skoro svaki četvrti slučaj maligne bolesti u svetu može dovesti u vezu sa infektivnim agensom od kojih je približno svaki treći uzrokovan HPV. Karcinom grlića materice uzrokovan perzistentnom infekcijom visokorizičnim genotipovima HPV je drugi vodeći uzrok smrti kod žena uzrasta od 15 do 44 godine. Testovi zasnovani na molekularno biološkim metodama koji se danas uobičajeno koriste u dijagnostici HPV infekcija omogućavaju dokazivanje prisustva genoma i određivanje pojedinačnih tipova HPV u uzorcima cervikalnih briseva. Međutim, ovaj dijagnostički pristup ne pruža uvid u vrstu infekcije (tranzijentna ili perzistentna) i procenu rizika od nastanka cervikalnog karcinoma. Poslednjih godina brojna istraživanja se bave unapređenjem primarnog testa u cilju pronalaženja odgovarajuće dijagnostičke metode, kojom bi se stekao uvid u tip infekcije. Ciljevi istraživanja su bili usmereni na utvrđivanje i međusobno poređenje onkogene aktivnosti najčešće dijagnostikovanih visokorizičnih HPV u uzorcima cervikalnih briseva primenom iRNK testa, kao i poređenje u odnosu na stepen težine cervikalne intraepitelne lezije. Materijal i metode: Istraživanjem je bilo obuhvaćeno 365 uzoraka cervikalnih briseva pacijentkinja starijih od 18 godina, upućenih od strane ginekologa u Centar za virusologiju, Instituta za javno zdravlje Vojvodine u periodu od 2017–2021. godine. Uzorci su bili grupisani prema stepenu težine cervikalne intraepitelne lezije po 2014 Bethesda System klasifikaciji (NILM, ASCUS, LSIL, HSIL). U svakoj grupi se nalazilo najmanje 25 uzoraka cervikalnih briseva u kojima je dokazano prisustvo HPV DNK. Evidentirani su demografski podaci i faktori rizika koji doprinose sticanju i perzistiranju HPV infekcije cervikalnog epitela. Primenom kvalitativnog real time PCR testa je izvršeno dokazivanje i genotipizacija HPV DNK u uzorcima cervikalnih briseva, dok je metodom reverzne transkripcije i amplifikacije ciljne sekvence dokazano prisustvo iRNK onkogena E6/E7, odnosno onkogena aktivnost ispitanih HPV. Statistička analiza izvršena je primenom parametarskih i neparametarskih testova, kao i korelacione, univarijantne i multivarijantne logističke regresione analize. Rezultati ukazuju da su najzastupljeniji genotipovi u populaciji žena Južnobačkog okruga HPV 16, 31, 33 i 51. U 84,3% analiziranih uzoraka dokazana je infekcija izazvana pojedinačnim genotipom, dok je u 15,7% slučajeva prisutna udružena infekcija. Utvrđena je statistički značajna razlika u zastupljenosti broja pozitivnih nalaza HPV 16 (p = 0,035) i HPV 31 (p = 0,017) u zavisnosti od stepena težine citološkog nalaza, što nije utvrđeno za HPV 33 i 51. Prisustvo HPV 16 podjednako je zastupljeno u svim uzrasnim kategorijama, detekcija HPV 31 i 33 genotipova se smanjuje sa godinama života, dok se HPV 51 povećava. Onkogena aktivnost je dokazana kod 64,5% HPV pozitivnih pacijentkinja. Statistički značajna razlika je utvrđena u broju pozitivnih nalaza iRNK E6/E7 HPV 16 u odnosu na citološki status (p = 0,000) i uzrasne kategorije (p = 0,026). Približno svaki drugi HPV 16 genotip je onkogeno eksprimiran (48,6%) i najzastupljeniji je u grupi pacijentkinja sa HSIL citološkim nalazom (64,2%), dok je prisustvo iRNK E6/E7 HPV 31 najmanje detektovano u HSIL (7,5%). Distribucija onkogene aktivnosti preostalih genotipova je približno ista kroz različite citološke grupe i zadržava se na niskom nivou (2,2% – 11,4%). Komparacija testova za detekciju HPV i njihove onkogene aktivnosti u cilju procene progresije cervikalne intraepitelne lezije ukazala je da je statistički značajno veća specifičnost (89,1%) i pozitivna prediktivna vrednost (69,8% – 78,7%) iskazana za iRNK E6/E7 test, dok se značajno veća senzitivnost beleži pri upotrebi HPV DNK testa (67,6% – 88%). Rezultati ROC krive determinišu veću verovatnoću detekcije HPV infekcije za 7% koju pruža iRNK test. U konačnom delu rezultata definisan je statistički značajan finalni model, pri čemu su kao najjači prediktori za nastanak prekanceroznih lezija imenovani onkogena aktivnosti HPV 16 i uzrasna kategorija HPV pozitivnih pacijentkinja. Analiza parametara posmatranih demografskih faktora i faktora rizika HR HPV pozitivnih ispitanica ukazala je na određene razlike u odnosu na stepen težine cervikalne lezije. Zaključci: Najveći udeo inficiranih žena Južnobačkog okruga izazvan je visokorizičnim genotipovima HPV 16, 31, 33, 51 koji su u više od polovine ispitanih slučajeva onkogeno aktivni. Ukupna onkogena aktivnost ispitanih genotipova HPV raste sa porastom stepena težine cervikalne intraepitelne lezije, pri čemu se onkogeno aktivan HPV 16 najčešće detektuje u visokostepenim cervikalnim lezijama. Nasuprot tome, zastupljenost onkogeno aktivnog HPV 31 se najmanje detektuje u visokostepenim lezijama, dok je zastupljenost HR HPV 33 i 51 niska i nije srazmerna stepenu težine cervikalne lezije. Zastupljenost HPV infekcije je obrnuto proporcionalna uzrastu pacijentkinja Južnobačkog okruga što ukazuje da je regresija infekcije dominantan proces koji je u skladu sa adekvatnim imunskim odgovorom organizma. Veća specifičnost i pozitivna prediktivna vrednost iRNK testa u odnosu na HPV DNK test ukazuje na veću verovatnoću detekcije perzistentne HPV infekcije prilikom njegove upotrebe. Onkogena aktivnost najčešće detektovanih visokorizičnih HPV ima prediktivni potencijal u proceni nastanka visokostepene lezije cervikalnog epitela. Biomarkeri sa najjačim prediktivnim vrednostima za nastanak ovih lezija su onkogena aktivnost HPV 16 i uzrast pacijentkinja., Introduction: It is estimated that almost one-quarter of worldwide malignancy can be associated with infectious agents, of which approximately one third is caused by HPV. Cervical cancer caused by persistent infection with high-risk HPV genotypes is the second leading cause of death in women aged 15 to 44. Tests based on molecular biological methods commonly used today in diagnosing HPV infections enable genome detection and determination of individual HPV genotypes in cervical smear samples. However, this diagnostic approach does not provide insight into the type of infection and assessment of the risk of cervical cancer. In recent years, numerous studies have focused on improving the primary test to find an appropriate diagnostic method to provide insight into the type of infection. The study's objectives were to determine the oncogenic activity of the most commonly diagnosed high-risk HPVs in cervical smear samples using the mRNA test and compare the results according to the severity of the cervical intraepithelial lesion. Material and methods: The study included 365 samples of cervical swabs of women older than 18 years, referred by gynecologists to the Center for Virology, Institute of Public Health of Vojvodina from 2017 to 2021. According to the Bethesda classification, samples were grouped according to the severity of the cervical intraepithelial lesion (NILM, ASCUS, LSIL, HSIL). There were at least 25 samples of cervical smears in each group in which the presence of HPV DNA was proven. Demographic data and risk factors that contribute to the acquisition and persistence of HPV infection of the cervical epithelium were recorded. Using a qualitative real time PCR test, HPV DNA was detected and genotyped in cervical smear samples, while the reverse transcription and amplification method proved the presence of mRNA oncogenes E6 and E7, the oncogenic activity of tested HPV. Statistical analysis was performed using parametric and nonparametric tests, correlation, univariate, and multivariate logistic regression analysis. The results indicate that the most common genotypes in the female population of South Bačka District are HPV 16, 31, 33, and 51. In 84.3% of the analysed samples, the infection caused by a single genotype was proven, while in 15.7% of cases, a co-infection is present. A statistically significant difference was found for HPV 16 (p = 0.035) and HPV 31 (p = 0.017) depending on the severity of the cytological results, which did not determine for HPV 33 and 51. The presence of HPV 16 is equally present in all age categories. The detection of HPV 31 and 33 genotypes decreases with years of life, while HPV 51 increases. The oncogenic activity was demonstrated in 64.5% of HPV-positive women. A statistically significant difference was found in the number of positive mRNA E6/E7 HPV 16 results concerning cytological status (p = 0.000) and age categories (p = 0.026). Approximately every other HPV 16 genotype was oncogenically active (48.6%). It was most prevalent in women with HSIL cytological results (64.2%), while the presence of mRNA E6/E7 HPV 31 was minimally detected in HSIL (7.5%). The distribution of oncogenic activity of the remaining genotypes is approximately the same through different cytological groups and remains at low level (2.2% – 11.4%). A comparison of tests for the detection of HPV and their oncogenic activity to assess the progression of cervical intraepithelial lesion indicated that statistically significantly higher specificity (89.1%) and positive predictive value (69.8% – 78.7%) were expressed for mRNA E6/E7 test, while significantly higher sensitivity is recorded when using the HPV DNA test (67.6% – 88%). The results of the ROC curve determine the higher probability of detecting HPV infection by 7% provided by the mRNA test. A statistically significant final model was defined. The oncogenic activity of HPV 16 and the age category of HPV-positive women were named as the strongest predictors for the development of precancerous lesions. Analysis of the parameters of the observed demographic factors and risk factors of HR HPV-positive subjects showed a difference concerning the severity of the cervical lesion. Conclusions: The largest number of infected women in the South Bačka District is caused by high-risk genotypes HPV 16, 31, 33, 51, which are oncogenic in more than half of the examined cases. The total oncogenic activity increases with increasing severity of the cervical intraepithelial lesion, with oncogenic active HPV 16 being most commonly detected in high-grade cervical lesions. In contrast, the prevalence of oncogenic active HPV 31 is minimally detected in high-grade lesions, while the prevalence of HR HPV 33 and 51 is low and not proportional to the severity of the cervical lesion. The prevalence of HPV infection is inversely proportional to the age of women in the South Bačka District, which indicates that regression of infection is the dominant process following the adequate immune response. The higher specificity and positive predictive value of the mRNA test than the HPV DNA test indicate a higher probability of detecting persistent HPV infection. The oncogenic activity of the most commonly detected high-risk HPVs has a predictive potential in assessing the occurrence of high-grade cervical epithelial lesions. The oncogenic activity of HPV 16 and age were the biomarkers with the strongest predictive values for the development of these lesions.

Infection control; Multidrug resistance; Stewardship Control de infección; Resistencia a múltiples fármacos; Administración Control d'infecció; Resistència a múltiples fàrmacs; Administració We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases–International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%−90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs’ implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

Hirurško vađenje impaktiranih donjih umnjaka veoma je česta oralnohirurška intervencija, koja je, u postoperativnom toku, obično praćena neprijatnim tegobama (bol, edem i trizmus), a nekad i potencijalno ozbiljnim komplikacijama (alveolitis i postoperativna infekcija). Stoga se savetuje primena različitih medikamenata i postupaka kojima bi se pojava ovih tegoba i komplikacija predupredila ili ublažila. S tim u vezi, u stručnoj i naučnoj literaturi vodi se rasprava o svsishodnosti profilaktičke primene antibiotika. Interesantno je da se mogu naći brojni radovi u kojima se preporučuje profilaktička primena antibiotika prilikom hirurškog vađenja impaktiranih donjih umnjaka, ali i radovi kojima se obrazlaže neslaganje sa takvim pristupom, potkrepljujući sumnju u odnos koristi spram rizika od uzgrednih efekata antibiotika, tim pre što je rastuća rezistencija mikroorganizama na antibiotike potencijalno ozbiljna pretnja globalnom zdravlju. Po pitanju profilaktičke primene antibiotika u ovoj indikaciji još nije postignut konsenzus, a nijedan od dva suprostavljena stava nije verifikovan ubedljivim naučno potvrđenim dokazima. Cilj. Imajući sve napred rečeno u vidu, osnovni cilj istraživanja bio je da se utvrdi opravdanost profilaktičke primene antibiotika u cilju ublažavanja osnovnih tegoba i komplikacija nakon hirurškog vađenja impaktiranih donjih umnjaka i da se, istovremeno, ispita efikasnost novijih vrsta antibiotika (moksifloksacin i cefiksim) primenjenih na taj način. Pri tom, izvršena su i laboratorijska (mikrobiološka) istraživanja senzitivnosti izolovanih mikroorganizama na antibiotike korišćene u istraživanju, koja bi mogla korisno da verifikuju klinički dobijene rezultate. Imajući to u vidu, na osnovu naučno verifikovanih rezultata, mogu se očekivati dve velike koristi od planiranog istraživanja: (1) potvrda ili negiranje opravdanosti profilaktičke primene antibiotika radi suzbijanja bilo koje od tegoba ili komplikacija posle hirurškog vađenja impaktiranih donjih umnjaka; (2) potvrda efikasnosti fluorohinolona (moksifloksacin) i cefalosporina (cefiksim) u suzbijanju dentogenih infekcija. Materijal i metode. Kliničko istraživanje sprovedeno je u Službi oralne hirurgije sa operacionim blokom i stacionarom Klinike za stomatologiju Vojvodine, po dizajnu dvostruko-slepe prospektivne kliničke studije, koje je obuhvatilo 177 ispitanika. Mikrobiološka istraživanja, sprovedena su u Centru za mikrobiologiju Instituta za javno zdravlje Vojvodine, na uzorcima brisa iz operativne rane pacijenata s postoperativnom infekcijom ili eksudata (gnoja) dobijenog iz perikoronarnog prostora pacijenata sa perikoronitisom. Pri tom, antibiogramom je utvrđivana senzitivnost izolovanih mikroorganizama na moksifloksacin, cefiksim i druge antibiotike koji se često koriste u oralnoj hirurgiji (penicilin i njegovi derivati, eitromicin, klindamicin i etraciklin). U studiju su uključeni samo ispitanici dobrog opšteg zdravstvenog stanja (ispitanici klasifikovani kao ASA I i ASA II), a u studiji nisu mogli da budu uključeni ispitanici kod kojih postoji sumnja na alergiju na antibiotike uopšte, a posebno na antibiotike koji su korišćeni u istraživanju, te maloletna lica, trudnice i dojilje. Zbog nepridržavanja datih uputstava u postoperativnom periodu ili neodazivanja na zakazane kontrolne preglede iz studije je isključeno 20 ispitanika. Istraživačke grupe formirane su nakon završenog istraživanja i otkrivanja odgovarajućeg šifarnika. Nakon završenog istraživanja, po otvaranju šifarnika, ustanovljeno je da je prvu studijsku grupu (M) činilo 52 ispitanika, kojima je u postoperativnom periodu ordiniran moksifloksacin. Drugu studijsku grupu (C) činilo je 53 ispitanika, kojima je u postoperativnom periodu ordiniran cefiksim. Treću, kontrolnu grupu (P) činilo je 52 ispitanika, kojima u postoperativnom periodu nije ordiniran antibiotik, već placebo tablete (koje su bile, izgledom, identične korišćenim antibioticima, ali su sadržavale samo indiferentne supstancije). Zavisno od preoperativno postojeće infekcije oko krune delimično izraslog umnjaka, tj. perikoronitisa, ispitanici sve tri formirane grupe, u svakoj od njih, svrstani su u dve podgrupe: podgrupu a (bez znakova perikoronitisa) i podgrupu b (sa prisutnim perikoronitisom). Na osnovu ovog kriterijuma, u grupi M, podgrupu a činilo je 39 ispitanika, a podrgupu b 13 ispitanika; u grupi C, podgrupu a činilo je 39 ispitanika, a podgrupu b 14 ispitanika; u kontrolnoj grupi (P), podgrupu a činilo je 39 ispitanika, a podgrupu b 13 ispitanika. Procena efekata primenjenih lekova vršenaje na osnovu postoperativnih tegoba ili komplikacija. Procena postoperativne analgezije vršena je pomoću vizuelno analogne skale (VAS) i verbalne skale rangiranja (VRS). Kod svakog ispitanika bio je registrovan momenat nastanka postoperativnog bola i njegov intenzitet, a registrovana je i potreba za dodatnim analgeticima. Postoperativni koeficijent edema dobijen je milimetarskim premeravanjem preoperativnog i postoperativnog odstojanja između pojedinih referentnih tačaka: spoljašnjeg ugla oka i ugla donje vilice; ugla usana i tragusa; vrha brade i tragusa. Procena stepena postoperativnog trizmusa vršena je merenjem razdaljine između mezijalno-incizalnih uglova gornjih i donjih centralnih sekutića pri maksimalno otvorenim ustima. U postoperativnom periodu registrovana je i pojava alveolitisa, kao i znaci postoperativne infekcije. Statistička analiza dobijenih podataka izvršena je primenom parametarskih (ANOVA i ANOVA ponovljenih merenja) i neparametarskih testova (Kruskal-Wallis test, Friedman test, Wilcoxon Signed Ranks test, McNemar test i Pearson χ2 test). Rezultati. Opisana prospektivna, dvostruko-slepa klinička studija, kao i izvršeno mikro-biološko istraživanje, pružili su sledeće rezultate: (1) kod ispitanika kod kojih su profilaktički primenjivani moksifloksacin ili cefiksim, utvrđena je statistički značajno manja učestalost, kao i manji intenzitet i kraće trajanje postoperativnih tegoba (bol, edem i trizmus) u odnosu na ispitanike kod kojih je primenjen placebo; (2) ispitanici kod kojih je profilaktički, u sklopu hirurškog vađenja impaktiranih donjih umnjaka, primenjivan moksifloksacin, imali su statistički značajno manju učestalost alveolitisa u odnosu na ispitanike kod kojih je primenjen cefiksim, kao i u odnosu na ispitanike kod kojih je primenjen placebo; (3) ispitanici kod kojih su profilaktički primenjivani moksifloksacin ili cefiksim, imali su statistički značajno manju učestalost postoperativne infekcije u odnosu na ispitanike kod kojih je primenjen placebo, pogotovu ako je inflamacija bila i preoperativno prisutna oko krune umnjaka. Pri tom, kod ispitanika koji su primili moksifloksacin, postoperativna infekcija nije zabeležena ni u jednom slučaju; (4) mikroorganizmi izolovani iz brisa perikoronoranog prostora kod ispitanika sa perikoronitisom ili iz brisa operativne rane u slučaju pojave postoperativne infekcije, na osnovu antibiograma, bili su osetljivi na moksifloksacin i na cefiksim, što ukazuje na efikasnost ovih antibiotika na prozrokovače oralnih infekcija, dok je zapažen povećan procenat rezistencije mikroorganizama na standardno primenjivane antibiotike, pogotovu na penicilin i njegove derivate. Zaključak. Na osnovu svih rezultata istraživanja, zaključeno je da su potvrđene hipoteze o efikasnosti moksifloksacina i cefiksima u profilaksi postoperativne infekcije nakon hirurškog vađenja impaktiranih donjih umnjaka i da su mikroorganizmi oralne flore, generalno, senzitivni na pomenute antibiotike. Međutim, hipoteze da moksifloksacin i cefiksim neće ispoljiti efekat na profilaksu inflamacijskih postoperativnih tegoba (bol, edem i trizmus), kao i alveolitisa, nisu potvrđene i mogu se odbaciti. Iz svih navedenih rezultata, može se zaključiti da je profilaktička primena moksifloksacina ili cefiksima u sklopu hirurškog vađenja impaktiranih donjih umnjaka svrsishodna u smislu ublažavanja i suzbijanja postoperativnih inflamacijskih tegoba i komplikacija., Surgical removal of impacted mandibular wisdom teeth is a frequent intervention, usually accompanied by unpleasant sequelae (pain, oedema and trismus) in the postoperative period, sometimes even with possibly serious complications (dry socket and postoperative infection). It is therefore advisable to use various medications and procedures to prevent or alleviate the occurrence of these sequelae and complications. Accordingly, there is a debate in the literature on the expedience of prophylactic use of antibiotics. It is interesting that numerous articles recommending prophylactic antibiotic use to patients undergoing the impacted mandibular third molar surgerymay be found, as well as those providing arguments for the disagreement with such an approach, considering that its benefits do not outweigh the risks of adverse side effects, especially due to growing resistance of microorganisms towards antibiotics, which is a possible serious threat to global health. Concerning the prophylactic use of antibiotics for this indication, consensus has not yet been reached, and neither of the views has been verified by convincing scientific evidence. Aim. Having the aforementioned dilemma in mind, the main goal of the study was to determine the validity of prophylactic use of antibiotics as to alleviate customary sequelae and possible complications after surgical removal of impacted mandibular third molars and, at the same time, the effectiveness of newer antibiotics (moxifloxacin and cefixime) when used for this purpose. Moreover, microbiological investigations of sensitivity of the isolated microorganisms to antibiotics used in this research were performed, which could verify the clinically obtained results.With this in mind, two major contributions, based on scientifically verified results, could be expected from the research: (1) confirmation or refuting the validity of prophylactic antibiotic use to controlsequelae or complications that could follow the impacted mandibular third molar surgery; and (2) confirmation of the efficacy of fluoroquinolones (moxifloxacin) and cephalosporins (cefixime) in controlling odontogenic infections. Materials and methods. Clinical research was conducted at the Oral Surgery Department of the Dentistry Clinic of Vojvodina, adopting the double-blind prospective clinical study design, which included 177 subjects. Microbiological studies were performed at the Center for Microbiology of the Institute of Public Health of Vojvodina, on swab samples obtained from the surgical wounds of patients with postoperative infection or the exudate (pus) obtained from the peri-coronal space of patients with pericoronitis. The sensitivity of isolated microorganisms to moxifloxacin, cefixime and other antibiotics commonly used in oral surgery (penicillin and its derivatives, erythromycin, clindamycin and tetracycline) was tested microbiologically. Only subjects in good general health (subjects classified as ASA I and ASA II) were included in the study, while excluding those with suspected allergy to antibiotics in general, and in particular to the antibiotics used in the research, as well as under-age persons and pregnant and lactating women. Due to non-compliance with the instructions given for the postoperative period or failure to attend the scheduled check ups, 20 subjects were later on excluded from the study. Study groups were formed upon the study completion, once the treatment codebook was opened. Following the completion of the study, after opening the codebook, it was established that the first study group (M) consisted of 52 subjects, to whom moxifloxacin was administered in the postoperative period. The second study group (C) consisted of 53 subjects, to whom cefixime was administered in the postoperative period. The third, control group (P) consisted of 52 subjects who, instead ofreceiving an antibiotic in the postoperative period, were given placebo tablets (which were identical in appearance to the studied antibiotics, but contained only indifferent substances). Depending on the presence of preoperative infection around the crown of the partially erupted third molar, i.e. pericoronitis, subjects in all three groups were further separated into two subgroups: subgroup a (without signs of previous pericoronitis) and subgroup b (with pericoronitis present). Based on this criterion, in group M, subgroup a consisted of 39 participants, and subgroup b had 13 participants; in group C, subgroup a consisted of 39 participants, and subgroup b had 14 participants; and in the control group (P), subgroup a comprised of 39 participants and subgroup b of 13 participants. Evaluation of the effects of the applied medication was performed on the basis of postoperative sequelae or complications. Postoperative analgesia was assessed using a visual analogue scale (VAS) and a verbal rating scale (VRS). For each subject, the timing of postoperative pain emergence and its intensity was noted, and the need for additional analgesics was registered as well.The postoperative oedema coefficient was obtained by measuring the preoperative and postoperative distance between specific reference points in millimetres. The reference points were: the outer corner of the eye and the angle of the lower jaw; lipcorner and tragus; and chin tip and tragus.The degree of postoperative trismus was assessed by measuring the distance between mesial-incisal angles of the upper and lower central incisors at the maximum mouth opening ability. In the postoperative period, emergence of dry socket was registered, along with signs of postoperative infection as well. Statistical analysis of the obtained data was performed via parametric (ANOVA and repeated measures ANOVA) and nonparametric (Kruskal-Wallis test, Friedman test, Wilcoxon Signed Ranks test, McNemar test and Pearson χ2 test) tests. Results. The described prospective, double-blind clinical study, as well as the performed microbiological study, yielded the following results: (1) in subjects who were prophylactically administered moxifloxacin or cefixime, a lower incidence, as well as a lower intensity and shorter duration of postoperative sequelae (pain, oedema and trismus) was noticed, which was statistically significant in relation to subjects who received placebo; (2) subjects who prophylactically received moxifloxacin did not manifested dry socket at all, which statistically significantly differed from subjects who were administered cefixime or placebo; (3) subjects who prophylactically received moxifloxacin or cefixime did not have postoperative infection at all, unlike those who received placebo, especially if inflammation around the crown of the third molarwas present preoperatively; (4) microorganisms isolated from swabs taken from peri-coronal space in subjects with pericoronitis or from surgical wound in case of postoperative infection, based on bacterial sensitivity test, were sensitive to moxifloxacin and cefixime, indicating the efficacy of these antibiotics against bacteria causing oral infections; however, an increased rate of resistance of oral bacteria was noticed to commonly prescribed antibiotics, particularly to penicillin and its derivatives. Conclusion. Based on all the study results, it was concluded that the hypotheses that moxifloxacin and cefixime effectively prevent infection after surgical removal of impacted mandibular third molars and that the microorganisms of the oral flora are generally sensitive to these antibiotics were confirmed and supported. However, the hypotheses that moxifloxacin and cefixime will not affect the prophylaxis of inflammatory postoperative sequelae (pain, oedema and trismus), as well as dry socket, were not confirmed by the findings and they were rejected. Based on all aforementioned results, it can be concluded that prophylactic use of moxifloxacin or cefixime in patients undergoing the impacted mandibular third molar surgery is appropriate for alleviating and suppressing postoperative inflammatory sequelae and complications.

Endodontska terapija predstavlja relativno složenu mikrohiruršku intervenciju na patološki promenjenoj ili traumatsko oštećenoj pulpi. Najčešći uzrok neuspeha endodontske terapije predstavlja apikalno curenje, koje najčešće omogućava progresiju mikroorganizama usled nepotpune kanalne opturacije. Dalji uzroci nespeha su: anatomo-morfološke varijacije kanalnog sistema, kalcifikovani i neprohodni kanali, jako zakrivljeni i zaboravljeni (netretirani) kanali itd. Za kanalnu opturaciju se najčešće koristi gutaperka zbog dobrih fizičkih i bioloških svojstava, ali usled slabe adhezije za dentin i nedovoljnog ispunjavanja mikroprostora unutar kanalnog sistema, uvek se mora koristiti u kombinaciji sa cementom za opturaciju (engl. sealer). Endodontski cementi su odgovorni za popunjavanje nepravilnosti u preparisanim kanalima, eliminisanje preostalih bakterija i hermetičko zaptivanje kanalnog sistema. Idelan endodontski cement ima sposobnost da se lako adaptira za zidove kanala korena zuba, da popuni aksesorne kanale i apikalne ramifikacije, područja resorpcije, nepravilnosti unutar kanalnog sistema, odnosno sve prostore koje gutaperka ne može da ispuni i koji su kao takvi potencijalni rezervoar za bakterijsku kolonizaciju. Endodontski cementi koji poseduju sposobnost penetracije unutar dentinskih tubula mogu ispoljiti potencijalno antibakterijsko svojstvo i time dodatno uticati na broj preostalih bakterija. Cilj ovog istraživanja je bio da se odredi kvalitet zaptivnih svojstava biokeramičkog cementa na bazi kalcijum silikata u odnosu na konvencionalne cemente na bazi epoksi-bisfenol smola i na bazi epoksi-bisfenol smola i kalcijum hidroksida, dve tehnike opturacije kanalnog sistema: monokona tehnika i opturacija tehnikom zagrejane gutaperke na čvrstom nosaču. Materijali i metode: U studiji, uzorak su činili vitalni jednokoreni humani zubi, sa sličnom morfologijom, ekstrahovani iz parodontoloških i ortodontskih razloga. U ispitivanje je uključeno 66 zuba. Uzorak je podeljen u dve grupe na osnovu tehnike opturacije, a svaka grupa je dodatno podeljena na još tri podgrupe u zavisnosti od endodontskog cementa koji je ispitivan, što ukupno čini 6 grupa od po 10 kanala. Zubi sa intaktnim krunicama (n=3) predstavljali su negativnu kontrolnu grupu, dok su uzorci (n=3) opturisani samo gutaperkom predstavljali pozitivnu kontrolnu grupu. Rezultati: Pojava mikrocurenja kod monokone tehnike i tehnike zagrejane gutaperke na čvrstom nosaču (Thermafil) prvi put se pojavljuje 14. dana od momenta inokulacije bakterijskim sojem. Kod monokone tehnike opturacije u 50% uzoraka do 33. dana došlo je do pojave mikrocurenja nakon inokulacije bakterijskim sojem. Kod tehnike zagrejane gutaperke na čvrstom nosaču (Thermafil) u 53,33% uzoraka do 33. dana došlo je do pojave mikrocurenja nakon inokulacije bakterijskim sojem. AH plus cement pokazuje statistički značajno bolje rezultate zaptivanja kanala korena od BC sealer cementa i Acroseal cementa, bez obzira na korišćenu teniku opturacije. AH plus pokazuje statistički značajno manju pojavu mikrocurenja uz primenu monokone tehnike opturacije. Acroseal cement je obezbedio adekvatno zaptivanje kanala korena u obe korišćene tehnike opturacije u periodu od 23 dana od inokulacije što je statistički značajno bolje u odnosu na odnosu na AH plus i BC sealer, bez obzira na korišćenu teniku opturacije Zaključak: Na osnovu dobijenih rezultata može se zaključiti da kanalno punjenje može da prevenira pojavu mikrocurenja maksimalno do 14 dana, te je u tom periodu neophodno izvršiti definitivnu koronarnu restauraciju, u suprotonom neophodno je ponoviti endodontski tretman., Endodontic therapy is a relatively complex microsurgical intervention on a pathologically altered or traumatically damaged pulp. The most common cause of failure of endodontic therapy is apical leakage, which most often allows the progression of microorganisms due to incomplete canal obstruction. Further causes of failure are: anatomo-morphological variations of the canal system, calcified and impassable canals, heavily curved and forgotten (untreated) canals, etc. Gutta-percha is most commonly used for canal obturation because it has a good physical and biological properties, but due to poor dentin adhesion and insufficient filling of the micro space within the canal system, it has to be used in combination with sealer. Endodontic sealers are responsible for filling imperfections in the prepared canals, eliminating the remaining bacteria, and sealing the canal system. Ideal endodontic cement has the ability to adapt to the walls of the root canal, to fill the accessory canals and apical ramifications, areas of resorption, irregularities within the canal system and spaces that the gutta-percha cannot fill, which as such are a potential reservoir for bacterial colonization. Endodontic cements that have the ability to penetrate the dentinal tubules may have exhibit a potential antibacterial capacity and thus further affect the number of bacteria remaining. The aim of this study was to determin the quality of sealing properties of calcium silicate-based bioceramic cement over conventional epoxy-bisphenol resin and epoxy-bisphenol resin and calcium hydroxide cements and two obturation techniques: single-cone technique and Thermafil technique. Materials and methods: In the study, the sample was consisted of vital single-rooted human teeth, with similar morphology, extracted by periodontal and orthodontic reasons. 66 teeth were included in the test. The sample was divided into two groups on the basis of the technique of opturation, and each group was further divided into three more subgroups depending on the endodontic cement that was examined, making a total of 6 groups of 10 canal each. Teeth with intact crowns (n = 3) represented a negative control group, whereas specimens (n = 3) only gutta-percha-treated specimens represented a positive control group. Results: The occurrence of micro leakage in the monocone technique and Thermafil technique first appears on 14th day from the moment of inoculation with bacterial strain. With the monocone technique of opturation, micro leakage occurred in 50% of the samples by day 33 after inoculation with bacterial strain. In Thermafil technique 53.33% of samples by day 33 showed microleakage after inoculation with bacterial strain. AH plus cement shows statistically significantly better root canal sealing results than BC sealer cement and Acroseal cement, regardless of the used techiques. AH plus sealer shows a statistically significantly lower incidence of microleakage with the use of a single-cone technique. Acroseal cement provided adequate root canal sealing in both used techniques of inoculation over a period of 23 days after inoculation, which is statistically significantly better than that of AH plus and BC sealer, regardless of the technique used. Conclusion: Based on the obtained results, it can be concluded that canal filling can prevent the occurrence of microleakage for up to 14 days, then during this period it is necessary to perform definitive coronary restoration, otherwise it is necessary to do retreatment.

Uvod/cilj U poslednjoj deceniji zabeleženo je povećanje rezistencije Grampozitivnih koka na antibiotike iz grupe makrolida, linkozamida i streptogramina A/B (MLSa/b). Složeni mehanizmi rezistencije na MLS antibiotike uključuju: modifikaciju ribozoma, aktivno izbacivanje antibiotika i modifikaciju antibiotika. Porodica gena odgovornih za kodiranje enzima koji vrše metilaciju ribozoma je označena skraćenicom erm (od engl. erythromycin resistance methylase) i dovode do pojave unakrsne rezistencije na makrolide, linkozamide i streptogramine grupe B (MLSb). Profil rezistencije poznat kao MLSb fenotip može biti: inducibilan (iMLSb) i konstitutivan (cMLSb). Sojevi sa erm posredovanom eritromicin rezistencijom mogu se pokazati osetljivim na klindamicin u rutinskom disk difuzionom testiranju osetljivosti. Ciljevi Utvrditi učestalost fenotipova i gena rezistencije na MLS antibiotike kod Gram-pozitivnih koka na području jugoistočne Srbije. Metode MLS fenotipovi rezistencije: konstitutivni (cMLSb), inducibilni (iMLSb), M/MSb i LSa/b, bili su utvrđeni dupli-disk difuzionom metodom (D-testom). Ispitano je 2366 kliničkih izolata Gram-pozitivnih koka, sakupljenih u toku jednogodišnjeg perioda u Centru za mikrobiologiju Zavoda za javno zdravlje Vranje. Geni koji kodiraju MLSb rezistenciju (ermA, ermB, ermC, msrA, msrB, mefA/E, lnuA, lnuB, lsaA i lsaC) su identifikovani korišćenjem multipleks PCR-a. Rezultati Najveću učestalost rezistencije na eritromicin imali su izolati meticilin-rezistentnih koagulaza-negativnih stafilokoka (MRCNS, 91,5%), zatim meticilin-rezistentnih S. aureus (MRSA, 86,4%) i enterokoka (80,8%). Niža, ali još uvek visoka stopa rezistencije na eritromicin je bila prisutna i kod drugih izolata Gram-pozitivnih koka. Nasuprot makrolidima, izuzev za izolate Enterococcus spp. (96,7%), Streptococcus pneumoniae (35,9%) i MRSA (28,4%), drugi izolati Grampozitivnih koka su pokazali značajno nižu rezistenciju na klindamicin. Otkrili smo da je iMLSb fenotip najučestaliji kod stafilokoka, kod enterokoka i bakterija S. agalactiae i S. pnemoniae bio je dominantan cMLSb fenotip, dok je M/MSb fenotip bio najčešće prisutan kod bakterija S. pyogenes. Od ukupnog broja izolata četiri soja suV pokazala novi "keyhole" fenotip. Najčešći pojedinačni geni i njihove kombinacije detektovane kod stafilokoka su bile msrA/B, ermC i ermS+msrA/B, dok su kod enterokoka i ß-hemolitičkih streptokoka bile lsaA, ermB i ermB+lsaA. Zaključak Utvrdili smo visoku stopu rezistencije na eritromicin kod Grampozitivnih koka. Meticilin-rezistentne stafilokoke su bile značajno rezistentnije na MLS antibiotike u odnosu na meticilin-senzitivne stafilokoke. Najčešće identifikovani gen MLS rezistencije među stafilokokama bio je ermC, dok je među enterokokama i ß-hemolitičkim streptokokama bio ermB gen. Utvrđena je jasna razlika u obrascu MLS osetljivosti među stafilokokama i enterokokama/streptokokama i potvrđena je neophodnost uvođenja D testa u rutinskom testiranju antimikrobne osetljivosti kod izolata stafilokoka. Introduction The increase of resistance to macrolide, lincosamide, and streptogramin a/b antibiotics (MLSa/b) among Gram-positive cocci has been reported in the last decade. The complex mechanisms of resistance to MLS antibiotics include: modification of ribosome, active efflux of antibiotics and antibiotic inactivation. The gene family called erm (erythromycin resistance methylase) that encoding enzymes responsible for ribosome methylation leads to cross- resistance to macrolides, lincosamides and streptogramin b (MLSb resistance phenotype). The antimicrobial resistance profile known as MLSb resistance phenotype can be either inducible (iMLSb) and constitutive (cMLSb). Macrolide resistant strains carrying erm gene can show false sensitivity to clindamycin, using routine antimicrobial susceptibility test. Objective This study investigated the prevalence of MLS resistance phenotypes and genes in Gram-positive cocci in region of the Southeast Serbia. Methods MLS resistance phenotypes: constitutive (cMLSb), inducible (iMLSb), M/MSb, and LSa/b, were determined by the double-disk diffusion method. We have analyzed 2366 clinical isolates of Gram-positive cocci, collected during 1-year period at the Center for Microbiology of the Public Health Institute in Vranje, Serbia. The MLS resistance genes (ermA, ermB, ermC, msrA, msrB, mefA/E, lnuA, lnuB, lsaA, and lsaC) were identified by multiplex PCR. Results The highest frequencies of isolates resistant to erythromycin were found among methicillin-resistant coagulase-negative staphylococci (MRCNS, 91.5%), methicillin-resistant S. aureus (MRSA, 86.4%) and Enterococcus strains (80.8%). Lower, but still high resistance rate to erythromycin was found among other Gram-positive cocci. Contrary to macrolides, except for Enterococcus spp. (96.7%), S. pneumoniae (35.9%), and MRSA (28.4%), other Gram-positive cocci showed significantly lower resistance to clindamycin. We have found that iMLSb is the most prevalent phenotype in staphylococci, the cMLSb is predominantly in enterococci, S. agalactiae, and S. pnemoniae, whereas the M/MSb phenotype is the most frequent in S. pyogenes. LSa/b phenotype was the most common in enterococci and beta haemolytic streptococci, but nearly or totally absented among staphylococci, S. pneumoniae, and S. pyogenes. The novel keyhole zone phenomenon was detected in four out of total number of clinical isolates. The most prevalent MLS resistance genes and their combinations detectedVII in staphylococci were msrA/B, ermC and ermС+msrA/B, whereas lsaA, ermB и ermB+lsaA were predominantly found in enterococci and beta haemolytic streptococci. Conclusion Generally, high rates of erythromycin resistance in Gram-positive cocci was found. The methicillin-resistant staphylococci were significantly more resistant to MLS antibiotics than methicillin-sensitive staphylococci. The most frequent MLS resistance gen among staphylococci isolates was ermC, whereas the ermB gen was the most prevalent in enterococci and ß-haemolytic streptococci. We have also discovered a clear differences of MLS resistance pattern in staphylococci and enterococci/streptococci, and confirmed the necessity of routine D-testing of all clinical isolates of staphylococci.