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Distribution of resistance phenotypes and genes to macrolides and lincozamides in gram-positive cocci

dc.contributor.advisorBaskić, Dejan
dc.contributor.otherKocić, Branislava
dc.contributor.otherRanin, Lazar
dc.contributor.otherMedić, Deana
dc.creatorMišić, Milena
dc.date.accessioned2020-02-26T15:44:43Z
dc.date.available2020-02-26T15:44:43Z
dc.date.available2020-07-03T15:15:28Z
dc.date.issued2019-09-30
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/11999
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=7105
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1201/bdef:Content/download
dc.description.abstractUvod/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.sr
dc.description.abstractIntroduction 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.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41010/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/46012/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172016/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectGram-pozitivne kokesr
dc.subjectGram-positive coccien
dc.subjectD-testsr
dc.subjectMLS fenotip rezistencijesr
dc.subjectermsr
dc.subjectmsrAsr
dc.subjectBsr
dc.subjectlsaAsr
dc.subjectlnuAsr
dc.subjectB gensr
dc.subjectMLSb resistance phenotypesen
dc.subjectD-testen
dc.subjectermen
dc.subjectmsrAen
dc.subjectBen
dc.subjectlsaAen
dc.subjectlnuАen
dc.subjectB genesen
dc.titleDistribucija fenotipova i gena rezistencije na makrolide i linkozamide kod gram-pozitivnih kokasr
dc.title.alternativeDistribution of resistance phenotypes and genes to macrolides and lincozamides in gram-positive coccien
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-SA
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48643/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48644/Milena_Misic_Medicinski.pdf


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