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The relationship between macrolide resistance mechanisms and serotypes of Streptococcus pneumoniae

Yıl 2012, Cilt: 2 Sayı: 3, 124 - 129, 30.01.2014

Öz

Objective: Increased resistance rate to macrolides used as empirical treatment of pneumococcal infections is a major problem in our country and all over the world. In our study, we aimed to determine macrolide resistance mechanisms of the erythromycin-resistant Streptococcus pneumonia isolated from clinical samples and to investigate serotype and resistance relationship within our region with the high macrolide resistance rates among pneumococci.

Methods: Fifty isolates were studied for erythromycin, azithromycin, clarithromycin, clindamycin susceptibilities with disk diffusion, and liquid microdilution methods. Genetic determinants of macrolide resistance, mef(A), mef(E), erm(B), erm(TR) genes were investigated by PCR using specific primers for each gene, multiplex PCR was used to determine the serotypes. 

Results: Constitutive and inducible MLSB phenotypes and M phenotype were expressed in 86%, 4% and 10% of the isolates, respectively. Total of 42% of the isolates (n=21) were positive for erm(B), 12% (n=6) for mef(E) gene, in 46% (n=23) of the isolates both genes were detected. Serotype distribution was as follows: 28 (56%) 19F, 6 (12%) 6A/B, 5 (10%) 23F, 1 (2%) 39, 2 (4%) 15A-F, 1 (2%) 14, 1 (% 2) 23B and 6 (%12) isolates were nontypeable. 12 isolates carry erm(B), and 16 isolates carry both erm(B) and mef(E) in serotype 19F. One isolate carries erm(B), and 5 isolates carry both erm(B) and mef(E) in serotype 6A/B. Four isolates carry erm(B) and one isolate carries both erm(B) and mef(E) in serotype 23F.

Conclusion: The most striking results of this study are the presence of macrolide efflux pump coding mef(E) gene in 58% of our isolates, the presence of additional erm(B) gene in %46 of isolates, and high rate of erm(B)+ mef(E) genes combination (56%) in predominant serotype 19F isolates.


Key words: Macrolide resistance, erm(B), mef(E), serotype, Streptococcus pneumoniae

Kaynakça

  • Tomasz A. Antibiotic resistance in Streptococcus pneumoniae. Clin Infect Dis.1997;24(Suppl 1):85-88.
  • Reinert RR. The antimicrobial resistance profile of Streptococcus pneumoniae. Clin Microbiol Infect. 2009;15(Suppl 3):7-11.
  • Hasdemir U. Çoklu ilaç direncinde bakteri hücre duvarı organizasyonunun ve aktif pompa sistemlerinin rolü. Mikrobiyol Bul.2007;41:309-327.
  • Henrichsen J. Six newly recognized types of Streptococcus pneumoniae. J Clin Microbiol. 1995;33:2759-2762.
  • AlonsoDeVelasco E, Verheul AF, Verhoef J, Snippe H. Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines. Microbiol Rev. 1995;59:591-603.
  • Musher DM. Streptococcus pneumoniae. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Churchill Livingstone, 2004:p.2392-2411.
  • Appelbaum PC. Resistance among Streptococcus pneumoniae: Implications for drug selection Clin Infect Dis. 2002;34:1613-1620.
  • Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Winn Jr WC. The Gram positive cocci Part II: Streptococci,Enterococci, and the “Streptococci-Like “ Bacteria. Color Atlas and Textbook of Diagnostic Microbiology. 6th ed.Philadelphia, Lippincott,2006. p.578-610.
  • Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Approved Standard, 7 th ed. Clinical and Laboratory Standards Institute, Wayne, PA. CLSI, 2006.
  • Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Nineteenth informational supplement. M100-S19. Wayne, PA: CLSI; 2009.
  • Werno AM, Murdoch DR. Medical microbiology: Laboratory diagnosis of invasive pneumococcal disease. Clinical Infectious Disease. 2008;46:926-932.
  • Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Eighteenth informational supplement. M100-S18. Wayne, PA: CLSI; 2008.
  • Amezaga MR, Carter PE, Cash P, McKenzie H. Molecular epidemiology of erythromycin resistance in Streptococcus pneumoniae isolates from blood and noninvasive sites. J Clin Microbiol. 2002;40:3313-3318.
  • Pai R, Gertz RE, Beall B. Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates. J Clin Microbiol. 2006; 44:124-131.
  • Gürler N. Pnömokok infeksiyonlarında mikrobiyoloji ve direnç, ANKEM Dergisi. 2008; 22 (Ek 2): 238-251.
  • hpsc.ie[Internet]. EARSS Quarterly Surveillance Reports
  • –2005 [cited 2012 Aug 25]. Available from: http://www. hpsc.ie/hpsc/A-Z/MicrobiologyAntimicrobialResistance/ EuropeanAntimicrobialResistanceSurveillanceSystemEARSS/EARSSS urveillanceReports/2005Reports/
  • hpsc.ie[Internet]. EARSS Quarterly Surveillance Reports–2008 [cited 2012 Aug 25]. Available from: http://www.hpsc. i e / h p s c / A - Z / M i c r o b i o l o g y A n t i m i c r o b i a l R e s i s t a n c e / EuropeanAntimicrobialResistanceSurveillanceSystemEARSS/EARSSS urveillanceReports/2008Reports/
  • Sağıroğlu P. Aksu B, Hasdemir U. Streptococcus pneumoniae’da makrolid direnç mekanizmalarının araştırılması: 2005-2008, Marmara Üniversitesi Hastanesi Sonuçları. Marmara Med Journal. 2011;24:15- 20.
  • Reinert RR, Reinert S, van der Linden M, Cil MY, Al-Lahham A, Appelbaum P. Antimicrobial susceptibility of Streptococcus pneumoniae in eight European countries from 2001 to 2003. Antimicrob Agents Chemother. 2005;49:2903-2913.
  • Gür D, Mülazımoğlu L, Ünal S. In vitro susceptibility of respiratory isolates of Streptococcus pneumoniae and Streptococcus pyogenes to telithromycin and 11 other antimicrobial agents: Turkish results of e-BASKETT II Surveillance Study. Mikrobiyol Bul. 2007;41:1-9.
  • Gülay Z, Özbek ÖA, Biçmen M, Gür D. Macrolide resistance determinants in erythromycin- resistant Streptococcus pneumoniae in Turkey. Japanese Journal of Infectious Diseases. 2008;61:490-493.
  • Imöhl M, Reinert RR, Mutscher C, van der Linden M. Macrolide susceptibility and serotype specific macrolide resistance of invasive isolates of Streptococcus pneumoniae in Germany from 1992 to 2008. BMC Microbiol. 2010;10:299.
  • Telli M, Eyigör M, Gültekin B, Aydın N. Evaluation of resistance mechanisms and serotype and genotype distributions of macrolide- resistant strains in clinical isolates of Streptococcus pneumoniae in Aydın, Turkey. J Infect Chemother. 2011;17:658-664.
  • Farrell DJ, Morrissey I, Bakker S, Felmingham D. Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999-2000 study. J Antimicrob Chemother. 2002;50(S1):39-47.
  • Klaassen CH, Mouton JW. Molecular detection of the macrolide efflux gene: to discriminate or not to discriminate between mef(A) and mef(E). Antimicrob Agents Chemother. 2005;49:1271-1278.
  • Leclercq R, Courvalin P. Resistance to macrolides and related antibiotics in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2002;46:2727-2734.

Streptococcus pneumoniae’da makrolid direnç mekanizmaları ile serotip ilişkisi

Yıl 2012, Cilt: 2 Sayı: 3, 124 - 129, 30.01.2014

Öz

Amaç: Pnömokok enfeksiyonlarının tedavisinde ampirik olarak kullanılan makrolid grubu antibiyotiklerdeki direnç oranlarının artışı, tüm dünyada ve ülkemizde önemli bir sorundur. Çalışmamızda; pnömokoklarda makrolid direncinin yüksek olduğu bölgemizde, başvuran hastaların klinik örneklerinden izole edilen eritromisin dirençli Streptococcus pneumoniae izolatlarında makrolid direnç mekanizmalarının belirlenmesi ve direncin klinik izolatlarımızın serotipleri ile ilişkisinin incelenmesi amaçlanmıştır. 

Yöntemler: Toplam 50 izolatın eritromisin, azitromisin, klaritromisin, klindamisin duyarlılıkları disk difüzyon yöntemi ile; minimum inhibitor konsantrasyonları ise sıvı mikrodilüsyon yöntemi ile belirlenmiştir. Makrolid direncinin genetik determinantları mef(A), mef(E), erm(B), erm(TR) her gene özgü primerler kullanılarak PZR yöntemiyle, serotip tayini ise multipleks PZR ile araştırılmıştır.

Bulgular: İzolatların %86’sı yapısal, %4’ü indüklenebilir MLSB fenotipi; %10’u M fenotipi göstermiştir. İzolatların %42’sinde (n:21) sadece erm(B), %12’sinde (n:6) sadece mef(E) geni, %46’sında da (n:23) her iki gen birlikte saptanmıştır. İzolatların serotip dağılımı; 28’i (%56) 19F, 6’sı (%12) 6A/B, 5’i (%10) 23F, 1’i (%2) 39, 2’si (%4) 15A-F, 1’i (%2) 14, 1’i (%2) 23B şeklindedir; 6 (%12) izolat ise tiplendirilememiştir. 19F serotipindeki izolatların; 12’si sadece erm(B), 16’sı erm(B) ile mef(E) genini birlikte taşımaktadır. 6A/B serotipindeki izolatların 1’i sadece erm(B), 5’i mef(E) ile beraber erm(B) geni bulundurmaktadır. 23F serotipindeki izolatların ise 4’ü sadece mef(E), 1’i mef(E) ile birlikte erm(B) geni taşımaktadır. 

Sonuç: Makrolid atım pompa geni mef(E)’nin kökenlerimizin %58’inde bulunması, %46’sında bu genin erm(B)’ye eşlik ettiğinin gösterilmesi ve koleksiyonumuzda baskın olarak saptanan 19F serotipindeki izolatlarda erm(B)+mef(E) gen birlikteliğinin çok yüksek oranda (%56) bulunması çalışmamızın çarpıcı sonuçlarıdır.


Anahtar Kelimeler : akrolid direnci, erm(B), mef(E), serotip, Streptococcus pneumoniae

Kaynakça

  • Tomasz A. Antibiotic resistance in Streptococcus pneumoniae. Clin Infect Dis.1997;24(Suppl 1):85-88.
  • Reinert RR. The antimicrobial resistance profile of Streptococcus pneumoniae. Clin Microbiol Infect. 2009;15(Suppl 3):7-11.
  • Hasdemir U. Çoklu ilaç direncinde bakteri hücre duvarı organizasyonunun ve aktif pompa sistemlerinin rolü. Mikrobiyol Bul.2007;41:309-327.
  • Henrichsen J. Six newly recognized types of Streptococcus pneumoniae. J Clin Microbiol. 1995;33:2759-2762.
  • AlonsoDeVelasco E, Verheul AF, Verhoef J, Snippe H. Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines. Microbiol Rev. 1995;59:591-603.
  • Musher DM. Streptococcus pneumoniae. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia: Churchill Livingstone, 2004:p.2392-2411.
  • Appelbaum PC. Resistance among Streptococcus pneumoniae: Implications for drug selection Clin Infect Dis. 2002;34:1613-1620.
  • Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Winn Jr WC. The Gram positive cocci Part II: Streptococci,Enterococci, and the “Streptococci-Like “ Bacteria. Color Atlas and Textbook of Diagnostic Microbiology. 6th ed.Philadelphia, Lippincott,2006. p.578-610.
  • Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Approved Standard, 7 th ed. Clinical and Laboratory Standards Institute, Wayne, PA. CLSI, 2006.
  • Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Nineteenth informational supplement. M100-S19. Wayne, PA: CLSI; 2009.
  • Werno AM, Murdoch DR. Medical microbiology: Laboratory diagnosis of invasive pneumococcal disease. Clinical Infectious Disease. 2008;46:926-932.
  • Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Eighteenth informational supplement. M100-S18. Wayne, PA: CLSI; 2008.
  • Amezaga MR, Carter PE, Cash P, McKenzie H. Molecular epidemiology of erythromycin resistance in Streptococcus pneumoniae isolates from blood and noninvasive sites. J Clin Microbiol. 2002;40:3313-3318.
  • Pai R, Gertz RE, Beall B. Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates. J Clin Microbiol. 2006; 44:124-131.
  • Gürler N. Pnömokok infeksiyonlarında mikrobiyoloji ve direnç, ANKEM Dergisi. 2008; 22 (Ek 2): 238-251.
  • hpsc.ie[Internet]. EARSS Quarterly Surveillance Reports
  • –2005 [cited 2012 Aug 25]. Available from: http://www. hpsc.ie/hpsc/A-Z/MicrobiologyAntimicrobialResistance/ EuropeanAntimicrobialResistanceSurveillanceSystemEARSS/EARSSS urveillanceReports/2005Reports/
  • hpsc.ie[Internet]. EARSS Quarterly Surveillance Reports–2008 [cited 2012 Aug 25]. Available from: http://www.hpsc. i e / h p s c / A - Z / M i c r o b i o l o g y A n t i m i c r o b i a l R e s i s t a n c e / EuropeanAntimicrobialResistanceSurveillanceSystemEARSS/EARSSS urveillanceReports/2008Reports/
  • Sağıroğlu P. Aksu B, Hasdemir U. Streptococcus pneumoniae’da makrolid direnç mekanizmalarının araştırılması: 2005-2008, Marmara Üniversitesi Hastanesi Sonuçları. Marmara Med Journal. 2011;24:15- 20.
  • Reinert RR, Reinert S, van der Linden M, Cil MY, Al-Lahham A, Appelbaum P. Antimicrobial susceptibility of Streptococcus pneumoniae in eight European countries from 2001 to 2003. Antimicrob Agents Chemother. 2005;49:2903-2913.
  • Gür D, Mülazımoğlu L, Ünal S. In vitro susceptibility of respiratory isolates of Streptococcus pneumoniae and Streptococcus pyogenes to telithromycin and 11 other antimicrobial agents: Turkish results of e-BASKETT II Surveillance Study. Mikrobiyol Bul. 2007;41:1-9.
  • Gülay Z, Özbek ÖA, Biçmen M, Gür D. Macrolide resistance determinants in erythromycin- resistant Streptococcus pneumoniae in Turkey. Japanese Journal of Infectious Diseases. 2008;61:490-493.
  • Imöhl M, Reinert RR, Mutscher C, van der Linden M. Macrolide susceptibility and serotype specific macrolide resistance of invasive isolates of Streptococcus pneumoniae in Germany from 1992 to 2008. BMC Microbiol. 2010;10:299.
  • Telli M, Eyigör M, Gültekin B, Aydın N. Evaluation of resistance mechanisms and serotype and genotype distributions of macrolide- resistant strains in clinical isolates of Streptococcus pneumoniae in Aydın, Turkey. J Infect Chemother. 2011;17:658-664.
  • Farrell DJ, Morrissey I, Bakker S, Felmingham D. Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999-2000 study. J Antimicrob Chemother. 2002;50(S1):39-47.
  • Klaassen CH, Mouton JW. Molecular detection of the macrolide efflux gene: to discriminate or not to discriminate between mef(A) and mef(E). Antimicrob Agents Chemother. 2005;49:1271-1278.
  • Leclercq R, Courvalin P. Resistance to macrolides and related antibiotics in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2002;46:2727-2734.
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Articles
Yazarlar

Nebahat Tiryakioğlu Bu kişi benim

Burak Aksu Bu kişi benim

Ufuk Över Hasdemir Bu kişi benim

Yayımlanma Tarihi 30 Ocak 2014
Gönderilme Tarihi 30 Ocak 2014
Yayımlandığı Sayı Yıl 2012 Cilt: 2 Sayı: 3

Kaynak Göster

APA Tiryakioğlu, N., Aksu, B., & Över Hasdemir, U. (2014). Streptococcus pneumoniae’da makrolid direnç mekanizmaları ile serotip ilişkisi. Clinical and Experimental Health Sciences, 2(3), 124-129.
AMA Tiryakioğlu N, Aksu B, Över Hasdemir U. Streptococcus pneumoniae’da makrolid direnç mekanizmaları ile serotip ilişkisi. Clinical and Experimental Health Sciences. Şubat 2014;2(3):124-129.
Chicago Tiryakioğlu, Nebahat, Burak Aksu, ve Ufuk Över Hasdemir. “Streptococcus pneumoniae’da Makrolid Direnç Mekanizmaları Ile Serotip ilişkisi”. Clinical and Experimental Health Sciences 2, sy. 3 (Şubat 2014): 124-29.
EndNote Tiryakioğlu N, Aksu B, Över Hasdemir U (01 Şubat 2014) Streptococcus pneumoniae’da makrolid direnç mekanizmaları ile serotip ilişkisi. Clinical and Experimental Health Sciences 2 3 124–129.
IEEE N. Tiryakioğlu, B. Aksu, ve U. Över Hasdemir, “Streptococcus pneumoniae’da makrolid direnç mekanizmaları ile serotip ilişkisi”, Clinical and Experimental Health Sciences, c. 2, sy. 3, ss. 124–129, 2014.
ISNAD Tiryakioğlu, Nebahat vd. “Streptococcus pneumoniae’da Makrolid Direnç Mekanizmaları Ile Serotip ilişkisi”. Clinical and Experimental Health Sciences 2/3 (Şubat 2014), 124-129.
JAMA Tiryakioğlu N, Aksu B, Över Hasdemir U. Streptococcus pneumoniae’da makrolid direnç mekanizmaları ile serotip ilişkisi. Clinical and Experimental Health Sciences. 2014;2:124–129.
MLA Tiryakioğlu, Nebahat vd. “Streptococcus pneumoniae’da Makrolid Direnç Mekanizmaları Ile Serotip ilişkisi”. Clinical and Experimental Health Sciences, c. 2, sy. 3, 2014, ss. 124-9.
Vancouver Tiryakioğlu N, Aksu B, Över Hasdemir U. Streptococcus pneumoniae’da makrolid direnç mekanizmaları ile serotip ilişkisi. Clinical and Experimental Health Sciences. 2014;2(3):124-9.

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