Publication: Streptococcus Pneumoniae’nin makrolid direncinde mef denetimindeki aktif ilaç pompasının rolü
Abstract
Streptococcus pneumoniae toplum kaynaklı solunum yolu enfeksiyonlarının en önemli etkeni olup, morbiditesi ve mortalitesi yüksek enfeksiyonlara yol açan bir patojendir. Makrolidlerin toplum kaynaklı solunum yolu enfeksiyonlarının tedavisinde yaygın ve uygunsuz kullanımı, bu grup antibiyotiklere dirençli pnömokokların tüm dünyada yayılmasına yol açmıştır. Ülkemizde makrolidlere dirençli pnömokokların insidansı % 25’in üzerindedir. Çalışmamızda amacımız; hastanemizde klinik örneklerden enfeksiyon etkeni olarak izole edilen ve makrolid direnci gösteren pnömokok izolatlarının makrolid direncinde, mef denetimindeki aktif ilaç pompasının rolünü ortaya koymaktır. İzolatların disk difüzyon yöntemi ile eritromisin, azitromisin, klaritromisin, klindamisin duyarlılığı ve sıvı mikrodilüsyon yöntemi ile minimum inhibitör konsantrasyonları belirlenmiştir. Makrolid direnç fenotipinin saptanmasında eritromisin ve klindamisin çift disk yöntemi kullanılmıştır. İzolatlarda makrolid direncinin genetik determinantları mef(A), mef(E), erm(B), erm(TR) her gene özgü primerler kullanılarak PZR yöntemiyle tespit edilmiştir. İzolatların % 40’ında (n:20) sadece erm(B), % 30’unda (n:15) sadece mef(E) geni, % 30’unda (n:15) da her iki gen birlikte bulunmuştur. erm(B) taşıyan izolatlar cMLSB fenotipinde olup, makrolid ve linkozamid MİK’leri yüksek düzeydedir. Sadece mef(E) taşıyan izolatların 14’ünde M fenotipi saptanmış ve makrolid MİK’leri göreceli olarak düşük bulunmuştur. mef(E) taşıyan 1 izolat iMLSB fenotipinde bulunmuştur. Çalıştığımız kökenlerdeki yüksek eritromisin direncinden sorumlu olan ana mekanizma hedef bölge değişikliği [erm(B)] olarak bulunmasına rağmen, yalnız başına ya da erm(B) ile birlikte bulunan yüksek mef(E) geni varlığı, bölgemizdeki makrolid dirençli pnömokoklar açısından yeni bir tehdit olarak karşımıza gelmektedir. Anahtar sözcükler: erm(B), makrolid direnci, mef(E), Streptococcus pneumoniae
The Role of the Active Macrolide Efflux Pump Mediated by mef in the Macrolide Resistance of Streptococcus pneumoniae Streptococcus pneumoniae is the most important pathogen of the community-acquired respiratory tract infections and causes high morbidity and mortality rates. Widespread and improper use of macrolides for the treatment of the community-acquired respiratory tract infections has led to the quick spread of the antibiotic-resistant pneumococci throughout the world. Incidence rate of the macrolide-resistant pneumococci is 25 % in our country. Our aim in this study is to display the role of the active drug pump under the control of mef in the macrolide resistances of pneumococcus isolates that are isolated from the clinical samples as the infection factor in our hospital and show macrolide resistance. Erytromycin, azithromycin, clarithromycin, clindamycin sensitivity of the isolates were determined with disc diffusion method and their minimum inhibitory concentrations investigated with liquid microdilution method. Erytromycin and clindamycin double disc method was used for the determination of macrolide resistance phenotype. Genetic determinants of the macrolide resistance: mef(A), mef(E), erm(B), erm(TR) genes were detected in the isolates with PCR method by using primers specific to each gene. erm(B) was the only gene in 40 % (n:20) of the isolates while mef(E) gene was detected alone in 30 % (n:15) of the isolates and both genes were detected in 30 % (n:15). Isolates carrying erm(B) show cMLSB phenotype and their macrolide and lincosamide MIC levels are high. M phenotype was detected in 14 of the isolates carrying only mef(E) and their macrolide MIC levels were found to be relatively low. One isolate carrying mef(E) was found to show iMLSB phenotype. Although the main mechanism responsible for the high erytromycin resistance in the origins of our study was found out to be the target area change [erm(B)], presence of mef(E) gene either alone or with erm(B) emerges as a new threat to the macrolide-resistant pneumococci in our region. Key words: erm(B), macrolide resistance, mef(E), Streptococcus pneumoniae
The Role of the Active Macrolide Efflux Pump Mediated by mef in the Macrolide Resistance of Streptococcus pneumoniae Streptococcus pneumoniae is the most important pathogen of the community-acquired respiratory tract infections and causes high morbidity and mortality rates. Widespread and improper use of macrolides for the treatment of the community-acquired respiratory tract infections has led to the quick spread of the antibiotic-resistant pneumococci throughout the world. Incidence rate of the macrolide-resistant pneumococci is 25 % in our country. Our aim in this study is to display the role of the active drug pump under the control of mef in the macrolide resistances of pneumococcus isolates that are isolated from the clinical samples as the infection factor in our hospital and show macrolide resistance. Erytromycin, azithromycin, clarithromycin, clindamycin sensitivity of the isolates were determined with disc diffusion method and their minimum inhibitory concentrations investigated with liquid microdilution method. Erytromycin and clindamycin double disc method was used for the determination of macrolide resistance phenotype. Genetic determinants of the macrolide resistance: mef(A), mef(E), erm(B), erm(TR) genes were detected in the isolates with PCR method by using primers specific to each gene. erm(B) was the only gene in 40 % (n:20) of the isolates while mef(E) gene was detected alone in 30 % (n:15) of the isolates and both genes were detected in 30 % (n:15). Isolates carrying erm(B) show cMLSB phenotype and their macrolide and lincosamide MIC levels are high. M phenotype was detected in 14 of the isolates carrying only mef(E) and their macrolide MIC levels were found to be relatively low. One isolate carrying mef(E) was found to show iMLSB phenotype. Although the main mechanism responsible for the high erytromycin resistance in the origins of our study was found out to be the target area change [erm(B)], presence of mef(E) gene either alone or with erm(B) emerges as a new threat to the macrolide-resistant pneumococci in our region. Key words: erm(B), macrolide resistance, mef(E), Streptococcus pneumoniae