Evaluation of the current disease severity scores in paediatric FMF: Is it necessary to develop a new one?

Objectives: Modified adult disease severity scoring systems are being used for childhood FMF. We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease.Methods. Two hundred and fifty-eight children with FMF were cross-sectionally studied. Assessment of the disease severity was performed by using the modified scoring systems of Mor et al. and Pras et al. Genetic analysis was performed using PCR and restriction endonuclease digestion methods for the presence of 15 FMF gene mutations. FMF mutations were grouped into three based on well-known genotypic-phenotypic associations. Correlation between the mutation groups and the severity scoring systems was assessed. The consistency of the severity scoring systems was evaluated.Results. The results of two scoring systems were not statistically consistent with each other (κ = 0.171). This inconsistency persisted even in a more homogeneous subgroup of patients with only homozygote mutations of M694V, M680I and M694I (κ = 0.125). There was no correlation between the mutation groups and either of the scoring systems (P = 0.002, r = 0,196 for scoring systems of Mor et al.; P = 0.009, r = 0.162 for Pras et al.).Conclusions. The inconsistency of the two scoring systems and lack of correlation between the scoring systems and mutation groups raises concerns about the reliability of these scoring systems in children. There is a need to develop a scoring system in children based on a prospective registry. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved

The relationship between antibiotic resistance and virulence factors in urinary Enterococcus isolates

Son yıllarda tüm dünyada nozokomiyal enterokok suşlarında artan çoklu antimikrobiyal direnç gelişimi, özellikle virülans faktörleri olmak üzere enterokokların daha iyi incelenmesi gerektiğini ortaya koymuştur. Klinik izolatların virülans faktörleri konusunda halen pek çok şey bilinmemektedir. Bu çalışmada, hastanemizde Ocak 2008-Haziran 2010 ayları arasında yatan hastaların idrar kültürlerinden izole edilen toplam 91 enterokok izolatının (59 E.faecalis, 31 E.faecium ve 1 E.gallinarum) çeşitli antibiyotiklere direnç durumları ve potansiyel virülans faktörlerinin araştırılması amaçlanmış ve aralarında bir ilişkinin var olup olmadığı irdelenmiştir. Bu amaçla, enterokokların virülans faktörlerinden agregasyon faktörü (AF), enterokok yüzey proteini (ESP) ve hiyalüronidazı (HYL) kodlayan genler (sırasıyla asa1, esp, hyl) moleküler yöntemlerle, hemolizin üretimi ve jelatinaz aktivitesi ise fenotipik yöntemlerle araştırılmıştır. Vankomisine dirençli bulunan enterokoklar, ayrıca vanA ve vanB genlerinin varlığı açısından incelenmiştir. E.faecium suşlarından 8 (%25.8)’inin glikopeptidlere dirençli olduğu saptanmış, bunların yedisinin vanA, birinin ise vanA-vanB dışı direnç tipinde olduğu belirlenmiştir. Yüksek düzey gentamisin ve yüksek düzey streptomisin direnci, E.faecium suşlarında sırasıyla %74.2 ve %61.3 iken, E.faecalis suşlarında %22 ve %27.1 olarak tespit edilmiştir. İncelenen suşların hiçbirisinde beta-laktamaz üretimi ve linezolid direnci tespit edilmemiştir. Tetrasiklin, minosiklin, doksisiklin ve streptogramin dışında test edilen antibiyotiklere E.faecium izolatlarının, E.faecalis izolatlarına göre daha dirençli (p< 0.001-0.013), bu dört antibiyotiğe ise daha duyarlı (p< 0.001) oldukları saptanmıştır. E.faecalis izolatlarında esp (p= 0.003) ve asa1 (p< 0.001) gen pozitifliğinin yanı sıra hemolizin üretimi (p= 0.014) ve jelatinaz aktivitesi (p= 0.029), E.faecium izolatlarında ise hyl gen pozitifliği (p< 0.001) anlamlı düzeyde yüksek bulunmuştur. AF ve ESP, sırasıyla %26.7 ve %25.6 pozitiflik oranları ile çalışmamızda en sık saptanan virülans faktörleri olmuştur. İzolatlarımızdan 5 (%5.6)’inin üçer, 16 (%17.8)’sının ikişer ve 37 (%41.1)’sinin ise sadece birer virülans faktörü içerdiği, 32 (%35.6) izolatın ise herhangi bir virülans faktörü içermediği belirlenmiştir. İncelenen virülans faktörlerinden tümünü veya dördünü bir arada içeren izolat saptanmamıştır. Çalışmamızda ayrıca asa1 geni pozitif E.faecalis izolatlarının siprofloksasin (p= 0.001), norfloksasin (p= 0.006) ve levofloksasine (p= 0.001), esp geni pozitif E.faecalis izolatlarının doksisikline (p= 0.043) ve hyl geni pozitif E.faecium izolatlarının ise nitrofurantoine (p= 0.011), söz konusu genleri içermeyen izolatlara göre anlamlı düzeyde daha dirençli oldukları saptanmıştır. Bu çalışma, üriner enterokok izolatlarının antibiyotik direnci ile virülans faktörleri arasındaki ilişkinin incelendiği ülkemizdeki ilk hasta kaynaklı çalışma olma özelliğini taşımaktadır.Increasing multidrug resistance in nosocomial Enterococcus strains from all over the world recently enhances the need for further investigation of enterococci, especially their virulence factors. There are still many lacking parts about virulence factors of clinical enterococcus isolates. In this study, it was aimed to investigate the antibiotic resistance and the presence of potential virulence factors of 91 Enterococcus strains (59 E.faecalis, 31 E.faecium and 1 E.gallinarum) isolated from urine cultures of inpatients between January 2008-June 2010 in our hospital and also to evaluate whether a correlation existed between antibiotic resistance and potential virulence factors. The genes which encoded virulence factors of enterococci; aggregation substance (AS), enterococcal surface protein (ESP) and hyaluronidase (HYL) (asa1, esp, hyl respectively) were studied by molecular methods and haemolysin production and gelatinase activity were studied by phenotypic methods. Vancomycin-resistant strains were checked for the presence of vanA and vanB genes. Eight (25.8%) E.faecium isolates were found glycopeptide resistant. In seven of these isolates resistance type was vanA and in one it was neither vanA nor vanB. High-level gentamicin and high-level streptomycin resistance rates were 74.2% and 61.3% in E.faecium strains and were 22% ve 27.1% in E.faecalis strains, respectively. Beta-lactamase production and linezolid resistance were not detected in any of the strains. E.faecium isolates were more resistant (p&lt; 0.001-0.013) than E.faecalis isolates to all tested antibiotics except tetracycline, minocycline, doxycycline and streptogramin (p&lt; 0.001). hyl gene positivity (p&lt; 0.001) was found higher in E.faecium isolates whereas esp (p= 0.003) and asa1 (p&lt; 0.001) gene positivity, haemolysin production (p= 0.014) and gelatinase activity (p= 0.029) were higher in E.faecalis isolates. AS and ESP were the most frequent virulence factors, with the rates of 26.7% and 25.6%, respectively. There were 32 (35.6%) strains without any of the investigated virulence factors. We have also detected that asa1 gene positive E.faecalis isolates were more resistant to ciprofloxacin (p= 0.001), norfloxacin (p= 0.006) and levofloxacin (p= 0.001) than asa1 gene negative isolates; esp gene positive E.faecalis isolates were more resistant to doxycycline (p= 0.043) than esp gene negative isolates and hyl gene positive E.faecium isolates were more resistant to nitrofurantoine (p= 0.011) than hyl gene negative isolates. This was the first clinical sample originated study, investigating the corelation between antibiotic resistance and virulence factors in urinary Enterococcus isolates in Turkey

Evaluation of the current disease severity scores in paediatric FMF: is it necessary to develop a new one?

Objectives. Modified adult disease severity scoring systems are being used for childhood FMF. We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease