Çocuklarda helicobacter pylori gastritinde virülans faktörleri ve antibiyotik direnci
Yükleniyor...
Dosyalar
Tarih
2012
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Helicobacter pylori (Hp) dünya nüfusunun yarısından fazlasını kronik olarak enfekte eden bir patojendir. Hp gastrit, peptik ülser, gastrik mukoza ilişkili lenfoit doku lenfoması ve mide kanserinin en önemli sebebidir. Helicobacter pylori, genetik olarak farklı virulansa sahip suşları bulunan ve belli suşların daha ağır hastalığa yol açabildiği bir mikroorganizmadır. Taşıdıkları cagA, cagE, babA, iceA ve vacA gibi virülans faktörleri mide mukozasında oluşan inflamasyonun derecesinde etkilidir. Helicobacter pylori virülans faktörleri ve klinik önemleri, erişkin hastalarda yoğun olarak araştırıldığı halde çocuklarda yapılmış çalışmalar azdır. Helicobacter pylori tedavisinde kullanılan antibiyotiklere karşı tüm dünyada giderek artan bir direnç mevcuttur. Türkiye'de ve özellikle de çocuklarda Hp'nin antibiyotik direnci ile ilgili bilgiler sınırlıdır. Bu nedenle Hp suşlarının antimikrobiyal direnç durumunu belirlemek tedavinin başarısını öngörmede önemlidir. Çalışmamızda Türkiye'nin doğusunda Hp gastriti bulunan çocuklarda virülans faktörlerinin durumunu, antibiyotik dirençlerini, gastrit tablosu ve antibiyotik direncinin Hp genotipleri ile ilişkisini belirlemeyi amaçladık. Hastalar ve Yöntem: Tekrarlayan karın ağrısı şikayeti bulunan 159 hastaya üst gastrointestinal endoskopi yapılarak her hastadan iki adet antral biyopsi alındı. Polimeraz zincir reaksiyonu (PCR), kültür ve histopatolojik inceleme ile Hp enfeksiyonu saptanmaya çalışıldı. Antibiyotik duyarlılıkları disk difüzyon yöntemi ile araştırıldı. Virülans faktörlerinin tespit edilmesi için PCR kullanıldı. Histopatolojik olarak gastritin değerlendirilmesinde güncellenmiş Sydney sınıflanması kullanıldı. Bulgular: Helicobacter pylori sıklığı kültür ile %32,1, histopatoloji ile %40,9 ve PCR ile % 61,6 olarak tespit edildi. Hastaların %76,5'inde antral nodülarite görüldü. PCR sonuçlarına göre histopatolojik incelemenin duyarlılık ve özgüllüğü sırasıyla %66,3 ve %100, kültürün duyarlılık ve özgüllüğü %52 ve %100 idi. Kültürde Hp üremesi tespit edilen 51 olgunun antibiyogram sonuçlarına göre antibiyotik direnç oranları; Klaritromisinde %23,5, metronidazolde %11,7 ve amoksisilinde %3,9 idi. Hastaların %51'inde cagA, %70,4'ünde cagE, %49'unda babA2, %34,7'sinde iceA1 ve %25,5'inde iceA2 pozitif saptandı. PCR pozitif tüm hastalarda vacA da pozitif iken, %81,6'sı vacAs1, %19,4'ü vacAs2, %38'i vacAm1 ve %62'si vacAm2 idi. VacA subtipleri arasında en sık rastlananlar; s1am2 (%32,7), s1am1 (%14,3) ve s2m2 (%12,) idi. CagA pozitif olgularda antral nodülarite anlamlı olarak daha fazla görüldü (p<0,05). IceA2 pozitiflerde ülser sıklığı yüksek iken lenfoid aggregat, inflamasyon ve Hp yoğunluğu anlamlı olarak düşük saptandı. VacAs1a pozitif olanlarda histopatolojik aktivasyon ve kronik aktif gastrit daha sık görülmekte idi (p<0,05). VacAs1c pozitif olanlarda nötrofil aktivasyonu ve özofajit daha az idi (p<0,05). CagE, iceA1, babA2 ve vacAs1c pozitifliğinde klaritromisin direnci sıklığının, vacAs1 ve vacAs1c pozitif olanlarda ise metronidazol direnci sıklığının arttığı görüldü. Helicobacter pylori pozitifliğini etkileyebilecek çevresel koşullara bakıldığında; sosyoekonomik düzeyi düşük olanlarda, ailede fert sayısı dörtten fazla olanlarda ve pasif sigara içiciliğinde anlamlı olarak Hp sıklığında artış saptandı (p<0,05). Sonuç: Helicobacter pylori enfeksiyonu bölgemiz için önemli bir problemdir. Bölgemizde ve dünyada giderek artan bir oranda klaritromisin direnci görülmektedir. Kültür ve PCR yöntemleri ile klaritromisin direncinin saptanması başarılı Hp eradikasyonu için gereklidir. Tekrarlayan karın ağrısı ve Hp gastriti bıulunan Türk çocuklarında ağırlıklı bulunan Hp genotipleri cagE ve vacA s1a/m2'dir. Hastalarda cagA, vacAs1a ve iceA2 genotiplerinin bulunması gastrit belirtilerinin ağırlığı ile ilişkilidir.
Background: Helicobacter pylori (Hp) is a gastric pathogen that chronically infects more than half of the world?s population. It is the major cause of gastritis, peptic ulcer, gastric mucosa associated lymphoid tissue lymphoma and gastric adenocarcinoma. Helicobacter pylori is genetically diverse and certain strains are more virulent and cause more severe disease than others and such diversity is reflected on the clinical outcome. Many bacterial virulence genes, including cagA, cagE, babA, iceA and vacA alleles have been associated with a higher degree of gastric mucosal inflammation. Many of these genes have been studied in adult Hp isolates, however, have not been well characterized in Hp isolated from children. The frequency of primary resistance to antibiotics in Hp isolates is increasing worldwide. There are limited data regarding the pattern of Hp antibiotic primary resistance in Turkey especially in children. For these reasons, information regarding the prevalence of antimicrobial-resistant Hp strains is important in predicting the therapeutic response. Aims: To evaluate prevalence of drug resistance and virulence-factor genotype in children with Hp gastritis in eastern part of Turkey and to assess the association of genotypes with severity of gastritis and to investigate if there is any relationship between drug resistance and genotype. Patients and Methods: Upper gastrointestinal endoscopy was performed in 159 patients with recurrent abdominal pain and two biopsies were taken from gastric antrum. Polymerase chain reaction (PCR), culture and histopathologic analysis were used to detect Hp infection. Antimicrobial susceptibility was tested by the disk diffusion method. PCR assays were used for virulence factors. The features of gastritis were graded according to the updated Sydney System. Results: Helicobacter pylori infection was detected in 32.1% of the patients by culture, 40.9% by biopsy and 61.6% by PCR. Seventy-five patients (76.5%) exhibited nodularity in the antral mucosa. The sensitivity and specificity of the diagnostic tests in PCR proven cases were as follows: histopathology 66.3% and 100%, culture 52% and 100%, respectively. The resistance rate of 51 Hp isolates to clarithromycin, metronidazole and amoxicillin were 23,5%, 11.7% and 3.9%, respectively. All strains carried the vacA genotype, and 51% of strains were cagA positive, 70.4% were cagE positive, 49% were babA2 positive, 34.7% were iceA1 positive and 25.5% were iceA2 positive. Of those 98 specimens, 81.6% carried vacAs1, 19.4% carried vacAs2, 38.8% carried vacAm1 and 63.3% carried vacAm2. The dominant vacA type was s1am2 (32.7%), followed by s1am1 (14.3%) and s2m2 (12.2%). Antral nodularity rate in cagA+ group was significantly higher than in cagA? (p<0.05). Peptic ulcer frequency was significantly higher and scores of lymphoid aggregate, chronic inflammation, and Hp density were lower in iceA2 positive group (p<0.05). Neutrophil activity and chronic active gastritis were more frequent in vaAs1a positive group (p<0.05). Histopathologic neutrophil activity and esophagitis were lower in vacAs1c positive group (p<0.05). Significant rates of clarithromycin resistance were observed in cagE, iceA1, babA2 and vacAs1c positive groups. Presence of vacAs1 and vacAs1c might be a risk factor in development of metronidazole resistance. Low socioeconomic status, household density and passive smoking were determined as independent risk factors of Hp. Conclusion: Helicobacter pylori infection is an important problem for our region. Gradual increase in clarithromycin resistance is another problem both for our region and world. Detection of clarithromycin resistance by means of culture or PCR methods will be an essential part of successful Hp eradication. The cagE positive and vacA s1a/m2 genotypes were predominant in Turkish children with recurrent abdominal pain and Hp gastritis. The presence of cagA, vacAs1a and iceA2 genotypes was correlated with the severity of gastritis.
Background: Helicobacter pylori (Hp) is a gastric pathogen that chronically infects more than half of the world?s population. It is the major cause of gastritis, peptic ulcer, gastric mucosa associated lymphoid tissue lymphoma and gastric adenocarcinoma. Helicobacter pylori is genetically diverse and certain strains are more virulent and cause more severe disease than others and such diversity is reflected on the clinical outcome. Many bacterial virulence genes, including cagA, cagE, babA, iceA and vacA alleles have been associated with a higher degree of gastric mucosal inflammation. Many of these genes have been studied in adult Hp isolates, however, have not been well characterized in Hp isolated from children. The frequency of primary resistance to antibiotics in Hp isolates is increasing worldwide. There are limited data regarding the pattern of Hp antibiotic primary resistance in Turkey especially in children. For these reasons, information regarding the prevalence of antimicrobial-resistant Hp strains is important in predicting the therapeutic response. Aims: To evaluate prevalence of drug resistance and virulence-factor genotype in children with Hp gastritis in eastern part of Turkey and to assess the association of genotypes with severity of gastritis and to investigate if there is any relationship between drug resistance and genotype. Patients and Methods: Upper gastrointestinal endoscopy was performed in 159 patients with recurrent abdominal pain and two biopsies were taken from gastric antrum. Polymerase chain reaction (PCR), culture and histopathologic analysis were used to detect Hp infection. Antimicrobial susceptibility was tested by the disk diffusion method. PCR assays were used for virulence factors. The features of gastritis were graded according to the updated Sydney System. Results: Helicobacter pylori infection was detected in 32.1% of the patients by culture, 40.9% by biopsy and 61.6% by PCR. Seventy-five patients (76.5%) exhibited nodularity in the antral mucosa. The sensitivity and specificity of the diagnostic tests in PCR proven cases were as follows: histopathology 66.3% and 100%, culture 52% and 100%, respectively. The resistance rate of 51 Hp isolates to clarithromycin, metronidazole and amoxicillin were 23,5%, 11.7% and 3.9%, respectively. All strains carried the vacA genotype, and 51% of strains were cagA positive, 70.4% were cagE positive, 49% were babA2 positive, 34.7% were iceA1 positive and 25.5% were iceA2 positive. Of those 98 specimens, 81.6% carried vacAs1, 19.4% carried vacAs2, 38.8% carried vacAm1 and 63.3% carried vacAm2. The dominant vacA type was s1am2 (32.7%), followed by s1am1 (14.3%) and s2m2 (12.2%). Antral nodularity rate in cagA+ group was significantly higher than in cagA? (p<0.05). Peptic ulcer frequency was significantly higher and scores of lymphoid aggregate, chronic inflammation, and Hp density were lower in iceA2 positive group (p<0.05). Neutrophil activity and chronic active gastritis were more frequent in vaAs1a positive group (p<0.05). Histopathologic neutrophil activity and esophagitis were lower in vacAs1c positive group (p<0.05). Significant rates of clarithromycin resistance were observed in cagE, iceA1, babA2 and vacAs1c positive groups. Presence of vacAs1 and vacAs1c might be a risk factor in development of metronidazole resistance. Low socioeconomic status, household density and passive smoking were determined as independent risk factors of Hp. Conclusion: Helicobacter pylori infection is an important problem for our region. Gradual increase in clarithromycin resistance is another problem both for our region and world. Detection of clarithromycin resistance by means of culture or PCR methods will be an essential part of successful Hp eradication. The cagE positive and vacA s1a/m2 genotypes were predominant in Turkish children with recurrent abdominal pain and Hp gastritis. The presence of cagA, vacAs1a and iceA2 genotypes was correlated with the severity of gastritis.
Açıklama
Anahtar Kelimeler
Beslenme ve Diyetetik, Nutrition and Dietetics, Çocuk Sağlığı ve Hastalıkları, Child Health and Diseases
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Karabiber, H. (2012). Çocuklarda helicobacter pylori gastritinde virülans faktörleri ve antibiyotik direnci. Yayımlanmış Uzmanlık Tezi, İnönü Üniversitesi, Malatya.
