- 學位論文
侵襲性及非侵襲性的Streptococcus pyogenes的危險因子分析 -M protein是侵襲性的關鍵嗎?
Risk Factor Analysis for Severe Streptococcus pyogenes infection -Is M type the Pivot of Invasiveness?
摘要
背景: 自1980年代開始，侵襲性的Streptococcus pyognes (S. pyogenes)在許多國家，特別是西方國家，發生率明顯增加。以M protein為基礎的疫苗目前正在開發中。台灣地區沒有完整的S. pyogenes感染的M protein 流行病學資料。 方法: 自2008年四月一日到十二月三十一日，收集來自馬偕醫院，長庚醫院，台中榮民總醫院，中國醫藥學院附設醫院，埔里基督教醫院，高雄醫學大學附設醫院，花蓮慈濟醫院的病人所分離出來的侵襲性及非侵襲性S. pyogenes感染的菌株和臨床資料。作菌株的抗藥性分析及emm型別分析及菌株生長速度，以得到流行病學資料，並分析侵襲性S. pyogenes感染的危險因子分析。 結果: 在研究期間，總計由醫院收集並鑑定211株菌株為S. pyogenes。最盛行的emm型別是emm1 (27.1%)，emm102.2 (9.5%)，emm11.0 (9.5%)，emm12.0 (9.0%)。目前開發中的26價疫苗對台灣地區S. pyogenes的emm型別涵蓋率是60.0%，其中對侵襲性及非侵襲性感染的涵蓋率分別是70.7%及54.1%。台灣地區S. pyogenes對erythromycin及tetracycline的抗藥性分別是15%及48%。Tetracycline在北區較其它區有較低的抗藥性，達到統計上的顯著性(36% v.s. 64%, p<0.001)。酗酒，菌株型別emm 1.0，年長者與女性是侵襲性感染的危險因子 (各別的p=0.05，<0.001，<0.001，0.012)。此外，高齡亦和侵襲性感染有顯著相關。病患有痛風石，菌株型別為emm 1.0，與腎功能不全是壞死性肌膜炎的危險因子 (各別的p=0.005，0.01，0.029)。女性，菌株型別emm 1.0及emm 22是鏈球菌毒性休克症候群的危險因子(各別的p=0.046，0.006，0.022)。 造成侵襲性感染的菌株生長速度顯著地較造成非侵襲性感染的菌株生長速度為快(p<0.001)，型別emm 1.0 菌株的生長速度較型別非emm 1.0的菌株生長速度更快(p<0.001)。57株型別為emm 1.0 菌株中，有48株 (84%)是屬於同一個PFGE 型別。其餘的9株中，有八株是由中部地區分離出來。 結論: S. pyogenes 會造成嚴重的感染症，造成顯著的致病性和致命性。 型別emm1的菌株與侵襲性感染、壞死性肌膜炎、鏈球菌毒性休克症候群有顯著的相關。型別emm1.0的菌株生長速度較型別非emm1.0的菌株生長速度為快，且別emm1.0的菌株中84%是屬於同一個PFGE 型別。
並列摘要
Background. The incidence of invasive Streptococcus pyogenes (S. pyogenes) infection had increased since 1980s, especially in western countries. Few report in epidemiologic characteristics of invasive and noninvasive S. pyogenes infection was available in Taiwan. Methods. From April 2008 through October 2008, we collected S. pyogenes strains and clinical data from 7 medical centers in Taiwan. The enrolled strains were characterized by the emm types, drug susceptbility profiles and growth rate. Logistic regression model was used to identify the risk factors associated with invasive infection, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS) caused by S. pyogenes. Results. During the study periods, we collected and identified 211 strains of S. pyogenes. The most prevalent emm types were emm1 (27.1%), emm102.2 (9.5%), emm11.0 (9.5%), and emm12.0 (9.0%). The 26-valent S. pyogenes vaccine covered 60.9% (126/207) of these strains, including those from invasive cases (70.7%, 53/75) and noninvasive cases (54.1%, 73/135). The resistant rates against erythromycin and tetracycline were 15% (31/211) and 48% (102/211), respectively. Alcohol abuse, isolates with emm 1.0, older age and female were risk factors for invasive infection. Tophaceous gout, isolates with emm 1.0 and renal function impairment were risk factors for ncerotizing fasciitis. Female, isolates with emm 1.0, isolates with emm 22 were significant risk factors of STSS. Isolates obtained from cases with invasive infection possess faster growth rate than those from cases with non-invasive infection. Isolates with emm type 1.0 possess significantly faster growth rate than those with other emm types. Among the 57 isolates with emm type 1.0, 48 (84%) have the same PFGE type. Conclusion. S. pyogenes infection caused significant morbidity and mortality in Taiwan. Isolates with emm type 1 are associated with invasive infection, STSS and NF. Penicillin and otherβ-lactams tested still exerted high levels of activity against S. pyogenes isolates.