台灣成人社區相關抗青黴素金黃色葡萄球菌移生之盛行率及危險因子，與其對院內血流感染預後之影響

背景與目的：社區相關性抗青黴素金黃色葡萄球菌（community-associated methicillin-resistant Staphylococcus aureus，簡稱CA-MRSA菌株），自1990年代興起後，仍有許多流行病學及臨床上的問題尚未釐清；本論文乃針對下列三點加以研究：其一，社區成年人之CA-MRSA帶菌狀況與危險因子；其二，加護病房住院成年患者之CA-MRSA帶菌狀況與危險因子；其三，由CA-MRSA所引起的MRSA院內血流感染，是否有不同的死亡率。研究方法：在我們的研究中，微生物學部分的採用如下一致的研究方法：針對培養出的金黃色葡萄球菌先進行青黴素的感受性測試，以確定其為MRSA，而後測定其對各種抗生素的感受性，再以multi-locus sequence typing、staphylococcal cassette chromosome mec (SCCmec) element分型，辨別其是否為CA-MRSA。在社區成年人之CA-MRSA帶菌狀況與危險因子的研究中，選擇在2007年10月1日到2007年12月31日的三個月間，參與職場健康檢查的成年人，篩檢其鼻腔的MRSA帶菌狀況；並收集其相關的人口學資料，生活習性，醫療機構、抗生素的暴露狀況等因素。在加護病房住院成年患者之CA-MRSA帶菌狀況與危險因子的研究中，利用在2008年9月1日至2009年9月30日，住在亞東紀念醫院內科加護病房與心臟血管加護病房的患者，對所有住進加護病房的患者，在剛住進的當天與之後的每三天採檢鼻腔拭子、腋下、喉嚨或痰液、與鼠蹊部進行細菌培養；並收集其相關的人口學資料，潛在性系統性疾病、相關醫療行為暴露、抗生素的暴露狀況等因素。在MRSA院內血流感染的研究中，利用在2006年1月1日至2008年12月31日，住在台大醫院、發生MRSA院內血流感染的患者，進行MRSA血流感染癒後的回溯性研究。研究結果：在社區成年人之CA-MRSA帶菌狀況與危險因子的研究中，計有3098人接受篩檢，有687人帶有金黃色葡萄球菌，而其中有111人所帶的MRSA菌株屬於CA-MRSA菌株；社區中成年人CA-MRSA菌株帶菌的盛行率為3.6%。相對於沒有金黃色葡萄球菌移生的人，家中有7歲以下的兒童、與一年內曾使用過抗生素的人，是CA-MRSA菌株移生的危險因子；相對於有MSSA移生的人，家中有7歲以下的小孩、過去一年內曾使用過抗生素的人，是CA-MRSA菌株移生的危險因子。而我們發現抽煙可以抑制S. aureus（包含CA-MRSA）在鼻腔的移生。在加護病房住院成年患者之CA-MRSA帶菌狀況與危險因子的研究中，在計有1906位加護病房患者被篩檢，有203位被發現在一到加護病房時即帶有MRSA，81位患者被發現是在停留於加護病房中時，才新得到MRSA。在81位新得到MRSA的患者中，有31人其分離出的MRSA菌株屬於CA-MRSA菌株。加護病房中心得到CA-MRSA菌株帶菌的發生率為每1000人日數3.0次。相對於沒有金黃色葡萄球菌移生的人，使用過anti-pseudomonal penicillin和anti-fungals、以及使用過鼻胃管的患者，是新得到CA-MRSA菌株移生的危險因子；相對於新得到HA-MRSA移生的人，使用過carbapenems卻是不會新得到CA-MRSA菌株移生的保護因子。在MRSA院內血流感染的研究中，總計有308次MRSA院內感染菌血症被納入分析、取得了253次菌血症的致病菌株。在253株致病菌株中，有47株屬於CA-MRSA菌株。菌血症發生後14天內的不分原因死亡率為19.8%，30天內為30.5%。統計的結果發現，發生菌血症時有敗血性休克、血小板低下、以及菌血症發生48小時內沒有使用有效抗生素，是14天內死亡的危險因子。而發生菌血症時有敗血性休克、患有惡性腫瘤疾病、貧血、血小板低下、以及分離出的MRSA菌株之vancomycin最低抑菌濃度為2 mg/L，是30天內死亡的危險因子。而CA-MRSA菌株感染，則非影響預後的獨立因子結論：總之，我們的研究釐清了CA-MRSA菌株在社區中、在加護病房中成年人移生的盛行率，指出了先前抗生素的使用是影響後續移生的重要危險因子、抽菸可以抑制S. aureus在鼻腔的移生；而CA-MRSA菌株侵入醫院環境後，造成院內菌血症感染，並不會導致更高的死亡率。我們應定期進行追蹤研究，以瞭解社區中CA-MRSA盛行率、分子分型、藥物感受性、以及其所引起之感染的預後變化。然而在目前，鑑定引起院內血流感染的MRSA是否為CA-MRSA似乎仍無其必要性。

關鍵字

社區相關性抗青黴素金黃色葡萄球菌；移生；菌血症；危險因子

並列摘要

Background: Since the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), some epidemiologic and clinical issues caused by it remain unresolved. Our studies were focus on the following three issues: the prevalence of and risk factors for carriage of CA-MRSA among community healthy adults, the prevalence of and risk factors for carriage of CA-MRSA among intensive care unit (ICU) adult patients, and the impact of CA-MRSA on mortality of nosocomial MRSA bloodstream infection. Materials and methods: The microbiologic studies of all S. aureus isolates were as following: identification of methicillin resistance by drug susceptibility, then multi-locus sequence typing and typing for staphylococcal cassette chromosome mec (SCCmec) element for all MRSA isolates to determine whether they belonging to CA-MRSA or not. In the study about the prevalence of and risk factors for carriage of CA-MRSA among community healthy adults, we enrolled adults attending mandatory health examination at 3 medical centers and sign the informed consents during Oct. 1, 2007 to Dec. 31, 2007 to screen their nasal carriage of MRSA. In the study about the prevalence of and risk factors for carriage of CA-MRSA among ICU adult patients, we enrolled all patients staying in two ICUs at the Far Eastern Memorial Hospital from Sep. 1, 2008 to Sep. 30, 2009 to clarify the prevalence and risk factors of carriage of CA-MRSA among ICU adult patients. Surveillance cultures from nostril, sputum or throat, axillae, and inguinal area were taken on all patients when they just arrived at ICUs and then every three days. In the study about the mortality of nosocomial MRSA bloodstream infection, we retrospectively analyzed all adult patients hospitalized at National Taiwan University Hospital with nosocomial MRSA bloodstream infection from Jan. 1, 2006 to Dec. 31, 2008 to clarify the impact of CA-MRSA on prognosis of nsocomial MRSA infection. Results: In the study about the prevalence of and risk factors for carriage of CA-MRSA among community healthy adults, 3098 people were enrolled, and 687 were found to carry S. aureus, among whom 111 carried CA-MRSA isolates. The prevalence of CA-MRSA carriage was 3.6%. Presence of household member aged ≤ 7 years, and use of antibiotics during the past year were the risk factors for carriage with CA-MRSA in comparison with both those without carriage of S. aureus and those with carriage of MSSA. Smoking was a significant factor inhibiting the nasal carriage of S. aureus. In the study about the prevalence of and risk factors for carriage of CA-MRSA among ICU adult patients, 1906 patients were screened, and 203 patients were found to carry with MRSA before admission to ICU, while 81 were found to newly acquire MRSA during their stay in ICUs. Among the 81 patients, 31 carried with CA-MRSA isolates. The incidence rate of newly acquiring CA-MRSA carriage in ICU was 3.0 per 1000 patient-days. Prior usage of anti-pseudomonal penicillins and anti-fungals, as well as presence of nasogastric tube were independent risk factors for acquiring CA-MRSA during ICU stay compared to those without carriage of S. aureus. Prior usage of carbapenems was a protective factor against acquiring CA-MRSA compared to those acquiring HA-MRSA during ICU stay. In the study about mortality of nosocomial MRSA bloodsteam infection, 308 patients with nosocomial MRSA bloodstream infection were enrolled and 253 MRSA isolates, among which 47 belonged to CA-MRSA, were available for microbiologic studies. The Day 14 and Day 30 all-cause mortality were 19.8% and 30.5%, respectively. Septic shock, thrombocytopenia, and no effective antibiotics within 48 hours were independent risk factors for Day 14 mortality. Septic shock, having underlying malignancies, anemia, thrombocytopenia, and a causative MRSA isolate with a vancomyin minimum inhibitory concentration of 2 mg/L were independent risk factors for Day 30 mortality. In contrast, bloodstream infection caused by CA-MRSA isolates did not associated with a poorer outcome. Conclusion: Prior usage of antibiotics is strongly associated with subsequent carriage of CA-MRSA among adults. Smoking could inhibit the nasal carriage of S. aureus. Nosocomial MRSA bacterermia caused by CA-MRSA was not associated with a poorer outcome. It is necessary to perform periodical surveillance on the prevalence, molecular types, drug susceptibilities, and impact on infection prognosis of CA-MRSA. However, it might not be indicated to identify whether the causative MRSA of nosocomial bloodstream infection was CA-MRSA or not at current time.

並列關鍵字

community-associated methicillin-resistant Staphylococcus aureus ； colonization ； bloodstream infection ； risk factor ； CA-MRSA

參考文獻

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