主動篩檢及介入措施對外科加護病房抗藥性金黃色葡萄球菌感染發生率之影響

Effect of Active Surveillance Intervention on Incidence of Methicillin-Resistant Staphylococcus aureus (MRSA)Infections in Surgical Intensive Care Unit

陳貞蓉(Jen-Zon Chen)

指導教授 ： 方啟泰

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.01913

摘要

研究背景及目的
抗藥性金黃色葡萄球菌 (Methicillin-resistant Staphylococcus aureus, MRSA) 是醫療照護相關感染重要的致病菌，許多研究顯示如果病人發生MRSA醫療照護相關感染會增加死亡風險及住院費用，所以控制MRSA醫療照護相關感染是很重要的議題。
鼻腔帶有MRSA會增加醫療照護相關MRSA感染的風險，尤其是住加護病房的病人。先前在荷蘭的隨機分派臨床試驗結果顯示，運用主動篩檢措施及去移生治療，可以有效減少MRSA感染，但類似措施是否在常規的臨床情境下仍然可以產生控制MRSA感染的作用？目前還不清楚。本研究的目的為探討在外科加護病房例行主動篩檢及去移生治療的介入措施對MRSA感染的影響。

方法
本研究採用回溯性世代研究法，研究期間自2007年1月1日至2011年6月30日止，研究地點在北部某區域教學醫院外科加護病房，該院共有702床，其中外科加護病房共有18床。
本研究的介入措施為在病人入住外科加護病房後，進行鼻腔主動篩檢，早期偵測無症狀的MRSA帶菌者，當細菌培養出是MRSA後，使用mupirocin藥膏及chlorhexidine抗菌劑進行鼻腔及皮膚連續5天的去移生治療，並施予接觸隔離及環境清潔。
本研究期間總共區分為4個階段，第一階段是從2007年1月到2007年9月，為baseline階段，沒有執行介入措施，當時MRSA感染管制措施僅有接觸隔離、環境清潔，病人感染培養出MRSA後才進行去移生治療。第二階段是從2007年10月到2008年4月，因為有申請到經費，所以執行介入措施。第三階段是從2008年5月到2009年8月，因為研究計畫結束，沒有經費無法繼續執行，而停止介入措施。第四階段是從2009年9月到2010年9月，因為MRSA感染率再度升高，院方同意將介入措施的內容列入外科加護病房常規感染管制措施。

本研究除了比較有無執行介入措施對外科加護病房MRSA感染的影響外，並利用向衛生署統計室申請的內政部死亡檔及健保資料庫重大傷病檔資料，分析有介入及無介入期間病人1年內死亡率及新發重大傷病率 (severe morbidity) 的差異。所謂新發重大傷病是指病人住外科加護病房後，新產生長期呼吸器依賴或長期洗腎，而獲核發重大傷病證明。
利用SAS統計軟體進行資料分析，統計的方法包含類別變項利用χ2 test,連續變項利用t test，利用Poisson regression分析感染率的變化，Kaplan-Meier及log- rank test檢定mortality及severe morbidity的差異，並利用Logistic regression, Cox regression進行單變項及多變項分析。

結果
研究期間前後共有2373的病人入住外科加護病房。研究期間外科加護病房MRSA感染密度從3.58 ‰ 降至0.18 ‰，以Logistic regression進行多變項分析調整其他干擾因子作用後，發現執行介入措施是在外科加護病房發生MRSA感染的獨立保護因子 (adjusted odds ratio [OR]: 0.1, 95% CI, 0.02-0.4 )。研究期間從入住外科加護病房後到出院期間的MRSA感染密度則從1.42 ‰ 降至0.24 ‰，以Logistic regression進行多變項分析調整其他干擾因子作用後，發現執行介入措施也是從入住外科加護病房後到出院期間發生MRSA感染的獨立保護因子 (adjusted OR: 0.3, 95% CI, 0.1-0.8)。
另外利用行政院衛生署統計室提供的死亡及重大傷病資料庫，追蹤第一階段及第二階段病人住外科加護病房後180天內死亡及新發重大傷病率情形，以Cox regression進行多變項分析調整其他干擾因子作用後，發現執行介入措施也是180天內死亡 (adjusted Hazard ratio [HR]: 0.4, 95% CI, 0.3 - 0.6) 及180天內死亡或出現新發重大傷病的獨立保護因子(adjusted HR: 0.4, 95% CI, 0.3 - 0.6)。
進行成本分析，發現有MRSA感染的病人住加護病房期間平均醫療費用約新台幣75萬元，比沒有MRSA感染的病人多出64萬元。介入期間共減少13個病人發生感染，經比較病人的醫療費用與介入成本，結果發現投資1元於介入措施可節省30元的醫療費用。

結論
本研究結果顯示在外科加護病房常規運用主動篩檢及去移生治療可以有效減少MRSA感染，另外也降低病人的死亡或出現新發重大傷病的風險及醫療費用。建議可將主動鼻腔篩檢措施納入常規加護病房感染管制政策，以維護病人安全，提升醫療服務品質。

關鍵字

methicillin抗藥性金黃色葡萄球菌 ； 醫療照護相關感染 ； 主動鼻腔篩檢 ； 去移生治療

並列摘要

Background and aim:
Methicillin-resistant Staphylococcus aureus (MRSA) is a one of the leading pathogens in healthcare-associated infections. Patients with healthcare-associated MRSA infections suffer increased mortality and morbidity, as well as prolonged hospital stays and extra medical costs. Strategies to prevent systemic S. aureus infections by eliminating nasal carriage of S. aureus have been proposed, as a substantial proportion of S. aureus bacteremia cases appear to be of endogenous origin from colonies in the nasal mucosa.
A recent randomized controlled trial conclusively showed that active surveillance to identify asymptomatic MRSA carriers followed by MRSA eradication can effectively reduce surgical-site MRSA infection rates. Nevertheless, whether similar intervention strategies can also reduce MRSA infections in non-RCT daily practice remains unclear.
This study aimed to evaluate the effectiveness of routine active surveillance culture followed by a mupirocin treatment of MRSA carriers in controlling healthcare–associated MRSA infections in surgical ICU patients.

Methods:
This retrospective cohort study was conducted in the surgical intensive care unit (SICU) of a tertiary care, university-affiliated teaching hospital in northern Taiwan. This hospital has a 702-bed capacity, with 18 beds (all single-bed rooms) in the SICU. The study was conducted from January 2007 through September 2010.
The intervention consisted of active surveillance cultures from the anterior nares of all patients admitted to the SICU for the identification of asymptomatic MRSA carriers. When the nasal swab culture was positive for MRSA, the MRSA was eradicated by administration of mupirocin ointment to the nares three times a day for 5 days, and the skin was decolonized with 4% chlorhexidine gluconate once daily for 5 days. Contact precautions were also employed,” if this maintains the intended meaning.
The study period was divided into four stages. The first period (from January to September 2007) was the baseline period, and no active intervention was conducted. Contact precautions, eradication and environmental disinfection before patient discharge were performed only when clinical cultures were positive for MRSA. Active intervention, which was supported by a research grant from the hospital, was initiated at the start of the second period, lasting from October 2007 through April 2008. The intervention was halted in the third period (from May 2008 through August 2009), due to a lack of research grants. The intervention was resumed in the fourth period (from September 2009 through September 2010) after a surge in the SICU MRSA infection rate in the third period prompted the hospital leadership to provide financial support for active MRSA interventions.
We compared healthcare-associated MRSA infection rates between patients admitted during the intervention and non-intervention periods. We further surveyed the Department of Health Death registry database and the National Health Insurance database to obtain information on 1-year outcomes. All causes of 1-year mortality and severe morbidity rates in patients admitted during the intervention and non-intervention periods were analyzed. Severe morbidity was defined as the onset of permanent dialysis or ventilator dependence registered with a catastrophic illness card by the National Health Insurance.

Results:
During the study period, a total of 2373 patients were admitted to the SICU. The MRSA infection rate in the surgical ICU was 3.58‰ (period 1), 0.42‰ (period 2), 2.21‰ (period ), and 0.18‰ (period 4). Multiple logistic regression analysis showed that intervention is an independent protective factor for MRSA infection in ICUs (adjusted odds ratio [OR]: 0.1, 95% CI, 0.02-0.4), after adjusting for the effects of potential confounding factors.
The in-hospital MRSA infection rates was 1.42‰ (period 1), 0.29‰ (period 2), 0.75‰ (period ), and 0.24‰ (period 4). Multiple logistic regression analysis showed that intervention is an independent protective factor for in-hospital MRSA infection (adjusted OR: 0.3, 95% CI, 0.1-0.8), after adjusting for the effects of potential confounding factors.
The time to mortality or to the onset of severe morbidity in the patients admitted during periods 1 and 2 were analyzed by multiple Cox regression analysis, which showed that intervention is an independent protective factor for mortality or the onset of severe morbidity (adjusted hazard ratio [HR]: 0.4, 95% CI, 0.3-0.6), after adjusting for the effects of potential confounding factors.
The median costs of SICU hospitalization for patients with healthcare-associated MRSA infections were NT $754,845, an excess of NT $640,000 in comparison with patients without healthcare-associated MRSA. The number of MRSA cases averted by the intervention was estimated to be 13 during the intervention period. For every dollar spent on interventions, $30 can be saved in medical costs.

Conclusion:
Our study results showed that routine active surveillance and MRSA eradication in the SICU can effectively reduce MRSA infection rates, mortality, and the onset of severe morbidity, as well as medical costs. We recommend routine active surveillance and eradication intervention in SICUs to increase patient safety and enhance the quality of medical services.

並列關鍵字

Methicillin-resistant Staphylococcus aureus ； healthcare-associated infections ； active surveillance culture ； eradication

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