針對住院病人對碳青黴烯抗藥性鮑氏不動桿菌的 風險因子分析

Risk Factors of Carbapenem-Resistant Acinetobacter Baumannii Infection among Hospitalized Patients

陳逸瑄(Yi-Hsuan Chen)

指導教授 ： 李仁愛

共同指導教授 ： 闕壯卿(Chuang-Chin Chiueh)

臺北醫學大學/藥學院/藥學研究所/碩士(2012年)

摘要

研究背景:
Carbapenem抗藥性鮑氏不動桿菌（Carbapenem-resistant Acinetobacter baumannii, 簡稱CRAB），是醫療照護相關感染常見的抗藥性致病菌，當病人發生CRAB感染後，會加重病人的疾病嚴重度、死亡率、增加住院天數、增加醫療人力物力的成本，且會增加後線抗生素的使用。依據台灣國家衛生研究院的「全國微生物抗藥性監測計畫」報告顯示，對carbapenem具抗藥性的鮑氏不動桿菌由2002年之低於3%，於2004年已增加至約16%，2006年更增加至約32%，另有研究顯示先前曾使用某些特定類別抗生素可能會增加鮑氏不動桿菌產生對carbapenem抗藥性的機率。
研究目的:
根據臺灣大學附設教學醫院於2010年發表的研究報告，CRAB的抗藥性產生與先前使用過cephalosporin, carbapenem及penicillin有相關性，且發現與病人的住院天數及侵入性治療措施也有相關性，但可惜的是此研究在實驗設計時有些嚴重的限制，在藥物的分析上，使用的是大類別來做分析，可是即使是同一大類的抗生素在抗菌範圍或是臨床治療上的角色及使用時機有著很大的差別。所以放在一個變相中分析，對於臨床建議上的實用性不足。再加上這個台灣唯一的鮑氏不動桿菌抗藥性研究在設計時只有使用非抗藥性的鮑氏不動桿菌與抗藥性菌株做一比較，這樣的實驗設計的缺陷在近年來國外的期刊中時常被討論。 因為此設計可能會因為一開始就選擇不具抗藥性的感染案例而產生偏見，以至於實驗的結果會過分的去突顯出抗生素的影響，進而導致這份研究的結果無法被信任而用以制定醫院的抗生素使用管控政策。本研究目的主要探討病房抗藥性鮑氏不動桿菌產生的風險因子，特別是感染發生前三個月抗生素使用的相關性。
研究方法:
研究設計為回溯性案例-案例-對照研究（retrospective case-case control study），收集98年1月1日至100年6月30日病房住院病人，比較抗藥性鮑氏不動桿菌感染案例 (CRAB) 與非抗藥性鮑氏不動桿菌感染案例 (CSAB) 與性別年齡配對的病房中未感染鮑氏不動桿菌案例之間個別風險因子對於抗藥性產生機率的影響。使用Statistical Package for Social SciencesR Statistic 20 (SPSS Inc. Chicago, Illinois, USA)統計軟體分析，類別資料使用卡方檢定，連續資料使用Student t-test，比較CRAB與性別及年齡配對的non-CRAB之住院病人之間不同風險因子對於感染發生率的影響，以及CSAB與性別及年齡配對的non-CSAB之住院病患之間不同風險因子對於感染發生率的影響，進而找出對CRAB具有專一性的風險因子。
研究結果:
本研究結果發現先前有使用過piperacillin/tazobactam (CRAB, OR: 2.5, 95% CI, 1.05 to 5.98; CSAB, OR: 2.5, 95% CI, 1.05 to 5.98) 或 amikacin (CRAB, OR: 5.48, 95% CI, 1.51 to 19.94; CSAB, OR: 2.5, 95% CI, 1.05 to 5.98) 或病人本身具有糖尿病病史(CRAB, OR: 6.26, 95% CI, 2.23 to 17.59; CSAB, OR: 6.26, 95% CI, 2.23 to 17.59) 或病人有裝置呼吸器(CRAB, OR:13.51, CI, 5.45 to 33.51; CSAB, OR: 4.72, 95% CI, 2.31 to 9.66) 都具有增加CRAB及CSAB感染的趨勢。另外若病人先前曾經使用過meropenem (OR: 4.99, 95% CI, 1.04 to 23.97) 則有專一性的增加CRAB感染的趨勢。
研究結論:
本研究發現若病人先前有使用過piperacillin/tazobactam 或 amikacin這兩種抗生素的其中一種，則有會增加鮑氏不動桿菌的感染之趨勢。另外若病人本身有使用呼吸器這項侵入性裝置或者病人本身具有糖尿病的病史，也有增加鮑氏不動桿菌的感染之趨勢，包括CSAB和CRAB。在本研究裡有發現meropenem的使用有增加CRAB的感染之趨勢。

關鍵字

抗藥性鮑氏不動桿菌 ； 抗藥性細菌案例案例對照研究

並列摘要

BACKGROUNDS:
Carbapenem-resistant Acinetobacter baumannii (CRAB), is one of the most common pan-resistant pathogen in healthcare-related infection of Taiwan. Once the patient was infected by CRAB, the disease severity, the mortality, days of hospitalization, and the cost were significantly increased. It is known that the CRAB infection is the consequence of increase of the consumption of antimicrobials. According to Taiwan National Health Research Institutes report, the percentage of CRAB has been soared from less than 3% in 2002 to 16% in 2004, and even increased to 32% in 2006. Recently, CRAB infection rate in hospitalized patients soars to 70% to 80%. There are some researches revealing that increasing antimicrobial consumption might cause the soared percentage of CRAB infection, especially certain antimicrobials might increase such resistant bacteria.
OBJECTIVE:
In the study of National Taiwan University Hospital, (Sheng et al., 2010) the development of resistance of A. baumannii has associate with the invasive medical procedure, the length of hospital staying, and the history of previous use of cephalosporin, penicillin and carbapenem. Unfortunately this study has some limitation which largely reduced the practicality. This study analyze antimicrobial agents by a rough category, such as cephalosporin without giving the detail information for which generation of the cephalosporin, but the different generation of cephalosporin are very different in use in treating infection disease, so the result of this study is not so practical in clinical use. The other limitation is the study designed as a case-control study which chooses the CRAB infected patient compare to carbapenem-sensitive Acinetobacter baumannii (CSAB) infected patient. This sampling error will leave bias because the patients with CSAB cannot represent the real population, which cause misestimating the relative risk because of distorted exposure frequency and cause the over estimation of the effect of antimicrobial agents. Taking concern of the two limitations above, the clinical physician and infection control expert in Taiwan hospital cannot make a strategic decision based on the result of this study. The present study was a case-case-control study, which conquered the limitation of traditional case-control study. In addition, using a more detail way to categorize antimicrobial agents to give a more practically information for the clinical physicians and infection control team to make a new strategy.
METHODS:
Our research was a retrospective case-case control study. The cases were collected from the adult hospitalized patient data from 2009/1/1 to 2011/6/30. A case-case-control design was actually composed of two parallel case-control studies. Two study groups of CRAB (n = 73) and CSAB (n = 77) were compared with each age- and gender-matched control groups with equal patient number, and the risk factors were statistically analyzed. By comparing the results of these two case-control studies, the specific risk factors for CRAB and the specific risk factors for CSAB were investigated. Statistical Package for Social SciencesR Statistic 20 (SPSS Inc. Chicago, Illinois, USA) was used to analyze statistically. Category variables were analyzed with chi-square and the continuous variables were analyzed with Student t-test. Our research aimed to find the specific risk factor of inducing CRAB in hospitalized patients.
RESULTS:
The common risk factors for both infection by CRAB and CSAB were prior exposure to piperacillin/tazobactam (CRAB,OR: 2.5, 95% CI, 1.05 to 5.98; CSAB, OR: 2.5, 95% CI, 1.05 to 5.98), amikacin (CRAB, OR: 5.48, 95% CI, 1.51 to 19.94; CSAB, OR: 2.5, 95% CI, 1.05 to 5.98), diabetes (CRAB, OR: 6.26, 95% CI, 2.23 to 17.59; CSAB, OR: 6.26, 95% CI, 2.23 to 17.59) or using of ventilator (CRAB, OR:13.51, CI, 5.45 to 33.51; CSAB, OR: 4.72, 95% CI, 2.31 to 9.66), all of which were associated with a significant trend of increased infection by A. baumannii. Furthermore, prior exposure to meropenem (OR: 4.99, 95% CI, 1.04 to 23.97) led to increase in infection of CRAB groups when hospitalized within 3 months after the exposure.
CONCLUSIONS:
Prior exposure to piperacillin/tazobactam, amikacin, diabetes or installation of ventilator had trend to increase both CRAB and CSAB infection. The prior use of meropenem had statistically significant tendency which was observed only on CRAB infection.

並列關鍵字

Carbapenem-resistant A. baumannii ； antimicrobial agent resistance case-case control study

參考文獻

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