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標題: | 癌症病人的抗生素使用對Stenotrophomonas maltophilia移生或感染之影響 Influence of Antibiotics Use on Stenotrophomonas maltophilia Colonization or Infection in Patients with Malignancies |
作者: | Yu-Hsin Chiu 邱愉心 |
指導教授: | 陳宜君,陳秀熙 |
關鍵字: | Stenotrophomonas maltophilia,抗生素,血液腫瘤,時間序列,生態學研究,個體研究,多層次分析, Stenotrophomonas maltophilia,antibiotics,malignancy,time series,ecological study,individual study,multi-level analysis, |
出版年 : | 2008 |
學位: | 碩士 |
摘要: | 背景
Stenotrophomonas maltophilia (SMA) 院內感染逐漸增多,且因天生多重抗藥之特性已成為重要的病原菌,尤其是在血液腫瘤病人。雖已有研究探討過SMA移生或感染與抗生素使用壓力之關係,但是過去大部分的研究設計是使用橫斷性生態學設計(cross-sectional ecological design)。極少研究採用時間數列設計(longitudinal time series design)來說明這些相關性,特別是在血液腫瘤病人身上。此外,過去的文獻報告也缺乏以病人個體層級的研究設計來探討不同種類的抗生素使用對SMA移生或感染的影響。而且也缺乏使用兩種或三種不同抗生素是否會產生協同作用之研究。 病人與方法 本研究採用二種時間數列的研究設計。第一種是生態學的時間數列研究設計(ecological time series design)。利用一醫學中心2002年至2006年血液腫瘤病房前瞻性院內感染監測資料,來評估醫院推行手部衛生運動和抗生素的使用對SMA移生或感染發生率之間的相關性。第二種是以病人個體為基礎的交叉性時間數列研究設計(case-based only cross-over time series design),一病人住院的月份若有SMA移生或感染,則該月份被定義為事件。關於過去曾使用過抗生素,定義為在培養出SMA前14 天內有使用全身性抗生素。 結果 在血液病房,SMA的發生率在每1000人日是3.9±2.1次,比腫瘤病房的發生率高3.27倍(95%CI:1.96-5.44; p<0.001)。手部衛生運動之推行對SMA發生率沒有影響。在排除病房及個別病人的效應之後,在培養前14天曾使用過單一的抗生素,包括第4代頭芽孢素(HR:1.80; 95%CI:1.34-2.42),對抗綠膿桿菌的盤林西林 (HR:1.60; 95%CI:1.19-2.16),carbepenem (HR:1.45; 95%CI: 1.09-1.93),或在培養前14天曾使用過兩種抗生素,例如:carbapenem和第4代頭芽孢素(HR:1.57; 95%CI:1.15-2.15),或carbapenem和對抗綠膿桿菌的盤林西林 (HR:1.54; 95%CI:1.07-2.22),都與SMA移生或感染有統計相關。而磺胺類抗生素(sulfamethoxazole/trimethoprim)的使用則會減少48%產生SMA移生或感染的機會,具有保護作用(HR:0.52; 95%CI:0.30-0.90)。Carbapenem和第4代頭芽孢菌素或對抗綠膿桿菌的盤林西林彼此不具有協同作用。 結論 藉由分析在病房層級與病人層級與SMA移生或感染發生率相關的因素顯示在血液病房發生率比腫瘤病房高。歸因於多種廣效性抗生素選擇壓力,而加強手部衛生以減少交叉傳播對SMA此多重抗藥細菌的移生或感染發生率並沒有影響。另外,我們的研究也顯示出,諸多全身性抗生素中,第4代頭芽孢素、對抗綠膿桿菌的盤林西林,和carbapenem對SMA的移生或感染有顯著影響。如預期的,SMA治療的首選藥物,sulfamethoxazole/trimethoprim對SMA是保護因素。研究結果建議,應審慎使用廣效性抗生素,以降低SMA的移生或感染。本研究建立的時間數列分析方法可應用於多重抗藥細菌監測資料之分析。 Background Nosocomial infections caused by Stenotrophomonas maltophilia (SMA), an emerging pathogen attributed to inherited multi-drug resistance, has increased and frequently seen in patients with hematologic malignancies. Although previous studies have reported the relationships of antibiotic uses to colonization of SMA, there are several drawbacks in previous studies. The majority of study designs are based on a cross-sectional ecological design. Very few studies applied a longitudinal time series ecological design to elucidate these associations, especially in patients with hematologic malignancies. It is also lacking of a study design at individual level to throw light on the effect of the combination of different kinds of antibiotic uses on the risk for SMA. Whether the combined use of two or three kinds of drugs in hematologic malignancy patients is synergistic is hardly addressed. Patients and Methods There are two kinds of time series study design used in our study. The first is an ecological time series design that is tailored for estimating the burden of SMA, assessing the impact of hospital-wide hand hygiene program, and studying the correlation between the consumption of antibiotic uses and incidence density of SMA at ward level by using five-year period data from 2002 to 2006. The second design is a case-based only cross-over time series design which is regarded as an atomic level. In this design, the episode of having SMA colonization or infection during a month is defined as event. A series of time epochs over five-year period was constructed for elucidating the association between antibiotic use and SMA infection at individual level. Prior therapy of antibiotic uses was defined as 14 days before culture for the ascertainment of SMA. Results The incidence density of SMA colonization or infection in patients with malignancies was 3.9±2.1 SMA isolates per 1000 patient-days, which is higher than oncologic wards. Patients at hematologic ward were 3.27-fold (95%CI:1.96-5.44; p <0.001) risk for SMA colonization or infection compared with patients at oncologic wards, but hand hygiene promotion program to avoid exogenous transmission was lacking of significant effect on SMA colonization or infection. After excluding the effects of ward and patients, the use of 4th generation cephalosporins (HR:1.80; 95%CI:1.34-2.42), anti-Pseudomonas penicillins (HR:1.60; 95%CI:1.19-2.16), carbepenem (HR:1.45; 95%CI: 1.09-1.93), and exposure to carbapenem and 4th generation cephalosporins (HR:1.57; 95%CI:1.15-2.15), or carbapenem and anti-Pseudomonas penicillins (HR:1.54; 95%CI:1.07-2.22) were responsible for SMA colonization or infection . Sulfamethoxazole/trimethoprim (HR:0.52; 95%CI:0.30-0.90) decreased the chance of 48% of SMA colonization or infections and had protective effect. Carbapenem and 4th generation cephalosporins or anti-Pseudomonas penicillins made independent contribution to SMA colonization or infection. However, carbapenem in combination with 4th generation cephalosporins or anti-Pseudomonas penicillins had no synergistic effects. Conclusions By using data at ward level and patient level from a tertiary hospital in Taiwan, we found the incidence density of SMA colonization or infection was higher at hematological ward than oncology ward. In patients with malignancies, the high burden of such endogenous SMA infection may be attributed to the exposure to more kinds of broad-spectrum antibiotics. Our study demonstrated that 4th generation cephalosporins, anti-Pseudomonas penicillins, and carbapenem make significant contribution to SMA colonization or infection independent of the frequent use of carbapenem. We also found that sulfamethoxazole/trimethoprim was a protective factor for SMA. These findings suggest that to avoid broad-spectrum antibiotic use may prohibit patients from colonization or infection of SMA in the patients with hematologic malignancies. Our time-series design ca be applied to the surveillance of multi-drug resistance. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40471 |
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顯示於系所單位: | 流行病學與預防醫學研究所 |
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