某醫學中心社區發作型菌血症之流行病學與處方型態分析

Abstract

研究背景 菌血症屬於嚴重的感染症，經驗性抗生素的適當與否將可能影響病人之臨床 結果。菌血症的來源、菌種分布與抗藥性情形是決定經驗性抗生素的重要因素。 與院內感染相比，社區發作型感染細菌的抗藥性程度較低，然近年研究發現社區 型感染的菌種(如 E. coli、Klebsiella spp.)的抗藥性比例有增加的趨勢，因此本 研究進行社區發作型(community-onset; CO)菌血症研究，並同時與醫院發作型 菌血症比較，分析菌種分佈、抗藥性，及所使用的抗生素，以做為臨床選用抗生 素之參考。 研究目的 比較社區發作型菌血症以及醫院發作型菌血症之菌種分佈、抗藥性分佈以及 抗生素使用情形，並著重於社區發作型菌血症之探討。 研究設計、地點及對象 本研究為回溯性研究，收納 2016 年 1 月 1 日至 2017 年 12 月 31 日期間，至 國立臺灣大學醫學院附設醫院(以下簡稱臺大醫院)進行血液培養且呈陽性的成 年病人，資料來源為臺大醫院整合醫學資料庫。 研究方法 由臺大醫院整合醫學資料庫收集病人的基本資料、共病症、過去醫療處置及 用藥、血液培養結果、抗生素感受性結果、本次使用的藥品，並與醫院發作型 (hospital-onset)菌血症相比較，同時分析社區發作型病人之抗生素適當性，以 及使用到不適當抗生素的風險因子。統計方法包括卡方檢定、Kruskal-Walis 檢 定、羅吉斯回歸，統計分析的軟題為 SAS(9.4 版)，並以 Microsoft Excel 2016(Microsoft Crop., Redmond, WA, USA)輔以記錄。 研究結果 本研究最後總收案人數為 2542 人。社區發作型、醫院發作早發型、醫院發 作晚發型組別分別有 488 人、363 人、1691 人。社區發作型組別進一步分為社區 型(205 人)與醫療照護相關型組別(283 人)。社區型組別的 Charloson’s comorbidity index 分數最低(中位數:2 分，四分位距:0-4 分)，醫療照護相關 型感染組別最高(6 分，四分位距:3-7 分)。固態腫瘤是各組最常見的共病症， 社區型組別比例最低(31.7%)，醫療照護相關型組別最高(74.6%)。 社區發作型組別中，多重菌種感染的比例在社區型組別較醫療照護相關型組 別低(5.8% vs. 16.2%，P=0.0004)、在不具癌症的病人較具癌症病人的比例低 (7.6% vs. 14.3%，P=0.0219)。菌種比例依序為革蘭氏陰性菌(64%)、革蘭氏陽 性菌(31%)、厭氧菌(5%)。E. coli 是比例最高的菌種(21.2%)，其次為 Klebsiella spp.(13.0%)、S. aureus(11.2%)。社區發作型 E. coli 與 Klebsiella spp. 對於 cefotaxime 的感受性比例分為 65.6%、75.3%，比例與醫院發作型病人，以及 病人是否具有惡性腫瘤分組比較未達統計顯著差異。 Cephalosporins 是社區發作型組別使用比例最高之經驗性抗生素(47.5%)。 使用多種抗生素的病人比例為 26.7%，該比例在社區型組別低於醫療照護相關型 組別(23.0% vs. 29.4%，P=0.0031)，單一菌種與多重菌種感染、不具惡性腫瘤與 具惡性腫瘤組別的使用多種抗生素的比例則無顯著差異。社區發作型組別有 139 人(28.5%)使用到不適當的抗生素。使用到不適當抗生素的比例在社區型與醫 療照護相關型組別(30.2% vs. 27.2%，P=0.4782)，以及不具/具有惡性腫瘤組別 (29.0% vs. 28.6%，P=1.0000)並無顯著差異，然而多重菌種菌血症使用到不適 當抗生素的比例顯著高於單一菌種菌血症病人(43.1% vs. 26.5%，P=0.0126)。多變項分析使用到不適當抗生素的因子中，使用多種抗生素為保護因子 (aOR=0.422);third-generation cephalosporin resistant E. coli, Klebsiella spp., Proteus spp., Enterobacter spp., Citrobacter spp.,(aOR=5.966)、enterococci (aOR=2.579)，則為風險因子。 結論 各菌種在社區發作、醫院早發型、醫院晚發型有不同的分佈。本研究中，社 區發作型病人最常見的菌種為革蘭氏陰性菌(64%)。在革蘭氏陰性菌中，E. coli (33.4%)、Klebsiella spp.(20.5%)比例最高，顯示經驗性抗生素之抗菌範圍應 涵蓋 E. coli 與 Klebsiella spp.。然而，本研究社區發作型 E. coli、Klebsiella spp.對 於 cefotaxime 的感受性分別為 65.6%、75.3%。多變項分析發現病人若接受抗生素 多重療法，較會使用到適當之抗生素;若患 third-generation cephalosporin resistant E. coli, Klebsiella spp., Proteus spp., Enterobacter spp., Citrobacter spp.、enterococci 菌血症，則較會使用到不適當之抗生素。

Background Bacteremia is one of the serious infections. Appropriateness of empirical therapy might affect patients’ clinical outcomes. Factors which may influence the choice of empirical therapy include patients’ infection focus and probable pathogens. Compared to nosocomial infection, pathogens from community settings usually have lower resistant rates. However, recent studies showed that there was a trend toward higher resistant rates in community pathogens such as E. coli and Klebsiella spp. Therefore, it is essential to conduct a study to analyze pathogen distribution, resistance patterns and antibiotics use in community-onset (CO) bacteremia. Study objective To describe and compare the patient characteristics, pathogen distribution, resistance patterns and antibiotic use between community-onset and hospital-onset bacteremia, and focus on the analysis of community-onset bacteremia. Study design and population Patients having at least 1 positive blood culture of bacteria in National Taiwan University Hospital (NTUH) between January, 2016 and December, 2018 were identified from the NTUH integrated medical database. Methods Data were collected from NTUH integrated medical database. Patients’ demographic profiles, comorbidities, previous medical status, previous drug use, blood culture and susceptibility test results, antibiotic regimens, appropriateness of antibiotic therapy and factors associated with inappropriate antibiotic use were analyzed. Statistical methods included Chi-square test, Kruskal-Walis test, logistic regression for uni- and multi- variate analysis, and were conducted via SAS 9.4 and Microsoft Excel 2016 (Microsoft Crop., Redmond, WA, USA). Results 2542 patients were included in the study. There were 488, 363, 1691 patients in CO group, hospital-onset early-onset (HOEO) group, and hospital-onset late onset (HOLO) group, respectively. CO group was further classified into community-acquired (CA) (205 patients) and healthcare-associated (HCA) groups (283 patients). CA group had the lowest Charloson’s comorbidity index (CCI) (median: 2; IQR: 0-4) while HCA group had the highest CCI (median: 6; IQR: 3-7). Solid organ tumor was the most prominent comorbidity in all groups. CA group had the lowest rate of solid tumor (31.7%) while HAC group had the highest rate (74.6%). In CO group, percentage of patients with poly-microbial bacteremia were lower in CA group compared to HCA group (5.8% vs. 16.2%, P=0.0004), and lower in patients without malignancy (7.6% vs. 14.3%, P=0.0219). Gram-negatives, gram-positives and anaerobes composed 64%, 31%, 5% of total isolates respectively. E. coli was the most common pathogens (21.2%), followed by Klebsiella spp. (13.0%) and S. aureus (11.2%). The susceptibility rate of E. coli and Klebsiella spp. to cefotaxime was 65.5% and 75.3% respectively, which did not show significant different compared to HOEO, HOLO groups and in patients with/without malignancy. Cephalosporins were the most prescribed empirical antibiotic in CO groups (47.5%). The percentage of patients receiving multi-drug was lower in CA group compared to HCA group (23.0% vs. 29.4%, P=0.0031), while there was no significant difference in mono-/poly-microbial bacteremia and in patients with/without malignancy. 139 (28.5%) patients in CO group received inappropriate antibiotics. The percentage of patients receiving inappropriate antibiotics was similar between CA/HCA groups and patients with/without malignancy, but was higher in patients with poly-microbial bacteremia compared to mono-microbial bacteremia (43.1% vs. 26.5%, P=0.0126). In multivariate analysis, multi-drug therapy (aOR=0.422) was a protective factor against receiving inappropriate antibiotics, while third-generation cephalosporin resistant E. coli, Klebsiella spp., Proteus spp., Enterobacter spp., Citrobacter spp. (aOR=5.966) and enterocci (aOR=2.579) were risk factors. Conclusion There were different patterns of distribution of pathogens among CO, HOEO and HOLO groups. Gram-negatives composed the majority of CO isolates (64%). E. coli (33.4%) and Klebsiella spp. (20.5%) were the most prevalent in Gram-negatives, suggesting that empirical therapy should cover these organisms. However, only 65.6% of E. coli and 75.3% of Klebsiella spp. were susceptible to cefotaxime in CO group. Multivariate analysis showed that multi-drug therapy was a protective factor against receiving inappropriate antibiotics, while patients with third-generation cephalosporin resistant E. coli, Klebsiella spp., Proteus spp., Enterobacter spp., Citrobacter spp., and enterocci were at risk of receiving inappropriate antibiotics.