輔助性氣霧氨基糖苷類抗生素在靜脈注射抗生素治療綠膿桿菌肺炎的結果

Outcomes of adjunctive aerosolized aminoglycosides in intravenous antibiotics therapy for Pseudomonas aeruginosa pneumonia

張曉維(Hsiao-Wei Chang)

指導教授 ： 蔡東榮

高雄醫學大學/藥學院/藥學系碩士在職專班/碩士(2015年)

摘要

研究背景:
綠膿桿菌感染所導致之肺炎在台灣的加護病房是常見的。由於抗生素的濫用，綠膿桿菌的抗藥性越來越高。由過去的研究顯示，利用吸入性投與抗生素治療肺部感染，可以使抗生素在肺部的濃度比注射投與高，至於病人後續的療效是否隨著抗生素在肺部的濃度增加而跟著增加則還沒有明確的證據支持。
研究設計、地點及對象：
此研究於南部某區域教學醫院進行，為單中心、病歷回溯性研究。研究對象為20 ∼ 99歲，於2010 年1 月1 日至2013 年12 月31 日期間經細菌培養確定有綠膿桿菌感染之加護病房肺炎病人。依據病人所使用的治療方式，將病人分成兩組，一組為單獨使用靜脈注射抗綠膿桿菌抗生素；另一組為合併使用吸入投與Aminoglycodsides與靜脈注射抗綠膿桿菌抗生素。
研究方法:
藉由病歷回顧的方式收集病人的基本資料與臨床相關數據。臨床資料以時間作為區分，記錄病人加護病房住院天數、呼吸器使用天數、肺炎臨床症狀改善程度和抗藥性細菌發生率等等資料，使用臨床肺部感染量表 (Modified clinical pulmonary infection score , CPIS)和急性生理和慢性健康評估分數 (Acute Physiology and Chronic Health Evaluation score II , APACHE-Ⅱ score)作為評估工具，並以感染後30天的死亡率作為觀察終點，進行資料統計分析比較。
統計分析包括卡方檢定 (χ2 test)、T 檢定 (t-test)、費雪精確檢定（Fisher’s exact test）。
研究結果:
於 2010 年1 月1 日至2013 年12 月31 日之研究期間，總共收案病人為67人，單用組有44人；合併組則有23人。由全體病人資料可發現平均年齡為76.5 ± 13.9歲，男女比例為71.6% ： 28.4%。而在兩組組間比較的部分，除了男性比例在單獨使用抗綠膿桿菌針劑那組的人數較多 (p= 0.047)，其他在開始治療前，無論是在年齡、急性生理和慢性健康評估分數、臨床肺部感染量表、腎功能或有無肺炎以外其他感染的部分，兩組之間都無顯著差異。兩組所收入的病人年齡族群，約八成以上都超過六十歲。兩組在治療結束後，加護病房的住院天數 (p= 0.452)、呼吸器使用天數 (p= 0.061)、靜脈注射抗綠膿桿菌針劑的天數 ( p= 0.066)、急性生理和慢性健康評估分數 (p= 0.589)、臨床肺部感染量表在治療前後的平均差異 (p= 0.078)、肌酸酐數值上升超過1的比率 (p= 0.523)、再度培養出綠膿桿菌 (p= 0.46)或培養出抗藥性綠膿桿菌 (p= 0.603)、30天內死亡率 (p= 0.308)皆無顯示顯著差異。
結論:
使用合併針劑與吸入性投與Aminoglycosides與單用針劑兩者之間對於綠膿桿菌的療效相比較，併用針劑與吸入性投與Aminoglyco-
sides，雖然對於腎功能是沒有影響的，但是並沒有顯著改善病人的肺炎症狀、注射針劑使用天數、加護病房住院天數、離開加護病房時的急性生理和慢性健康評估分數、綠膿桿菌的再感染率與抗藥性菌種的產生。
由於本篇研究為一病歷回溯性研究，相對於有嚴格制定試驗流程的前瞻性研究而言有更多的限制，因此本篇研究的結果並無法代表整個患者族群。如欲明確研究各變項之預測性，最佳之方法仍為可控制各干擾因素之前瞻性試驗。

關鍵字

肺炎 ； 綠膿桿菌 ； 氨基糖苷類抗生素 ； 吸入投與 ； 靜脈注射

並列摘要

Background:
It is common that pneumonia of the ICU in Taiwan is caused by Pseudomonas aeruginosa. Due to the abuse of antibiotic prescription, the resistance of Pseudomonas aeruginosa is increasing. The previous study shows that when treating pulmonary infection, inhaled antibiotics yields higher pulmonary concentrations than intravenous administration. Whether the follow up efficacy also increased with the higher pulmonary antibiotic concentration is yet to be proven by evidence.
Study design, location and subjects:
This study was conducted south of a regional teaching hospital for the single-center, retrospective study of medical records. The study objects are those age between 20 and 99 years old, infected with Pseudomonas aeruginosa pneumonia in ICU and confirmed by bacterial culture from January 1st 2010 to December 31th 2013. Based on treatment methods, patients are divided into two groups, one is given antibiotics by intravenous route only and the other group is given intravenous and inhaled antibiotics in combination.
Methods:
All patients’ basic information and clinical data are collected by chart review. Clinical data are divided by timeline and recorded days of patients’ ICU stay, days of ventilation patient use, improvement of clinical symptoms of pneumonia and the incidence of drug-resistant bacteria, etc. Use Acute Physiology and Chronic Health Evaluation Score and Clinical Pulmonary Infection Score as assessment tool. The endpoint is mortality of 30 days after infection and all data undergo statistical analysis and comparison.
Statistical analysis includes chi-square test (χ2 test), T test (t-test), and Fisher exact test (Fisher's exact test).
Results:
During the study period from January 1st 2010 to December 31th 2013, a total of 67 patients were included, 44 of them used monotherapy (intravenous antibiotics alone) and 23 of then used combination therapy(intravenous and inhaled antibiotics). The patients information showed that the average age was 76.5 years old(standard deviation 13.9), male to female ratio was 71.6% to 28.4%. In comparison between the two group, other than male percentage in monotherapy group (p-0.047), there were no significant differences between the two group before treatment in age, Acute Physiology and Chronic Health Evaluation score, Clinical Pulmonary Infection Score, renal function, other infection site. More than 80 percent of patients' age in both groups were over 60. After treatment, there were no significant difference in days of ICU stays (p= 0.452), days or ventilator use (p= 0.061), days of intravenous injection of antibiotics(p= 0.066), Acute Physiology and Chronic Health Evaluation score (p= 0.589), difference of Clinical Pulmonary Infection Scale before and after treatment (p= 0.078), ratio of elevated creatinine value more than 1(p= 0.523), re-cultured Pseudomonas aeruginosa (p= 0.46), cultured drug-resistance Pseudomonas aeruginosa(p= 0.603), or 30-day mortality(p= 0.308).
Conclusions:
In comparison of monotherapy with combination therapy, the latter posed no effect on renal function but yielded not significantly difference regarding symptoms of pneumonia, days of intravenous injection, days of ICU stays, Acute Physiology and Chronic Health Evaluation score when leaving ICU, re-infected rate of Pseudomonas aeruginosa, or drug resistance strains.
Due to our study was a chart review retrospective one, there were more limitation comparing to prospective study with respect to strict protocol. Therefore our study was not representative of the entire patient populations. To clear all predictive variables, the best method was still prospective trials available to control various of confounding factors.

並列關鍵字

Pneumonia ； Pseudomonas aeruginosa ； Aminoglycosides ； Inhalation administration ； Intravenous injection

參考文獻

第八章 參考文獻

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