醫療照顧相關結核感染:院內結核感染管制及器官移植病人結核感染的研究

Healthcare-associated tuberculosis: studies of infection control of nosocomial tuberculosis and tuberculosis in solid organ transplant recipients

孫幸筠(Hsin-Yun Sun)

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/博士(2020年)

https://doi.org/10.6342/NTU202003609

摘要

因共病症住院之未診斷出肺結核的病患，是院內結核控制上的一大挑戰。我們第一篇研究於一照顧高結核病患數量的台北醫學中心(每年約通報400位結核病患)，評估將痰液抗酸性抹片，從傳統顯微鏡檢查改為高敏感性的螢光顯微鏡檢查，對經痰液培養確診為肺結核病患，於痰液抗酸性抹片偵測率，空氣隔離的時效，和未接受空氣隔離俱傳染性時間的影響。轉換為螢光顯微鏡檢查後，未空氣隔離俱傳染性時間從原本的12.5天縮短為3天 (p值為<0.001)。相較於傳統顯微鏡檢查，螢光顯微鏡檢查增加兩倍的痰液抗酸性抹片偵測率(對所有納入研究的肺結核病患而言，從22.8% 增加到48.1%，p值為<0.001。若針對肺部開洞的肺結核病患，則從43%增加到82%，p值為0.029)，且接受空氣隔離的可能性增加兩倍(經痰液抹片調整後的勝算比為1.8，95%信賴區間為1.3-2.5)。整體未接受空氣隔離俱傳染性時間降低69%(從每年4,778人日降為每年1,502人日)。在一照顧高結核病患數量的醫療機構，高敏感性的痰液抗酸性抹片螢光顯微鏡檢查大幅改善偵測到肺結核病患的比例，使其能即時接受空氣隔離，進而減少院內結核病傳播的風險。
結核病是器官移植後一重要感染症，會造成嚴重的罹病率和死亡率。目前仍未知是否有特定的免疫抑制劑處方會增加器官移植後結核病的風險。我們第二篇研究藉由病例對照的方式，罹患結核病且在台大醫院接受器官移植的病患和未罹患結核病的器官移植病患，根據年紀(加減五歲)，移植器官和年代(加減五年)以1:4的比例進行配對。共有27位罹患結核的個案和101對照病患納入研究。在調整年紀和B型肝炎病毒感染後，診斷結核病前六個月內使用超過三個月含有mTOR抑制劑的免疫抑制劑處方，有較高罹患結核病的風險(調整後的勝算比為4.5，95%信賴區間為1.1-18.6，p值為0.037)，但使用含有calcineurin抑制劑的免疫抑制劑處方，反而有保護作用(調整後的勝算比為0.1，95%信賴區間為0.01-0.99，p值為0.048)。使用含有mTOR抑制劑的免疫抑制劑處方的器官移植病患有較高罹患結核病的風險，應考慮對此群病患進行結核病的風險評估。

關鍵字

結核感染 ； 院內感染管制 ； 器官移植病人

並列摘要

Undiagnosed tuberculosis (TB) patients hospitalized because of comorbidities pose a great challenge to TB control in hospitals. We assessed the impact of introducing highly sensitive fluorescent microscopy for examining sputum smear to replace conventional microscopy on the smear detection rate of culture-confirmed pulmonary TB, timing of respiratory isolation, and total non-isolated infectious person-days in hospital at a high-caseload medical center (approximately 400 TB cases annually) in Taipei. After the switch to fluorescence microscopy, median non-isolated infectious duration decreased from 12.5 days to 3 days (P<0.001). Compared with conventional microscopy, fluorescence microscopy increased sputum smear detection rate by two-fold (for all patients: from 22.8% to 48.1%, P<0.001; for patients with cavitary lung lesion: from 43% to 82%, P=0.029) and was associated with a 2-fold higher likelihood of prompt respiratory isolation (odds ratio mediated by the increase in sputum smear detection rate: 1.8, 95% conference interval [CI] 1.3–2.5). Total non-isolated infectious patient-days in hospital decreased by 69% (from 4,778 patient-days per year to 1,502 patient-days per year). In a high TB caseload setting, highly sensitive rapid diagnostic tools could substantially improve timing of respiratory isolation and reduce the risk of nosocomial TB transmission.
TB is an important post-transplant infection causing significant morbidities and mortality in solid organ transplant (SOT) recipients. Whether certain immunosuppressive regimens put solid organ transplant (SOT) recipients at a higher risk for TB remains unknown, so we conducted a case-control study to identify TB risk factors in SOT recipients. Controls and cases were matched by age (+5 years), transplant organ type and year (+5 years) at a ratio of 4:1. A total of 101 controls were selected for 27 cases. After the adjustment of age and HBV infection, mammalian target of rapamycin inhibitors (mTORi)-containing regimens (adjusted odds ratio [aOR] 4.5, 95% CI 1.1-18.6, P = 0.037) used for more than 3 months within 6 months of TB diagnosis was significantly associated with TB while calcineurin inhibitors-containing regimens was not (aOR 0.1, 95% CI 0.01-0.99, P=0.048). SOT recipients on mTORi-containing regimens had a higher risk for TB, and TB risk assessment should be considered for those patients.

並列關鍵字

tuberculosis ； infection control ； solid organ transplant recipients

參考文獻

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