適應症及臨床療效評估

4.7.1 適應症評估

I. 預防性使用

分為兩種適應症: 血液腫瘤病人接受化學治療而引起中性球低下，與造血幹 細胞移植後出現植體宿主反應而接受免疫抑制劑治療。

II. 治療性使用

請感染科醫師依照 2008 年 EORTC/MSG 訂定之侵入性黴菌感染定義

（Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group）⁶⁵， 評估使用 posaconazole 的適應症。此方法依據診斷確定性分為確定（proven）感 染、極有可能（probable）感染，和可能（possible）感染三種級別。確定感染的 定義為病理組織、培養皿培養、或血液培養證實之黴菌感染；有宿主風險因子

（host factor）、符合微生物學標準（microbiological criteria）和臨床標準（clinical criteria）則歸類為極有可能（probable）感染；若僅有宿主風險因子（host factor）， 以及符合微生物學標準（microbiological criteria）或臨床標準（clinical criteria）

之其中一項，則視為可能（possible）感染。詳細定義請見表 4.4、4.5。

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4.7.2 臨床反應評估

I. 預防性使用

在停止 posaconazole 預防當日，及停藥 7 天後進行評估。預防成功的定義為：

未出現新侵入性黴菌感染（breakthrough IFI）、病人在 neutropenia 期間退燒

（defeverense）、仍然存活，三者同時達到方可視為成功。若 posaconazole 改為 治療劑量（排除因濃度未達目標而經驗性增加劑量者）或改用其他抗黴菌藥物、

或出現新侵入性黴菌感染、或在 neutropenia 前間持續發燒、或死亡則為預防失 敗。亦會請感染科醫師針對預防失敗的案例，依照 EORTC/MSG 侵入性黴菌感

染定義，做診斷確定性的評估⁶⁵。

II. 治療性使用

由感染科醫師依據 2008 年 EORTC/MSG 訂定之侵入性黴菌感染療效反應定 義來評估⁶⁶，評估時間點為停用 posaconazole 時或追蹤終止日（2013 年 6 月 30 日）。治療反應可分為完全治癒（complete response）、部分治癒（partial response）、

疾病無進展（stable response）、疾病惡化（progression of disease）、死亡（death），

若病人於使用 posaconazole 期間死亡，則再細分為因黴菌感染死亡（death due to IFI）或非因黴菌感染死亡（death with IFI）。若為完全治癒及部分治癒則定義為 治療成功；疾病無進展、疾病惡化或死亡則視為治療失敗。詳細定義請見表 4.6。

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表 4.4 Criteria for proven invasive fungal infection⁶⁵ Analysis and or direct microscopic examination of a specimen obtained by needle aspiration or biopsy in which hyphae or melanized yeast-like forms are seen accompanied by evidence of associated tissue damage

Histopathologic, cytopathologic, or direct microscopic examination of a specimen obtained by needle aspiration or biopsy from a normally sterile site (other than mucous membranes) showing yeast cells—for example, Cryptococcus species indicated by encapsulated budding yeasts or Candida species showing pseudohyphae or true hyphae Culture:

Sterile material

Recovery of a mold or “black yeast” by culture of a specimen obtained by a sterile procedure from a normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process,

excluding bronchoalveolar lavage fluid, a cranial sinus cavity specimen, and urine

Recovery of a yeast by culture of a sample obtained by a sterile procedure （including a freshly placed [<24 h ago] drain） from a normally sterile site showing a clinical or radiological

abnormality consistent with an infectious disease process

Blood Blood culture that yields a mold

（e.g., Fusarium species）in the context of a compatible infectious disease process

Blood culture that yields yeast

（e.g., Cryptococcus or Candida species） or yeast-like fungi（e.g., Trichosporon species）

Serological analysis:

CSF

Not applicable Cryptococcal antigen in CSF indicates disseminated cryptococcosis

NOTE. Adapted from Clin Infect Dis 2008;46:1813-21.

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表 4.5 Criteria for probable and possible invasive fungal infection⁶⁵ 1. Host factors

 Recent history of neutropenia (<500 neutrophils/mm³ for >10 day) temporally related to the onset of fungal disease

 Receipt of an allogeneic stem cell transplant

 Prolonged use of corticosteroid (excluding among patients with allergic

bronchopulmonary aspergillosis) at a mean minimum dose of 0.3 mg/kg/day of prednisone equivalent for 13 weeks

 Treatment with other recognized T cell immunosuppressants, such as cyclosporine, TNF-a blockers, specific monoclonal antibodies (such as alemtuzumab), or nucleoside analogues during the past 90 days

 Inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency)

2. Clinical criteria

 Lower respiratory tract fungal disease: the presence of 1 of the following 3 signs on CT:

a. Dense, well-circumscribed lesions(s) with or without a halo sign b. Air-crescent sign

c. Cavity

 Tracheobronchitis: tracheobronchial ulceration, nodule, pseudomembrane, plaque, or eschar seen on bronchoscopic analysis

 Sinonasal infection: imaging showing sinusitis plus at least 1 of the following 3 signs:

a. Acute localized pain (including pain radiating to the eye) b. Nasal ulcer with black eschar

c. Extension from the paranasal sinus across bony barriers, including into the orbit

 CNS infection: 1 of the following 2 signs:

a. Focal lesions on imaging

b. Meningeal enhancement on MRI or CT

 Diseminated candidiasis: at least 1 of the following 2 entities after an episode of candidemia within the previous 2 weeks:

a. Small, target-like abscesses (bull's-eye lesions) in liver or spleen b. Progressive retinal exudates on ophthalmologic examination

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續表 4.5

3. Mycological criteria

 Direct test (cytology, direct microscopy, or culture)Mold in sputum, bronchoalveolar lavage fluid, bronchial brush, or sinus aspirate samples, indicated by 1 of the following:

a. Presence of fungal elements indicating a mold

b. Recovery by culture of a mold (e.g., Aspergillus, Fusarium, Zygomycetes, or Scedosporium species)

 Indirect tests (detection of antigen or cell-wall constituents)

a. Aspergillosis: Galactomannan antigen detected in plasma, serum, bronchoalveolar lavage fluid, or CSF

b. Invasive fungal disease other than cryptococcosis and zygomycoses: β -D-glucan detected in serum

NOTE. Adapted from Clin Infect Dis 2008;46:1813-21.

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表 4.6 Responses to antifungal therapy- invasive mold disease⁶⁶ Response Criteria

Complete response

All of the followings:

1. Survival and resolution of all attributable symptoms and signs 2. Resolution of radiological lesion(s); persistence of only a scar or

postoperative changes can be equated with a complete radiological response

3. Documented clearance of infected sites that are accessible to repeated sampling (e.g., mold diseaseinvolvingthe palate, sinuses, or cutaneous lesions)

Partial response

All of the followings:

1. Survival and improvement of attributable symptoms and signs 2. At least 25% reduction in diameter of radiological lesion (s) 3. Documented clearance of infected sites that are accessible to

repeated sampling (e.g., mold disease involving the palate, sinuses, or cutaneous lesions)

 In cases of radiological stabilization (defined as a 0%–25%

reduction in the diameter of the lesion), resolution of all

attributable symptoms and signs of fungal disease can be equated with a partial response

 In cases of radiological stabilization, biopsy of an infected site (e.g., lung biopsy) showing no evidence of hyphae and negative culture results can be equated with a partial response

Stable response

Survival and minor or no improvement in attributable symptoms and signs of disease, plus at least one of followings:

1. Radiological stabilization (defined as a 0%–25% reduction in the diameter of the lesion

2. Persistent isolation of mold or histological presence of invasive hyphae in infected sites

Progression of disease

Worsening clinical symptoms or signs, plus at least one of followings:

1. New sites of disease or radiological worsening of preexisting lesions; or

2. Persistent isolation of mold species from infected sites Death Death during the prespecified period, classify as:

1. Death due to invasive fungal infections 2. Death with invasive fungal infections

NOTE. Adopted from Clin Infect Dis 2008;47:674-83.

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