ATB FUNGUS试剂盒在新生隐球菌药敏测定中的应用及其临床意义——附24例报告

目的:探讨ATB FUNGUS试剂盒在新生隐球菌药敏测定中的临床价值.方法:对分离于24例隐球菌性脑膜炎患者脑脊液的24株新生隐球菌,采用ATB FUNGUS试剂盒测定其对两性毒素B、氟胞嘧啶、制霉菌素、咪康唑、益康唑和酮康唑等6种抗真菌药的敏感度.结果:24株隐球菌对两性霉素B、氟胞嘧啶、制霉菌素和咪康唑均为敏感或中度敏感,而对益康唑和酮康唑部分表现为耐药.18例使用两性霉素B和氟胞嘧啶联合治疗的患者中,治疗后50%(9/18)治愈,50%(9/18)好转,总有效率达100%.另4例采用两性霉素B、氟胞嘧啶和氟康唑治疗,2例采用两性霉素B和氟胞嘧啶治疗,达到临床治愈后采用氟康唑口服,治愈1例,好转2例,无效3例(无进展2例,死亡1例).结论:ATB FUNGUS药物敏感试剂盒可用于新生隐球菌性脑膜炎治疗过程中对耐药菌株的监测,增加对氟康唑和伊曲康唑等新的高效的高效抗真菌药物的敏感性检测也许能提高其临床应用价值.     

急性侵袭性肺曲霉病的诊治--附1例报道

目的：观察伏立康唑注射剂静脉滴注治疗1例严重急性呼吸综合征(SARS)并发急性侵袭性肺曲霉病患的疗效及安全性。方法：该患因SARS住院，经大剂量激素、广谱抗菌药物、机械通气等治疗，后合并急性侵袭性肺曲霉病。因不能耐受两性霉素B胆固醇复合物试验剂量而改用伏立康唑注射剂静脉滴注，首日负荷剂量为6mg／kg，每12小时1次，以后维持剂量为4mg／kg每12小时1次，疗程5周。结果：经伏立康唑治疗后痊愈，不良反应表现为乏力、轻度眩晕和纳差。结论：伏立康唑治疗SARS并发急性侵袭性肺曲霉病的效果令人鼓舞。     

经验治疗、抢先治疗和针对性治疗侵袭性霉菌病随机对照临床试验结果混合比较的系统回顾

<正>侵袭性霉菌病是恶性血液病患者发病和死亡的主要原因之一。在20年前,治疗侵袭性霉菌病药物只有两性霉素B和伊曲康唑。目前,已开发出脂质体两性霉素B、卡泊芬净、伏立康唑、泊沙康唑等新型抗真菌药。这些新药大大提高侵袭性霉菌病的治疗疗效并增加经验积累。多种治疗方案和新的诊断方法使治疗策略发生了变化。虽然嗜中性粒细胞缺乏伴持续发热患者的抗真菌经验治疗仍被广泛应用,但只证明新型唑类药物的预防应用对侵袭性曲霉病有效,并     

化疗后骨髓抑制期发生鼻脑曲霉菌病——一例报告附文献复习

目的　报道 1例急性髓系白血病 (AML) M2a患者化疗后骨髓抑制期发生侵袭性鼻脑曲霉菌病 (invasiverhinocerebralaspergillosis,IRA)及其治疗经过 ,并进行文献复习。方法　 1例AML M2a患者 ,化疗后骨髓抑制期发生IRA ,连续给予两性霉素B(AmB) ,包括脂质体AmB治疗 ,同时给予大蒜素、5 氟胞嘧啶 (5 FC)、氟康唑、伊曲康唑、酮康唑、益康唑及制霉菌素等联合治疗 ,并先后 2次行开颅病灶切除、减压术。结果　经过上述治疗 ,患者生存时间虽略有延长 ,但最终仍因感染无法彻底控制而死亡。结论　对于大部分IRA目前尚无特效治疗措施 ,AmB也仅对少部分患者有效 ,结合手术切除病灶是目前为止最佳的治疗方法。     

化疗后骨髓抑制期发生鼻脑曲霉菌病—一例报告附文献复习

目的 报道1例急性髓系白血病（AML）－M2a患者化疗后骨髓抑制期发生侵袭性鼻脑曲霉菌病（invasive rhinocerebral aspergillosis,IRA)及其治疗经过,并进行文献复习。方法 1例AML－M2a患者,化疗后骨髓抑制期发生IRA,连续给予两性霉素B（AmB),包括脂质体AmB治疗,同时给予大蒜素、5－氟胞嘧啶（5－FC）、氟康唑、伊曲康唑、酮康唑、益康唑及制霉菌素等联合治疗,并先后3次行开颅病灶切除、减压术。结果 经过上述治疗,患者生存时间虽略有延长,但最终仍因感染无法彻底控制而死亡。结论 对于大部分IRA目前尚无特效治疗措施,AmB也仅对少部分患者有效,结合手术切除病灶是目前为止最佳的治疗方法。     

复发性外阴阴道念珠菌病63例菌种鉴定及药敏试验分析

目的了解复发性外阴阴道念珠菌病(RVVC)的菌种类别及药物敏感性。方法分析63例RVVC的菌种类别和药敏试验,念珠菌采用API20C AUX方法进行鉴定,药敏试验采用ATB FUNGUS方法。结果 63例RVVC以白假丝酵母菌为主,检出39例,占61.9%;念珠菌对两性霉素B、5-氟胞嘧啶、伏力康唑、伊曲康唑、氟康唑的敏感性分别为95.2%、85.7%、23.8%、14.3%和14.3%,对伊曲康唑、氟康唑、伏力康唑、氟胞嘧啶、两性霉素B的耐药性分别为57.1%、57.1%、52.4%、14.3%和0。结论 RVVC以白假丝酵母菌为主,对两性霉素B、5-氟胞嘧啶敏感性高,耐药率低。     

167例痰培养念珠菌感染及药敏试验结果的探讨

目的探讨住院患者痰培养念珠菌感染的分布和药敏试验结果。方法对2006年2月至2007年2月780例住院患者送检的痰标本进行细菌培养鉴定，并对鉴定出的念珠菌进行5-氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑4种抗真菌药敏试验。结果780例患者标本共分离出念珠菌167例，检出率21.4％，其中自假丝念珠菌143例，阳性率85．6％，其他依次为热带念珠菌19例，阳性率为11．4％，光滑念珠菌5例，阳性率0．3％。念珠菌对4种抗真菌药物的敏感率依次为：5-氟胞嘧啶96．0％、两性霉素B94．0％、氟康唑77．2％、伊曲康唑34．0％。结论由于呼吸道感染的患者多数情况下长时间在社区医院进行抗炎治疗，滥用大剂量抗生素，抑制了机体的正常菌群，为条件致病菌的生长提供了良好条件，其中念珠菌的感染率较高。以5-氟胞嘧啶和两性霉素B抗真菌敏感性较佳，建议临床治疗首选。     

临床常见念珠菌对四种抗真菌药物体外敏感性研究

目的：了解临床常见致病念珠菌对4种抗真菌药物的敏感性情况，旨在为临床治疗此类菌株引起的感染提供实验依据。方法：采用美国国家临床实验室标准化委员会推荐的微量肉汤稀释法(NCCLS M27-A2)，测定从临床血液、痰液和尿液等标本中分离的226株常见念珠菌对氟康唑、伊曲康唑、两性霉素B和氟胞嘧啶的最低抑菌浓度(MIC)。结果：226株受试菌对氟胞嘧啶100％敏感，MIC90为≤0．125-0．5μg／ml；168株白色念珠菌对氟康唑、伊曲康唑和两性霉素B的MIC90分别为32μg／ml、1μg／ml和1μg／ml，敏感率分别为90．5％(S88．1％ SDD2．4％)、92．3％(S87．5％ SDD4．8％)和91．7％；31株热带念珠菌对氟康唑、伊曲康唑和两性霉素B敏感率分别为96．8％(S93．6％ SDD3．2％)、93．5％(S83．9％ SDD9．6％)和100％；16株近平滑念珠菌对氟康唑、伊曲康唑和两性霉素B均敏感；11株光滑念珠菌对氟康唑和伊曲康唑的敏感率分别为81．8％(S18．2％ SDD63．6％)和72．8％(S36．4％ SDD36．4％)，而对两性霉素B100％敏感。在白色念珠菌、热带念珠菌和光滑念珠菌中有3．2％～27．2％菌株对氟康唑和伊曲康唑等唑类药物耐药。结论：临床常见致病念珠菌对氟胞嘧啶和两性霉素B的敏感性最高，对唑类药物存在不同程度耐药。     

气道支气管曲霉病1例报告及文献复习

目的了解气道侵袭性曲霉病的临床特征、诊断和治疗。方法对1例气道侵袭性曲霉病患者的临床表现、纤维支气管镜检查和病理诊断进行分析并作文献复习。结果1例患者临床表现为咳嗽，胸闷，气急。纤维支气管镜下表现为新生物突出于管腔，病理示大量曲霉菌丝浸润至气道黏膜基层，伊曲康唑治疗24周后痊愈。结论气道侵袭性曲霉病以曲霉浸润到气道黏膜的基底层为特征，纤维支气管镜检查是有效的诊断手段，伊曲康唑是治疗气道侵袭性曲霉病的有效药物之一。     

住院危重患者深部真菌感染的致病菌与耐药性研究

目的探讨住院危重患者深部真菌感染的致病菌分布与耐药性。方法选取该院2015年1月至2016年12月ICU收治的557例危重患者临床资料进行回顾性分析,对患者的真菌感染情况、病原菌分布及药敏试验结果进行比较。结果 2016年侵袭性真菌感染(IFI)发病率(23.62%)较2015年(19.48%)有所增长,但差异无统计学意义(χ~2=1.354,P=0.245);122例IFI患者共培养分离真菌66株,其中白色念珠菌45株(68.18%),热带假丝酵母菌9株(13.64%),光滑假丝酵母菌2株(3.03%),近平滑假丝酵母菌3株(4.55%),克柔念珠菌7株(10.61%);各真菌对两性霉素B和5-氟胞嘧啶的敏感性较高,且差异无统计学意义(P0.05);各真菌对氟康唑、伏立康唑和伊曲康唑的敏感性普遍较差,5种真菌对伊曲康唑敏感率比较,差异有统计学意义(P0.05);122例IFI患者治疗首选氟康唑72例(59.02%),伏立康唑23例(18.85%),两性霉素B 10例(8.20%),5-氟胞嘧啶9例(7.38%),伊曲康唑8例(6.56%),其中目标治疗以伏立康唑使用率最高为50.00%,抢先治疗和经验治疗以氟康唑使用率最高,分别为64.47%和52.63%。结论该院ICU病房危重病患者IFI发病率有逐年增长的趋势,对于临床诊断和拟诊的患者可首选对常见真菌敏感性普遍较高的两性霉素B和5-氟胞嘧啶进行治疗,确诊的患者则可选择相应敏感性高的药物进行目标治疗。     

Cerebral aspergillosis in the critically ill: two cases of successful medical treatment

Objective Invasive aspergillosis is associated with a poor prognosis, especially in critically ill patients with cerebral involvement. We present two cases of cerebral invasive aspergillosis successfully treated in the intensive care unit with combination antifungal therapies and without surgery.Case presentation The first patient was a 49-year-old man with rheumatoid arthritis who received corticosteroid and cyclophosphamide treatment and developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole the patient had a successful outcome with voriconazole and liposomal amphotericin B therapy. The patient returned home after an 8-month hospital stay. The second patient was a 54-year-old woman with pulmonary neoplasia and corticosteroid treatment who developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole and liposomal amphotericin B therapy the patient had a favorable outcome with liposomal amphotericin B and caspofungin therapy. The patient died 10 months after initial diagnosis of cardiac tamponade unrelated to fungal infection.Discussions These cases illustrate the improving prognosis of invasive aspergillosis due to the availability of new treatments, especially in cases of cerebral involvement. It also demonstrates that the outcome of critically ill patients requiring mechanical ventilation for invasive aspergillosis can be favorable. The treatment of patients with invasive cerebral aspergillosis in the intensive care setting should be encouraged.     

Activity of micafungin (FK463) against an itraconazole-resistant strain of Aspergillus fumigatus and a strain of Aspergillus terreus demonstrating in vivo resistance to amphotericin B

We compared the activity of four doses of micafungin (FK463) with that of amphotericin B, liposomal amphotericin B and itraconazole in a murine model of disseminated aspergillosis. Temporarily neutropenic mice were infected with a lethal dose of either an itraconazole-resistant Aspergillus fumigatus isolate or Aspergillus terreus, a species that is less susceptible to amphotericin B. Treatment was started 24 h after infection and lasted for 7 days. Mice were treated with either amphotericin B (0.5 or 5 mg/kg), liposomal amphotericin (5 or 25 mg/kg), itraconazole (25 or 75 mg/kg) or FK463 (either 1, 2, 5 or 10 mg/kg). Treatment of the A. fumigatus model with either amphotericin B, liposomal amphotericin or FK463 prolonged survival. Doses of FK463 5 and 10 mg/kg had a 100% survival. Treatment of A. terreus infection with either itraconazole or FK463, but not amphotericin B, also prolonged survival. Doses of liposomal amphotericin of 5 and 25 mg/kg were ineffective against A. terreus infection. No treatment regime was able to totally clear the liver or kidneys in either model. The data indicate that FK463 may have a clinical role in the treatment of life-threatening invasive aspergillosis.     

Efficacy of aerosolized amphotericin B desoxycholate and liposomal amphotericin B in the treatment of invasive pulmonary aspergillosis in severely immunocompromised rats.

The effects of treatment with aerosolized amphotericin B desoxycholate and aerosolized liposomal amphotericin B were evaluated in severely immunosuppressed rats with invasive pulmonary aspergillosis. Aerosol treatment with amphotericin B desoxycholate consisted of a single dose (60 min) with amphotericin B concentrations in the nebulizer reservoir of 1, 2 and 4 mg/mL, respectively. For liposomal amphotericin B, aerosol treatment consisted of single, double or quadruple doses with a nebulizer reservoir concentration of 4 mg/mL of amphotericin B. Treatment, started at 30 h after inoculation, with aerosolized amphotericin B desoxycholate (nebulizer reservoir concentration 2 mg/mL) significantly prolonged survival of rats as compared with placebo-treated rats, whereas treatment with aerosolized amphotericin B desoxycholate with nebulizer reservoir concentration of 1 or 4 mg/mL did not have a significant effect on survival. Treatment with aerosolized liposomal amphotericin B significantly prolonged survival with all treatment regimens when compared with placebo-treated animals. Aerosol treatment did not prevent dissemination of the infection. The effects of amphotericin B desoxycholate and liposomal amphotericin B on pulmonary surfactant function were also evaluated in vitro. Amphotericin B desoxycholate inhibited surfactant function in a dose-dependent fashion. Liposomal amphotericin B had no detrimental effect on surface activity of surfactant. These results indicate that aerosol administration of amphotericin B, especially the liposomal formulation, could be an additional approach to optimizing treatment of invasive pulmonary aspergillosis.     

Pretreatment with empty liposomes attenuates the immunopathology of invasive pulmonary aspergillosis in corticosteroid-immunosuppressed mice

In a nonneutropenic murine model of invasive pulmonary aspergillosis, pretreatment with empty liposomes (E-lipo) was nearly as effective as 10 mg/kg of body weight liposomal amphotericin B and superior to 1 mg/kg amphotericin B deoxycholate. The beneficial immunomodulatory properties of E-lipo appear to compensate for their lack of direct antifungal activity.     

Itraconazole for experimental pulmonary aspergillosis: comparison with amphotericin B, interaction with cyclosporin A, and correlation between therapeutic response and itraconazole concentrations in plasma.

Itraconazole and amphotericin B were compared by using a newly developed model of invasive pulmonary aspergillosis in rabbits immunosuppressed with methylprednisolone and cyclosporin A (CsA). Both itraconazole at 40 mg/kg (given orally) and amphotericin B at 1 mg/kg (given intravenously) had in vivo antifungal activity in comparison with controls. At these dosages, amphotericin B was more effective than itraconazole in reducing the tissue burden (log10 CFU per gram) of Aspergillus fumigatus (P < 0.05) and the number of pulmonary lesions (P < 0.01). However, there was considerable variation in the near-peak concentrations of itraconazole in plasma (median, 4.15 micrograms/ml; range, < 0.5 to 16.8 micrograms/ml) and a strong inverse correlation between concentrations of itraconazole in plasma and the tissue burden of A. fumigatus. An inhibitory sigmoid maximum-effect model predicted a significant pharmacodynamic relationship (r = 0.87, P < 0.001) between itraconazole concentrations in plasma and antifungal activity as a function of the tissue burden of A. fumigatus. This model demonstrated that levels in plasma of greater than 6 micrograms/ml were associated with a significantly greater antifungal effect. Levels in plasma of less than 6 micrograms/ml were associated with a rapid decline in the antifungal effect. Itraconazole, in comparison with amphotericin B, caused a twofold elevation of CsA levels (P < 0.01) but was less nephrotoxic (P < 0.01). This study of experimental pulmonary aspergillosis demonstrated that amphotericin B at 1 mg/kg/day was more active but more nephrotoxic than itraconazole at 40 mg/kg/day, that itraconazole increased concentrations of CsA in plasma, and that the antifungal activity of itraconazole strongly correlated with concentrations in plasma in an inhibitory sigmoid maximum-effect model. These findings further indicate the importance of monitoring concentrations of itraconazole in plasma as a guide to increasing dosage, improving bioavailability, and optimizing antifungal efficacy in the treatment of invasive pulmonary aspergillosis.     

Nebulized amphotericin B combined with intravenous amphotericin B in rats with severe invasive pulmonary aspergillosis

Nebulized amphotericin B (AMB) combined with intravenous AMB was studied in persistently leukopenic rats with invasive pulmonary aspergillosis. Pulmonary concentrations of AMB after aerosol treatment were substantially higher than after intravenous liposomal AMB. Nebulized liposomal AMB in addition to intravenous AMB resulted in significantly prolonged survival compared to controls.     

Clearance of Fungal Burden during Treatment of Disseminated Histoplasmosis with Liposomal Amphotericin B versus Itraconazole

Animal studies have shown that fungal burden correlates with survival during treatment with new antifungal therapies for histoplasmosis. The purpose of this report is to compare the clearance of fungal burden in patients with histoplasmosis treated with liposomal amphotericin B versus itraconazole. In two separate closed clinical trials that evaluated the efficacy of liposomal amphotericin B and itraconazole treatment of disseminated histoplasmosis in patients with AIDS, blood was cultured for fungus and blood and urine were tested for Histoplasma antigen. The clinical response rates were similar; 86% with liposomal amphotericin B (n = 51) versus 85% with itraconazole (n = 59). Of the patients with positive blood cultures at enrollment, after 2 weeks of therapy cultures were negative in over 85% of the liposomal amphotericin B group versus 53% of the itraconazole group (P = 0.0008). Furthermore, after 2 weeks, median antigen levels in serum fell by 1.6 U in the liposomal amphotericin B group versus 0.1 U in the itraconazole group (P = 0.02), and those in urine fell by 2.1 U in the liposomal amphotericin B group and 0.2 U in the itraconazole group (P = 0.0005). The more rapid clearance of fungemia supports the use of liposomal amphotericin B rather than itraconazole for initial treatment of moderately severe or severe histoplasmosis.     

Aspergillosis in liver transplant recipients: successful treatment and improved survival using a multistep approach

BACKGROUND: Invasive aspergillosis is a life-threatening complication in liver transplant recipients, with a reported mortality rate of more than 90%. Treatment is difficult, and no single agent is uniformly effective in treating this patient population. METHODS: We retrospectively reviewed all fungal cultures from 200 liver transplant patients between 1996 and 1999 at a single tertiary referral center. RESULTS: A diagnosis of aspergillosis was made in 6 patients. Five patients had pulmonary involvement; 1 presented with an inguinal mass. Time from transplant to infection ranged from 1 week to 34 months. Treatment included surgical intervention and medical treatment. All patients infected with Aspergillus fumigatus were treated with a sequential protocol of lipid complex amphotericin followed by itraconazole. The major side effect of treatment was worsening renal function. One patient died of intracranial hemorrhage during treatment. CONCLUSION: Successful treatment of aspergillosis in liver transplant recipients should include early diagnosis, sequential medical treatment with lipid amphotericin B and itraconazole, and surgical intervention for invasive disease.     

Effect of direct infusion of antifungal agent on invasive pulmonary aspergillosis in a patient with acute leukemia

Invasive pulmonary aspergillosis is a serious problem in the treatment of patients with acute leukemia. A 52-year-old woman with acute myeloid leukemia developed invasive pulmonary aspergillosis during remission induction chemotherapy. Initially, we treated her with a continuous intravenous drip infusion of amphotericin B, together with itraconazole, given orally. A peripheral crescentic cavity formed in the fungal lesion after the number of neutrophils recovered, and we therefore performed a direct infusion of miconazole into the cavity transbronchially. The lung lesion resolved dramatically shortly after this treatment. In this patient, the transbronchial infusion of an antifungal agent seemed to have been very useful for bringing about prompt resolution of the fungal lesion. Received: May 30, 2001 / Accepted: September 21, 2001