卡泊芬净治疗白血病并发侵袭性肺部真菌感染4例的临床观察

卡泊芬净是一种新型葡聚糖合成酶抑制剂类抗真菌药,我院血液肿瘤病房自2004年11月～2006年4月对4例白血病并发侵袭性肺部真菌感染的患者使用卡泊芬净治疗,现报告治疗体会.     

日本警示卡泊芬净的严重皮肤反应风险

<正>2017年4月20日,日本卫生部、劳工和福利部(MHLW)以及药品和医疗器械管理局(PMDA)宣布更新卡泊芬净的药品说明书,将中毒性表皮坏死松解症(TEN)和眼-黏膜-皮肤综合征(Stevens-Johnson综合征)作为临床显著不良反应纳入产品说明书中。卡泊芬净主要用于治疗疑似由真菌感染引起的发热性中性粒细胞减少以及治疗念珠菌或曲霉菌引起的真菌感染。此次更新是继收到来自日本和其他国家接受卡泊芬净治疗的患者发生TEN和/或Stevens-Johnson综合征的病例,     

卡泊芬净治疗恶性血液病并发侵袭性真菌感染患者的疗效观察

恶性血液病患者因接受大剂量化疗,应用免疫抑制剂及广谱强效抗生素,造成中性粒细胞严重减少,免疫功能明显下降,极易发生侵袭性真菌感染(IFI)。抗真菌治疗疗程长,而多数并发真菌感染者的基础疾病重,对药物耐受性差,老年患者更为突出。我院采用卡泊芬净治疗恶性血液病并发IFI患者41例,观察其疗效和安全性,报告如下。     

卡泊芬净治疗恶性血液病合并侵袭性肺部真菌感染的临床疗效观察

目的 观察卡泊芬净在恶性血液病患者肺部真菌感染治疗中的疗效及安全性.方法 回顾性分析我科2007年10月～2014年1月间49例恶性血液病合并侵袭性肺部真菌感染患者的临床资料,评估其静脉应用卡泊芬净治疗的临床疗效,并于治疗期间监测肺部影像学、肝肾功能等.结果 49例患者中,临床诊断10例,拟诊39例;卡泊芬净治疗7 d ～ 210 d,总有效率为53.6％;临床诊断10例患者中,临床治愈0例,临床显效4例,进步2例,无效4例,有效率为40％;拟诊39例患者中,临床治愈8例,临床显效14例,进步8例,无效9例,有效率为56.4％;初始治疗组37例,有效率54.5％,挽救性治疗组12例,有效率50.0％;仅1例患者在治疗期间出现一过性谷丙转氨酶增高,至67 IU/L,其他患者用药过程中均未出现明显不良反应.结论 卡泊芬净治疗恶性血液病患者合并侵袭性肺部真菌感染患者具有一定疗效且安全性好.     

肾移植术后并发卡氏肺孢子菌肺炎的治疗方案选择

摘要 目的：探讨肾移植术后并发卡氏肺孢子菌肺炎（PCP）患者用卡泊芬净治疗PCP感染的疗效。方法：将125例肾移植后并发PCP患者分为磺胺组（42例）、卡泊芬净组（37例）和磺胺+卡泊芬净组（46例），比较3组临床特征，分析各组治疗后患者体温恢复正常时间、卡氏肺孢子菌（PC）核酸转阴时间和治疗结局。结果：治疗前，3组患者年龄、性别、发热症状及实验室检测（G实验和乳酸脱氢酶）方面比较，差异无明显统计学意义（P均>0.05）。治疗后，磺胺组、卡泊芬净组、磺胺+卡泊芬净组体温恢复正常时间分别为（7.9±1.4）d，(8.1±1.7)d和(7.7±1.5)d，组间比较，差异无明显统计学意义（P>0.05）；PC核酸转阴时间分别为（13.4±1.6）d、（16.3±2.9）d、（13.9±2.5）d；卡泊芬净组PC核酸转阴时间明显长于磺胺组、磺胺+卡泊芬净组（P均<0.05），磺胺组和磺胺+卡泊芬净组比较，差异无明显统计学意义（P>0.05）；3组间的治疗结局比较，差异无明显统计学意义（P均>0.05）。结论：卡泊芬净单药治疗PCP能获得肯定的疗效，包括体温恢复正常、PC核酸转阴和治愈出院。卡泊芬净对于肾移植术后PCP患者的治疗是一个较好的选择。     

卡泊芬净治疗侵袭性真菌感染疗效观察

目的探讨卡泊芬净治疗侵袭性真菌感染（IFI）的疗效与安全性。方法对20例外科ICU IFI患者使用卡泊芬净50mg／d,观察临床疗效与不良反应。结果IFI痊愈8例,显效6例,进步4例,无效2例,有效率为70％,未出现严重不良反应。结论卡泊芬净治疗IFI患者疗效确切,不良反应小。     

卡泊芬净治疗危重病难治性侵袭性真菌感染临床研究

目的 评价卡泊芬净治疗氟康唑治疗无效的危重病侵袭性真菌感染患者的疗效和安全性.方法 采用开放性临床研究,对2005年5月至2007年6月浙江省人民医院ICU住院患者氟康唑治疗无效的44例侵袭性真菌感染患者,给予卡泊芬净首日负荷剂量70 mg,之后以50 mg/d维持治疗,疗程为10～40 d.结果 42例可评价患者中,痊愈18例(42.86%),显效14例(33.33%),总有效率76.19%,真菌清除率为62.22%.不良反应少,所有患者均耐受治疗.结论 卡泊芬净治疗危重病患者难治性侵袭性真菌感染安全、有效.     

卡泊芬净治疗心脏术后侵袭性真菌病20例临床分析

目的:探讨卡泊芬净治疗心脏术后并发侵袭性真菌感染(IFI)的疗效与安全性。方法:回顾分析我院呼吸科、心外科和急诊重症监护室(ICU),接受过卡泊芬净治疗的心脏术后合并IFI患者临床资料。结果:2005年5月至2010年12月,共有20例接受了卡泊芬净治疗。男性12例,女性8例,中位年龄65岁(23～82)岁。确诊10例,皆为念珠菌血症(白念珠菌4例,近平滑念珠菌3例,光滑念珠菌、热带念珠菌和克柔念珠菌各1例);临床诊断肺IFI 5例(念珠菌3例,曲霉2例);拟诊肺IFI 5例,病原真菌不明。冠状动脉搭桥(CABG)术8例,瓣膜手术8例,胸主动脉瘤手术2例,先天性心脏病(先心病)和马方综合征手术各1例。卡泊芬净的使用时间中位数为18(1～55)d。1例于用药当天死于心脏骤停疗效无法判断,19例可评估患者中,痊愈10例(10/19,52.6%),显效4例(4/19,21.1%),总有效率为73.7%,进步3例,无效2例。死亡6例(6/20,病死率30.0%)。治疗过程中未发现与卡泊芬净有关的不良反应。结论:卡泊芬净是治疗心脏术后并发IFI的有效安全药物,值得进一步临床验证。     

卡泊芬净联合复方磺胺甲嗯唑治疗重症肺孢子菌肺炎

目的 探讨卡泊芬净联合复方磺胺甲嗯唑治疗重症肺孢子菌肺炎的疗效.方法 分析总结6例肺孢子菌肺炎患者的临床特点和诊治经过.结果 6例患者均接受卡泊芬净联合复方磺胺甲噁唑治疗,除1例放弃治疗外,其余5例均收到满意疗效.其中3例患者初始单用复方磺胺甲噁唑治疗,病情无好转,后改为联合卡泊芬净,病情得到控制.结论 卡泊芬净联合复方磺胺甲噁唑治疗肺孢子菌肺炎取得了满意疗效,值得推荐作为单用复方磺胺甲噁唑不能控制的肺孢子菌肺炎的治疗选择.     

1例选择性IgA缺乏症合并继发性嗜酸性粒细胞增多症并发耶氏肺孢子菌肺炎的临床分析

目的 探讨1例选择性IgA缺乏症（SIgAD）合并继发性嗜酸性粒细胞增多症并发耶氏肺孢子菌肺炎（PJP）患者的临床特点及诊治方法。方法 对1例SIgAD合并继发性嗜酸性粒细胞增多症并发PJP患者的临床表现、影像学特点、治疗及预后进行回顾性分析。结果 患者男,75岁,发热,活动后气短,偶有咳嗽咳痰,持续应用糖皮质激素2月余;胸部CT示双肺可见多发散在磨玻璃影,肺泡灌洗液（BALF）病原微生物宏基因组二代高通量测序结果示耶氏肺孢子菌,确诊PJP。给予卡泊芬净联合复方磺胺甲噁唑片（TMP/SMZ）、甲泼尼龙及其他对症治疗,患者体温逐渐下降至正常,咳嗽气短较前缓解,20 d后出院。结论 SIgAD合并继发性嗜酸性粒细胞增多症患者因长期应用激素或免疫抑制剂,易出现免疫缺陷而发生PJP;患者多伴随反复发热不退,咳嗽气喘等肺部症状,肺部CT显示相应的斑片状或磨玻璃影,早期发现并采用卡泊芬净联合TMP/SMZ治疗的效果较好。     

Efficacy and safety of micafungin as an empirical antifungal therapy for suspected fungal infection in neutropenic patients with hematological disorders

This prospective multicenter study was performed to clarify the efficacy and safety of micafungin (MCFG) as an empirical antifungal therapy for suspected fungal infection in patients with hematological disorders and neutropenia. Three hundred and eighty-eight patients were enrolled; 151 patients with possible fungal infection diagnosed by radiological imaging or serological testing and 237 patients with refractory fever were included in this study. The mean dose and duration of treatment with MCFG were 154.6?mg/day and 14.0?days, respectively. The clinical response rate for patients with possible fungal infection and refractory fever was 60.1% and 65.3%, respectively. Even in persistent neutropenic patients with a neutrophil count of <500/μL throughout the MCFG treatment, the clinical response rate was 46.9%. Ninety-one drug-related adverse events (DAEs) were observed in 56 patients (14.4%) and 9 serious DAEs were observed in 6 patients (1.5%). Neither daily dose nor duration of MCFG treatment affected the incidence of DAEs. It was confirmed that MCFG has adequate clinical efficacy and is safe for the treatment of suspected fungal infections in patients with hematological disorders and neutropenia.     

Metamizole-associated neutropenia: Comparison of patients with neutropenia and metamizole-tolerant patients

Reports of metamizole-induced neutropenia have increased in Switzerland and Germany over the last decades, most likely reflecting increased use of metamizole. To date, there are no effective strategies to identify patients at increased risk of metamizole-induced neutropenia. In this observational, multi-center comparative study, characteristics of patients with metamizole-associated neutropenia were compared with patients treated with metamizole without developing adverse hematological reactions. Patients with metamizole-induced neutropenia treated at the University Hospitals Basel and Bern between 2005 and 2017 were included. Tolerant comparison patients with continuous metamizole treatment (≥500 mg/day for at least 28 days) were recruited from GP offices and community pharmacies. Forty-eight patients with metamizole-induced neutropenia, consisting of 23 and 25 cases with inpatient-acquired and outpatient-acquired neutropenia, respectively, were compared to 39 metamizole tolerant comparison patients. Median latency until first diagnosis of neutropenia was 6 days (1–61 days) in inpatient cases and 19 days (2–204 days) in outpatient cases. There was no association between non-myelotoxic and non-immunosuppressive co-medication (p = .6627), history of drug allergy (p = .1304), and preexisting auto-immune diseases (p = .2313) and the development of metamizole-induced neutropenia. Our results suggest that autoimmune diseases, history of drug allergy, and concomitant treatment with non-myelotoxic and non-immunosuppressive drugs are likely not individual risk factors for metamizole-associated neutropenia.     

The clinical impact of antibacterial prophylaxis and cycling antibiotics for febrile neutropenia in a hematological malignancy and transplantation unit

Febrile neutropenia is an expected complication during treatment of aggressive hematological malignancies and hematopoietic cell transplantation. We conducted a prospective cohort trial to determine the effects and safety of prophylactic fluoroquinolone administration, and rotation of empiric antibiotics for neutropenic fever in this patient population. From March 2002 through 2004, patients were treated with prophylactic levofloxacin during prolonged neutropenia, and a cycling schedule of empiric antibiotic therapy for neutropenic fever was initiated. The rates of bacteremia, resistance and complications were compared to a retrospective cohort of previously treated patients. The rate of gram-negative bacteremia decreased after the initiation of prophylactic levofloxacin (4.7 vs 1.8 episodes/1000 patient days, P<0.05). Gram-positive bacteremia rates remained unchanged, but more isolates of Enterococcus faecium were resistant to vancomycin after the intervention began. Resistance to the antibiotic agents used in the rotation did not emerge. There was no change in mortality during the intervention period. A prophylactic and cycling antibiotic schedule was successfully implemented on a hematological malignancy and hematopoietic cell transplant unit. gram-negative bacteremia was significantly decreased, without emergence of resistance. Concerns with Gram-positive resistance will require further observation.     

米卡芬净治疗恶性血液病合并侵袭性真菌病的疗效分析

目的观查注射用米卡芬净钠治疗恶性血液病合并侵袭性真菌病的疗效。方法2007年2月至10月对福建医科大学附属协和医院福建省血液病研究所12例恶性血液病合并侵袭性真菌病患者,应用注射用米卡芬净钠,剂量100mg/d,分析其疗效、起效时间及不良反应发生率。结果临床总有效率为66.7%,临床诊断病例与拟诊病例有效率分别为57.14%(4/7)和80%(4/5);临床诊断病例与拟诊病例有效率相比,差异无显著性意义;注射用米卡芬净钠起效时间1~5d。结论注射用米卡芬净钠疗效显著,不良反应少,对恶性血液病合并侵袭性真菌病患者疗效较好。     

Applying the Multinational Association for Supportive Care in Cancer risk scoring in predicting outcome of febrile neutropenia patients in a cohort of patients

The purpose of this study was to determine if the Multinational Association for Supportive Care in Cancer (MASCC) risk-index score is able to predict the outcome of febrile neutropenia in patients with underlying hematological malignancy and to look at the other possible predictors of outcome. A retrospective study of 116 episodes of febrile neutropenia in patients who were admitted to the hematology ward of a local medical center in Malaysia between January 1st 2004 and January 31st 2005. Patient characteristics and the MASCC score were compared with outcome. The MASCC score predicted the outcome of febrile neutropenic episodes with a positive predictive value of 82.9%, a sensitivity of 93%, and specificity of 67%. Other predictors of a favorable outcome were those patients who had lymphomas versus leukemias, duration of neutropenia of less than 7 days, low burden of illness characterized by the absence of an infective focus and absence of lower respiratory tract infection, a serum albumin of >25 g/l, and the absence of gram-negative bacteremia on univariate analysis but only serum albumin level, low burden of illness, and presence of respiratory infection were significantly associated with unfavorable outcome after multivariate analysis. The MASCC score is a useful predictor of outcome in patients with febrile neutropenia with underlying hematological malignancies. This scoring system may be adapted for use in local settings to guide the clinical management of patients with this condition.     

Predictors of hematological abnormalities in patients with chronic hepatitis C treated with interferon and ribavirin

Hematological abnormalities including neutropenia, anemia, and thrombocytopenia are commonly seen in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The aim of this study was to identify factors which would help to predict the development of hematological abnormalities in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. During a 4-year period, all patients with chronic hepatitis C started on treatment with pegylated interferon and ribavirin were identified. Patients were defined as having hematological abnormalities if they had the presence of either anemia, neutropenia, thrombocytopenia, or a combination of the above during treatment with pegylated interferon and ribavirin. A total of 136 patients with chronic hepatitis C were included in this study. Fifty-two (38.2%) of the patients developed significant hematological abnormalities during treatment with pegylated interferon and ribavirin with 28 (20.6%), 30 (22.1%), and 11 (8.1%) developed neutropenia, anemia, and thrombocytopenia, respectively. Genotype 1, history of hypertension, low baseline platelet count, low baseline hemoglobin, as well as a raised creatinine were significant factors associated with the development of hematological abnormalities. Significant hematological abnormalities are commonly present in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. This study identifies pretreatment parameters that may help identify high-risk patients who are more likely to develop hematological abnormalities during treatment for chronic hepatitis C.     

Long-term efficacy and toxicity of rituximab plus fludarabine and mitoxantrone (R-FM) for gastric marginal zone lymphoma: a single-center experience and literature review

There is no consensus about the best treatment option for patients with HP-negative gastric MALT lymphomas or persistent disease after HP eradication.We have investigated fludarabine and mitoxantrone with rituximab (R-FM) as first-line treatment. A cohort of 13 patients was analyzed. Induction treatment consisted of fludarabine (25 mg/m² i.v. on days 2 to 4), mitoxantrone (10 mg/m² i.v. on day 2), and rituximab (375 mg/m² i.v. on day 1), for up to six cycles every 28 days. All patients achieved a complete remission, a median of four cycles was given. Treatment-related toxicities were mainly hematologic, with grade 3–4 neutropenia observed in 11/13 patients (84.6%). One patient had grade 3 febrile neutropenia, two patients developed prolonged pancytopenia (15%), and one patient experienced CMV reactivation at 2 months. After a median follow-up of 84 months, 1/13 had disease relapse and received total gastrectomy; estimated 10-year progression-free survival and overall survival were 92.4 and 100%, respectively. Our study suggests R-FM regimen has a high long-term efficacy for untreated HP-negative gastric MALT lymphoma patients and HP-positive patients who failed HP eradication. The elevated incidence of grade 3–4 hematological toxicity, yet manageable, makes this treatment less safe compared to rituximab in combination with chlorambucil or bendamustine.     

Antineutrophil cytoplasmic antibody-associated neutropenia

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) can be associated with various disorders. However, their association with neutropenia has never been reported. METHODS: Nine patients with chronic unexplained neutropenia and ANCA were studied. Clinical charts were extensively analyzed and all patients underwent hematological and immunological investigations. RESULTS: All patients (6 women and 3 men) were Caucasian and had a mean age of 49 years (range 16-67 years). All presented with a neutropenia below 1.5x10(9)/L for more than 6 months. The neutropenia was <0.5x10(9)/L in six cases and moderate in three. There was no evidence of toxic- or drug-related neutropenia or of a hematological malignancy. Autoimmune anemia and/or thrombocytopenia were present in five patients. ANCA, with various specificities, were present in all patients. ANCA were associated with various other autoantibodies in eight patients, including antisurface-neutrophil antibodies in three cases. Four of the six patients with severe neutropenia experienced infections. Five patients were treated with hematopoietic growth factors, steroids, intravenous immunoglobulins, splenectomy, methotrexate and/or cyclophosphamide, allowing the neutrophil count to be restored transiently or permanently. CONCLUSIONS: A subset of patients with neutropenia of possible autoimmune origin may develop ANCA. Their detection would provide strong evidence of an autoimmune mechanism. Neutropenia should be added to the list of ANCA-associated diseases.     

Liposomal amphotericin B and surgery in the successful treatment of invasive pulmonary mucormycosis in a patient with acute T-lymphoblastic leukemia

Pulmonary mucormycosis is a usually fatal opportunistic infection in immunocompromised patients. We describe the first case of an adult patient with hematological malignancy and profound neutropenia to survive a disseminated pulmonary Rhizomucor pusillus infection. Early diagnostic procedures combined with high doses of liposomal amphotericin B and surgical resection may have contributed to the successful outcome.     

Micafungin compared with caspofungin for the treatment of febrile episodes in neutropenic patients with hematological malignancies: A retrospective study

BACKGROUND:Invasive fungal infections are associated with morbidity and mortality in neutropenia secondary to hematological malignancies. Empirical antifungal agents are used to reduce their consequences. Caspofungin is the only echinocandin approved for this indication. Micafungin was compared with caspofungin for the treatment of patients with hematological malignancies and prolonged neutropenia.METHODS:A retrospective cohort study was conducted involving patients who had hematological malignancies with profound neutropenia for a minimum of 10 days, and received empirical micafungin or caspofungin for a minimum of five days, between April 2005 and November 2009. Successful outcome was based on a composite end point: survival for a minimum of seven days following antifungal cessation, successful treatment of baseline fungal infection, absence of adverse events and absence of breakthrough fungal infection. Fungal infections were defined according to 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 (EORTC-MSG) criteria, with modification of the diagnostic imaging criteria.RESULTS:Micafungin had similar overall success to caspofungin (60.4% [29 of 48] versus 57.3% [47 of 82], respectively; P=0.729). Survival was higher in the micafungin group compared with the caspofungin group (100% [48 of 48] versus 89% [73 of 82]; P=0.02). No baseline invasive fungal infections were identified in the micafungin group, compared with three proven infections treated successfully with caspofungin (3.7%; P=0.18). Three proven breakthrough infections were observed in the micafungin group (three of 48 [27.3%]) compared with none in the caspofungin group (zero of 82; P=0.02).CONCLUSION:Micafungin has similar efficacy to caspofungin as empirical antifungal therapy in febrile neutropenic patients with hematological malignancies. Verification of these results in a prospective trial is warranted.