1例伏立康唑不耐受的侵袭性肺曲霉病患者抗真菌药物的选择

临床药师对1例伏立康唑不耐受的侵袭性肺曲霉病患者,结合患者实际情况,提出合理选药建议,并对伊曲康唑胶囊可能出现的不良反应给予药学监护。医师采纳临床药师建议,在保障患者治疗效果的同时,为患者节约了医疗费用。临床药师与临床医师密切合作,积极开展药学服务,有利于临床治疗的开展。     

临床药师参与1例肺毛霉菌感染患者诊治并文献分析

目的 探讨临床药师在糖尿病酮症酸中毒合并肺毛霉菌感染患者临床治疗实践中的作用。方法 临床药师参与1例糖尿病酮症酸中毒并肺毛霉病感染患者的治疗过程,从问诊病史、危险因素分析、药物品种选择、给药方式、给药剂量、不良反应监护和用药教育等方面进行药学服务。结果 根据患者的年龄、经济条件、肾功能、耐受性个体化给予两性霉素B 25 mg qd静滴和5 mg雾化吸入bid治疗。用药过程中监测肾功能、电解质K⁺水平并进行相应处理。患者病情好转,未发生严重不良反应,生命体征平稳出院。结论 临床药师协助医师为肺毛霉菌感染患者制定安全、有效的治疗方案并进行药学监护,可预防不良反应发生、促进临床合理用药。     

两性霉素B静脉和雾化联合给药治疗肺曲霉病1例报告

1例47岁男性患者因“肺曲霉病”住院治疗。因抗真菌药敏试验显示耐药或用药后治疗效果欠佳及肝功能异常而先后停用卡泊芬净和伏立康唑。换用两性霉素B脂质体静脉滴注治疗病灶吸收缓慢,且肾功能有受损趋势。给予联合两性霉素B（AmB）雾化吸入治疗,因出现呛咳、咽痛等局部刺激症状而停用。临床药师认为两性霉素B雾化吸入疗效好,安全性高,局部药物浓度维持时间长,虽然局部不良反应发生率较高,但降低吸入药物浓度可以避免或减轻不良反应。建议继续联合雾化吸入两性霉素B。临床医生采纳临床药师意见,减低雾化吸入两性霉素B的浓度,待患者耐受后再逐渐提高浓度和剂量。联合给药2周后,咳嗽症状基本消失。复查纤支镜示支气管腔病灶显著减少。随访肾功能无进一步恶化。     

1例肺曲霉菌合并血小板减少症患者的用药监护

目的探讨临床药师在肺曲霉病合并血小板减少症患者治疗中的作用。方法临床药师参与1例肺曲霉病合并血小板减少症患者的治疗,分别从抗细菌药物和抗真菌药物选择、药物不良反应等方面实施全程药学监护,提出药学建议并对患者进行用药教育。结果医师采纳临床药师建议,患者病情得到有效控制,23 d后出院。结论临床药师积极开展药学监护,协助医师完善用药方案,有助于临床合理用药,保障患者用药安全有效。     

1例侵袭性肺曲霉病患者的诊治与用药分析

目的:分析临床药师参与的1例侵袭性肺曲霉病患者的诊治与用药全程,为制定侵袭性肺曲霉菌抗感染治疗方案提供参考.方法:临床药师参与1例侵袭性肺曲霉菌患者的诊断及药物治疗,发挥自身优势,协助临床医师制定抗感染治疗方案,全程实施个体化监护.结果:临床药师协助医师最终制定伏立康唑和卡泊芬净的联用的方案,有效控制了患者的感染症状,确保了治疗的安全性和有效性,且无不良反应.结论:临床药师深入临床对患者的诊治起到了积极作用,保障了患者用药的合理性.     

侵袭性肺部真菌感染的药学监护1例

临床药师对1例侵袭性肺部真菌感染患者实施药学监护,在抗真菌药物选择上针对患者实际情况,提出合理选药建议;对两性霉素B可能出现和已经出现的不良反应给予密切监护和对症处理。医生采纳临床药师建议,患者感染症状缓解。在保障患者安全用药的同时,为患者节约了医疗费用。临床药师应与临床医师密切合作,积极开展药学监护,协助临床医生优化给药方案。     

1例肺癌合并侵袭性肺真菌感染与多种并发症患者的药学监护与分析

目的 通过对1例肺癌合并侵袭性肺真菌感染患者的药学监护及用药分析,探讨临床药师进行药学监护工作的具体方法.方法 临床药师对患者进行全程药学监护,分别对抗真菌药、抗肿瘤药、降糖药和降压药的应用加以分析,探讨药师参与临床药物治疗方案的切入点.结果 医师采纳药师部分用药建议,患者病情得到缓解.结论 临床药师对患者进行药学监护,与临床医师密切合作,可进一步优化治疗方案,确保临床合理用药.     

1例侵袭性肺曲霉菌病治疗方案分析

目的探讨临床药师参与侵袭性肺曲霉菌抗感染治疗方案制定中的作用。方法临床药师分析伏立康唑治疗无效的原因,和临床医师共同探讨抗感染治疗方案,并实施个体化监护。结果制定了伏立康唑和卡泊芬净联合用药方案,患者的感染症状得到有效控制,保障了治疗安全有效,无不良反应发生。结论临床药师深入临床起到积极的作用。     

59例恶性血液病患者合并侵袭性真菌病的临床分析

目的观察59例恶性血液病合并侵袭性真菌病患者的临床特征,并探讨两性霉素B脂质体联合伏立康唑治疗恶性血液病患者合并侵袭性真菌病的临床疗效及安全性。方法回顾性分析2010年至2015年入住我院血液科合并侵袭性真菌病(IFI)的恶性血液病患者59例的病例资料,依据使用抗真菌药物的不同进行分组,其中17例应用两性霉素B脂质体联合伏立康唑治疗(联合治疗组),24例单用伏立康唑治疗(伏立康唑组),18例单用两性霉素B脂质体治疗(两性霉素B脂质体组)。收集、总结临床特征、分析其治疗效果及安全性,并进行统计学分析。结果联合治疗组的有效率为82.3%,伏立康唑组的有效率为37.5%,两性霉素B脂质体组的有效率为61.1%。三组之间治疗有效率差异均有统计学意义(P0.05)。而联合治疗组的不良反应发生率为58.8%,伏立康唑组的不良反应发生率为25.0%,两性霉素B脂质体组的不良反应发生率为55.5%。结论应用两性霉素B脂质体联合伏立康唑治疗恶性血液病合并侵袭性真菌病的效果较单用伏立康唑或单用两性霉素B脂质体,可明显提高疗效,且安全性上并不比单用两性霉素B脂质体差,患者往往能够耐受。     

恶性血液病合并侵袭性真菌感染的治疗方案及临床分析

目的了解恶性血液病合并侵袭性真菌感染的临床现状,探讨和研究恶性血液病合并侵袭性真菌感染的易感因素、有效治疗方案及临床分析。方法将120例于2011年6月至2012年6月期间在我院进行恶性血液病合并侵袭性真菌感染治疗的患者分成三个观察组,每组40人。第一组患者使用伊曲康唑治疗;第二组患者使用氟康唑组治疗;第三组患者使用两性霉素B组治疗。对三个观察组患者的致病因素和临床治疗效果进行及时分析。结果 120例患有恶性血液病合并侵袭性真菌感染的患者的感染部位多为呼吸道感染(70.83%)和肠道感染(18.33%)。应用氟康唑组治疗合并侵袭性真菌感染的效果低于伊曲康唑和两性霉素B组;应用两性霉素B组治疗合并侵袭性真菌感染出现不良反应的概率高于氟康唑组和伊曲康唑。结论应用伊曲康唑和两性霉素B组治疗恶性血液病合并侵袭性真菌感染的效果比较明显,氟康唑组的治疗安全性优于伊曲康唑和两性霉素B组。     

Nebulization of four commercially available amphotericin B formulations in persistently granulocytopenic rats with invasive pulmonary aspergillosis: evidence for long-term biological activity

The nebulization of amphotericin B desoxycholate (AMB-DOC), liposomal amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated aerosol droplets were measured. Pulmonary amphotericin B deposition and amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized amphotericin B formulations was evaluated in persistently granulocytopenic rats with invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals. Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 microm for AMB-DOC, L-AMB, ABLC and ABCD, respectively. Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16 h after fungal inoculation, resulted in a significantly prolonged survival as compared with sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations. Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for L-AMB only. All commercially available amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of invasive pulmonary aspergillosis.     

Current strategies in the treatment of invasive Aspergillus infections in immunocompromised patients.

Aspergillus infections have a very high mortality rate. Their incidence is growing because of the increasing number of immunocompromised patients. Treatment of Aspergillus infection is difficult, and the agents used have numerous adverse effects and toxicities. Recently, new and less nephrotoxic formulations of amphotericin B have come onto the market and other new drugs, such as voriconazole and terbinafine, are under evaluation for this infection. Restoration of host immune defences by tapering of immunosuppressive therapy in transplant patients or correction of granulocytopenia in haematological disease is the cornerstone of modern treatment of aspergillosis in immunocompromised patients. In patients with invasive aspergillosis it is very important to achieve therapeutic concentrations of antimycotic drugs as quickly as possible. Patients at high risk of developing aspergillosis (e.g. those with granulocytopenia) should be treated on the basis of clinical or radiological criteria alone if microbiological or histological diagnosis would significantly delay treatment. Conventional amphotericin B is still the first-line treatment for patients with invasive aspergillosis. In transplant patients receiving other nephrotoxic drugs, particularly cyclosporin, first-line therapy with one of the new amphotericin B formulations should be considered. If the emergence of renal toxicity in any patient precludes aggressive treatment, the patient should be switched to one of the new formulations of amphotericin B. For patients cured with amphotericin B, secondary prophylaxis is needed at the end of the intravenous therapy. Amphotericin B by aerosol or itraconazole are possible solutions. In non-invasive forms of aspergillosis, such as suppurative bronchitis, patients could be treated either with amphotericin B or itraconazole as first-line therapy.     

Aerosolized liposomal amphotericin B: Prediction of lung deposition, in vitro uptake and cytotoxicity

To predict the efficacy and toxicity of pulmonary administration of liposomal amphotericin B (L-AMB) for the treatment or the prevention of pulmonary invasive aspergillosis, a multistage liquid impinger was used to estimate the concentrations of drug that could be attained in different lung compartments after nebulization. The highest concentration of amphotericin B was found in the alveolar compartment, where it was calculated that the concentration in the lung surfactant could reach 54μM or more when 21.6μmoles of drug as liposomes was nebulized. The uptake and toxicity of L-AMB were studied in vitro using the A549 human lung epithelial cell line. Uptake was time and concentration-dependent and reached intracellular concentrations exceeding the minimal inhibitory concentrations for most Aspergillus species. The toxicity of L-AMB toward these cells, estimated by the MTT reduction assay, was reduced compared with the conventional form, deoxycholate amphotericin B (D-AMB), with an IC(50) value of about 120μM after 24h of exposure for D-AMB, but only a 13% reduction in viability for 200μM L-AMB at 24h. These results indicate that aerosol therapy with nebulized L-AMB could be efficient but that doses need to be carefully controlled to avoid toxicity.     

Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients

Morbidity and mortality caused by invasive Aspergillus infections are increasing. This is because of the higher number of patients with malignancies treated with intensive immunosuppressive therapy regimens as well as their improved survival from formerly fatal bacterial infections, and the rising number of patients undergoing allogeneic haematopoietic stem cell or organ transplantation. Early initiation of effective systemic antifungal treatment is essential for a successful clinical outcome in these patients; however, clinical clues for diagnosis are sparse and early microbiological proof of invasive aspergillosis (IA) is rare. Clinical diagnosis is based on pulmonary CT scan findings and non-culture based diagnostic techniques such as galactomannan or DNA detection in blood or bronchoalveolar lavage samples. Most promising outcomes can be expected in patients at high risk for aspergillosis in whom antifungal treatment has been started pre-emptively, backed up by laboratory and imaging findings. The gold standard of systemic antifungal treatment is voriconazole, which has been proven to be significantly superior to conventional amphotericin B and has led to a profound improvement of survival rates in patients with cerebral aspergillosis. Liposomal amphotericin B at standard dosages appears to be a suitable alternative for primary treatment, while caspofungin, amphotericin B lipid complex or posaconazole have shown partial or complete response in patients who had been refractory to or intolerant of primary antifungal therapy. Combination therapy with two antifungal compounds may be a promising future strategy for first-line treatment. Lung resection helps to prevent fatal haemorrhage in single patients with pulmonary lesions located in close proximity to larger blood vessels, but is primarily considered for reducing the risk of relapse during subsequent periods of severe immunosuppression. Strict reverse isolation appears to reduce the incidence of aspergillosis in allogeneic stem cell transplant recipients and patients with acute myeloid leukaemia undergoing aggressive anticancer therapy. Well designed, prospective randomised studies on infection control measures effective to prevent aspergillosis are lacking. Prophylactic systemic antifungal treatment with posaconazole significantly improves survival and reduces IA in acute myeloid leukaemia patients and reduces aspergillosis incidence rates in patients with intermediate-to-severe graft-versus-host reaction emerging after allogeneic haematopoietic stem cell transplantation. Voriconazole prophylaxis may be suitable for prevention of IA as well; however, the results of large clinical trials are still awaited.     

Successfully treated invasive pulmonary aspergillosis in a patient with diabetic ketoacidosis

We report herein a case of diabetic ketoacidosis associated with invasive aspergillosis that was successfully treated with liposomal amphotericin-B (L-AMB). Early intervention after confirming the diagnosis of invasive pulmonary aspergillosis is very important, and initiating early treatment with L-AMB can lead to a full recovery.     

Aspergillus susceptibility testing in patients with cancer and invasive aspergillosis: difficulties in establishing correlation between in vitro susceptibility data and the outcome of initial amphotericin B therapy

STUDY OBJECTIVES: As the failure of amphotericin B therapy in patients with invasive aspergillosis often exceeds 50%, we sought to determine the relationship between in vitro amphotericin B resistance and clinical failure of amphotericin B against invasive aspergillosis. DESIGN: Retrospective study. SETTING: University cancer center. PATIENTS: One hundred sixteen patients with cancer and invasive aspergillosis. MEASUREMENTS AND MAIN RESULTS: The correlation between in vitro amphotericin B susceptibility, defined by both the National Committee for Clinical Laboratory Standards and Etest methods, and other prognostic factors with failure of initial amphotericin B therapy was retrospectively evaluated. Data for correlation could be clearly assessed in only 18 (16%) of the 116 patients. Admission to the intensive care unit was the only prognostic factor associated with failure of initial amphotericin B treatment in these 18 patients (p = 0.01). CONCLUSIONS: Several important obstacles underlie the correlation of in vitro susceptibility testing with in vivo efficacy of individual antifungal agents in the treatment of invasive aspergillosis. Such correlations could be determined in only a small subset of patients.     

Aerosol delivery of amphotericin B desoxycholate (Fungizone) and liposomal amphotericin B (AmBisome): aerosol characteristics and in-vivo amphotericin B deposition in rats

In the treatment or prophylaxis of invasive pulmonary aspergillosis, it may be attractive to administer the antifungal agent amphotericin directly to the pulmonary route via aerosol inhalation. In this study, we describe the aerosol characteristics of aerosolized nonliposomal amphotericin B (Fungizone) and liposomal amphotericin B (AmBisome), and the in-vivo aerosol deposition. Aerosols were generated with a Collison nebulizer. Aerosol amphotericin concentrations and mass median diameters were measured. In-vivo pulmonary deposition was evaluated by measuring amphotericin concentrations in lungs of treated rats. Whole body aerosol deposition was determined by measuring radioactivity in tissues of rats after treatment with radiolabelled liposomes. For Fungizone and AmBisome, aerosol amphotericin concentrations were 24.5+/-4.9 and 23.8+/-3.0 microg L(-1), respectively. The values for the median mass diameter were 1.38 and 2.26 microm for Fungizone and 2.43 and 1.97 microm for AmBisome. Amphotericin concentrations in lungs after 60-min nebulization of Fungizone or AmBisome were 24.2+/-6.4 and 21.7+/-2.6 microg g(-1), respectively. After nebulization of radiolabelled liposomes, no radioactivity was retrieved from tissues other than the lungs or the gastrointestinal tract. Nebulization of either Fungizone or AmBisome leads to respirable aerosols and results in a substantial lung tissue concentration of amphotericin and low systemic exposure of amphotericin B. Aerosol administration of either Fungizone or AmBisome may be an attractive approach to prevent or treat pulmonary aspergillosis.     

Antifungal drugs and rational use of antifungals in treating invasive aspergillosis: the role of the hospital pharmacist

Aim:This review discusses the most common used antifungal agents in the treatment of invasive fungal infections. In addition, guidelines for the treatment of invasive aspergillosis, as used in the Ghent University Hospital, are described. Moreover, the importance of determining the effectiveness of antifungal therapy as well as the potential role of the hospital pharmacist in the management of this infection is highlighted. Methods:A review of the English-language literature was conducted using the MEDLINE database and scientific websites. Search terms including antimycotics, antifungal therapy and invasive aspergillosis were used to refine the search, and preference was given to studies published after 1992. This was completed with recent treatment guidelines. Results:An overview of the most recent advances in antifungal therapy is described. In addition, a flowchart for treatment of invasive aspergillosis (proven, probable or possible) has been developed. Conclusion:Invasive fungal infections will remain a frequent and important complication of modern medicine. Considering the clinical and financial outcome of invasive fungal infections, the role of the hospital pharmacist can be a paramount to the treatment.     

1例白血病合并侵袭性肺部真菌感染患者的药学监护

1例48岁男性患者,因确诊急性淋巴细胞白血病2个月入院化疗.入院后行Hyper-CVAD-A方案化疗后出现粒细胞缺乏,双下肺感染加重,结合患者既往用药史及相关抗真菌指南,临床药师建议联合采用两性霉素B和米卡芬净进行抗真菌治疗,并给予升白、补钾和护肝等支持治疗.同时,针对化疗方案和抗真菌药物可能导致的血液、胃肠道、肝肾功能等不良反应提供全面的药学监护.10d后,患者复查双肺炎症状明显减轻,出院.     

孕产妇感染侵袭性肺曲霉病1例并文献复习

目的 提高对孕产妇罹患侵袭性肺曲霉病的认识.方法 结合1例侵袭性肺曲霉病孕产妇患者的临床资料及诊治经过并复习相关文献,对侵袭性肺曲霉病的临床表现、影像学特点、诊断要点及治疗进行分析.结果 患者女,27岁,孕产妇,因咳嗽、咳痰、呼吸困难伴发热半个月于2011年4月18日入我院呼吸内科.患者半个月前(临产前1 d)突发咳嗽、咳痰、呼吸困难伴高热,在当地医院住院给予多种抗生素治疗,但病情无好转且喘息加重而紧急转入我院.入院后病情危重,影像显示双肺多发性侵袭性空洞,5次痰分离出烟曲霉菌,纤支镜刷检物培养出烟曲霉菌.在积极支持治疗和对症处理的基础上,先后给予伏立康唑、伊曲康唑、两性霉素B、卡泊芬净治疗4个月,复查双肺CT影像明显吸收、空洞愈合,患者康复出院.结论 随着人口老龄化及免疫抑制剂的广泛应用,侵袭性肺曲霉病目前已不少见,相关报道亦较多,但孕产妇感染本病、病情进展凶险且被成功救治的病例目前尚未见报道,此报道一例.