Intrabronchial Instillation of Amphotericin B Lipid Complex: A Case Report

Objective

We sought to present our results of topical intrabronchial installation of amphotericin B lipid complex (AmpB lipid).

Patient and Methods

A deposit of fungal material was observed in a bilateral lung transplant recipient who experienced stenosis of the left anastomosis and have been fitted with a double endobronchial prosthesis. The deposit was adherent to the prosthetic material, causing marked local laceration, risk of perforation, and exacerbation of the bronchial stenosis. Upon cultivation of a bronchial aspirate (BAS), we isolated Aspergillus fumigatus, Scedosporium prolificans, and Candida glabrata. Systemic antifungal treatment was begun with oral voriconazole (200 mg every 12 hours) and inhaled AmpB lipid (25 mg once daily). The fungal deposit on the prosthetic material was treated by topical instillation of a solution of 25 mg AmpB lipid before and after each therapeutic fibrobronchoscopy (FB), which was performed weekly at 5 consecutive examinations. Tolerance was excellent.

Results

The improvement obtained after the procedure made it possible to withdraw one of the displaced prostheses. Subsequent cultivation for the fungi found in the BAS was persistently negative over a follow-up of 2 years.

Conclusion

Topical intrabronchial instillation of AmpB lipid has proven effective and well tolerated for the treatment of localized fungal colonies. This use could be extended by protocol to FB in the early postoperative period after lung transplantation for antifungal prophylaxis.     

Antifungal Prophylaxis with Voriconazole or Itraconazole in Lung Transplant Recipients: Hepatotoxicity and Effectiveness

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients.
This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality.
Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.     

Native lung pneumonectomy for invasive pulmonary aspergillosis following lung transplantation: a case report.

Pulmonary aspergillosis occurs most commonly as a consequence of immunosuppression in recipients of pulmonary transplantation and is associated with a high mortality. It affects the native lung more commonly than the transplanted lung in single lung transplant patients. Infection often progresses despite aggressive medical therapy. The cornerstone of treatment of acute, semi-invasive, and invasive pulmonary aspergillosis (IPA) is medical, with intravenous amphotericin B, and oral itraconazole either as isolated or combined therapy. While newer, and more expensive liposomal forms of amphotericin B have been used to enhance tissue penetration and minimize renal toxicity, an appreciable improvement in clinical outcome has not been reported. The role of surgery in localized pulmonary aspergillus infection is well recognized, but remains undefined in immunosuppressed patients. We report a case where a pneumonectomy was performed for progressive, refractory angioinvasive aspergillosis in a lung transplant recipient whose disease progressed despite conventional antifungal therapy.     

Antifungal Prophylaxis and Treatment Among Lung Transplant Recipients in Early Postoperative Stage: A Single-Center Study

BackgroundLung transplantation remains the only feasible option for certain patients with end-stage lung disease. Lifelong immunosuppression increases the risk of infection, including fungal infections. The aim of this study was to assess the effect of antifungal prophylaxis and treatment among lung transplant recipients in the early postoperative stage.MethodsThis retrospective analysis included 127 patients who underwent lung transplantation between 2014 and 2021 in the lung transplant ward, 65.35% of whom were males. The most common indication for lung transplantation was cystic fibrosis (n = 59; 46.46%). All of the patients were receiving inhaled amphotericin B. Within this group there were patients who also were treated with intravenous caspofungin, intravenous/oral voriconazole, or both.ResultsThe difference in the efficacy against Candida spp. between caspofungin and voriconazole in the early post-transplant period was not statistically significant (χ₂ = 0.5, P = .477). Moreover, the difference in the efficacy against Candida spp. between itraconazole and voriconazole during the first post-transplant year was not statistically significant (χ₂ = 0.46, P = .496).ConclusionCaspofungin and voriconazole are proper and relatively efficient antifungal prophylaxis and treatment options after lung transplantation. There was no significant difference between voriconazole and caspofungin as antifungal agents used in the early post-transplant stage. There was no significant difference between voriconazole and itraconazole as antifungal agents used during the first post-transplant year. Further research on this issue is required.     

Dactylaria gallopava infection presenting as a pulmonary nodule in a single-lung transplant recipient.

We describe the first case of a pulmonary nodule caused by Dactylaria gallopava in a lung-transplant recipient. An asymptomatic lung-allograft recipient was found to have a 2-cm nodule in the native lung 450 days after transplantation. Culture of a transthoracic needle biopsy of the solitary pulmonary nodule revealed Dactylaria gallopava. Treatment was initiated with amphotericin B for a period of 21 days followed by oral itraconazole for an 8-month period.     

Refractory pulmonary aspergillosis treated with caspofungin after heart–lung transplantation

Invasive pulmonary aspergillosis (IPA) is a serious complication of lung transplantation. Pre-mortem diagnosis is difficult and is made according to defined criteria. Most patients with a post mortem diagnosis of IPA only reach the possible or probable levels of diagnostic certainty during life. Here, we report a case of probable IPA that was refractory to conventional treatment, including amphotericin, but which responded to therapy with caspofungin. A 23-year-old man underwent heart–lung transplantation for cystic fibrosis. Ten years after transplantation he developed IPA. His condition continued to deteriorate despite treatment with itraconazole, liposomal amphotericin and flucytosine together with treatment of a concomitant infection with Pseudomonas aeruginosa. Following treatment with caspofungin there was progressive and sustained clinical and radiological improvement. No adverse reaction occurred during treatment. Caspofungin should be considered as an alternative treatment for IPA in lung transplant recipients who fail to respond to other therapy.     

Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients

BACKGROUND: Liver transplant recipients at high risk for serious fungal infections frequently receive fluconazole or an amphotericin B preparation for antifungal prophylaxis. Because of concerns about fungal resistance with fluconazole, safety with amphotericin B, and the cost of lipid formulations of amphotericin, alternative prophylactic regimens are needed. In this randomized, controlled trial, we compared the efficacy and safety of oral itraconazole solution with intravenous/oral fluconazole for prevention of fungal infections. METHODS: Adult liver transplant recipients were randomized to receive either oral itraconazole solution (200 mg every 12 hr) or intravenous/oral fluconazole (400 mg every 24 hr). Each study drug was started immediately before transplant surgery and continued for 10 weeks after transplantation. Patients were evaluated for fungal colonization, proven invasive or superficial fungal infection, drug-related side effects, and death. RESULTS: Fungal colonization decreased from baseline to week 8 after transplantation in both the itraconazole patients (67% to 25%, P<0.001) and the fluconazole patients (77% to 30%, P<0.001). Proven fungal infection developed in 9 (9%) of 97 itraconazole patients and in 4 (4%) of 91 fluconazole patients (P =0.25). The number of proven invasive fungal infections (seven with itraconazole [7%], three with fluconazole [3%]) and proven superficial fungal infections (two with itraconazole [2%], one with fluconazole [1%]) were also similar in both groups of patients. Organisms causing infection were (four patients), (three patients), and species (two patients) in the itraconazole group and (two patients), (one patient), and species (one patient) in the fluconazole group. Mortality from fungal infection was very low and occurred in only 1 (0.5%) of 188 patients. Except for more frequent gastrointestinal side effects (nausea, vomiting, diarrhea) with itraconazole, both itraconazole and fluconazole were well tolerated and not associated with any hepatotoxicity. Mean trough plasma concentrations of itraconazole were greater than 250 ng/mL throughout the study and were not affected by H -receptor antagonists or antacids. CONCLUSION: Oral itraconazole solution has adequate bioavailability in liver transplant recipients for effective antifungal prophylaxis. Similar to fluconazole, prophylactic oral itraconazole decreases fungal colonization and is associated with a low incidence of serious or fatal fungal infections. Except for gastrointestinal side effects, oral itraconazole solution is well tolerated and has no significant hepatotoxicity.     

肝移植术后侵袭性曲菌病的防治

目的探讨原位肝移植术后侵袭性曲菌病的防治。方法回顾性分析2000年1月至2005年1月完成的576例原位肝移植的临床资料,总结术后侵袭性曲菌病的预防和治疗经验。结果9例患者术后并发侵袭性曲菌病,发病率为1.74%(9/576),首发感染部位为肺部8例,中枢神经系统感染1例。6例患者停用免疫抑制治疗,3例患者将他克莫司(FK506)或CsA降低到最低有效血药浓度。6例患者选用两性霉素B脂质体(其中1例先试用氟康唑)、3例首选伊曲康唑进行治疗。5例肺部感染患者痊愈,2例因肺部感染无法控制死亡,2例因并发多器官曲霉菌感染死亡。结论早发现并及时调整免疫抑制治疗方案,早期、足量和足程使用抗真菌药物,积极行手术治疗是降低肝移植术后侵袭性曲菌病发病率和病死率的根本措施。     

Invasive pulmonary aspergillosis after living donor liver transplantation should be eradicated or not? A case report

Background

Invasive pulmonary aspergillosis (IPA) is a rare complication with a high mortality rate after organ transplantation. Early antifungal therapy improves survival. In some cases, surgical resection is necessary for a complete remission. We have reported herein a case of sustained (but stationary) IPA cured by the modulation of immunosuppression with discontinuation of antifungal therapy.

Case

A 34-year-old man underwent liver transplantation experiencing are early bile leak and an acute rejection episode. Steroid pulse therapy was accompanied by intensified immunosuppression. After a week he developed intermittent hemoptysis, which was treated with antibiotics due to a diagnosis of pneumonia by chest X ray. Meanwhile the bile leak progressed to a huge biloma at reoperation 3 weeks after the initial operation he was converted from a choledochocholedochostomy to a hepaticojejunostomy. After 1 week, follow-up chest X ray showed the lesion had progressed to form an abscess. Subsequent chest computed tomography (CT) detected a pulmonary mass with internal necrosis and CT-guided lung biopsy revealed Aspergillus fumigatus on isolation. Antifungal therapy with voriconazole and/or amphotericin B for 3 months stopped disease progression but the lesion was sustained. We stopped antifungal therapy due to side effects and reduced the intensity of immunosuppression. Follow-up chest CT 5 months later showed improvement with a persistent cavitary lesion containing a fungal ball. However, after 9 months, there was no focal lesion in either lung. This unusual case of IPA was cured by reducing immunosuppression without antifungal therapy.

Conclusion

IPA should be eradicated with prompt antifugal therapy, but stationary IPA can be observed cautiously while reducing immunosuppression.     

Cerebral aspergillosis in immunocompromised patients]

Three cases of central nervous system (CNS) aspergillosis in immunocompromised patients are reported. All three had neurological symptoms with normal cerebrospinal fluid (CSF). The CT scan showed poorly defined low density lesions which were not enhanced by contrast medium. They also had pulmonary signs and fever despite antibiotic treatment. Aspergillus fumigatus was isolated from bronchoalveolar lavage fluid. Antifungal therapy was started promptly, associating amphotericin B, itraconazole and flucytosine. Unfortunately, they died within 2 days to 2 weeks after admission in the intensive care unit. Postmortem examinations revealed disseminated aspergillosis with colonization of brain, lung, heart and kidney. The CT scan signs were quite different from those seen with the more usual bacterial ring lesions. In immunocompromised patients, the agents responsible for producing these findings are Aspergillus, Nocardia, Cryptococcus, Toxoplasma and Mycobacterium tuberculosis. Signs involving organs other than the CNS, and an examination of the CSF, should provide elements for establishing a differential diagnosis. Early antifungal treatment is the only chance of survival. Recrudescent fever and pulmonary signs occurring in neutropenic patients after antibacterial antibiotic treatment has been started are sufficient criteria for empirically starting amphotericin B administration unless clinical judgement dictates otherwise.     

Topical amphotericin B application in severe bronchial aspergillosis after lung transplantation: report of experiences in 3 cases

Ulcerative tracheobronchial aspergillosis after lung transplantation (ltx) may lead to bronchial-pulmonary artery fistula that results in fatal bleeding. We report our early experience with combined systemic, aerolized and topical application of amphotericin B in 3 cases of bronchial aspergillosis after ltx. Two patients are still alive, but 1 died of bleeding from a fistula between the left upper lobe bronchus and the pulmonary artery. Aspergillosis in the second patient resolved with minimal stenosis of the left main and the left upper lobe bronchus, and the third patient developed an anastomotic stenosis that was successfully dilated.     

Fungal bezoars of the upper urinary tract

We report our experience with 6 cases of upper tract fungal bezoars involving 9 renal units-3 bilateral aspergillomas and 3 Candida bezoars. The Aspergillus bezoars were notably more morbid: 2 patients required nephrectomy after failure of medical therapy, whereas the 3 unilateral Candida bezoars all resolved with medical therapy and endourological access. In 1 patient whose aspergilloma was resistant to amphotericin B the investigational drug itraconazole proved effective. These opportunistic infections, seen increasingly in immunocompromised patients, can present a difficult management problem. A combined approach is necessary, including medical therapy with topical and systemic antifungal agents, and endourological access for extraction, lavage and debulking.     

单肺移植治疗终末期慢性阻塞性肺疾病患者单中心经验

目的探讨单肺移植治疗终末期慢性阻塞性肺疾病（COPD）患者的疗效、预后相关因素及术后并发症防治。方法回顾性分析同济大学附属上海市肺科医院2003年1月至2011年2月施行的23例终末期COPD患者单肺移植的临床资料,分析术后临床疗效、预后和并发症发生情况,并探讨性别、年龄、原发病等因素对受者预后的影响。结果 COPD患者术后肺通气功能和动脉血气分析结果均明显改善。气管吻合口并发症发生率为13.0%;围手术期病死率为4.3%。术后肺部真菌感染发生率为39.1%,伊曲康唑或卡泊芬净＋两性霉素B预防性抗真菌治疗的受者术后真菌感染的发生率明显降低（P=0.035）。急性排斥反应发生率为34.8%,闭塞性细支气管炎发生率为26.1%。受者术后1、3和5年存活率分别为83%、66%和45%。单肺再次移植2例。结论单肺移植治疗终末期COPD是安全、有效的方法,受者选择和术后并发症的防治对受者长期生存有重要意义。     

Disseminated ochroconis gallopavum infection in a renal transplant recipient: the first reported case and a review of the literature

Ochroconis gallopavum is a potentially fatal dematiaceous fungus causing opportunistic infections in immunocompromised hosts. We report the first case of disseminated O. gallopavum infection in a 13-year-old renal transplant recipient, which involved the brain, lung and spleen. He was treated with amphotericin B, itraconazole and voriconazole, a new antifungal agent first used to treat such an infection. Besides antifungal treatment, all immunosuppressive agents were stopped and automated peritoneal dialysis was resumed. The initial infection was under control with both clinical and radiological improvements after treatment. However, the patient later acquired Acremonium spp. peritonitis; he failed to respond to high-dose amphotericin B, and finally succumbed. A total of 13 reported O. gallopavum human infections, including the one described here, are reviewed. The most common site of involvement is the brain and the crude mortality rate is up to 46%. As the disease is potentially lethal in immunocompromised hosts, empirical antifungal coverage should be considered in post-renal transplant recipients with suspected brain abscess. Early biopsy of lesion for histopathological and microbiological diagnosis would be essential in managing such cases.     

肾移植术后侵袭性肺曲霉菌病的诊治

目的 探讨肾移植受者侵袭性肺曲霉菌感染的诊断与治疗. 方法肾移植术后侵袭性肺曲霉菌病患者10例.男7例,女3例.年龄28～56岁,平均43岁.感染发病时间为术后平均59 d.患者低氧血症和呼吸困难严重.10例均行纤维支气管镜、肺部CT检查和血清半乳甘露聚糖(GM)抗原检测.其中纤维支气管镜取分泌物培养阳性3例,肺部CT检查有明显影像学特征6例,血清GM抗原检测阳性5例.应用伊曲康唑和两性霉素B脂质体治疗,剂量为伊曲康唑第1天400mg静脉滴注,第2天起200 mg静脉滴注,共14 d;两性霉素B脂质体治疗剂量为50 mg加入5%葡萄糖注射液500 ml中慢速静脉滴注约8 h,共14～28 d.结果 3例应用伊曲康唑治愈,5例应用两性霉素B脂质体治愈,2例死亡.结论 侵袭性肺曲霉菌感染是肾移植术后肺部感染的严重并发症,早期诊断与正确治疗可降低病死率.     

Aspergillus osteomyelitis after liver transplantation

A 57-year-old woman underwent liver transplantation and developed osteomyelitis in the femur attributable to Aspergillus fumigatus. The patient was treated successfully with amphotericin B and 5-fluorocytosine for 30 days, and then switched to itraconazole for 12 months. Plasma (1->3)-beta-D-glucan levels decreased significantly after the chemotherapy. Early diagnosis by (1->3)-beta-D-glucan measurement and extended treatment with itraconazole can improve the prognosis of invasive Aspergillus infection. (Liver Transpl 2002;8:1073-1075.)     

Use of nebulised liposomal amphotericin B in the treatment of Aspergillus fumigatus empyema.

A 28 year old man with asthma, bronchopulmonary aspergillosis, pulmonary thromboembolic disease, and pulmonary hypertension developed Aspergillus fumigatus empyema complicating a pneumothorax. His condition progressively deteriorated despite treatment with intravenous and intrapleural amphotericin B, but improved promptly after substituting nebulised liposomal amphotericin B and oral itraconazole. This experience suggests that nebulised liposomal amphotericin B is well tolerated and merits further assessment in the treatment of pulmonary fungal disease.     

Pulmonary Aspergillosis in Solid Organ Transplant Patients: A Report From Iran

Background

Aspergillosis is one of the most important opportunistic infections after organ transplantation. Early diagnosis and initiation of appropriate antifungal therapy are key factors for better prognosis.

Methods

We reviewed the medical records of patients with solid organ transplantation with evidence of Aspergillus infections from December 2001 to January 2008, evaluating patient demographics, time of onset after transplantation, risk factors, radiologic appearance, diagnostic criteria, antifungal therapy, and outcome.

Results

We observed aspergillosis in 8 lung, 3 kidney, and 1 heart recipient, with overall mean age of 40.6 years. Seven cases of Aspergillus tracheobronchitis were diagnosed in lung transplant recipients, all of them in the first 6 months after transplantation. All patients responded to antifungal therapy and bronchoscopic debridement. We observed 5 cases of invasive pulmonary aspergillosis. Three patients survived in response to antifungal treatment. The two patients who died were treated with a combination of itraconazole and amphotericin B, whereas all cured patients had been treated with voriconazole alone or in combination with caspofungin.

Conclusion

It seems that the prognosis of aspergillosis in solid organ recipients is improving with new treatment regimens, particularly if they are used in early stages of infection.     

Efficiency and Safety of Inhaled Amphotericin B Lipid Complex (Abelcet) in the Prophylaxis of Invasive Fungal Infections Following Lung Transplantation

Background

Invasive fungal infections (IFIs) in patients undergoing lung transplantation (LT) are associated with significant mortality. Previous studies have shown the efficacy of aerosolized amphotericin B deoxycholate and oral fluconazole for antifungal prophylaxis. Evolving data show a potential advantage of prophylaxis with lipid-based formulations of amphotericin B in the prevention of IFIs. We reviewed the incidence of IFIs among patients receiving aerosolized amphotericin B lipid complex (ABLC) in LT.

Methods

We undertook a retrospective review of the results of our antifungal protocol in a cohort of 60 LT patients. We analyzed the efficiency, safety, and tolerability of 50 mg of aerosolized ABLC administered postoperatively for IFI prophylaxis once every 2 days for 2 weeks and then once per week for at least 13 weeks. In addition, these transplanted patients received fluconazole (200 mg/d) during the first 21 days posttransplant. The prophylaxis-related efficiency and safety were quantified for IFIs and adverse events (AEs) for 6 months after study drug initiation.

Results

Prophylaxis was efficient in 59 (98.3%) patients. Only one patient developed a possible IFI, due to Aspergillus fumigatus. Four patients presented nausea and vomiting as an AE, although aerosolized amphotericin B was ongoing.

Conclusions

Nebulized ABLC was effective, safe, and well tolerated for the prophylaxis of aspergillosis in lung transplant patients during the early posttransplant period.     

Treatment of pulmonary aspergilloma in cystic fibrosis by percutaneous instillation of amphotericin B via indwelling catheter.

Pulmonary aspergilloma is a rare complication of cystic fibrosis and is a contraindication to transplantation. The elimination of an aspergilloma in a 24 year old patient with cystic fibrosis by percutaneous instillation of amphotericin B is described, enabling her to be accepted on a lung transplantation programme.