Fungal infection and liposomal amphotericin B (AmBisome) therapy in liver transplantation: a 2 year review.

We reviewed the use of liposomal amphotericin B in 30 patients receiving therapy following liver transplantation over a 2 year period. Five of these patients were treated for presumed invasive aspergillosis: four of them died despite therapy, each having combined renal and respiratory failure at the time of diagnosis of presumed aspergillosis. Post-mortem examination of three of these patients confirmed the diagnosis of aspergillosis. Twenty-five patients were treated empirically; 11 died and supportive evidence for invasive fungal infection following commencement of therapy was found in only one case. Following liver transplantation, the use of liposomal amphotericin B following confirmation of aspergillus infection or for empirical therapy is of uncertain value, and strategies based on selective prophylaxis for high-risk cases may be preferable.     

恶性血液病伴发侵袭性肺曲霉病3例诊治分析

侵袭性肺曲霉病诊断图难，病情凶险，死亡率高。本对合并有侵袭性肺曲霉病的3例恶性血液病(2例急性白血病和l例MDS-RA)患的诊治过程进行了回顾性分析。3例患均有免疫力低下的病史，虽经过预防性抗真菌治疗，仍发生了肺曲霉菌感染，经过痰培养确诊后采用脂质体两性霉素B，伊曲康唑和氟胞嘧啶联合治疗。结果表明，联合治疗7—14天后，3例中2例痊愈，l例显效。结论：对侵袭性肺曲霉病的早期诊治很关键，脂质体两性霉素B，伊曲康硅和氟胞嘧啶联合治疗起效快，效果好。     

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.     

Economic evaluation of targeted treatments of invasive aspergillosis in adult haematopoietic stem cell transplant recipients in the Netherlands: a modelling approach

OBJECTIVES: The aim of this study was to assess the cost-effectiveness of a targeted treatment model of antifungal treatment strategies for adult haematopoietic stem cell transplant (HSCT) recipients in the Netherlands from a hospital perspective, using a decision analytic modelling approach. METHODS: The economic evaluation of desoxycholate amphotericin B, liposomal amphotericin B, voriconazole and caspofungin was undertaken. These drugs could be used alone, in various combinations or sequentially. In our model, first-line therapy consisted of either voriconazole or liposomal amphotericin B. If necessary, treatment was switched to a second-line treatment, including combination antifungal therapy. The theoretical population in this model consisted of adult HSCT recipients with proven or probable invasive aspergillosis (IA). Long-term survival was extrapolated from survival after 12 weeks of treatment and life expectancy. RESULTS: First-line antifungal treatment strategies with voriconazole were both more effective and less costly over first-line strategies employing liposomal amphotericin B at a dosage of 4 mg/kg/day. The strategy of voriconazole followed by caspofungin (voriconazole/caspofungin) was dominant over the strategies of voriconazole followed by liposomal amphotericin B (voriconazole/liposomal amphotericin B) or desoxycholate amphotericin B (voriconazole/desoxycholate amphotericin B). However, the voriconazole followed by the combination of liposomal amphotericin B and caspofungin strategy (voriconazole/liposomal amphotericin B+caspofungin) was more effective though more expensive than the voriconazole/caspofungin strategy resulting in an incremental cost-effectiveness ratio (ICER) of about euro107,000 for a life-year saved. At a dosage of 1 mg/kg/day of liposomal amphotericin B, the voriconazole/caspofungin strategy was more effective but more costly than the voriconazole/desoxycholate amphotericin B strategy with an ICER of euro10,000 for each extra life-year saved. Between the voriconazole/liposomal amphotericin B+caspofungin and the voriconazole/caspofungin strategies, the ICER was euro40,000. CONCLUSIONS: Probabilistic analyses on net monetary benefit showed that the voriconazole/caspofungin strategy had the highest probability of being the most cost-effective strategy.     

Voriconazole for invasive aspergillosis in oncohematological patients: a single-center pediatric experience

Voriconazole is a new triazole active orally and parenterally that recently proved effective in the treatment of invasive aspergillosis and in empirical antifungal therapy for persistently febrile neutropenic patients. Limited data are available for pediatric patients. We report our experience with voriconazole in seven children with invasive aspergillosis, i.e., four girls and three boys with a median age of 5 (range 2–13) years affected by acute lymphoblastic leukemia (3), acute myeloid leukemia (2), refractory anemia with excess of blasts (1), and severe aplastic anemia (1). First-line therapy in all patients was liposomal amphotericin B (AmBisome) administered at a dosage of 3–5 mg/kg day. Voriconazole was administered for a median 8 (range 2–15) weeks. Response was complete and partial in two patients, respectively, stable in one, and there was no response (failure) in two. The voriconazole treatment was well tolerated. Four patients died—two of progressive aspergillosis. Three patients are alive and well 6, 5, and 4 months after the diagnosis of aspergillosis. Voriconazole appears to be an effective salvage treatment for invasive aspergillosis in pediatric patients, with good responses in patients who recover from neutropenia or are not relapsing.     

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.     

Resistance to amphotericin B does not emerge during treatment for invasive aspergillosis.

Emergence of resistance to antifungal drugs during therapy for invasive aspergillosis has received scant attention. We recovered Aspergillus isolates from six patients with invasive aspergillosis, who were receiving amphotericin B before fungal isolation. Although isolates were susceptible to amphotericin B in vitro, none of the patients survived. The MIC of amphotericin B for isolates was similar to that for isolates from 35 patients with no prior exposure to amphotericin B. Laboratory attempts to produce amphotericin B resistance in Aspergillus were unsuccessful. These data indicate that emergence of resistance to amphotericin B is uncommon during therapy for invasive aspergillosis.     

Comparison of In Vitro Antifungal Activities of Free and Liposome-Encapsulated Nystatin with Those of Four Amphotericin B Formulations

The in vitro activity of a multilamellar liposomal formulation of nystatin (Nyotran) was compared with those of free nystatin and four pharmaceutical preparations of amphotericin B. MICs for 200 isolates of two Aspergillus spp., seven Candida spp., and Cryptococcus neoformans were determined by a broth microdilution adaptation of the method recommended by the National Committee for Clinical Laboratory Standards. Minimum lethal concentrations (MLCs) of the six antifungal preparations were also determined. Both nystatin formulations possessed fungistatic and fungicidal activities against the 10 species tested. Liposomal nystatin appeared to be as active as free nystatin, with MICs and MLCs that were similar to, or lower than, those of the latter. Neither formulation of nystatin was as active as amphotericin B deoxycholate (Fungizone) or amphotericin B lipid complex (Abelcet), but both were more effective than liposomal amphotericin B (AmBisome). Our results suggest that further evaluation of liposomal nystatin is justified.     

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.     

Lipid formulations of amphotericin B in the management of invasive fungal infections

Three lipid formulations of amphotericin B have been developed: amphotericin B colloidal dispersion, amphotericin B lipid complex, and liposomal amphotericin B. These three compounds differ by their lipid composition and therefore by their physical characteristics, their pharmacokinetics, and their safety and efficacy profile. There is a consensus to accept reduced toxicity of these formulations, especially reduced, but not absence of, renal toxicity as compared to amphotericin B deoxycholate. Few well-designed studies have been conducted and none of them demonstrated convincingly superiority in term of efficacy of any of the lipid preparations over amphotericin B deoxycholate. Recently a double blind randomized study compared a standard dose of 3 mg/kg/d of liposomal amphotericin B and a loading dose (10 mg/kg/d for 14 days and then the standard dose) in primary therapy of invasive filamentous fungal infections, mainly aspergillosis. Response rate at end of randomized therapy as well as survival at 12 weeks was numerically superior in the standard dose arm but this difference was not statistically significant. Lack of benefit of high dose liposomal amphotericin B in aspergillosis cannot yet be extrapolated to other filamentous fungal infections. Nephrotoxicity was substantially higher in the loading dose arm and this contraindicates its use in clinical practice.     

Second-line therapy with caspofungin for mucosal or invasive candidiasis: results from the caspofungin compassionate-use study

OBJECTIVES: To prospectively assess the efficacy and safety of caspofungin as second-line therapy for mucosal or invasive candidiasis in patients enrolled in the caspofungin compassionate-use study. MATERIALS AND METHODS: Thirty-seven patients with mucosal or invasive candida infections (17 oesophageal, four oropharyngeal and 16 invasive candidiasis) were enrolled in the caspofungin compassionate-use study. All patients were refractory to or intolerant of intravenous amphotericin B or lipid amphotericin formulation(s). Efficacy was assessed at the end of intravenous caspofungin therapy based on clinical (and, where appropriate, microbiological) response. RESULTS: HIV was the most common (91%) risk factor in patients with mucosal candidiasis; patients with invasive candidiasis commonly had acute leukaemia/lymphoma (50%) or diabetes mellitus (31%). Most patients with mucosal candidiasis (91%) and invasive candidiasis (94%) were refractory to >/=1 antifungal agent(s). A favourable response was noted in 82% (14/17) with oesophageal candidiasis, 100% (4/4) with oropharyngeal candidiasis and 87% (13/15) with invasive candidiasis. Caspofungin was generally well tolerated; one serious drug-related adverse event was reported. CONCLUSION: In this study, caspofungin was an effective alternative for patients with refractory candida infections.     

In-vitro antifungal activity of liposomal nystatin in comparison with nystatin, amphotericin B cholesteryl sulphate, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B desoxycholate, fluconazole and itraconazole.

The in-vitro susceptibilities of 120 clinical isolates of yeasts to liposomal nystatin were compared with those to amphotericin B lipid complex (ABLC), liposomal amphotericin B (LAB), amphotericin B cholesteryl sulphate (ABCD), amphotericin B desoxycholate, nystatin, fluconazole and itraconazole. Yeast isolates examined included strains of Candida albicans, Candida parapsilosis, Candida glabrata, Candida krusei, Candida guilliermondii, Candida tropicalis, Candida kefyr, Candida viswanathii, Candida famata, Candida rugosa, Rhodotorula rubra, Trichosporon spp., Cryptococcus laurentii and Cryptococcus neoformans. The mean MICs for all strains examined were: liposomal nystatin 0.96 mg/L; nystatin 0.54 mg/L; ABLC 0.65 mg/L; LAB 1.07 mg/L; ABCD 0.75 mg/L; amphotericin B 0.43 mg/L; fluconazole 5.53 mg/L; and itraconazole 0.33 mg/L. No significant differences were seen between the activity of liposomal nystatin and the polyene drugs or itraconazole, but liposomal nystatin was more active than fluconazole. MICs were lower than the reported blood concentrations following therapeutic doses of this drug, indicating the potential for a therapeutic use of liposomal nystatin in humans. These results indicate good activity in vitro against medically important yeasts, which compares favourably with the activities of other currently available antifungal drugs. Liposomal nystatin may have a role in the treatment of disseminated and systemic mycoses.     

Caspofungin: the first representative of a new antifungal class

Caspofungin (MK-0991; L-743,872) belongs to the echinocandin family, a new class of antifungal agents that act on the fungal cell wall by inhibiting glucan synthesis. Data in vitro, and experimental studies, have demonstrated that caspofungin has antifungal activity against yeasts of the genus Candida (including isolates resistant to azoles and amphotericin B), several species of filamentous fungi, including Aspergillus, and certain dimorphic fungi, such as Histoplasma, Blastomyces and Coccidioides. In vitro and in animals, caspofungin shows additive or synergic antifungal activity with amphotericin B and triazoles. It also possesses activity against Pneumocystis carinii. Clinical trials have shown caspofungin to be well tolerated and effective in invasive aspergillosis in patients refractory or intolerant to standard treatment (45% favourable responses), in oropharyngeal and oesophageal candidiasis (67-93% favourable responses with an efficacy similar to those of amphotericin B and fluconazole), and in invasive candidiasis with efficacy equivalent to that of amphotericin B, and better tolerability. The results of these first clinical trials were promising, and led to the approval of caspofungin for invasive aspergillosis after failure of, or intolerance to, standard therapy. Further studies are required to define the exact role of caspofungin in the antifungal armamentarium.     

Salvage therapy for invasive aspergillosis

Invasive aspergillosis (IA) makes a marked contribution to the mortality of immunocompromised hosts, especially those who have received cytotoxic chemotherapy for haematological malignancy or allogeneic haemopoietic stem cell transplantation. Salvage therapy, in the case of invasive fungal infection, generally refers to the treatment of infected individuals who are refractory or intolerant to initial therapy administered for at least 7 days. Although clinical trials of salvage therapy of IA have been undertaken, most were non-comparator studies or contained a non-randomized control group, and criteria for patient enrollment and the methods used to assess response were variable. Salvage therapy has produced relatively disappointing results, emphasizing the importance of early diagnosis and effective primary therapy for IA. Despite this, a number of agents have been studied in the treatment of IA and have demonstrated efficacy in a salvage setting. These include lipid-based formulations of amphotericin B, caspofungin, itraconazole, voriconazole, posaconazole and micafungin. Combinations of echinocandins with either azoles or amphotericin B have also been studied in small series. Further studies are required, ideally comparing newer agents and treatment strategies in randomized clinical trials, to clarify the optimal approach to salvage treatment of IA in this challenging group of patients.     

Anti-Aspergillus fumigatus efficacy of pentraxin 3 alone and in combination with antifungals

The collectin pentraxin 3 (PTX3) is an essential component of host resistance to pulmonary aspergillosis. Here we examined the protective effects of administration of PTX3 alone or together with deoxycholate amphotericin B (Fungizone) or liposomal amphotericin B (AmBisome) against invasive aspergillosis in a murine model of allogeneic bone marrow transplantation. PTX3, alone or in combination with the polyenes, was given intranasally or parenterally either before, in concomitance with, or after the intranasal infection with Aspergillus fumigatus conidia. Mice were monitored for resistance to infection and parameters of innate and adaptive T-helper immunity. The results showed the following: (i) complete resistance to infection and reinfection was observed in mice treated with PTX3 alone; (ii) the protective effect of PTX3 was similar or superior to that observed with liposomal amphotericin B or deoxycholate amphotericin B, respectively; (iii) protection was associated with accelerated recovery of lung phagocytic cells and T-helper-1 lymphocytes and concomitant decrease of inflammatory pathology; and (iv) PTX3 potentiated the therapeutic efficacy of suboptimal doses of either antimycotic drug. Together, these data suggest the potential therapeutic use of PTX3 either alone or as an adjunctive therapy in A. fumigatus infections.     

Amphotericin B lipid complex at 3 mg/kg/day for treatment of invasive fungal infections in adults with haematological malignancies

We treated 10 consecutive adults with a haematological malignancy, and an invasive aspergillosis (n = 8) or invasive candidosis (n = 2), with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Nine patients responded (five complete and four partial responses), and one died with invasive aspergillosis. Treatment was well tolerated, with only 4% of infusions followed by infusion-related adverse events, and the renal function improved in six patients who had an elevated serum creatinine before therapy. These data suggest that lower doses of ABLC may be equally effective but less toxic than higher doses. However, a controlled study is required to confirm these observations.     

Safety, Tolerance, and Pharmacokinetics of High-Dose Liposomal Amphotericin B (AmBisome) in Patients Infected with Aspergillus Species and Other Filamentous Fungi: Maximum Tolerated Dose Study

We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C(max)) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 microg/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC(24)) changed to 692, 1,062, 860, and 554 microg x h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of >or=7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n = 43) and in 52 and 13% of the patients in the 7-day evaluable population (n = 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections.     

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.     

气道侵袭性曲霉感染19例分析

目的 探讨气道侵袭性曲霉感染的临床表现、诊断及治疗方法。方法 对1999年12月至2003年12月间经病原学和（或）病理学证实的19例气道侵袭性曲霉感染患者的临床资料进行回顾性分析。结果 所有病例均有基础疾病．主要为原发肺部肿瘤（12例）、肺转移瘤（3例）、支气管结核（4例），其中因气道狭窄行支架植入术9例。感染的常见诱因有低蛋白血症（9例）、长期使用广谱抗生素（7例）、糖皮质激素（2例）及免疫抑制剂（10例）和化疗后粒细胞减少或缺乏（3例）；感染的病原菌以烟曲霉为主（14例，73．7％）；临床主要表现为咳嗽、咳痰（84．2％），痰为白色或黄色胶胨样，或为刺激性干咳，近半数患者伴咯血（47．4％）、胸闷、气急（26．3％）等，9例（47．4％）患者有发热；白细胞增高者12例（63．2％）。分别采用两性霉素B、两性霉素B脂质体、伊曲康唑全身用药，结合支气管镜腔内局部治疗，有效率为47．4％。结论 气道侵袭性曲霉感染是一种特殊类型的真菌感染，近年来呈逐年增加的趋势，这与长期大剂量广谱抗生素、大剂量糖皮质激素以及免疫抑制剂应用、肿瘤化疗等密切相关，也与检测技术的提高尤其是支气管镜腔内诊治技术的广泛开展有关；感染的病原以烟曲霉为主。治疗非常棘手，除全身应用抗真菌药物外，还须联合支气管镜腔内局部治疗。     

Invasive aspergillosis in AIDS

Invasive pulmonary aspergillosis was diagnosed in two patients with HIV infection, one with prolonged neutropenia and another receiving corticosteroid therapy. We found 17 additional cases in the literature. A known predisposing risk factor for invasive aspergillosis, eg, neutropenia, corticosteroid use, or intravenous drug abuse, was present in 79% of the cases. That the known immunologic defect of AIDS is not a major host defense against Aspergillus is supported by the empiric observation of the relative rarity of aspergillosis in patients with AIDS. The lung was the most common site of Aspergillus infection (75%), and transbronchial biopsy is diagnostically useful. Central nervous system involvement was seen in 55% and appears to be more frequent in HIV-infected patients than in other immunosuppressed patients with invasive aspergillosis. Prognosis is grim. Despite early institution of amphotericin B therapy in a few cases, the disease was uniformly fatal. Efficacy of therapy with amphotericin B plus rifampin or itraconazole remains to be evaluated. We conclude that aspergillosis is not an AIDS-related opportunistic infection.