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PubMed2002

Caspofungin: new preparation. A last resort in invasive aspergillosis.

(1) Invasive aspergillosis is rare. It usually occurs in immunocompromised patients and is fatal despite treatment in 40-90% of cases. The reference treatments are standard amphotericin B, liposomal amphotericin B, and itraconazole. (2) Caspofungin, an antifungal drug, is now approved in the Europe Union for the treatment of invasive aspergillosis, when reference drugs fail or are poorly tolerated. (3) In a non comparative trial in 69 patients, intravenous caspofungin infusion was at least partly effective: 40% of patients survived with few relapses for at least one year following treatment. A historical comparison also favours caspofungin therapy. (4) The safety profile of caspofungin is poorly documented. It includes local reactions at the injection site, systemic reactions linked to the infusion (especially due to histamine release) and hepatic disorders. (5) Caspofungin is known to interact with tacrolimus (lower tacrolimus concentrations), ciclosporin (increased caspofungin bioavailability) and rifampicin (reduced caspofungin bioavailability). (6) In practice, caspofungin is an acceptable option for the treatment of invasive aspergillosis when standard amphotericin B, liposomal amphotericin B, and itraconazole are ineffective or poorly tolerated. Its clinical assessment is limited and must be continued.

Amphotericin B↗
PubMed2002

[Invasive aspergillosis and pulmonary alveolar proteinosis in acute myeloid leukemia].

A 53-year-old woman with refractory acute myeloid leukemia had a cough and chest pain. Chest X-ray and computed tomography demonstrated a cavity for which antibiotics, antituberculosis and antifungal agents were not effective. A diagnosis of pulmonary aspergillosis and pulmonary alveolar proteinosis (PAP) was made on the basis of the detection of aspergillus using transbronchial lung biopsy and PAS-positive materials in the sputum. Even though some cases with PAP in hematological malignancy have been reported, the diagnosis of PAP was obtained in most of them at autopsy. In our experience three of seven cases of hematological malignancy had concomitant occurrence of aspergillosis and PAP. We should therefore pay particular attention to the possibility of PAP in patients with hematological neoplasia exhibiting pulmonary fungal infection, especially aspergillosis.

Acute Disease↗
PubMed2000

[Treatment of non-invasive aspergillosis of maxillary sinus by functional endoscopic sinus surgery].

OBJECTIVE: To evaluate the treatment of non-invasive aspergillosis of the maxillary sinus by using functional endoscopic sinus surgery (FESS) and the correlated factors that affect the treatment. METHOD: 41 cases of local, non-invasive aspergillosis of the maxillary sinus undergone FESS were studied. RESULT: The period of convalescence of double pathway (via ostium of maxillary sinus and canine fossa) was 4.7 weeks while single pathway (via ostium of maxillary sinus only) was 9.3 weeks. There was significant difference (P < 0.01). The period of convalescence of group using anti-fungal drugs to wash the operative cavity was 6.4 weeks while the group without using drugs was 6.7 weeks. There was no statistic significance (P > 0.05). CONCLUSION: FESS is effective in treating of non-invasive aspergillosis of the maxillary sinus. The operation of double pathway is superior to that of single pathway. Whether to use antifungal drugs to wash the operative cavity has no obvious effect on the efficacy.

Adult↗
PubMed2003

[Sinus cavernous syndrome caused by isolated aspergillosis of the sphenoid sinus].

Isolated aspergillosis of the sphenoid sinus is a rare condition that is frequently diagnosed at a late stage because of its nonspecific and varying symptomatology. We report the case of a 75-year-old diabetic woman with a long history of retroorbital pain before she developed a subacute cavernous sinus syndrome. Neuroimaging including CT scan and MRI suggested a malignant tumor involving the sphenoid sinus but the diagnosis of aspergillosis was made intraoperatively and by histopathological examination. Soon after surgical drainage of the sphenoid sinus and systemic anti-fungal drug therapy, both retroorbital pain and cavernous sinus syndrome had completely resolved. This case emphasizes the fact that invasive isolated sphenoid sinus aspergillosis must be considered in the list of lesions causing sinus cavernous syndrome.

Aged↗
PubMed2003

Chronic pulmonary aspergillosis: current classification and therapy.

A type of non-acute pulmonary aspergilloses, defined as 'semi-invasive' and 'chronic necrotizing aspergillosis', respectively, was described by Geffer, and later by Binder in the 1980s. Subsequently, a terminological uncertainty prevailed, favored by a preference in choosing the predisposing diseases. The simple term 'chronic pulmonary aspergillosis', as well as a classification based on the pulmonary anatomy, is proposed in this review. The most significant Medline and Embase indexed papers published between 1966 and the present day, including coverage of classification, diagnosis and treatment of aspergillosis are analyzed. In addition, an open study, carried out on 23 patients treated with terbinafine is reported. The results obtained suggest the need for further randomized studies.

Animals↗
PubMed2003

Successful treatment of subcutaneously disseminated aspergillosis with caspofungin acetate in an allogeneic peripheral blood stem cell transplantation patient.

We present a patient with acute myeloid leukaemia who developed subcutaneously disseminated aspergillosis after allogeneic peripheral stem cell transplantation (PSCT). Disseminated aspergillosis after stem cell transplantation has a high mortality despite treatment with amphotericin B or one of the azoles. Aspergillosis in our patient was refractory to amphotericin B and itraconazole but was successfully treated with caspofungin acetate.

Antifungal Agents↗
PubMed2003

[A case of broncho-pulmonary aspergillosis complicated by bronchial asthma attack].

A 55-year-old man was hospitalized for the treatment of severe asthma. However, his condition improved with steroid chemotherapy under artificial ventilation, but high fever and multiple patchy shadows of the lung that were not responsive to antibiotics appeared. We detected aspergillus hyphae, probably inhaled with a quantity of dust in the attic of his workplace, in the sputum. We diagnosed invasive broncho-pulmonary aspergillosis complicated with allergic broncho-pulmonary aspergillosis. His condition improved with anti-fungal drug treatment. We consider that the causes of invasive broncho-pulmonary aspergillosis in this case were massive inhalation of aspergillus conidia, artifical ventilation and steroid chemotherapy.

Anti-Inflammatory Agents↗
PubMed2003

[A case of chronic necrotizing pulmonary aspergillosis diagnosed using percutaneous intracavitary endoscopy].

A 65-year-old man with pneumoconiosis visited our hospital for dyspnea on effort. Chest radiography and computed tomography on admission showed cavities with an air-fluid level, consolidation in the right lower lung, and right pleural effusion. The thoracic cavity and an infected cyst were drained, and antibiotics were administered. On detection of molds like Aspergillus species and of aspergillus antigen from the sputum, aspergillosis was suspected and amphotericin B was administered intravenously. Renal dysfunction caused by amphotericin B led to its withdrawal. Abnormal shadows in the chest radiographs and computed tomograms did not improve. To aid in diagnosis, percutaneous intracavitary endoscopy was performed. Yellow-white mural nodules resembling cauliflower were found on endoscopic examination, and a biopsy specimen of the nodules showed hyphae of Aspergillus. Aspergillus fumigatus was cultured from the intracavity fluid. Pulmonary aspergillosis was diagnosed and amphotericin B was administered via the drainage catheter in order to protect renal function. The abnormal shadows then disappeared and the subsequent clinical course was good. In this case, percutaneous intracavitary endoscopy was useful in diagnosing pulmonary aspergillosis.

Aged↗
PubMed2003

[Invasive pulmonary aspergillosis complicated by complete atrioventricular block and aspergillus pericarditis after induction chemotherapy in a patient with acute lymphoblastic leukemia].

A 50-year-old man developed invasive pulmonary aspergillosis after induction chemotherapy for acute lymphoblastic leukemia. He was treated with 5-fluorocytosine and intravenous amphotericin B (AMPH-B). During antifungal therapy, he developed aspergillus pericarditis and complete atrioventricular (A-V) block. The pericardial effusion was decreased and the A-V block was improved after treatment with intravenous and intrapericardial instillation of AMPH-B. Because the patient's renal function deteriorated, AMPH-B was replaced with itraconazol after the latex agglutination (LA) test for an aspergillus-specific antigen showed a negative result. The patient, however, died from disseminated aspergillosis. Aspergillus DNA was detected in retrospective analysis of the serum which had been negative with the LA test. This case indicates that LA is not sufficient for diagnosis and post therapy evaluation of invasive aspergillosis. PCR or other methods should be used concomitantly with LA. Intrapericardial instillation of AMPH-B might be effective for patients with aspergillus pericarditis in whom surgical treatment is not indicated.

Aortic Valve Insufficiency↗
PubMed2003

Prevalence of aspergillosis in bronchogenic carcinoma.

Bronchoalveolar lavage of 42 patients of bronchogenic carcinoma was studied to find out the prevalence of aspergillosis. Sera of the patients were also analysed for presence of anti-Aspergillus antibodies by Immunodiffusion (ID), Enzyme linked immunosorbent assay (ELISA) and dot blot assay (DBA). Aspergillus was isolated in culture from 6 (14.2%) patients of bronchogenic carcinoma. Aspergillus fumigatus was the predominant species isolated. All the strains of Aspergillus were sensitive to itraconazole, ketoconazole and amphotericin B while resistance (33.3%) was found with fluconazole. Anti-aspergillus antibodies were detected equally by ID, ELISA and DBA in 9 (21.4%) cases. The present study revealed prevalence and seroprevalance of Aspergillus in bronchogenic carcinoma to be 14.2% and 21.4% respectively. Consistent reactivity against 18 kDa Aspergillus fumigatus antigen was noted in serologically positive cases. Antibodies against 18 kDa protein antigen in western blotting may be used as a reference marker for diagnosis of aspergillosis in bronchogenic carcinoma. It is also suggested that the simplest serological technique like ID may be performed along with culture for diagnosing Aspergillosis in patients of bronchogenic carcinoma since ID, ELISA and DBA showed similar sensitivity.

Adolescent↗
PubMed2004

Voriconazole: new preparation. Invasive aspergillosis: benefits to be confirmed.

(1) Amphotericin B is the antifungal drug of choice for the treatment of invasive aspergillosis, severe candidiasis and Fusarium infection. Voriconazole is an antifungal azole sold in France for oral and intravenous treatment of these infections. (2) In 391 patients with established or probable invasive aspergillosis, combined analysis of two trials comparing voriconazole (intravenously then orally) with conventional amphotericin (intravenously) showed that the 12-week survival rate was significantly higher with voriconazole (70.8% versus 57.9%). Unfortunately, these results are undermined by methodological flaws such as the lack of blinding, the very different intravenous treatment periods in the two groups, and subsequent oral treatment with different antifungal drugs. Voriconazole has not been compared with liposomal amphotericin B. (3) In the treatment of severe candidiasis, and severe Scedosporium and Fusarium infections, we only have the (favourable) results of non comparative trials in small numbers of patients refractory to other antifungal drugs. (4) The main adverse effects were visual disturbances, elevated hepatic enzyme levels, acute renal failure, and sometimes serious cutaneous reactions. It lengthens the QT interval and can cause torsades de pointes. It inhibits the cytochrome P450 isoenzymes CY3A4, CYP2C9 and CYP2C19, hence a high risk of potentially serious drug interactions. (5) Voriconazole can be given by mouth or by IV infusion, whereas liposomal amphotericin B must be given intravenously. (6) In practice, another more rigorous trial is needed to confirm the favourable results obtained with voriconazole in invasive aspergillosis. Voriconazole is the first-line treatment for severe Scedosporium infections, despite limited experience. It is a last resort for severe candidiasis and severe Fusarium infection.

Amphotericin B↗
PubMed2004

[A case of rapidly deteriorated pulmonary aspergillosis with various clinical manifestations].

A 62-year-old man with chronic hepatitis was admitted to the hospital because of severe asthma, fever, and a chest radiograph abnormality. He had previously been treated unsuccessfully with several antibiotics in another hospital. The chest radiographs and CT films showed multiple infiltrations along the bronchi and in the peripheral regions of both lungs. Aspergillus fumigatus was detected in a sputum culture and the non-specific serum IgE was elevated. Allergic broncho-pulmonary aspergillosis (ABPA) was suspected and then steroids were administered. Although the asthma symptoms improved after the steroid therapy, lung infiltration deteriorated rapidly, affecting both lungs, and cavitations appeared. We concluded that invasive aspergillosis had developed from ABPA. Itraconazole and amphotericin B were administered, resulting in gradual improvements in the bilateral infiltration seen in the chest radiographs. The patient underwent open lung biopsy to rule out systemic vasculitis. The histological diagnosis was organizing pneumonia without vasculitis and without aspergillus or other organisms. The pathological findings resulted from the intensive anti-fungal therapy. There is a possibility that the temporal steroid therapy may have affected the conversion of ABPA to invasive aspergillosis.

Aspergillosis↗
PubMedDate not supplied

Pulmonary aspergillosis in a child with hepatic failure.

Invasive aspergillosis is described more frequently as a complication of neoplastic disease and in immunocompromised patients. Hepatic failure is not a generally recognized risk for pulmonary aspergillosis. We report a 3-year-old boy who presented with hepatic failure and pneumonia and whose autopsy revealed liver cirrhosis and pulmonary aspergillosis.

Acute Disease↗
PubMed2003

[Invasive aspergillosis].

Invasive aspergillosis is one of the most frequent fungal infections in neutropenic patients, in whom it is associated with a high mortality. Its diagnosis is difficult by the traditionally used laboratory tests. In the last years, an ELISA (Platelia Aspergillus, Bio-Rad, France) to detect galactomannan in neutropenic and cancer patients with high risk of suffering invasive aspergillosis has been developed. The experience accumulated in Spain in the diagnosis of invasive aspergillosis by Platelia Aspergillus is presented in this monograph.

Aspergillosis↗
PubMed2004

Invasive pulmonary aspergillosis: retrospective case record review.

Invasive pulmonary aspergillosis is a severe infection, with a sharp increase during the last decades. Our study aimed at identification of the epidemiological characteristics of invasive pulmonary aspergillosis during a period of four years. All clinical records with pulmonary isolation of Aspergillus species were reviewed, as a part of surveillance program at Reina Sofia University Hospital, from January 1995 to December 1998. Diagnosis of invasive pulmonary aspergillosis was based on criteria of Centers for Disease Control and Prevention. Of the 50 patients identified 78% were males and 44% were current or ex-smokers. Chronic respiratory diseases were identified in 64% of them, and 60% were receiving immunosuppressives. Twenty percent of our patients had been subjected to lung transplantation and 28% to organ transplantation in general. Only 78% had received specific antifungal treatment and 56% had fatal prognosis. Our findings match with previous studies, apart from the high frequency of lung transplantation in our series. We recommend further studies on large prospective cohorts.

Aspergillosis↗
PubMed1992

[A case of intracerebral epidermoid associated with aspergillosis].

A case of intracerebral epidermoid associated with aspergillosis, which spread from the middle ear to the left temporal lobe, is reported. A 58-year-old woman was admitted on 6 June 1988, complaining of left temporalgia and motor aphasia. She had suffered from lt. chronic otitis media with cholesteatoma and had undergone a radical operation 11 years previously. CT scan revealed low density area with a mass effect in lt. temporal lobe. Bone image coronal CT scan revealed destruction of the roof of the pyramidal bone had resulted in communication between abscess cavity and external auditory meatus. On MRI scan lt. temporal lobe showed low signal intensity on T1WI, and high signal intensity on T2WI. In spite of strong antibiotic chemotherapy, mass effect on CT scan showed no sign of improvement. We performed total removal of the abscess on 15 July 1987. A number of characteristic aspergillus hyphae were recognized in the resected cyst. As the cyst wall consisted of keratinising squamous epithelium intermingled with granulation tissue, we had a diagnosis of epidermoid cyst. The diagnosis of epidermoid associated with aspergillosis was difficult. CT findings of epidermoid in general, show homogeneous low density without enhancement, but, in our case, CT scan showed heterogeneous low density area with capsular high dense. MRI of epidermoid usually shows a low signal intensity on T1WI, but our case showed iso-low signal intensity on T1WI. In spite of a poor prognosis of aspergillosis of the CNS, our patient has recovered well due to receiving prompt surgical treatment.

Aspergillosis↗
PubMed2005

Cavernous sinus thrombosis secondary to non-invasive sphenoid aspergillosis.

The sphenoid localization of aspergillosis is a rare sinusal disease, often latent or asymptomatic. The neurological complications are the result of invasive forms occurring in most cases for the immunocompromised or diabetic patients. Nevertheless, non-invasive sphenoid aspergillosis may cause also several complications and affect the vital prognosis of nonimmunocompromised patients. This report is about two cases of cavernous sinus thrombosis secondary to a non-invasive sphenoid aspergillosis. The authors refer to the clinical and radiological findings and therapeutic approach of this rare complication.

Aged↗
PubMed2005

Successful treatment of disseminated Aspergillosis in a leukemic child.

The incidence of severe fungal infections in the immunocompromised patient with malignancies has increased in recent years. This appears to be associated to the profound periods of immunosuppression and the extended use of broad spectrum antibiotics. Aspergillosis is the second most common fungal infection reported in the immunocompromised cancer patients. In patients with advanced immunosupression, the mortality due to invasive aspergillosis approaches 100% despite treatment with antifungal agents. Reports of complete or partial response to echinocandins are well demonstrated in adults, but very limited in the pediatric population. This report describes the case of a child with relapsed acute lymphoblastic leukemia (ALL) who developed cutaneous aspergillosis and subsequent multiorgan dissemination during therapeutic induction and was treated successfuly with caspofungin acetate.

Antifungal Agents↗