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[Diagnosis and treatment of lung aspergillosis after liver transplantation].

OBJECTIVE: To assess the diagnosis and treatment of invasive lung aspergillosis after liver transplantation. METHODS: Routine sputum culture was performed. Itraconazole and fluconazole were used to prevent fungal infection prophylactically. Amphyotericin B was only used on aspergillosis. In 54 patients receiving, liver transplantation, 3 patients with lung aspergillosis were reviewed. RESULTS: Of the 3 patients 2 died and 1 recovered. CONCLUSIONS: Over-immunosuppression is a main risk factor for aspergillosis. Amphotericin B is still the best choice for the treatment of aspergillosis and its gradual, interrupted, low concentration administration, cooperated with itraconazole can ease the side effects.

Adult↗

[Invasive pulmonary aspergillosis: possibility of radiologic diagnosis].

The incidence of invasive pulmonary aspergillosis is increasing in the patients with malignant hematologic diseases; this occurs in the phase of granulocytopenia induced by chemotherapy. In these cases an early diagnosis is mandatory to start a prompt antimycotic treatment. The authors reviewed the personal series of 56 patients with malignant hematologic diseases who, in the phase of granulocytopenia, developed a pulmonary lesion: 32/56 with invasive pulmonary aspergillosis; 8/56 with Candida and 16/56 with bacterial infection. All patients underwent several conventional radiologic controls: 9 cases with invasive pulmonary aspergillosis were also studied with Computed Tomography (CT). After a short pathologic introduction, the conventional radiologic and CT patterns of invasive pulmonary aspergillosis are analyzed, both at onset and over its evolutive phase. The most significant feature for an early conventional radiologic diagnosis is the nodular pattern--single or multiple--; this allowed a correct diagnosis, at onset, of 20/32 (62%) invasive pulmonary aspergillosis cases. CT provided a further diagnostic contribution by showing a peri-nodular halo. Of interest was also the CT demonstration of high-density pleural thickening adjacent to the mycotic lesion, probably due to fungal involvement of the sub-pleural space. The routine chest roentgenogram is the modality of choice; CT may be useful in questionable cases.

Aspergillosis↗

Primary cutaneous aspergillosis near central venous catheters in patients with the acquired immunodeficiency syndrome.

BACKGROUND: Aspergillosis in patients with the acquired immunodeficiency syndrome is unusual, and the clinicopathologic features of primary cutaneous aspergillosis in this setting are undefined. Our findings show that the manifestations can differ from those of primary cutaneous aspergillosis in other immunocompromised patients. OBSERVATIONS: Two men with the acquired immunodeficiency syndrome developed foci of primary cutaneous aspergillosis beneath adhesive tape near central venous catheter sites. Typical lesions were flesh-colored to pink, umbilicated papules that clinically resembled molluscum contagiosum. Biopsy specimens showed variably ruptured follicles that contained collections of fungal hyphae typical of Aspergillus species. Cultures in one case identified Aspergillus fumigatus. The use of nonocclusive dressings and local wound care resulted in involution of several lesions. CONCLUSIONS: Primary cutaneous aspergillosis begins as saprophytic involvement of hair follicles secondary to the altered microenvironment beneath adhesive tape. Systemic antifungal therapy is prudent, but in the absence of neutropenia or other traditional risk factors for dissemination, it appears that Aspergillus in patients with the acquired immunodeficiency syndrome can produce relatively indolent cutaneous lesions with a tendency to resolve once precipitating factors are removed.

Acquired Immunodeficiency Syndrome↗

A case report of endobronchial semi-invasive aspergillosis.

Pulmonary aspergillosis may be classified under three main categories. These are invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and aspergilloma. Sometimes more than one form of the disease may be present at the same time. Semi-invasive aspergillosis is different from aspergilloma in that there is local invasion of the lung tissue. We have observed a previously healthy 42 year old female with a solitary pulmonary nodule on her radiograms. A diagnosis of endobronchial semi-invasive aspergillosis was established in this patient. We aimed to present this case report with a review of the literature.

Adult↗

Scintigraphic detection of pulmonary aspergillosis in rabbits with a radiolabeled leukotriene b4 antagonist.

UNLABELLED: Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the 111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients. METHODS: Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection. RESULTS: Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for 111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate. CONCLUSION: The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of 111In-DPC11870 were superior to those obtained after injection of 67Ga-citrate.

Animals↗

[A case of resistant pulmonary and cerebral aspergillosis successfully treated with voriconazole].

Invasive pulmonary aspergillosis (IPA) is the most common fungal pulmonary infection in immunocompromised patients. In this disease, it is hard to diagnose, it's therapy process is variable and mortality is high. Prognosis is even worse in the cases which have cerebral aspergillosis. The patient was following up as a diagnosis of usual interstitial pneumonia and treating with corticosteroids and azothiopurine. Patient attended our clinic with headache and lose of vision. IPA and cerebral aspergillosis was the diagnosis as his examinations. Amphotericin B lipid complex treatment were given because of pulmonary and cerebral aspergillosis. Voriconazole was the second therapy because of the no response. Voriconazole is more effective in cerebral aspergillosis and treated this patient successfully.

Antifungal Agents↗

[Ph+ acute lymphoblastic leukemia combined with lung and brain invasive aspergillosis].

This study was aimed to investigate the clinical features and therapy of Ph(+) acute lymphoblastic leukemia (Ph(+)ALL) combined with invasive aspergillosis. A series of examination, including routine blood and bone marrow picture analysis, chest roentgenography, cranial computerized tomography and detection of cell genetics etc were carried out for a Ph(+)ALL patient combined with invasive aspergillosis. This patient received chemotherapy with DVCP, idarubicin and imatinib mesylate and was treated with sporanox and amphotericin B (Amb; including Amb-L) and cerebrotomy for drainage because the invasive aspergillosis occurred during myelosuppression. The results showed that patient gained complete remission and the invasive aspergillosis was controlled successfully. It is concluded that patient with Ph(+)ALL has poor prognosis despite intensive conventional chemotherapy, imatinib mesylate may prove to be an effective treatment for Ph(+)ALL. Because detection rate of the fungus is very low, itraconazole in combination with surgical excision of focus is the best treatment of lung and brain invasive aspergillosis.

Antifungal Agents↗

[Acute invasive pulmonary aspergillosis in chronic lung disease--a review].

INTRODUCTION: Apart from malignancies and solid organ transplant, chronic lung disease, in particular chronic obstructive pulmonary disease (COPD), is a third important predisposing factor for acute invasive pulmonary aspergillosis. STATE OF THE ART: COPD is present in 2% of patients dying from invasive aspergillosis. This opportunistic infection occurs because of an immunodeficiency linked both to altered local immunity and to systemic factors such as long term steroid treatment and malnutrition. In patients whose sputum and/or endotracheal aspirate specimens contain hyphal forms of filamentous Aspergillus, half will have a clinically significant aspergillus infection. Diagnostic tests include serum galactomannan antigen test, serum antibody titre, thoracic CT scan and bronchoalveolar lavage (BAL). The identification of fungal hyphae in BAL fluid by microscopy and/or on culture is critical for a positive diagnosis. The mortality rate for acute invasive pulmonary aspergillosis in chronic lung diseases reaches almost 100%. Antifungal monotherapy is still recommended as a first line treatment. Combined treatment can be used in refractory aspergillosis as a salvage therapy. The question of maintaining, decreasing or interrupting steroid treatment must be considered. PERSPECTIVES: Prospective studies are needed to evaluate a standardised diagnostic strategy such as exists for patients with haematological disease. Whether this will improve prognosis remains to be seen. CONCLUSION: Acute invasive pulmonary aspergillosis complicating chronic lung disease is not rare. Improved diagnosis procedures and recent therapeutic advances may have a positive impact on patient prognosis.

Antifungal Agents↗

Sinopulmonary aspergillosis in children with hematological malignancy.

Invasive pulmonary aspergillosis is a serious infectious complication in immunocompromised especially neutropenic patients. Despite improvements in early diagnosis and effective treatment, invasive pulmonary aspergillosis is still a devastating opportunistic infection. These infections also interfere with the anticancer treatment. We report our experience in the diagnosis and therapeutic management of sinopulmonary aspergillosis in 4 children with hematologic malignancy. All patients except the first were neutropenic when sinopulmonary aspergillosis was diagnosed. Clinical signs included fever, cough, respiratory distress, swallowing difficulty, headache, facial pain-edema and hard palate necrosis. Radiodiagnostic methods showed bilateral multiple nodular infiltrations, soft tissue densities filling all the paranasal sinuses, and bronchiectasis. Diagnosis of aspergillosis was established by bronchoalveolar lavage in one case, tissue biopsy, positive sputum and positive cytology, respectively, in the other 3 cases. One patient was treated with liposomal amphotericin B and other 3 cases were treated with liposomal amphotericin B + itraconozole. Outcome was favorable in all cases except the one who died due to respiratory failure. Early diagnosis, appropriate treatment and primary disease status are important factors on prognosis of Aspergillus infections in children with hematological malignancy.

Acute Disease↗

Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients.

The efficacy of inhaled amphotericin B in prevention of invasive aspergillosis in patients with granulocytopenia (granulocytes less than 0.5 X 10(9)/l for greater than 10 days) was investigated over a 12-month period. Amphotericin B prophylaxis was administered twice daily for the period of granulocytopenia to 34 patients who were at risk during 144 episodes of granulocytopenia. The cohort at risk was compared with historical controls. In the 2 years prior to institution of prophylaxis, 14 patients (11.4% of those at risk) developed invasive aspergillosis. All cases occurred whilst the patients were nursed on the open wards. Aspergillosis did not develop in 25 granulocytopenic patients nursed in single rooms with HEPA filtration. Since institution of prophylaxis, there have been no cases of invasive aspergillosis. These data suggest that nebulized amphotericin B may be useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients, especially those nursed on the open wards, and warrants further investigation.

Agranulocytosis↗

[Fatal cerebral and pulmonary aspergillosis in acute leukemia in a child].

Immediately after induction therapy for acute lymphoblastic leukemia, a 2 1/2-year-old child developed invasive pulmonary aspergillosis revealed by pneumothorax, an unusual manifestation. Despite treatment with amphotericin B, status epilepticus occurred; this manifestation was related to diffuse ischemic cerebral lesions probably caused by cerebral aspergillosis. Outcome was fatal. Early invasive pulmonary aspergillosis is responsible for non-specific pneumonia. Thoracic CT scan and fiberoptic bronchoscopy are informative investigations. At recovery of bone marrow aplasia, the occurrence of hemoptysis and the discovery of excavated lesions on roentgenograms are suggestive of the diagnosis. Cerebral aspergillosis should be routinely considered whenever neurologic symptoms develop in a patient with agranulocytosis, fever, and pneumonia. The prognosis of invasive aspergillosis depends above all on the promptness of treatment; amphotericin B should be given intravenously whenever broad spectrum antimicrobial therapy fails to induce apyrexia in a patient with agranulocytosis.

Amphotericin B↗

[The clinical study of fluconazole against pulmonary mycosis. Effects of fluconazole on pulmonary cryptococcosis and aspergillosis, and its pharmacokinetics in patients].

Effects on pulmonary cryptococcosis and aspergillosis and the pharmacokinetics of the new antimycotic agent, fluconazole, were examined. 1. Cases Pulmonary cryptococcosis: Two cases, 30 and 29 year-old men who were suspected of pulmonary tuberculosis by routine health examinations. Pulmonary aspergillosis: A 65 year-old man with collagen disease and a 62 year-old man with bacilli free cavities of tuberculosis. 2. Method Fluconazole was administered at a dose level of 400 mg/day per os for 2 to 4 weeks. One exception was the 65 year-old aspergillosis patient who was administered with fluconazole 50 mg/day for 4 weeks, 100 mg/day for 6 weeks then 400 mg/day for 4 weeks. Sera of the cases 1, 2 and 4 were harvested before, and 1/2, 1, 2, 4, 8 and 24 hours after administration of fluconazole on the 1st and the 7th day, and in every morning until the 9th day before administration and stored in a freezer. Serum fluconazole concentrations were determined at Pfizer Taito Laboratory. As pharmacodynamic parameters, T1/2, Tmax and Cmax were calculated. 3. Result Effects of fluconazole on 2 of the 2 cases with cryptococcosis were excellent. On the other hand, the effects on the aspergillosis were poor. The average Tmax was 2-4 hours. The average C maxs were 10.3 micrograms/ml on the 1st day and 30.6 micrograms/ml on the 7th day. Serum concentrations reached the plateau on the 5th-7th day, and the average C min (concentration before administration) was 21-23 micrograms/ml. Average T1/2s were 34.4 hours on the 1st day and 37.2 hours on the last (32th) day. 4. Conclusion Fluconazole may be regarded as the promising remedy for pulmonary cryptococcosis but not for pulmonary aspergillosis.

Adult↗

[Right endocarditis in disseminated aspergillosis].

A 53 year old man with an anaplastic bronchial carcinoma was hospitalised for septic shock and acute respiratory distress after a cutaneous, probably staphylococcal infection, and died in spite of anti-staphylococcal antibiotherapy. The autopsy showed pulmonary, cardiac, cerebral and renal aspergillosis. A right heart aspergillous endocarditis, very rare in this pathology, was also discovered but there were no cardiac valves lesions. The patient was in an "immunodepressed" state as usually observed in pulmonary aspergillosis. The endocardial localisation of aspergillosis and the "pseudo-miliary" appearances of the pulmonary lesion indicated an extra-pulmonary portal of entry, cutaneous or intravenous which is unusual in this pathology. This hypothesis is supported by previous reports of pulmonary aspergillosis where right heart endocarditis is exceptionally rare and by aspergillous left heart endocarditis after open heart surgery where pulmonary aspergillosis is absent.

Aspergillosis↗

[Cerebral aspergillosis as a cerebral vascular accident].

Cerebral aspergillosis is one of the most common mycotic infections in the central nervous system causing different clinical features such as brain abscess, granuloma, meningitis, and encephalitis. Cerebral aspergillosis, however, may lead to a cerebral vascular accident such as intracranial hemorrhage or cerebral infarction. In this report, we present two patients with cerebral aspergillosis accompanied by intracranial hemorrhage. A total of 124 reported cases of cerebral aspergillosis are reviewed to ascertain the pathogenesis of the associated vascular lesion. The first patient was a 9-year-old girl, who developed drowsiness with a headache during the medical treatment for acute myelocytic leukemia. CT disclosed subarachnoid and intraventricular hemorrhage. The autopsy revealed that the aspergillus arteritis was the cause of repeated hemorrhage. The second patient was a 15-year-old boy with allergic purpura and renal failure, who suddenly developed a stupor with convulsive seizure. CT disclosed an intracerebral hemorrhage in the right parieto-occipital area. The patient gradually deteriorated and died in spite of the surgical removal of the hematoma. The autopsy revealed that the hemorrhage was caused by the aspergillus arteritis. Cerebral aspergillosis has two routes of infection to the central nervous system: hematogenous dissemination from the distant site (usually the lung) and direct extension from the contiguous site (usually the paranasal sinuses or orbit). The primary mechanism of neuropathology is different between these two types. Primary cerebral arteritis is most often seen in patients with the former type, whereas primary basal meningitis occurs in the latter. The incidence of clinico-pathological features is different between hematogenous dissemination type and direct extension type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Disseminated aspergillosis complicating hepatic failure.

Disseminated aspergillosis is not generally known as a complication of hepatic failure. Three patients with subacute hepatic necrosis died of clinically unrecognized disseminated aspergillosis. All of the patients had pulmonary aspergillosis and Aspergillus infections of the CNS. Focal neurologic deficits were clinically misconstrued as intracerebral hemorrhages caused by the coagulopathy of liver failure. Signs of invasive pulmonary aspergillosis were ascribed to refractory bacterial pneumonia. Each patient had a hospital course of longer than three weeks and each received treatment with corticosteroids and intravenous antibiotics. Invasive aspergillosis should be considered as a cause of refractory pneumonia and of new focal neurologic deficits in patients with hepatic failure.

Abscess↗

Invasive aspergillosis complicating Cushing's syndrome.

Patients with Cushing's syndrome are susceptible to opportunistic infections. Invasive fungal infections in patients with Cushing's syndrome caused by endogenous glucocorticoid excess rarely are reported, and aspergillosis occurring in this setting, to our knowledge, has not been described. Two patients with Cushing's syndrome and notably elevated levels of circulating cortisol had invasive aspergillosis develop. A patient with endogenous hypercortisolism caused by adrenal cortical carcinoma suffered a subarachnoid hemorrhage from rupture of an Aspergillus mycotic aneurysm. The other patient, who had an adrenocorticotrophic hormone-producing prostatic carcinoma, had pulmonary and disseminated aspergillosis develop. Exogenous corticosteroids are known clinically and experimentally to facilitate disseminated aspergillosis. Endogenous hypercortisolism also may bae an important factor predisposing to invasive aspergillosis.

Aged↗

[Treatment of invasive aspergillosis].

With the increasing use of aggressive chemotherapy in patients with malignancies causing prolonged periods of granulocytopenia and severe mucosal damage and the progresses made in the prophylaxis and treatment of bacterial infections, the risk of invasive mycosis has increased particularly in patients with haematologic malignancies. Invasive aspergillosis used to occur almost exclusively in leukaemic patients. More recently the incidence of Aspergillus infections in these patients has increased and it also occurs in other immunocompromised hosts, such as patients with solid tumors or AIDS. Experiences from various institutions indicate a frequency of 10-30% for aspergillosis in leukaemic patients. Amphotericin B has been considered the standard antifungal in the therapy of aspergillosis in immunocompromised hosts. There is, however, some evidence that amphotericin B is not always effective in aspergillosis especially during neutropenia. Initial clinical studies of itraconazole in patients with aspergillosis showed promising activity of this new triazole compound.

AIDS-Related Opportunistic Infections↗

Invasive rhinosino-orbital aspergillosis with precipitous visual loss.

OBJECTIVE: To describe the clinicopathological and radiologic features in five cases of primary and secondary orbital aspergillosis. DESIGN: Case series. SETTING: Ophthalmology department of a university hospital. PATIENTS: Five patients over 65 years of age with invasive rhinosino-orbital aspergillosis. RESULTS: Presenting features were abrupt onset of proptosis, ophthalmoplegia and blepharoptosis with precipitous visual loss. All had debilitating periorbital pain or headache, but none had orbital inflammatory signs or appeared "toxic." Predisposing causes included alcoholism, low-dose prednisone therapy and insulin-dependent diabetes mellitus. One patient, suspected of having mucormycosis based on tissue biopsy and results of potassium hydroxide preparations, harboured Aspergillus fumigatus, which grew on culture. Secondary bacterial infections developed in three patients. Three patients died from their disease despite aggressive surgical treatment, including exenteration and sinus extirpation. The one patient with primary orbital aspergillosis survived after exenteration. CONCLUSIONS: Sinonasal aspergillosis with orbital extension and primary orbital aspergillosis have a precipitous clinical course that mimics that of mucormycosis and may be fatal despite early exenteration. Computed tomography and magnetic resonance imaging of the sinuses, orbit and head provide complementary diagnostic signs. While results of potassium hydroxide preparations and tissue biopsy guide treatment of fungal infection, definitive diagnosis requires fungal culture. Relatively good vision may be associated with massive orbital and secondary intracranial extension.

Aged↗