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PubMed2002

Aspergillosis in liver transplant recipients: successful treatment and improved survival using a multistep approach.

BACKGROUND: Invasive aspergillosis is a life-threatening complication in liver transplant recipients, with a reported mortality rate of more than 90%. Treatment is difficult, and no single agent is uniformly effective in treating this patient population. METHODS: We retrospectively reviewed all fungal cultures from 200 liver transplant patients between 1996 and 1999 at a single tertiary referral center. RESULTS: A diagnosis of aspergillosis was made in 6 patients. Five patients had pulmonary involvement; 1 presented with an inguinal mass. Time from transplant to infection ranged from 1 week to 34 months. Treatment included surgical intervention and medical treatment. All patients infected with Aspergillus fumigatus were treated with a sequential protocol of lipid complex amphotericin followed by itraconazole. The major side effect of treatment was worsening renal function. One patient died of intracranial hemorrhage during treatment. CONCLUSION: Successful treatment of aspergillosis in liver transplant recipients should include early diagnosis, sequential medical treatment with lipid amphotericin B and itraconazole, and surgical intervention for invasive disease.

Amphotericin B↗
PubMed2003

Successful treatment of invasive aspergillosis in two patients with acute myelogenous leukemia.

Invasive aspergillosis is a severe, devastating fungal infection that is seen in patients with hematologic malignancies and profound neutropenia. Despite aggressive treatment, the outcome is poor without neutrophil recovery. The authors describe two children with acute myelogenous leukemia (AML) with extensive invasive aspergillosis who were successfully treated both for their infection and the underlying malignancy. These patients were treated aggressively for their infections and simultaneously were able to complete treatment of their AML. Currently both patients are alive without evidence of fungal infection or AML. Patients with hematologic malignancies can survive severe, invasive aspergillosis during prolonged periods of neutropenia with a combination of antifungal and growth factor therapies, donor granulocyte infusions, and surgical debridement.

Adolescent↗
PubMed2002

Invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis is the most common fungal pulmonary infection in certain immunocompromised patients. The most commonly affected patients are hematopoietic stem cell transplant recipients and patients with hematological malignancies undergoing intensive chemotherapy. The survival of patients with invasive pulmonary aspergillosis is very poor because of difficulties in early diagnosis and lack of effective treatment options. Research efforts are being made constantly to improve different diagnostic techniques. Early, repeated, high resolution computed tomography of the chest, and sequential nonculture-based monitoring of Aspergillus antigen and DNA can improve earlier diagnosis. New antifungal drugs for treatment and prevention of invasive pulmonary aspergillosis continue to emerge, with better safety, efficacy, and pharmacologic profiles.

Antibiotic Prophylaxis↗
PubMed2006

Intracranial aspergillosis in children successfully treated with antifungal therapy and surgical intervention.

Invasive aspergillosis is an uncommon but often lethal complication in immunocompromised patients. Despite the progress obtained with new antifungal drugs, intracranial aspergillosis often requires a combined medical and surgical approach. Most cases previously reported in immunocompromised children were fatal. We describe 4 immunosuppressed children with intracranial aspergillosis successfully treated with surgery and antifungal long-term therapy.

Adolescent↗
PubMed2005

Klippel-Feil syndrome associated with pneumatocyst of the right cervical rib.

A patient with Klippel-Feil syndrome reported with a pneumatocyst of the proximal epiphysis of a right cervical rib. There was no additional skeletal abnormality except for fusion of the C3 and C4 vertebral bodies. To the best of our knowledge, this is the first reported instance of this particular association.

Adolescent↗
PubMed2006

Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.

BACKGROUND: : The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined. METHODS: : Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome. RESULTS: : Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome. CONCLUSIONS: : Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Adult↗
PubMedDate not supplied

Fatal haemoptysis associated with invasive pulmonary aspergillosis treated with high-dose amphotericin B and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Opportunistic pulmonary infections are a leading cause of morbidity and mortality in patients with chemotherapeutically treated neoplasias. With increasingly aggressive cytotoxic regimens causing prolonged neutropenia, the risk of systemic mycoses and in particular of invasive pulmonary aspergillosis has increased. We review the case of a 10-year-old child suffering from relapsed lymphoblastic leukaemia and from high-dose amphotericin B-treated invasive pulmonary aspergillosis acquired during long-standing neutropenia in the initial phase of remission induction chemotherapy. The patient died in remission after GM-CSF-induced bone marrow recovery and clinical and radiological improvement with stable plasmatic coagulation and normal thrombocyte count. Peracute massive pulmonary bleeding caused by the simultaneous arrosion of a greater pulmonary artery and a lobar bronchus by a liquefactive fungal focus was responsible. In patients with chemotherapeutically induced neutropenia and invasive aspergillosis, bone marrow recovery may lead to the liquefaction of pulmonary foci, and, in view of the well-known vasotropic nature of the infection, to a potentially lethal arrosion bleeding. With the emerging use of colony-stimulating factors for shortening and overcoming neutropenia, this so far rare complication may become of increasing importance.

Amphotericin B↗
PubMedDate not supplied

Specific antibody detection in human aspergillosis: a GEMO* multicentre evaluation of a rapid immunoelectrophoresis method (Paragon). Group d'Etude des Mycoses Opportunistes.

A new immunoelectrophoresis system, the Paragon system, was evaluated in three different hospital centres with the aim of improving standardization of the serodiagnosis of human aspergillosis. To select the most efficient antigen, various commercial and home-made antigens were first tested on 19 sera from 19 patients with highly probable aspergillosis. The value measured using the Paragon anti-Aspergillus antibody detection system was then compared with the results obtained by conventional serological diagnostic methods (conventional immunoelectrophoresis, enzyme linked-immunosorbent assay, indirect immunofluorescence): this step was performed using the first 19 sera as well as 16 other sera from 13 patients with suspected aspergillosis. Concordant results were obtained in 28 cases. The discrepancies observed with seven sera were probably related to differences in the nature of the antigens. Paragon immunoelectrophoresis proved to be a practicable technique requiring only a small amount of serum and giving results within a shorter time than competitive methods (24-48 h). Its major drawbacks compared with conventional immunoelectrophoresis are some difficulties in reading, fewer precipitin lines and the relatively high cost of routine analysis.

Antibodies, Fungal↗
PubMedDate not supplied

Outbreak of systemic aspergillosis in a neonatal intensive care unit.

Small pre-term neonates are susceptible to cutaneous aspergillosis because of their immature immune system and because of the vulnerability of their skin. In addition, the common therapy with broad-spectrum antibiotic drugs and corticoids creates a favourable milieu for fungal superinfections. We present four pre-term neonates who succumbed to cutaneous aspergillosis that subsequently developed into a systemic infection. The source of the infection proved to be contaminated latex finger stalls. Three of the four patients died. The poor prognosis for systemic aspergillosis can only be improved by an early therapy with amphotericin B, possibly in liposomal form.

Aspergillosis↗
PubMed1998

AIDS-related visceral aspergillosis: an underdiagnosed disease during life?

Five out of nine consecutive patients with HIV-related visceral aspergillosis observed by us since 1984 were diagnosed only at necropsy examination. The histopathological features of these five patients [two with isolated pneumonia, one with central nervous system (CNS) involvement, one with brain abscess and respiratory disease and one with pulmonary, pleural and kidney infection] have been evaluated according to epidemiological, clinical and radiological features. On the basis of our experience, life-threatening aspergillosis, which is often misdiagnosed or missed in the setting of HIV infection and AIDS, should be suspected in patients with far-advanced underlying disease and unexplained signs and symptoms, even in the absence of some presumed risk factors (i.e. neutropenia and prior steroid treatment). Plain chest radiography and bronchoscopy with broncholaveolar lavage may fail to reveal respiratory disease, CNS aspergillosis is not necessarily associated with suggestive neuroradiological features and disseminated disease may present with multiorgan failure. The unfavorable outcome of this emerging AIDS complication can be improved only by earlier diagnosis based on invasive techniques and appropriate and timely treatment.

AIDS-Related Opportunistic Infections↗
PubMed2004

Paranasal sinus aspergillosis: its categorization to develop a treatment protocol.

A prospective study was conducted in 25 consecutive patients of paranasal sinus aspergillosis to categorize and treat them based on a fixed treatment protocol. The three types of aspergillosis categorized as per definitive criteria were chronic invasive (six), non-invasive (fungus ball) (seven) and non-invasive destructive (12). Adjuvant chemotherapy was employed in non-invasive destructive and chronic invasive disease. Ketoconazole was used in the first variety and itroconazole in the latter. Only two patients had recurrence after a mean follow-up of 11 months (range: 6-20 months). They belonged to the non-invasive destructive category and the recurrence had progressed to invasive variety. It is suggested that non-invasive destructive disease should be followed up regularly with endoscopic examination, CT and fungal serology to detect recurrence. Categorization of the paranasal sinus aspergillosis helps to institute proper treatment. Adjuvant chemotherapy in the form of ketoconazole along with surgery is effective in non-invasive destructive disease to prevent recurrence and progression to invasive disease. Chronic invasive disease with its propensity to involve orbit and intracranial cavity should be managed at the earliest with surgery and itraconazole.

Adolescent↗
PubMed2005

Candidosis and aspergillosis as autopsy findings from 1994 to 2003.

We analysed the autopsy records of the Greifswald University Institute of Pathology (located in Eastern Germany) in respect of findings of candidosis and aspergillosis from 1994 to 2003. We also present eight immature aborted fetuses and premature infants with a mycosis. In a total of 2027 autopsies we found 164 cases of invasive candidosis and aspergillosis (8.1%) including a combination of both on four occasions. Other authors cited between 0.7 and 7.3%. In these 10 years in our material mycoses and in particular candidosis increased in spite of slightly decreased numbers of autopsies. The differences comparing the 5-years periods (1994-98 and 1999-2003) are highly significant for both mycoses and candidosis. They are not significant for aspergillosis. A similar relationship was observed in the distribution of mycotic organs and causative origin for candidosis alone. In the last 5 years the gastrointestinal and respiratory tracts, including the peritoneum, were more frequently infected by Candida. Non-haematological neoplasia and pneumonia as basic diseases more often appeared in cases of candidosis. All eight immature aborted fetuses and premature infants suffered from candidosis. The survey confirms the importance of autopsy as a tool for education and quality control in medical diagnostic and therapeutic activity in the field of mycoses, too.

Aborted Fetus↗
PubMed2005

Clinical evaluation of Aspergillus-PCR for detection of invasive aspergillosis in immunosuppressed patients.

We evaluated the utility of Aspergillus PCR as a tool in diagnosing invasive aspergillosis in patients at risk. Aspergillosis was assessed according to the European Organization for Research and Treatment of Cancer (EORTC), Mycosis Study Group definitions. Nine and seven patients with proven and probable aspergillosis respectively were evaluated. Whole blood samples prior (n = 41) and during antifungal treatment (n = 67), and tissue specimens (n = 9) and/or bronchoalveolar lavage fluids (n = 7) were investigated. In patients with proven infections, the sensitivities of PCR of lung samples were 100%, of blood samples prior treatment were 66%, and during treatment 55%. Clearance of fungal DNA from blood was associated with resolution of clinical symptoms in two of four patients with proven infection. Consecutive positive PCR results for Aspergillus are fatal as two of five patients died. In patients with probable infections, the sensitivities of PCR of lung fluids were 85%, of blood samples prior treatment were 57%, and during treatment 42%. The benefits of PCR diagnosing and screening of whole blood are limited if sampling takes place once treatment has started. The performance of Aspergillus PCR from tissue samples should be recommended in addition to microscopic examination and culture technique for sensitive detection of fungal infection.

Adolescent↗
PubMedDate not supplied

Open nasal cavity and frontal sinus treatment of chronic canine aspergillosis.

Five dogs with nasal aspergillosis were treated by surgical exposure and delayed closure of the nasal cavity and involved frontal sinus. Diseased tissue was excised, and 10% povidone-iodine solution was applied three times daily with cotton-tipped applicators. Skin wounds were closed at weeks 6 through 8. In one dog, the frontal sinus was partially obliterated with a temporalis muscle flap before skin closure. At months 6 through 34, all dogs were clinically free of aspergillosis. Open treatment has potential clinical application as a primary approach to nasal aspergillosis or for cases that are unresponsive to previous medical management.

Animals↗
PubMed2004

Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients.

The clinical utility of Platelia trade mark Aspergillus galactomannan antigen for the early diagnosis of invasive aspergillosis was prospectively assessed in 70 consecutive lung transplant recipients. Sera were collected twice weekly and tested for galactomannan. Invasive aspergillosis was documented in 17.1% (12/70) of the patients. Using the generalized estimating equation model, at the cutoff value of >or= 0.5, the sensitivity of the test was 30%, specificity 93% with positive and negative likelihood ratios of 4.2 and 0.75, respectively. Increasing the cutoff value to >or= 0.66 yielded a sensitivity of 30%, specificity of 95%, and positive and negative likelihood ratios of 5.5 and 0.74. A total of 14 patients had false-positive tests, including nine who had cystic fibrosis or chronic obstructive pulmonary disease. False-positive tests occurred within 3 days of transplantation in 43% (6/14) of the patients, and within 7 days in 64% (9/14). Thus, the test demonstrated excellent specificity, but a low sensitivity for the diagnosis of aspergillosis in this patient population. Patients with cystic fibrosis or chronic obstructive pulmonary disease may transiently have a positive test in the early post-transplant period.

Adult↗
PubMed2006

Diagnosis of canine nasal aspergillosis by cytological examination: a comparison of four different collection techniques.

OBJECTIVES: To compare the efficacy and diagnostic value of four different sample collection techniques for cytological identification of nasal aspergillosis-penicilliosis in dogs. METHODS: Fifteen dogs with a history of persistent nasal discharge and clinical and radiographic findings suggestive of aspergillosis were evaluated using four different cytological sampling techniques. These were a direct smear from the nasal discharge, blind swab collection under general anaesthesia, brushing from suspect lesions under direct endoscopic visualisation and a squash technique of mucosal biopsies from suspect lesions obtained under direct endoscopic visualisation. RESULTS: Direct smear collection and blind swab collection detected fungal hyphae in 13.3 and 20 per cent of examined cases, respectively; brush samples detected fungal hyphae in 93.3 per cent and fungal spores in the 45 per cent of examined cases and squash samples detected fungal hyphae in 100 per cent and fungal spores in 36 per cent of examined cases. CLINICAL SIGNIFICANCE: This study confirmed the high accuracy of cytology samples in the diagnosis of nasal aspergillosis-penicilliosis when collected under direct endoscopic visualisation and showed the poor value of samples that were collected by blind swabs or prepared from samples of nasal discharge.

Animals↗
PubMed2005

Granulocyte transfusions in children with chronic granulomatous disease and invasive aspergillosis.

The transfusion of granulocytes to restore host defenses in severely granulocytopenic patients or in patients with defective granulocyte functions has been studied for more than 60 years. However, inadequate dosage of cells and inconsistent efficacy has limited the usage of these transfusions. Recently, the use of mobilizing agents such as granulocyte colony stimulating factors and dexamethasone has renewed interest in these treatment modalities. The present study is conducted to determine an appropriate method of enriched granulocyte collection with Fresenius AS.TEC.204 cell separator (Fresenius, Bad Homburg, Germany) and to evaluate the preliminary clinical results of granulocyte transfusion therapy in patients with chronic granulomatous disease and invasive Aspergillosis in parallel with in vitro granulocyte function. Three patients who have been treated for chronic granulomatous disease and invasive Aspergillosis received a total of 20 granulocyte transfusions. To mobilize granulocytes, healthy donors were given 450 microg of granulocyte colony-stimulating factor (G-CSF) subcutaneously and 8 mg of dexamethasone orally approximately 12 h before collection. Five microg/kg/day of G-CSF was also subcutaneously administered prior to granulocyte transfusions. The first patient received 4; the second, 14 and the third, 2 transfusions. The granulocyte count given to these patients ranged between 0.4 and 3.0 x 10(9)/kg. Most transfusions were well tolerated. The nitroblue tetrazolium (NBT) tests that were done 16-24 h after the transfusion showed 14-46% dye reduction. Two of the three patients survived the infection. Granulocyte transfusions from G-CSF and dexamethasone stimulated donors could be a choice of treatment in chronic granulomatous disease patients, especially with disseminated invasive Aspergillosis.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Treatment of canine nasal aspergillosis with enilconazole.

Twenty-four dogs with nasal aspergillosis were treated with enilconazole (10 mg/kg bid for 7-14 days) administered topically through tubes surgically implanted into the nasal chambers. Aspergillosis was eliminated in 19 dogs over a median follow-up period of 18 months. Another dog died, but at necropsy there was no evidence of causative fungus. Two of the four dogs that were not cured had infection of periorbital soft tissues. An additional seven dogs received 6 weeks ketoconazole (5 mg/kg bid PO) and enilconazole therapy topically. Six of these dogs were disease-free over a median follow-up period of 35 months. The seventh dog responded to repeated treatment with enilconazole. Twenty-six of the 29 dogs (90%) without extranasal aspergillosis were cured.

Administration, Intranasal↗