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PubMed2001

Invasive aspergillosis in haematological malignancies: clinical findings and management for intensive chemotherapy completion.

Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acute lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, eight non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteristics, to ascertain the factors that influenced the outcome from mycotic infections, and whether early diagnosis and prolonged therapy permitted completion of scheduled intensive chemotherapy and bone marrow transplantation (BMT) without fungal recurrence. The patients were divided into three diagnostic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbiology) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of proven or probable aspergillosis was 7.1%. At onset of infection 92% of patients were neutropenic (< 0.5 x 10(9)/L). The most frequent site of infection was the lung (90%); disseminated disease was present in 20 patients. Among 44 assessable patients, 12 (27%) failed to respond to early antifungal therapy and died. Thirty-two patients were cured with antifungal treatment, three of five nonneutropenic with only itraconazole, the others with amphotericin B 1 mg/Kg/day with or without itraconazole subsequently or with liposomal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 neutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined with medical treatment in two cases before scheduled BMT. After infection nine patients were submitted to BMT (six allo, one marrow unrelated donor (MUD), two auto) with Ambisome or itraconazole as secondary prophylaxis without fungal relapse (follow-up: 25-99 months). The median time from fungal infection to transplant was five months, range 3-10. Thirteen of 29 surviving patients had leukemia relapse, but only three (23%) of these showed also fungal infection recurrence. In conclusion, a high index of suspicion and careful clinical and radiological examinations are the key to identifying infected patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifungal agents seems to improve the outcome of invasive fungal disease and to permit intensive chemotherapy completion and transplant.

Adult↗
PubMedDate not supplied

Aspergillosis of the nose and paranasal sinuses in neutropenic patients at an oncology center.

Invasive aspergillosis of the nose and paranasal sinuses is one of the presentations of aspergillosis in granulocytopenic patients with neoplastic disorders. It is most prevalent among patients with leukemia and granulocytopenia and is associated with a high mortality rate. We report five cases of invasive aspergillosis of the nose and paranasal sinuses in profoundly neutropenic patients treated with broad spectrum antibiotics. Both Aspergillus fumigatus and Aspergillus flavus were cultured and identified in this entity. Awareness of this disease and early diagnosis made by culture and histologic examinations of biopsy material are essential. Treatment consisting of amphotericin B therapy and surgical debridement can be effective in eradicating this form of aspergillosis.

Adult↗
PubMed1989

Nosocomial aspergillosis: environmental microbiology, hospital epidemiology, diagnosis and treatment.

The purpose of this review is to characterize the environmental microbiology, hospital epidemiology, diagnosis and treatment of nosocomial aspergillosis. Appropriate environmental control measures are important in preventing or arresting an outbreak of nosocomial aspergillosis. These include selective environmental microbiological surveillance and floor to ceiling barriers during construction or renovation. These is particularly important for the bone marrow transplant units and units with persistently granulocytopenic patients. We have summarized the point source and cited or formulated the environmental correction measures relating to 25 outbreaks of nosocomial aspergillosis involving a total of more than 100 patients. The most frequent settings of nosocomial invasive aspergillosis occurred in granulocytopenic patients following respiratory infection from an airborne source, associated with hospital construction or contaminated ventilation systems.

Aspergillosis↗
PubMed1992

Surveillance and treatment of liver transplant recipients for candidiasis and aspergillosis.

Between June 1988 and May 1991 88 orthotopic liver transplants and 1 liver and pancreas transplant were performed at the Liver Transplantation Department of the Ospedale Maggiore of Milan. All the patients underwent mycological surveillance and received antifungal prophylaxis with oral amphotericin B (6000 mg/day) or oral or intravenous fluconazole (200 mg/day) from the time of their transplant. The incidence of Candida colonization was 67%. Fluconazole was superior to oral amphotericin B in the treatment of C. albicans colonization (9/9 vs 6/15), but less effective in the treatment of colonization by other Candida spp. (0/3 vs 3/3). Deep-seated candidiasis developed in 5 patients, caused by C. albicans in 4 cases and C. krusei in 1. C. albicans infection resolved rapidly with fluconazole in 2 subjects, with intravenous amphotericin B alone in 1, and with amphotericin B plus flucytosine in the other. On the contrary, C. krusei infection did not respond to treatment with amphotericin B combined with flucytosine. Aspergillosis was diagnosed in 11 patients, of whom 4 died from invasive aspergillosis, despite 15 and 26 days of amphotericin B treatment in 2. In another patient invasive aspergillosis, diagnosed a few hours before retransplantation, improved with liposomal amphotericin B, but this man died from cytomegalovirus infection one month later. Aspergillosis was eradicated by itraconazole in 4 other patients and by topical amphotericin B in 2 whose infection was localized to surgical wound.

Adolescent↗
PubMed1975

Fatal aspergillosis in imported parrots.

Spontaneous fatal aspergillosis occurred in several species of parrots imported from Latin America, Australia, Malaya and Ghana for studies on the control of psittacosis. Over a period of 4 years, 655 parrots were imported for use in these studies. All birds that died during these investigations were necropsied, and the internal organs of 45 were found to have macroscopic lesions suggestive of aspergillosis. Of these 45 suspected cases, 32 were confirmed as aspergillosis by both histopathology and culture, and three others by histopathology alone. There was no evidence that the remaining 10 had this disease. Of the 32 culturally confirmed cases, 13 were found to be caused by Aspergillus fumigatus, 16 by A. oryzae, and three by both fungi. In this series, three sets of circumstances appear to have been associated with the development of fatal aspergillosis. Their capture and transport to the United States, the administration of chlortetracycline used in the control of psittacosis, and the administration of cortisone acetate in an attempt to activate existent latent psittacosis infections. The possible causal relationship of these factors are discussed.

Animals↗
PubMed1996

Outcome of ICU treatment in invasive aspergillosis.

OBJECTIVE: To assess the outcome of intensive care treatment in invasive aspergillosis. DESIGN: Retrospective study. SETTING: University Hospital, Medical Intensive Care Unit (ICU). PATIENTS: Twenty-five patients with invasive aspergillosis who were admitted to the medical ICU in a 5 1/2 year period. Twenty-two had received high-dose chemotherapy for (mainly hematologic) malignancies, one had been treated with cyclosporine and prednisolone for systemic lupus erythematosus, one with high-dose methylprednisolone for polyarteritis nodosa and one had an ARDS after near-drowning. MEASUREMENTS AND RESULTS: The medical records were reviewed for patient and disease characteristics, outcome, reasons for admission to the ICU, supportive care and antifungal therapy as well as for the results of cultures and autopsy. Out of 25 patients, a definite ante mortem diagnosis could be established in seven. When autopsied patients were included, a total of 15 suffered from proven invasive aspergillosis. Although standard antifungal treatment and maximal available supportive care were given, 23 of 25 patients (92%) died after a mean of 15 (1-51) days in the ICU. Both patients who recovered had received high-dose chemotherapy for hematologic malignancy and showed bone marrow recovery and/or had a localized pulmonary infection. CONCLUSIONS: In patients with highly suspected or proven invasive aspergillosis, admission to an ICU and mechanical ventilation should be considered in cases of localized infection and obvious signs of hematologic recovery. In most other circumstances ICU admission for mechanical ventilation does not seem to improve survival.

Adolescent↗
PubMed1993

Crossed immunoelectrophoresis of fungal antigens in tissues as a means of diagnosing systemic aspergillosis and zygomycosis in cattle.

A novel method for diagnosing bovine aspergillosis and zygomycosis is described. Rabbit hyperimmune antisera raised against somatic antigens of Aspergillus fumigatus and Absidia corymbifera were used in crossed immunoelectrophoresis with supernatants from disintegrated tissues from acute necrohaemorrhagic mycotic lesions from cattle. The method specifically identified 4 of 5 lesions with aspergillosis and 2 of 5 lesions with zygomycosis. One lesion dually infected with aspergillosis and zygomycosis was negative. The method worked with unabsorbed sera, was specific, and required only standard electrophoretic equipment. It can therefore supplement chemical detection of fungi in tissues in the diagnosis of bovine aspergillosis and zygomycosis.

Abomasum↗
PubMed1992

Invasive aspergillosis complicating induction chemotherapy of childhood leukaemia.

Two children with acute leukaemia developed histologically confirmed invasive aspergillosis within 2 weeks after onset of polychemotherapy. One child had received only prednisone and one pulse of vincristine and daunorubicin before. This child showed classical roentgenographic signs of aspergilloma following an upper pulmonary lobe infiltration. The second patient developed caecal aspergillosis obscured by clinical signs of appendicitis. He died of disseminated aspergillosis several weeks later in spite of systemic antifungal therapy. Both case reports illustrate that the possibility of invasive aspergillosis must also be expected in young patients soon after onset of induction chemotherapy.

Aspergillosis↗
PubMed2007

[Invasive aspergillosis of the skull base with orbit infiltration].

BACKGROUND: [corrected] Aspergillosis of the paranasal sinuses is subdivided into noninvasive and invasive types, depending on invasion of the tissue. The invasive form often occurs in immunodeficient patients and can be divided further into granulomatous, chronic invasive, and acute fulminating forms. CASE REPORT: We report the clinical course of an immunosuppressed 64-year-old male with invasive aspergillosis originating from the sphenoid sinus with infiltration of the orbit and intracranial extension into the cavernous sinus. The patient was referred to our hospital with loss of vision, ptosis, and ophthalmoplegia of 3-month duration. Additionally he suffered from diabetes mellitus II and kidney failure after kidney transplantation. After CT scanning, endonasal sinus debridement and decompression of the orbit were carried out immediately. Histology revealed invasive aspergillosis. Postoperatively, both systemic and local antimycotic therapy and antibiotic treatment were performed. According to recommendations of the Undersea and Hyperbaric Medicine Society, cerebral abscess is a certain indication of hyperbaric oxygenation. We decided to attempt therapy for that as well. The patient died 3 weeks after surgical intervention due to carotid dissection. CONCLUSION: Invasive aspergillosis of the paranasal sinuses and the skull base of immunsuppressed patients is usually lethal because of intracranial complications. Therefore, fast diagnosis using CT and MRI and surgical and antimycotic therapy are necessary.

Antifungal Agents↗
PubMed2003

The radiological spectrum of invasive aspergillosis in children: a 10-year review.

BACKGROUND: Invasive aspergillosis is an uncommon but life-threatening event in the immunocompromised child. Attempts at fungal isolation are often unrewarding and a high index of radiological suspicion is essential in the early diagnosis of infected children. OBJECTIVE: To document the radiological spectrum of disease in invasive aspergillosis in the paediatric population. MATERIALS AND METHODS: A retrospective review of the imaging performed in 27 consecutive patients (age 7 months to 18 years) with documented invasive Aspergillosis encountered over a 10-year period at a single institution. RESULTS: Radiographic findings of pulmonary disease (20 patients) included segmental and multilobar consolidation, perihilar infiltrates, multiple small nodules, peripheral nodular masses and pleural effusions. No cavitating lesions were seen on CXR. Small cavitating nodules were present on CT in two of eight children. Chest wall disease was particularly associated with underlying chronic granulomatous disease. Disseminated disease manifested as osteomyelitis (n=5), cerebral (n=3), oesophageal (n=1), hepatic (n=2), renal (n=2) and cutaneous (n=5) involvement. Imaging findings are discussed. Twelve patients (44%) subsequently died from Aspergillus-related complications. CONCLUSIONS: Invasive aspergillosis presents with a wide variety of radiographic findings involving multiple organ systems. Respiratory findings are varied but often non-specific, and a high index of suspicion is necessary in immunocompromised patients. In contrast to adult disease, the incidence of cavitation of pulmonary lesions appears low.

Adolescent↗
PubMed2002

Clinical manifestations and diagnosis of invasive aspergillosis in immunocompromised children.

UNLABELLED: Invasive aspergillosis (IA) is a serious life-threatening complication in immunocompromised children. The commonest risk groups are children with acquired immunodeficiency syndrome, leukaemia, corticosteroid and other immunosuppressive therapy, chronic granulomatous disease and severe combined immunodeficiency as well as neonates. The clinical manifestations are heterogeneous and many organ systems can be involved. Diagnosis based on the clinical presentation alone is cumbersome. Innovative and sensitive laboratory test systems which detect fungal antigens or DNA in clinical specimens have been recently developed. Specific Aspergillus antibody detection using recombinant antigen technique has also been introduced. Although each individual technique has drawbacks, the combined use of culture with antigen and antibody ELISA as well as PCR should result in an earlier and more definitive diagnosis of IA in children presenting with clinical and/or radiological signs of aspergillosis. In high risk children these methods are valuable for serial screening and early detection of Aspergillus infection. The implementation of accurate diagnostic criteria and standardised diagnostic flow charts in children at risk will lead to a better outcome of IA in the future. CONCLUSION: definite, well-timed early diagnosis and sufficient therapy is elementary for a successful outcome of invasive aspergillosis in immunocompromised children. To date, the diagnosis of invasive aspergillosis remains a combination of clinical presentation, radiology and microbiological tests.

Aspergillosis↗
PubMed2002

Invasive aspergillosis in 2002: an update.

Despite significant advances in the management of immunosuppressed patients, invasive aspergillosis remains an important life-threatening complication. In the past two decades, the incidence of invasive aspergillosis in this population has continued to increase. Factors that predispose patients to develop invasive aspergillosis include prolonged granulocytopenia, the development of graft-versus-host disease, immunosuppressive therapy, the use of adrenal corticosteroids, and the prolonged impairment of host defenses associated with diseases such as chronic granulomatous disease. Environmental factors also play a key part in the pathogenesis of this infection, and therefore, infection control measures play a critical role in reducing exposure of patients to Aspergillus. New exciting developments in the early diagnosis of invasive aspergillosis and the acceleration of antifungal drug discovery offer promise for the future.

Antifungal Agents↗
PubMed2002

[Pulmonary aspergillosis as initial manifestation of septic granulomatosis (chronic granulomatous disease, CGD) in a premature monozygotic female twin and FDG-PET diagnosis of spread of the disease].

PURPOSE: To present the unusual case of chronic granulomatous disease (CGD) manifestating as pulmonal aspergillosis in female enzygotic twins during the neonatal period. To demonstrate and to discuss the complex diagnosis and the diagnostic value of FDG-PET in monitoring the spread and activity of the disease. PATIENTS: Plain chest x-ray and CT of the lung showed multiple, mostly round lesions in one of the former preterm twins at the age of 8 weeks. The girl with known ASD II was then suffering from dyspnoea and recurrent pulmonary infections. Because of the imaging findings invasive pulmonary aspergillosis due to an underlying immunodeficiency was suspected. RESULTS: Aspergillosis was confirmed histologically and microbiologically by specimens taken from an open lung biopsy. Because of coexisting granulocytic dysfunction the diagnosis of CGD was made. This diagnosis was equally confirmed by noninvasive methods in the asymptomatic sister. FDG-PET did not show any evidence of extra-pulmonary spread of disease. CONCLUSION: CGD can present as isolated pulmonal aspergillosis even in the neonatal period when an immunodeficiency is discussed. In enzygotic twins screening of the asymptomatic twin is mandatory. FDG-PET is a useful tool in screening for spread of the disease and in evaluating disease activity.

Age Factors↗
PubMed2005

Systemic aspergillosis with predominant genitourinary manifestations in an immunocompetent man: what we can learn from a disastrous follow-up.

Prostatic aspergillosis is a rare finding with only ten cases reported previously. We report the first case of systemic aspergillosis predominantly presenting with prostatic involvement and, clinically, with urinary retention in an immunocompetent host. Routine transurethral resection was performed due to benign prostatic hyperplasia with subvesical obstruction. Concomitant prostatic aspergillosis was diagnosed without signs of systemic infection. In the clinical follow-up systemic aspergillosis became rapidly progressive requiring complex surgical interventions and long-term antifungal therapy. The current literature is reviewed, and diagnostic and management options are discussed.

Abscess↗
PubMed1979

Acute and chronic pulmonary function changes in allergic bronchopulmonary aspergillosis.

Pulmonary functions of patients with allergic bronchopulmonary aspergillosis were studied during an acute episode (n = 6); during a mean follow-up period of 44 months (range four months--14.8 years) (n = 16); and for any correlation between duration of ABPA and asthma with the total lung capacity (helium dilution), 1 second forced expiratory volume (FEV1), vital capacity, 1 second forced expiratory volume-forced vital capacity ratio (FEV1:FVC per cent) and diffusing capacity of carbon monoxide (DL:CO) (single breath) for the entire group (n = 22). All patients were treated with corticosteroids (intermittent or continuous) and bronchodilators. For the 16 patients, slopes using linear regression analysis were determined from the function as per cent predicted versus time in months from diagnosis and then analyzed for significance. Significant functional loss was shown in three of 16 patients for FEV1, two of 16 patients for vital capacity, one of 16 patients for FEV1:FVC per cent, none of 10 patients for DL:CO and one of 10 patients for total lung cital capacity, FEV1:FVC per cent and the duration of asthma or allergic bronchopulmonary aspergillosis was found by multiple regression analysis correcting for age and smoking (mean 4.24 years; range 0.3 to 14.8 years). Roentgenographic criteria and blood eosinophilia were used to define a "flare" of allergic bronchopulmonary aspergillosis. The six patients during a flare showed a significant reduction in total lung capacity (P less than 0.001), vital capacity (P less than 0.05), FEV1 (P less than 0.01) and DL:CO (P less than 0.001) which uniformly returned to baseline values during steroid therapy. The FEV1:FVC per cent remained unaltered. These findings, contrary to suggestions in the literature, indicate that in the majority of our patients there was no significant progressive functional deterioration after diagnosis. However, during acute episodes of allergic bronchopulmonary aspergillosis, transient reduction of volumes and DL:CO were uniformly present.

Adolescent↗
PubMed1989

Treatment of invasive aspergillosis with itraconazole.

PURPOSE: Invasive aspergillosis in the immunocompromised host is one of the most difficult therapeutic problems. Itraconazole, a new oral triazole, is inhibitory as well as fungicidal against Aspergillus species in vitro. It is active against Aspergillus infections in animal models. We present our experience with itraconazole therapy of 21 patients with aspergillosis. PATIENTS AND METHODS: Eighteen of the 21 patients received 400 mg of itraconazole orally per day; the other three received 100 to 200 mg daily. Serum concentrations of itraconazole were measured and susceptibility testing was performed according to previously described methods. RESULTS: Of 15 evaluable patients, responses were produced in 12. Four of five with invasive pulmonary disease, two of two with skeletal disease, one of two with pleural disease, one of one with pericardial, sinus, mastoid, or hepatosplenic aspergillosis, and one of one with onychomycosis responded. One patient with carotid artery disease did not show a response, although results of cultures were negative at autopsy. One responder with joint disease had a possible relapse three months after completing 12 months of therapy. Ten of these patients were immunocompromised (including four with neutropenia and two renal transplant recipients) and eight of these responded. Side effects with itraconazole, in contrast to previously available therapy, were rare. CONCLUSION: This experience suggests itraconazole may be an important advance in the therapy of aspergillosis.

Adult↗
PubMed1993

Cerebral aspergillosis in immunologically competent patients.

Aspergillosis of the central nervous system is a rare disease, especially if the patient's immune system is not compromised. The authors report three cases of cerebral aspergillosis in the immunocompetent state: a rhinocerebral form in a diabetic patient, a direct extension from chronic Aspergillus otitis media, and a postoperative Aspergillus brain abscess after brain tumor surgery. In spite of the poor prognosis of cerebral aspergillosis, two of the patients survived. The pathogenesis, predisposing factors, radiologic findings including magnetic resonance image, and the outcome are presented. The pertinent literature of cerebral aspergillosis is also reviewed.

Adult↗
PubMed2005

Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome?

PURPOSE: To assess early high-resolution computer tomographic (CT) signs of invasive pulmonary aspergillosis (IPA) in non-HIV immunosuppressed patients and their potential association with patient's outcome, including frequency and severity of pulmonary hemorrhage, taking also in consideration the impact of other known risk factors contributory to IPA. MATERIAL AND METHODS: A retrospective review of serial CT scans was performed in 45 immunocompromised patients with a total of 46 episodes of invasive pulmonary aspergillosis. All patients underwent CT beginning with the day they showed clinical or laboratory signs of infection. Serial follow-up CT included more than two, up to 12 CT examinations. Patient's outcome was judged by clinical and radiological follow-up and classified as survival, death by IPA, or death unrelated to IPA. The influence of patient's age, underlying disease, hematopoietic stem cell transplantation, neutropenia, graft versus host disease, and antifungal therapy onset was also statistically considered. RESULTS: Three main CT findings were identified: small nodules (<1cm) 43% (20/46), large nodules 21% (10/46) and consolidations, either in patchy+/-segmental 26% (12/46), or peribronchial distribution+/-tree in bud 9% (4/46). In 11 patients (24%) we found a combination of two or more of these signs: 9 (19%) patients presented concurrent small nodules accompanied by reticulation, tree in bud or peribronchial infiltrates, while 2 (4%) patients showed large pulmonary nodules accompanied by large consolidations. An accompanying "halo" sign was observed in 38 patients (82%). Crescent sign followed by cavitation was encountered in 29 patients (63%). Two patients succumbed to massive pulmonary bleeding caused by IPA. Twenty-one patients (15/46) deceased in this series, 12 of them succumbed to IPA, 1 died from cerebral invasive aspergillosis, while in 9 patients the cause of death was not primarily IPA. Manifest pulmonary hemorrhage occurred in 19% (9/46) of IPA episodes. CONCLUSION: Initial CT findings of invasive pulmonary aspergillosis consist mainly of small nodules or patchy consolidations, showing in 82% of cases an early halo sign. Serious pulmonary hemorrhage was an infrequent clinical complication in our series, with an attributable mortality of 4.3%. IPA-related lethality was 26%, in our cohort. None of the early HRCT signs seemed to predict outcome.

Adolescent↗