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PubMed1998

Primary aspergillosis of the larynx and squamous cell carcinoma.

Primary laryngeal aspergillosis is exceptionally rare, and only five cases have been reported in the literature. We present here two cases of invasive laryngeal aspergillosis without tracheobronchopulmonary extension and without any generalized immune deficit. Aspergillosis developed after local radiotherapy for a squamous cell carcinoma and preceded a recurrence of the tumor. The relationships between the clinical features, the histopathology, and the etiology of laryngeal aspergillosis and squamous cell carcinoma are discussed. We recommend that following treatment of laryngeal aspergillosis, these rare patients should systematically be investigated for a squamous cell carcinoma or a recurrence thereof.

Aspergillosis↗
PubMed1999

Successful treatment of an invasive aspergillosis of the skull base and paranasal sinuses with liposomal amphotericin B and itraconazole.

Invasive aspergillosis and fulminant aspergillosis are rarities with a high mortality. In the literature there is no patient surviving an extended invasive aspergillosis of the paranasal sinuses and skull base after failure of operative intervention and of postoperative amphotericin B therapy. We report a complete remission of an invasive, partially fulminant aspergillosis. After an incomplete removal of the mycotic mass, we started postoperative drug therapy with amphotericin B. Under this treatment, the mycosis progressed. Additionally, the patient developed severe side effects, so that the treatment was interrupted. At this moment, we started a combined antimycotic drug therapy with liposomal amphotericin B and itraconazole. Within 10 weeks, clinically and radiologically, there was complete remission. The patient died 63 weeks after this treatment, due to a fulminant bacterial pneumonia. Postmortem histologic examination showed no aspergillosis in the skull base, paranasal sinuses, or lung.

Amphotericin B↗
PubMedDate not supplied

Disseminated aspergillosis in the acquired immunodeficiency syndrome.

The relationship of disseminated aspergillosis with human immunodeficiency virus (HIV) infection is unclear. In the initial case definition of acquired immunodeficiency syndrome (AIDS) developed by the Centres for Disease Control (CDC), Atlanta, aspergillosis was included as an AIDS-defining opportunistic infection. In view of the primary relationship of aspergillosis with neutropenia rather than with lymphocyte depletion, as well as the lack of aspergillar infections among reported AIDS cases, aspergillosis was later deleted from the CDC case definition of AIDS. We describe a case of disseminated aspergillosis in a patient with AIDS, with an extensive literature review of the subject.

AIDS-Related Opportunistic Infections↗
PubMed1995

Invasive aspergillosis: a life-threatening complication of short-term steroid treatment.

OBJECTIVE: To describe a patient with invasive pulmonary aspergillosis related to short-term steroid treatment. CASE SUMMARY: A 78-year-old man with chronic obstructive pulmonary disease (COPD) developed an invasive pulmonary aspergillosis after short-term (less than 1 week) intravenous steroid therapy. The diagnosis was established by recovering Aspergillus fumigatus from a bronchoalveolar lavage and was confirmed by autopsy, with the additional finding of an aspergilloma. DISCUSSION: This case is of interest for 3 reasons: (1) it illustrates that invasive aspergillosis may be followed by a rapidly progressive respiratory failure, even in the absence of a fever; (2) this patient had simultaneously an aspergilloma and an invasive aspergillosis; and (3) it confirms reports indicating that short-term steroid therapy for COPD represents a significant risk factor for opportunistic lung infections. CONCLUSIONS: In patients with COPD who receive even short-term steroid therapy and who have progressive respiratory failure caused by pneumonia, invasive aspergillosis should be suspected early and acted upon accordingly.

Aged↗
PubMed2005

Improved outcome in central nervous system aspergillosis, using voriconazole treatment.

The mortality of central nervous system (CNS) aspergillosis approaches 100%, requiring improved therapies. Voriconazole gives superior efficacy and survival in invasive aspergillosis, compared with amphotericin B. Also, in contrast to other antifungal drugs, voriconazole penetrates well into the CNS. We evaluated, retrospectively, the outcome and survival of 81 patients who were treated with voriconazole for definite (n = 48) or probable (n = 33) CNS aspergillosis. Complete and partial responses were recorded in 35% of patients and varied by the underlying disease group: hematologic malignancies (54%), other underlying conditions (50%), chronic immunosuppression (45%), solid organ transplantation (36%), and hematopoietic stem cell transplantation (16%). Thirty-one percent of patients survived CNS aspergillosis for a median observation time of 390 days. There were 31 patients who underwent neurosurgical procedures, including craniotomy/abscess resection (n = 14), abscess drainage (n = 12), ventricular shunt (n = 4), and Ommaya-reservoir (n = 1). Multifactorial analysis revealed that neurosurgery was associated with improved survival (P = .02). Patients who underwent hematopoietic stem cell transplantation had a poorer survival (P = .02), but 7 (22%) of 32 survived for a median of 203 days. We conclude from this large cohort of patients that voriconazole treatment together with neurosurgical management, whenever feasible, is currently the best approach to treat patients with CNS aspergillosis.

Adult↗
PubMed2006

Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia.

BACKGROUND: Aspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA) according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography) and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible. CASE PRESENTATION: We report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful. CONCLUSION: This report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.

Adult↗
PubMed2006

Effective blood concentration of micafungin for pulmonary aspergillosis.

We previously reported that a 150 mg or higher daily dose is necessary for treatment of pulmonary aspergillosis with micafungin (MCFG) alone in patients with blood diseases. Since a delay in the treatment of pulmonary aspergillosis has a major influence on patient survival, clarification of the effective blood concentration of MCFG enables rapid treatment. Establishment of an appropriate dose is also useful for reducing the risk of adverse effects, such as MCFG-induced impairment of liver function. Aiming for the rapid and safe treatment of pulmonary aspergillosis, we established new clinical diagnostic criteria of mycosis and MCFG therapeutic effect judgment criteria, and investigated the effective blood concentration of MCFG for mycosis. The blood trough level of MCFG in patients with blood diseases at each clinical improvement rating of pulmonary aspergillosis was 5.23+/-2.44 microg/ml in markedly improved cases, 4.08+/-2.63 microg/ml in improved cases, and 3.45+/-1.63 microg/ml in successfully prevented cases, showing no significant difference among the 3 groups. Based on this finding, it is advisable to target a 5 microg/ml or higher blood trough level of MCFG in establishing the dose for aspergillosis in patients with blood diseases.

Adult↗
PubMed1985

Sino-orbital aspergillosis associated with total ophthalmoplegia.

Invasive aspergillosis of the paranasal sinuses involving the orbit is termed sino-orbital aspergillosis. Prognosis of sino-orbital aspergillosis, complicated by impaired visual acuity and neurological signs, is disastrous and usually fatal. We herein report two patients with sino-orbital aspergillosis associated with total ophthalmoplegia. One patient was successfully treated with surgical eradication including orbital exenteration. In contrast, the other died of cerebral infarction, probably due to fungal thrombosis of the middle cerebral artery, despite repeated local debridement followed by orbital exenteration and administration of antifungal agents. Experience with these cases strongly indicates the necessity of prompt surgical eradication, including orbital exenteration if necessary, in the treatment of sino-orbital aspergillosis.

Antifungal Agents↗
PubMed1996

Transmission of invasive aspergillosis from a subclinically infected donor to three different organ transplant recipients.

OBJECTIVE: To describe a cluster of donor-transmitted cases of invasive aspergillosis. DESIGN: Case series of epidemiologically linked cases of invasive aspergillosis. SETTING: Two tertiary care centers with solid-organ transplant programs. PATIENTS: Two kidney recipients, one heart recipient, and the single donor. MEASUREMENTS: Routine clinical, microbiological, and pathologic investigation as dictated for patient care. Epidemiologic analysis to establish linkage among cases. RESULTS: Three allografts (two kidneys and a heart) from a single donor transmitted invasive aspergillosis to the recipients. Three weeks after transplantation, the two kidney recipients had fever and urine cultures positive for Aspergillus fumigatus. The infected kidneys had multiple Aspergillus abscesses and had to be removed to cure the patients. The heart recipient had a negative workup when a diagnosis of aspergillosis was made for the kidney recipients but presented three months later with aspergillus endocarditis with hematogenous spread to the eyes and to the skin. Treatment included eye surgery, aortic valve replacement, and antifungal therapy; control of infection ensued. The donor was intensely immunosuppressed (17 days post-liver transplantation with death from intracerebral bleeding) but had no clinical or autopsy evidence of aspergillosis. Donor tracheal secretions obtained at the time of organ harvest later grew A fumigatus. CONCLUSION: Expanded criteria for organ donation have to be balanced against infectious risk to organ recipients. A fumigatus can be transmitted from a subclinically infected donor to solid-organ transplant recipients.

Abscess↗
PubMed2007

Galactomannan antigen detection in the diagnosis of invasive aspergillosis.

Invasive aspergillosis is a serious and lethal infection among immunocompromised patients, with reported mortality rates as high as 74-92%. The high mortality is related to the severe immunosuppression experienced by these patients as well as the difficulties for physicians in arriving at a timely diagnosis. Definitive diagnostic procedures (tissue biopsy for histopathology and culture) are often precluded by severe cytopenias and coagulation abnormalities. The development of minimally invasive, nonculture diagnostic methods is a major advance in the early diagnosis of invasive aspergillosis. Galactomannan is a heteropolysaccharide (mannan core and side residues of galactofuranosyl units) present in the cell wall of Aspergillus spp. The double sandwich enzyme immunoassay, which detects galactomannan in serum samples, has been available in Europe for almost a decade and in the USA since May 2003, for the diagnosis of invasive aspergillosis. However, availability of the double galactomannan enzyme immunoassay is center variable in the USA and, although its analytical performance in the diagnosis of invasive aspergillosis is well documented, its routine use in clinical practice is limited. As an adjunct in the diagnosis and management of invasive aspergillosis, incorporation of the galactomannan enzyme immunoassay into clinical trials will help to further define its role.

Animals↗
PubMed2002

Itraconazole prophylaxis for invasive gingival aspergillosis in neutropenic patients with acute leukemia.

BACKGROUND: Due to an increasing number of leukemic patients with invasive gingival aspergillosis during neutropenia (neutrophils <500 cells/microl for >10 days), we evaluated the efficacy of oral itraconazole prophylaxis for preventing this invasive infection at our hospital. METHODS: This was a retrospective, non-randomized study to analyze the onset of identified invasive gingival aspergillosis among 536 patients with acute leukemia at risk due to the presence of neutropenia from 1991 to 1998. Patients received itraconazole capsules 100 mg/day prophylactically between April 1994 and December 1996, and 200 mg/day between January 1997 and December 1998. Itraconazole serum levels at day 10 were measured in some patients. RESULTS: In the 39 months prior to April 1994 without itraconazole prophylaxis, 15 cases of invasive gingival aspergillosis were detected in 192 high risk patients with 469 episodes of neutropenia (7.8% of the high risk patients). Between April 1994 and December 1996, using itraconazole prophylaxis at 100 mg/day, there was a dramatic decrease in the infections resulting in 3 of 198 high risk patients with 511 episodes of neutropenia (1.5% of the high risk patients). Furthermore, between January 1997 and December 1998, using itraconazole prophylaxis at 200 mg/day, no cases of the infection were observed in the 146 high risk patients with 380 episodes of neutropenia. The incidence of invasive gingival aspergillosis was significantly lower among patients administered itraconazole than among those without itraconazole (100 mg/day; P = 0.006 and 200 mg/day; P = 0.001). The mean itraconazole serum level in 20 patients receiving 100 mg/day was 71.78 ng/mL and in 16 patients receiving 200 mg/day was 202.67 ng/ml. CONCLUSIONS: These findings suggest that oral itraconazole could be effective for preventing invasive gingival aspergillosis in neutropenic patients with acute leukemia and warrants further randomized investigation.

Administration, Oral↗
PubMed1977

Strontium-87m lung scans in pulmonary aspergillosis.

Experimental observations have indicated that radioactive strontium localizes in lesions infected with Aspergillus species. Preliminary clinical studies have recommended use of strontium lung scanning to evaluate patients thought to have pulmonary manifestations of aspergillosis. In view of the difficulty in accurately interpreting the clinical significance of recovery of Aspergillus species from sputum of patients with pulmonary disorders as well as the varied clinical presentations of pulmonary aspergillosis, we have attempted to confirm these reports. Ten patients with proven pulmonary aspergillosis and five selected control subjects without aspergillosis but with other pulmonary disorders were scanned after the injection of 2-3 mCi 87mSr citrate. The strontium lung scan correlated with the chest radiograph in four of 10 patients with aspergillosis; false positive scans were found in three of five patients with other pulmonary disorders. We conclude that strontium lung scans at present have no role in the diagnostic evaluation of patients suspected of clinically significant infections with aspergillus.

Adult↗
PubMed1999

Clinical evaluation of diagnostic methods using plasma and/or serum for three mycoses: aspergillosis, candidosis, and pneumocystosis.

Clinical evaluation was retrospectively made of the results of serological diagnostic methods using plasma and/or sera of patients for the diagnosis of aspergillosis, candidosis, and pneumocystosis. Specimens were drawn from 8 patients with invasive aspergillosis, 3 with aspergilloma, 9 with candidosis, 4 with pneumocystosis, and 15 with no fungal infections. In invasive aspergillosis, the sensitivities of the (1-3)-beta-D-glucan measurement test using chromogenic and turbidimetric methods were 78.6% and 82.1%, with specificities of 75% and 87.5%, respectively. The sensitivity of the Pastorex Aspergillus test for invasive aspergillosis was 16.7%, with a specificity of 92.3%. In candidosis, the sensitivities of the (1-3)-bata-D-glucan test using the above two methods were 84.2% and 100%, with specificities of 75% and 87.5%, respectively. The sensitivity of the CAND-TEC test and the Pastorex Candida test for candidosis were 68.8% and 16.7%, with specificities of 57.1% and 100%, respectively. These results indicate that the (1-3)-bata-D-glucan measurement methods are more reliable in clinical application than the other antigen detection methods, but they still lack efficiency in differentiating fungal infections such as aspergillosis, candidosis and pneumocystosis. For a more exact diagnosis of systemic fungal infections, detailed studies on the clinical symptoms are considered essential.

Aspergillosis↗
PubMed1999

[A case report on aspergillosis of the sphenoid sinus].

Aspergillosis of the paranasal sinus usually affects the maxillary sinus and isolated aspergillosis of the sphenoid sinus is less frequent. Aspergillosis of the paranasal sinus has been generally classified into the non-invasive type and the invasive type. There is controversy whether such difference of invasion depends on impairment of the host's immunological function or aspergillus offense factors. We report three cases of aspergillosis of the sphenoid sinus affecting individuals whose immunological states were different from each other. The prognosis among these cases was also different. These three cases suggest that the difference in the degree of aspergillus invasion may depend on the immunological state of each patient. Therefore, immediate diagnosis and therapy are very important for paranasal aspergillosis in the immunocompromised patient.

Aged↗
PubMed1999

Pulmonary aspergillosis in horses: 29 cases (1974-1997).

OBJECTIVE: To analyze medical records and identify factors that veterinarians can use to prevent pulmonary aspergillosis in horses or that would enable them to diagnose it as early as possible. DESIGN: Retrospective study. ANIMALS: 29 horses. PROCEDURE: Medical records were reviewed for horses with pulmonary aspergillosis diagnosed on the basis of characteristic postmortem findings. Information on history, clinical signs, disease progression, and postmortem findings was obtained. RESULTS: 25 of 29 (86.2%) horses had primary (n = 20) or secondary (5) disease compatible with loss of integrity of the gastrointestinal (GI) tract. The remaining 4 horses had a non-GI tract disorder; only 1 of these 4 had clinical signs associated with the respiratory tract (i.e., pleuropneumonia). Although 22 (75.9%) horses had various signs of respiratory tract disorders, an antemortem diagnosis of Aspergillus pneumonia was made in only 1 horse and was suspected in only 1 other. Fungal organisms were seen histologically in tissues other than the lung in 12 (41.4%) horses. CLINICAL IMPLICATIONS: Horses with enteritis, colitis, typhlitis, or other diseases of the GI tract that result in mucosal compromise, and horses with clinical signs of respiratory tract disease, particularly if the horse's condition is unresponsive to treatment with antimicrobial agents; should be considered at high risk of having pulmonary aspergillosis. Immunosuppression from debilitating disease may also predispose horses to aspergillosis. Because invasive pulmonary aspergillosis can be difficult to diagnose, clinicians should be aware of clinical and epidemiologic settings in which this disease would develop.

Animals↗
PubMed1999

[Invasive aspergillosis in patients with human immunodeficiency virus infection diagnosed by necropsy: the contribution of 4 cases and review of the literature].

BACKGROUND: Invasive aspergillosis is an infrequent clinicopathological entity which is difficult to diagnose (since it requires tissue samples, normally of the lung where the pathogenic effect of the fungi may be seen) and thus an important number of cases are not found until necropsy. In patients with human immunodeficiency virus (HIV) infection the real incidence has not been clearly defined and may be higher than reported. MATERIAL AND METHODS: We herein present a series of necropsy reviews performed over a five year period (January 1993 to December 1997) in the Hospital Universitario San Carlos in Madrid (Spain) in patients with HIV infection. In the patients who presented invasive aspergillosis a collection protocol of clinical, analytical and radiologic data was undertaken. RESULTS: Over this period necropsic studies were performed in 23 patients with HIV infection. Of these 4 (17.3%) presented invasive aspergillosis; 3 with disseminated involvement. Premortem diagnosis was not performed in any of the cases. The risk factors included: 3 had a CD4 count of less than 50, two were receiving glucocorticoids and only 1 had severe neutropenia. In 2 another opportunistic lung infection was also observed. CONCLUSIONS: Invasive aspergillosis is an entity witch is found on autopsy with relative frequency in patients with HIV infection with severe immunodepresion. Other opportunistic infections may also coincide and it may not be associated with neutropenia, glucocorticoid treatment, which are considered as classical risk factors for invasive aspergillosis.

AIDS-Related Opportunistic Infections↗
PubMed2001

[Bronchopulmonary aspergillosis: new developments].

Bronchopulmonary aspergillosis are in the news. Invasive pulmonary aspergillosis raise early diagnostic problems and prevention problems in immunocompromised patients. These infections are no unusual in chronic obstructive pulmonary disease. The diagnosis between aspergilloma and chronic necrotizing pulmonary aspergillosis can be difficult. In allergic bronchopulmonary aspergillosis, epidemiology and therapy are questionable. Real progress has been made due to thoracic computed tomographic scan and mycological methods. Better use of amphotericin B, of amphotericin B lipid formulations and of azole antifungal agents, combined with surgical resection if necessary should improve aspergillosis prognosis.

Amphotericin B↗
PubMed2003

[Diagnosis and treatment of invasive pulmonary aspergillosis in malignant hematological diseases-3 cases reported].

Invasive pulmonary aspergillosis is difficult to diagnose and a critical ill with high mortality. In this paper, the diagnosis and treatment of invasive pulmonary aspergillosis complicated in 3 cases of hematological malignancy (2 acute leukemias and 1 MDS-RA) were retrospectively analysed. All patients had histories of hypoimmunity and were received prophylactic antifungal treatment. Pulmonary aspergillosis infection still occurred and confirmedly diagnosed by sputum examination. After 7 to 14 days of combination treatment of liposomal amphotericin B, itraconazole and flucytosine, 2 cases were cured and another showed effective. In conclusion, early diagnosis and treatment of invasive pulmonary aspergillosis are very critical and the therapeutic effectiveness of combined scheme with liposomal amphotericin B, itraconazole and flucytosine is very effective for pulmonary aspergillosis.

Adult↗