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PubMedDate not supplied

Aspergillosis in a 24-week newborn: a case report.

Aspergillosis is an uncommon neonatal infection, diagnosed with an increasing frequency over the last two decades. We report a premature neonate who developed aspergillosis while receiving amphotericin B and fluconazole for candidiasis. Despite early recognition and diagnosis, the infant died. We review the clinical appearance of Aspergillus species, the distinctions between primary cutaneous aspergillosis and invasive aspergillosis, and advances in diagnosis and treatment.

Aspergillosis↗
PubMed2001

Clinical significance of Aspergillus fungaemia in patients with haematological malignancies and invasive aspergillosis.

The clinical significance of Aspergillus fungaemia in the setting of a deep-seated aspergillosis has not been clearly established. Among 107 microbiologically documented Aspergillus infections in patients with haematological diseases observed over a 17-year period, blood cultures grew Aspergillus species from 10 cases. Aspergillus fungaemia was documented in 9 out of 89 (10.1%) patients with pulmonary aspergillosis at a median of 5 d from the onset of clinical signs of infection, and in one patient with central venous catheter focal infection. Five (50%) patients died as a result of fungal infection a median of 12 d (range 4--48) from the documentation of Aspergillus fungaemia. A comparison between cases of invasive aspergillosis with or without fungaemia showed that fungaemic patients were similar to those without positive blood cultures regarding clinical presentation, risk factors, clinical course and outcome. The diagnostic role of Aspergillus fungaemia in the setting of a deep-seated infection is limited because blood cultures become positive when a microbiological or clinical diagnosis of aspergillosis has already been performed. Aspergillus fungaemia does not necessarily seem to be correlated with a disseminated infection or a poorer prognosis.

Adolescent↗
PubMed2001

The value of the determination of anti-Aspergillus IgG in the serodiagnosis of canine aspergillosis: comparison with galactomannan detection.

Diagnosis of canine aspergillosis is difficult using currently available methods. It often passes unnoticed or is diagnosed in the later phases of the disease. We developed an ELISA technique to detect anti-Aspergillus antibodies in canine serum using an Aspergillus antigenic mycelial extract, which could then be used for the diagnosis of canine aspergillosis. We used a cut-off of X + 3SD obtained from 20 control sera. The test was performed on 46 dogs with lesions indicating possible aspergillosis and gave nine positive results: one systemic mycosis, two discospondylitis, one uveitis, two bronchopulmonary processes and three rhinitis. We compared this methodology with the PLATELIA technique in the follow-up of the affected dogs, obtaining the same limitations as in the diagnosis of human aspergillosis. We consider our ELISA technique using sera samples a speedy, safe and reliable method which enables us to follow up the evolution of the disease and the efficacy of the therapy chosen. A definitive diagnosis must still take into account the results of other tests such as clinical examination, radiographic studies, endoscopy and biopsy.

Animals↗
PubMed2002

Invasive aspergillosis in cancer.

Ten confirmed cases of invasive aspergillosis (IA) in cancer patients were analysed retrospectively. Eight were pulmonary, one was sinonasal and one was cutaneous. The majority of patients had haematological malignancies (7), the remaining three were cases of solid tumours. Fever was present in all 10 cases. Cough and lung signs were present in all eight cases of invasive pulmonary aspergillosis. Haemoptysis was encountered in three of nine cases of pulmonary and sinonasal aspergillosis. Mortality was low (2%). While corticosteroids, antibiotics and anticancer chemotherapy/radiotherapy were factors predisposing the patients to IA, neutropenia was perhaps responsible for their mortality. Seven of the patients had other associated pathogens isolated in culture in addition to Aspergillus spp. Aspergillus fumigatus was the predominant species, followed by A. flavus, A. glaucus, A. nidulans and A. niger. Direct microscopic examination (in six of seven cases) and culture (six of seven cases) correlated well with radiographic and clinical findings in cases with lung involvement. Serology for anti-Aspergillus antibodies performed by gel diffusion precipitin test was positive in one case of sinonasal aspergillosis, wherein only one precipitin band was observed. Correlation of clinical symptoms, consistent radiographic findings and microbiological work-up (the latter including a triad of direct microscopy, culture and serology) are required to arrive at a diagnosis of IA, especially where histology cannot form the mainstay of diagnosis.

Adolescent↗
PubMed2006

Canine nasal aspergillosis.

Chronic nasal discharge is a common clinical sign of disease in dogs. Canine sinonasal aspergillosis is a relatively common disease in dogs. The three hallmarks of canine nasal aspergillosis are a profuse mucoid to hemorrhagic chronic nasal discharge that may alternate with periods of epistaxis, ulceration of the external nares with crusting, and pain or discomfort in the facial region. Diagnostic imaging (preferably computed tomography, CT) of the nasal cavity and paranasal sinuses is an important component of the evaluation of dogs with signs of nasal disease. Rhinoscopy is an important part of both the diagnosis and the therapy for nasal aspergillosis. Therapeutic recommendations for sinonasal aspergillosis have included surgery and the use of several systemic and topical antifungal drugs.

Animals↗
PubMed1997

[Drug treatment of invasive aspergillosis of the paranasal sinuses].

Aspergillosis belongs to the group of mycotic diseases of the paranasal sinuses. The invasive forms, and particularly the fulminant forms, are potentially fatal. Primary surgical intervention with complete removal of the mycotic mass should be performed. Additionally an antimycotic drug therapy with amphotericin B must be started. In a review of the literature, there is no case surviving an extended invasive aspergillosis after failure of the operative therapy and after failure of the postoperative amphotericin B treatment. We report an interesting case of a complete remission of an invasive, partially fulminant aspergillosis of the paranasal sinuses and frontal and basal regions. After incomplete removal of the mycotic mass by an endo- and extranasal approach, we started postoperative drug therapy with amphotericin B. Under this treatment the mycosis progressed. Additionally the patient developed severe renal side effects requiring suspension of the treatment. At this time, we started a combined antimycotic drug therapy with liposomal amphotericin B (AmBisome) and itraconazol. Within 10 weeks there was complete clinical and radiologic remission. The patient died 63 weeks after this treatment because of a fulminant bacterial pneumonia. Post mortem examination showed no aspergillosis in the skull base, the paranasal sinuses, or in the lung. The question arises as to whether this drug combination of liposomal amphotericin B (AmBisome) and itraconazol is a real alternative to high-risk surgical interventions in this region.

Amphotericin B↗
PubMed1987

Primary cutaneous aspergillosis associated with Hickman intravenous catheters.

We describe nine patients with underlying hematologic cancer in whom primary cutaneous aspergillosis developed at the sites of Hickman intravenous catheters. Our patients, 17 to 74 years of age, were all immunocompromised either from their primary disease or from chemotherapy, and the Hickman catheters had been placed to provide venous access for chemotherapy or hyperalimentation or both. Clinical signs of infection included erythema, induration, and cutaneous or subcutaneous necrosis at the point of entry into the subclavian vein, in the subcutaneous tunnel, or at the exit site from the skin. Diagnosis was confirmed by positive wound culture for Aspergillus flavus in all but one patient. Treatment consisted of intravenous amphotericin B, oral flucytosine, and local wound care. Three patients recovered completely without operative débridement; three others recovered after operative débridement and delayed grafting. Two patients died of disseminated aspergillosis, and one died of unrelated causes while recovering from primary cutaneous aspergillosis. Successful treatment required resolution of aplasia or leukopenia, catheter removal, systemic treatment with amphotericin B, and local wound care. We conclude that primary cutaneous aspergillosis, a rare infection, may occur at the sites of Hickman catheters in immunocompromised patients, and that it is a serious complication requiring prompt diagnosis and treatment.

Adolescent↗
PubMed2001

A cluster of invasive aspergillosis in a bone marrow transplant unit related to construction and the utility of air sampling.

BACKGROUND: An investigation was launched to identify the source of a cluster of invasive aspergillosis in the bone marrow transplant unit (BMTU) when construction was taking place on the floor directly below the unit. The utility of air sampling for Aspergillus was examined. METHODS: Cases of Aspergillus colonization and infection were identified in the BMTU and in the wards adjacent to the construction site. Air sampling was performed in the BMTU before and after room and air duct cleaning and then randomly during a 6-month period, beginning 6 months after construction ended. The results were correlated with the incidence of Aspergillus infections. RESULTS: The cluster of cases of invasive aspergillosis could not be directly linked to the construction. In the BMTU, the rate of Aspergillus colonization and infection during construction was 2.5 times higher than that for the 6 months before the construction and 2.9 times higher for the adjacent wards. After construction ended, the rates returned to pre-construction rates. Two cases of invasive aspergillosis were observed in the BMTU during random air sampling, but the results of air sampling could not be correlated to cases. CONCLUSIONS: Although the cluster of cases of invasive aspergillosis could not be linked to the construction, the construction did increase the rates of Aspergillus colonization in the BMTU and adjacent wards. Periodic air samplings could not correlate conidia counts to invasive Aspergillus infection.

Air Microbiology↗
PubMed1989

Invasive aspergillosis: clinical and pathological features of a new animal model.

A new animal model of invasive aspergillosis is described in which female New Zealand White rabbits were immunosuppressed with corticosteroids and cyclophosphamide and were given an intratracheal inoculation of 4 x 10(4) conidia of Aspergillus fumigatus. Thirteen of 15 animals survived during a 10-day-period of observation. Most had clinical signs of a respiratory infection (dyspnoea) and at autopsy there was macroscopic and microscopic evidence of invasive pulmonary aspergillosis. Six control animals (infected but not immunosuppressed) showed no such signs. The extent of hyphal invasion was assessed histologically and quantified by calculating the number of colony forming units (c.f.u.) g-1 of tissue: in the experimental group the mean c.f.u. value for the lungs was 1.25 x 10(3) compared to 73.3 c.f.u. g-1 of lung for the control group (P = 0.003). The infection was also quantified by a whole lung chitin assay: in the experimental group the mean chitin content (expressed as a glucosamine equivalent) was 3.05 micrograms g-1 lung tissue compared to a 0.53 micrograms g-1 lung tissue for the control group (P = 0.01). We conclude that this model of invasive aspergillosis in rabbits reflects closely the pathological features of the disease in man and that it may prove useful for studies of the pathogenesis and the treatment of invasive aspergillosis.

Animals↗
PubMed2004

Combination antifungal therapy for invasive aspergillosis.

BACKGROUND: Aspergillosis therapy with amphotericin, azoles, or echinocandins is associated with substantial mortality, ranging from 30% to 80%, depending on the stage of infection and the host's underlying disease. The results of in vitro studies and animal models suggest that combination therapy with azoles and echinocandins may have additive activity against Aspergillus species. METHODS: We evaluated the outcomes of patients with aspergillosis who experienced failure of initial therapy with amphotericin B formulations and received either voriconazole (n=31) or a combination of voriconazole and caspofungin (n=16) for salvage therapy. RESULTS: The combination of voriconazole and caspofungin was associated with improved 3-month survival rate, compared with voriconazole alone (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.17-1.1; P=.048). In multivariable models, salvage therapy with the combination of voriconazole and caspofungin was associated with reduced mortality, compared with therapy with voriconazole (HR, 0.28; 95% CI, 0.28-0.92; P=.011), independent of other prognostic variables (e.g., receipt of transplant and type of conditioning therapy). The probability of death due to aspergillosis was lowest in patients who received the combination regimen. CONCLUSIONS: Randomized trials are warranted to determine whether this combination should be used as primary therapy for aspergillosis.

Adolescent↗
PubMed2005

Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study.

BACKGROUND: To facilitate the design of strategies for prevention of invasive aspergillosis in solid-organ transplant recipients, this study investigates whether the development of early-onset and late-onset aspergillosis are related to different risk factors, thereby distinguishing 2 risk populations for this serious complication. METHODS: A retrospective case-control study was performed, including 156 cases of proven or probable invasive aspergillosis in patients recruited from 11 Spanish centers since the start of the centers' transplantation programs. RESULTS: Among all patients, 57% had early-onset IA (i.e., occurred during the first 3 months after transplantation). Risk factor analysis in this group identified as significantly associated risk factors a more complicated postoperative period, repeated bacterial infections or cytomegalovirus disease, and renal failure or the need for dialysis. Among patients with late-onset infections (i.e., occurred > 3 months after transplantation), who comprised 43% of cases, the patients at risk were older, were in an overimmunosuppressed state because of chronic transplant rejection or allograft dysfunction, and had posttransplantation renal failure. CONCLUSIONS: Risk factors in patients with early-onset cases and patients with late-onset cases of posttransplantation invasive aspergillosis are not the same, a fact that could have implications for the preventive approaches used for this infection.

Adolescent↗
PubMed2000

Refinements of environmental assessment during an outbreak investigation of invasive aspergillosis in a leukemia and bone marrow transplant unit.

OBJECTIVES: To investigate an outbreak of aspergillosis in a leukemia and bone marrow transplant (BMT) unit and to improve environmental assessment strategies to detect Aspergillus. DESIGN: Epidemiological investigation and detailed environmental assessment. SETTING: A tertiary-care university hospital with a 37-bed leukemia and BMT unit PARTICIPANTS: Leukemic or BMT patients with invasive aspergillosis identified through prospective surveillance and confirmed by chart review. INTERVENTIONS: We verified the diagnosis of invasive fungal infection by reviewing medical charts of at-risk patients, performing a case-control study to determine risk factors for infection, instituting wet mopping to clean all floors, providing N95 masks to protect patients outside high-efficiency particulate air (HEPA)-filtered areas, altering traffic patterns into the unit, and performing molecular typing of selected Aspergillus flavus isolates. To assess the environment, we verified pressure relationships between the rooms and hallway and between buildings, and we compared the ability of large-volume (1,200 L) and small-volume (160 L) air samplers to detect Aspergillus spores. RESULTS: Of 29 potential invasive aspergillosis cases, 21 were confirmed by medical chart review. Risk factors for developing invasive aspergillosis included the length of time since malignancy was diagnosed (odds ratio [OR], 1.0; P=.05) and hospitalization in a patient room located near a stairwell door (OR, 3.7; P=.05). Two of five A. flavus patient isolates were identical to one of the environmental isolates. The pressure in most of the rooms was higher than in the corridors, but the pressure in the oncology unit was negative with respect to the physically adjacent hospital; consequently, the unit acted essentially as a vacuum that siphoned non-HEPA-filtered air from the main hospital. Of the 78 samples obtained with a small-volume air sampler, none grew an Aspergillus species, whereas 10 of 40 cultures obtained with a large-volume air sampler did. CONCLUSIONS: During active construction, Aspergillus spores may have entered the oncology unit from the physically adjacent hospital because the air pressure differed. Guidelines that establish the minimum acceptable pressures and specify which pressure relationships to test in healthcare settings are needed. Our data show that large-volume air samples are superior to small-volume samples to assess for Aspergillus in the healthcare environment.

Analysis of Variance↗
PubMed2002

Efficacy of high-efficiency particulate air filtration in preventing aspergillosis in immunocompromised patients with hematologic malignancies.

OBJECTIVES: To describe and investigate the cause of an outbreak of 10 cases of nosocomial invasive infection with Aspergillus flavus in a hematologic oncology patient care unit. DESIGN: A retrospective cohort study. SETTING: The hematologic oncology unit of a comprehensive cancer center. PATIENTS: Ninety-one patients admitted to the hematologic oncology service between January 1 and December 31, 1992, for 4 or more consecutive days were included in the study. RESULTS: Ten (18%) of 55 patients admitted from July to December 1992 were diagnosed as having invasive aspergillosis compared with 0 (0%) of 36 patients admitted from January to June 1992 to the same patient care units. Patient characteristics, mortality rate, autopsy rate, and admitting location did not change significantly during the course of the year to result in a sudden increase in the number of aspergillosis cases. The source of the outbreak was the high counts of Aspergillus conidia determined from air sampling in the non-bone marrow transplant wing during the outbreak. After high-efficiency particulate air (HEPA) filters were installed as an infection control measure, there were only two additional cases of nosocomial aspergillosis in the 2 years following the outbreak. CONCLUSIONS: This outbreak occurred among hematologic oncology patients with prolonged granulocytopenia housed in an environment with neither HEPA filters nor laminar air flow units. Our data demonstrate that in the setting of an outbreak of aspergillosis, HEPA filters are protective for highly immunocompromised patients with hematologic malignancies and are effective at controlling outbreaks due to air contamination with Aspergillus conidia.

Adolescent↗
PubMed2006

Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis.

BACKGROUND: A double-sandwich enzyme-linked immunosorbent galactomannan assay has been approved for surveillance for invasive aspergillosis in immunocompromised patients. We undertook a meta-analysis to assess the accuracy of a galactomannan assay for diagnosing invasive aspergillosis. METHODS: Studies of the galactomannan assay that used the European Organization for Research and Treatment of Cancer or similar criteria as a reference standard and provided data to calculate sensitivity and specificity were included. Pooled sensitivity and specificity and summary measures of accuracy, Q* (the upper left-most point on the summary receiver-operating characteristic curve), mean D (a log odds ratio), and Youden index were calculated. Subgroup analyses were performed to explore heterogeneity. RESULTS: Twenty-seven studies from 1966 to 28 February 2005 were included. Overall, the galactomannan assay had a sensitivity of 0.71 (95% confidence interval [CI], 0.68-0.74) and specificity of 0.89 (95% CI, 0.88-0.90) for proven cases of invasive aspergillosis. The Youden index, mean D, and Q* were 0.54 (95% CI, 0.41-0.65), 2.74 (95% CI, 21.12-3.36), and 0.80 (95% CI, 0.74-0.86), respectively, indicating moderate accuracy. Subgroup analyses showed that the performance of the test differed by patient population and type of reference standard used. Significant heterogeneity was present. CONCLUSIONS: The galactomannan assay has moderate accuracy for diagnosis of invasive aspergillosis in immunocompromised patients. The test is more useful in patients who have hematological malignancy or who have undergone hematopoietic cell transplantation than in solid-organ transplant recipients. Further studies with attention to the impact of antifungal therapy, rigorous assessment of false-positive test results, and assessment of the utility of the test under nonsurveillance conditions are needed.

Aspergillosis↗
PubMed2006

Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in vitro and in vivo correlation.

Combination antifungal therapy is increasingly used in the treatment of invasive aspergillosis. Whether the interaction between amphotericin B and triazoles is antagonistic against invasive aspergillosis is a controversial issue that is not likely to be resolved through a randomized clinical trial. Here, we found both in vitro and in vivo antagonism between liposomal amphotericin B and ravuconazole in simultaneous treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. Bliss independence-based drug-interaction modeling showed significant antagonism in vitro and in vivo, with the observed drug effects being 20%-69% lower than would be expected if the drugs were acting independently. These in vitro and in vivo findings of antagonism were consistent with the findings from Loewe additivity-based drug-interaction modeling. No pharmacokinetic interaction was found. The combination of a triazole and polyene may be antagonistic in the treatment of invasive pulmonary aspergillosis.

Amphotericin B↗
PubMed2006

Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial.

BACKGROUND: Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. METHODS: We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. RESULTS: Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. CONCLUSIONS: Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.

Antifungal Agents↗
PubMed1996

Control of construction-associated nosocomial aspergillosis in an antiquated hematology unit.

OBJECTIVE: To determine the incidence of aspergillosis in patients with leukemia or bone marrow transplants during a construction-associated outbreak, and the effect of an environmental control program for Aspergillus. DESIGN: Clinical, microbiological, and pathological records were reviewed retrospectively once the outbreak was appreciated, and prospectively thereafter, to determine the presence or absence of aspergillosis and duration of neutropenia. SETTING: A university tertiary-care center with a single designated hematology-oncology unit. PATIENTS: From January 1988 to September 1993, there were 141 patients with leukemia or bone marrow transplants identified as being neutropenic during 231 admissions to this specialized unit. INTERVENTIONS: Installation of wall-mounted portable high-efficiency particulate air (HEPA)-filter air purifiers, application of copper-8-quinolinolate-formulated paint, replacement of perforated ceiling tiles with nonperforated type, sealing of all windows, replacement of horizontal, dust-accumulating blinds with vinyl, opaque, roller shades, and systematic and regular cleaning of surfaces. RESULTS: Thirty-six cases of nosocomial aspergillosis were diagnosed during this period. The incidence density (ID) in the preconstruction period was 3.18 per 1,000 days at risk. During construction activity-before the implementation of a control strategy-the ID increased dramatically to 9.88 per 1,000 days at risk. With infection control measures implemented and continued construction work, the ID decreased to 2.91 per 1,000 days at risk, comparable to the preconstruction baseline rate. CONCLUSIONS: An environmental control strategy incorporating widely available technology may have played an important role in controlling this outbreak of construction-associated invasive aspergillosis.

Air Pollution, Indoor↗
PubMed1993

Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years' experience.

Over 13 years, we have seen 16 cases of proven invasive aspergillosis in 446 bone marrow transplant recipients, an incidence of 3.6%. The incidence of infection is low in patients with uncomplicated allogeneic or autologous bone-marrow transplants (< 2% and 0, respectively). Of the 16 episodes following transplantation, 10 occurred in patients with late transplant complications who were no longer in protective isolation. In patients who had focal pulmonary lesions (as diagnosed by computed tomographic scanning), culture of bronchoalveolar lavage (BAL) fluid was not an effective diagnostic procedure. In diffuse pulmonary disease due to Aspergillus, culture of BAL fluid had a sensitivity of 100%. Aspergillus species were isolated from an additional six patients who had no evidence of invasive aspergillosis. Graft rejection was a significant predisposing factor for the development of invasive aspergillosis (P < .001, log-rank test), and in our hospital, these patients now receive intravenous amphotericin B as prophylaxis. None of the six patients whose chest roentgenograms showed abnormalities before transplantation and who underwent surgical resection as part of the treatment for invasive aspergillosis developed recurrent infection.

Adolescent↗