Systemic Infections with &lt;i&gt;Aspergillus&lt;/i&gt; Species in Patients with Hematological Malignancies: Current Serological and Molecular Diagnostic Approaches

Buchheidt, Dieter; Spieß, Birgit; Hehlmann, Rüediger

doi:10.1159/000055140

Cited by 4 publications

(4 citation statements)

References 56 publications

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“…High-resolution computed tomography of the lung is accepted as a hint but not as proof of IPA (2,10,11). A novel serological enzyme-linked immunosorbent assay based on the detection of galactomannan showed high rates of sensitivity and specificity (9,35), but additional appropriate imaging techniques are recommended to improve the diagnosis (26,36).…”

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confidence: 99%

Development of a LightCycler PCR Assay for Detection and Quantification ofAspergillus fumigatusDNA in Clinical Samples from Neutropenic Patients

et al. 2003

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The increasing incidence of invasive aspergillosis, a life-threatening infection in immunocompromised patients, emphasizes the need to improve the diagnostic tools for this disease. We established a LightCyclerbased real-time PCR assay to detect and quantify rapidly, specifically, and sensitively Aspergillus fumigatus DNA in both bronchoalveolar lavage (BAL) and blood samples from high-risk patients. The primers and hybridization probes were derived from an A. fumigatus-specific sequence of the mitochondrial cytochrome b gene. The assay is linear in the range between 13.2 fg and 1.3 ng of A. fumigatus DNA, corresponding to 3 to 300,000 CFU per ml of BAL fluid or blood. No cross-amplification was observed with human DNA or with the DNA of fungal or bacterial pathogens. For clinical evaluation we investigated 10 BAL samples from nine neutropenic patients with malignant hematological diseases and 12 blood samples from seven neutropenic patients with malignant hematological diseases. Additionally, we tested one blood sample and one BAL sample from each of two neutropenic patients. In order to characterize the validity of the novel PCR assay, only samples that had shown positive results by a previously described sensitive and specific nested PCR assay were tested. Twelve of 12 BAL samples and 6 of 14 blood samples gave positive results by the LightCycler PCR assay. Eight of 14 blood samples gave negative results by the novel method. The LightCycler PCR-mediated quantification of the fungal burden showed 15 to 269,018 CFU per ml of BAL sample and 298 to 104,114 CFU per ml of blood sample. Twenty of 20 BAL samples and 50 of 50 blood samples from subjects without evidence of invasive pulmonary aspergillosis (IPA) were PCR negative. Compared to a previously described nested PCR assay, these preliminary data for the novel real-time PCR assay indicate a less sensitive rate of detection of IPA in high-risk patients, but the assay may be valuable for quantification of the fungal burden in individual clinical samples.

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confidence: 99%

Development of a LightCycler PCR Assay for Detection and Quantification ofAspergillus fumigatusDNA in Clinical Samples from Neutropenic Patients

et al. 2003

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“…oncological patients, are at risk [3][4][5][6][7]. Due to their broad antibiotic resistances, these nosocomial infections caused by VRE are difficult to treat.…”

Section: Outbreak Of Vancomycin-resistant Enterococci (Vre) In a Hemamentioning

confidence: 99%

“…Due to their broad antibiotic resistances, these nosocomial infections caused by VRE are difficult to treat. They are associated with a substantial rate of complications, raised morbidity and lethality [3][4][5][6][7]. Martone reports that for example the Centers for Disease Control and Prevention describe a rise in incidence of VRE from 0.8% (1989) to 23.2% (1997) of the cases of nosocomial infections in patients on intensive-care units (ICU) in US hospitals [8].…”

Section: Outbreak Of Vancomycin-resistant Enterococci (Vre) In a Hemamentioning

confidence: 99%

Outbreak of Vancomycin-Resistant Enterococci (VRE) in a Hematological Oncology Ward and Hygienic Preventive Measures. A Long-Term Study

Knöll

Daeschlein²,

Okpara-Hofmann³

et al. 2005

Oncol Res Treat

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Background: We report on two endemic outbreaks of VRE (vancomycin-resistant enterococci, vanA type Ente-rococcus faecium) on a hematological oncology ward in a university hospital and a new strategic concept to fight against spread of VRE. Patients and Methods: During management of the outbreak, a total of 1,124 patients and 1,700 specimens were investigated from June 1999 to December 2001. Protective measures were instituted. Intensive prophylactic infection control was practiced until December 2003. Results: Of the 1,124 patients, 44 were VRE-positive. From 1,700 environment speci-mens, 110 VRE isolates were obtained from the inani-mate environment, 5 from the living environment. Mole-cular biological typing identified 5 different clones which had spread on the ward in different locations. Conclu-sion: The study shows the need for prophylactic microbi-ological screening investigations in the risk group of hematological oncology patients and consistent imple-mentation of protective hygiene measures to prevent the spread of multiresistant infectious pathogens on risk wards. It is also shown that intervention can to control such an endemic outbreak.

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“…IPA is considered highly lethal in the immunocompromised host despite ongoing therapy. Therefore, work-up must be prompt and aggressive and therapy may need to be initiated upon suspicion of the diagnosis even without definitive proof [2, 3, 7, 15]. Furthermore, considering the critical clinical condition of affected patients, a rapid, tolerable and effective therapy is mandatory, not only to prevent an aggravation by life-threatening complications like haemoptysis or further spread of the infection, but also to allow the continuation of cytotoxic chemotherapy to fight the primary disease.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Invasive Pulmonary Aspergillosis in Neutropenic Patients by Additional Bronchoscopic Amphotericin B Instillation

Winkler¹,

Müller²,

Nenoff³

et al. 2007

Respiration

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Background: Invasive pulmonary aspergillosis (IPA) remains a life-threatening condition despite systemic antifungal therapy. Objectives: This retrospective analysis investigated whether additional bronchoscopic instillation of amphotericin B (amB) would improve efficacy of antifungal treatment in patients with haematological malignancies suffering from IPA. Methods: Twenty patients (40.6 ± 14.2 years, 14 male) with preceding chemotherapy, bone marrow or stem cell transplantation complicated by severe IPA who did not respond sufficiently to systemic antifungal therapy were additionally treated by repeated bronchoscopic instillations of amB solution (91 instillations, on average 4.6 ± 2.2 instillations per patient over a period of 24.1 ± 21.0 days). Therapeutic response to this combined treatment regimen was monitored by chest X-ray and CT scan. Results: The mean infiltration sizes during systemic antifungal therapy alone (mean duration 11.9 ± 9.9 days) did not change significantly. However, after additional bronchoscopic instillation of amB solution infiltration sizes were reduced significantly (p < 0.05). A total resolution of infiltrates was seen in 3 and a partial reduction in 13 of 20 patients. Mean duration of total antifungal treatment was 50.1 ± 24.0 days. The mean follow-up period was 34.1 ± 31.2 months. The IPA-related mortality rate was 18.8% (3 of 16 patients). Conclusions: Additional bronchoscopic instillation of amB may improve the efficacy of systemic antifungal therapy in patients with haematological malignancies complicated by severe IPA. Bronchoscopic instillation of amB should be considered as an additional treatment option in cases with IPA unresponsive to systemic therapy.

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Systemic Infections with <i>Aspergillus</i> Species in Patients with Hematological Malignancies: Current Serological and Molecular Diagnostic Approaches

Cited by 4 publications

References 56 publications

Development of a LightCycler PCR Assay for Detection and Quantification ofAspergillus fumigatusDNA in Clinical Samples from Neutropenic Patients

Development of a LightCycler PCR Assay for Detection and Quantification ofAspergillus fumigatusDNA in Clinical Samples from Neutropenic Patients

Outbreak of Vancomycin-Resistant Enterococci (VRE) in a Hematological Oncology Ward and Hygienic Preventive Measures. A Long-Term Study

Treatment of Invasive Pulmonary Aspergillosis in Neutropenic Patients by Additional Bronchoscopic Amphotericin B Instillation

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