Diagnosing filamentous fungal infections in immunocompromised patients applying computed tomography-guided percutaneous lung biopsies: a 12-year experience

Abstract

BackgroundInvasive fungal diseases (IFD) are an important cause of morbidity and mortality in immunocompromised patients, and early diagnosis and management are a challenge. We evaluated the clinical utility of computed tomography (CT)-guided percutaneous lung biopsies in diagnosing IFD.MethodsBetween 2003 and 2014, we analyzed 2671 CT-guided lung biopsies, from which 157 were IFD associated; we aimed to determine microbiological-based diagnostic accuracy of calcofluor white staining (CFWS), culture, Aspergillus antigen detection (GM), broad-range fungal PCR, and Aspergillus PCR per sample.Results127 (81%) specimens were microscopically positive for any fungal elements, 30 (19%) negative. Aspergillus and non-Aspergillus like hyphae were obtained in 85 (67%) and 42 (33%) specimens, respectively. CFWS positivity was defined as proof of infection. Sensitivity, specificity, and positive (PPV) and negative predictive (NPV) values for CT scan were 100, 44, 80, and 100%, for Aspergillus PCR 89, 58, 88, and 58%, for broad-range fungal PCR 90, 83, 95, and 90%, and for GM 94, 83, 95, and 90%. The most common CT features were patchy opacifications with central necrosis (78%) or cavern defects (50%), less common were air bronchograms (39%) or ground glass halos (39%), and all other features were rare. The overall pneumothorax rate subsequent to biopsy was 19%, but in only 2% of all cases the placement of a chest tube was indicated. One case of fatal air embolism occurred.ConclusionsCT-guided lung biopsies have high diagnostic accuracy in terms of microscopic examination, and complication rates are low. Molecular-based and antigen tests applied on fungal hyphae-positive specimens showed comparable results.

A nationwide passive surveillance on fungal infections shows a low burden of azole resistance in molds and yeasts in Tyrol, Austria

“…Applying the new EUCAST breakpoints categorized a few isolates of A. terreus species complex to be posaconazole resistant with the clinical importance being unclear; a CBP of > 0.25 µg/ml for posaconazole was applied, and most of the patients involved were treated with voriconazole and improved [ 2 ]. At our institution, infections due to A. terreus were prevalent over the last 3 decades; however, the timely use of targeted treatment with voriconazole and the widespread use of posaconazole/micafungin prophylaxis decreased invasive aspergillosis from 12 to 6% in patients with haematological malignancies [ 9 ]; fungal breakthrough infections due to A. terreus are lacking [ 2 ], and hence, the role of resistance against posaconazole in A. terreus needs further clinical and molecular-based evaluation.…”

“…Invasive fungal infections (IFI) are associated with a high rate of morbidity and mortality in at-risk patients [ 1 ]. Candida and Aspergillus species remain the predominant pathogens with a shift towards resistant fungal pathogens being noted [ 2 ]. Reports on resistance prevalence on fungi and bacteria vary, depending on regions, populations, and health-care facilities evaluated [ 3 ].…”

Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

“…A so‐called reversed halo sign has been described on computed tomography scans, but is not entirely specific for mucormycosis 182‐184 . Such ring‐shaped consolidation surrounding a central infiltrate should prompt a diagnostic work‐up including bronchoalveolar lavage and biopsy 8,185 …”

The pathogenicity ofAspergillus fumigatus, drug resistance, and nanoparticle delivery

“…Otherwise, biopsies were performed, though this procedure is difficult to handle for patients who may already be in critical health (Carrafiello et al 2006). However, there is improved accuracy when combining computed tomography with guided biopsies followed by culturing or additional tests (Lass-Flörl et al 2017). A noninvasive commercial immunoenzymatic assay using a rat monoclonal antibody (Platelia™ Aspergillus Ag, Bio-Rad) became available in the United States during 2003, previously available in France in the late 1990s, for detecting the presence of galactomannan in the Aspergillus cell wall in serum and bronchoalveolar lavage fluid from patients at risk for IA (Stynen et al 1992).…”