Most cited article - PubMed ID 32570979
Rhizoferrin Glycosylation in Rhizopus microsporus
Advances in the early diagnosis of systemic mycoses are urgently needed, given the morbidity and mortality of such infections and the correlation between delays in treatment and poor outcomes. We demonstrated the prospective application of liquid chromatography-mass spectrometry in the diagnosis of a mixed fungal infection. In this study, we compared the performance of chest radiography, galactomannan (sGM), and beta-d-glucan (sBDG) serology with a novel diagnostic method based on creatinine-indexed microbial siderophores in urine. A woman with angioblastic T-cell lymphoma presented with neutropenia following allogeneic transplantation. sGM and sBDG remained positive throughout the 28-day intensive care unit stay. A. fumigatus DNA was detected in the induced sputum samples on sampling days 0 and 18. On day 18, a CT scan showed a typical nest sign, and R. microsporus DNA was detected in sputum. The patient was discharged from the hospital on day 28 and expired 7 days later. With our novel strategy based on mass spectrometry, A. fumigatus was consistently detected in the urine from day 0 to the end of the stay by the detection of triacetylfusarinine C (uTafC), an A. fumigatus-specific hydroxamate siderophore. An additional invasive R. microsporus infection was revealed by the detection of a mucoromycete-specific carboxylate siderophore in urine, rhizoferrin (uRhf), from day seven onward. Both creatinine-normalized siderophore indices (uTafC/Cr, uRhf/Cr) were sensitive to antifungal therapy and correlated with fast relapses of the invasive disease in time. This study illustrates how such an early and specific new approach can unravel the complexities of dual fungal infections.
- Publication type
- Journal Article MeSH
Invasive pulmonary aspergillosis (IPA) may be a rare cause of granulomatous pneumonia in horses. The mortality of IPA is almost 100%; direct diagnostic tools in horses are needed. Bronchoalveolar lavage fluid (BALF) and serum samples were collected from 18 horses, including individuals suffering from IPA (n = 1), equine asthma (EA, n = 12), and 5 healthy controls. Serum samples were collected from another 6 healthy controls. Samples of BALF (n = 18) were analyzed for Aspergillus spp. DNA, fungal galactomannan (GM), ferricrocin (Fc), triacetylfusarinin C (TafC), and gliotoxin (Gtx). Analysis of 24 serum samples for (1,3)-β-D-glucan (BDG) and GM was performed. Median serum BDG levels were 131 pg/mL in controls and 1142 pg/mL in IPA. Similar trends were observed in BALF samples for GM (Area under the Curve (AUC) = 0.941) and DNA (AUC = 0.941). The fungal secondary metabolite Gtx was detected in IPA BALF and lung tissue samples (86 ng/mL and 2.17 ng/mg, AUC = 1).
The multiple forms of pulmonary aspergillosis caused by Aspergillus species are the most common respiratory mycoses. Although invasive, the analysis of diagnostic biomarkers in bronchoalveolar lavage fluid (BALF) is a clinical standard for diagnosing these conditions. The BALF samples from 22 patients with proven or probable aspergillosis were assayed for human pentraxin 3 (Ptx3), fungal ferricrocin (Fc), and triacetylfusarinine C (TafC) in a retrospective study. The infected group included patients with invasive pulmonary aspergillosis (IPA) and chronic aspergillosis (CPA). The BALF data were compared to a control cohort of 67 patients with invasive pulmonary mucormycosis (IPM), non-Aspergillus colonization, or bacterial infections. The median Ptx3 concentrations in patients with and without aspergillosis were 4545.5 and 242.0 pg/mL, respectively (95% CI, p < 0.05). The optimum Ptx3 cutoff for IPA was 2545 pg/mL, giving a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100, 98, 95, and 100%, respectively. The median Ptx3 concentration for IPM was high at 4326 pg/mL. Pentraxin 3 assay alone can distinguish IPA from CPA and invasive fungal disease from colonization. Combining Ptx3 and TafC assays enabled the diagnostic discrimination of IPM and IPA, giving a specificity and PPV of 100%.
- Keywords
- bronchoalveolar lavage fluid, invasive fungal disease, non-neutropenic, pentraxin-3, pulmonary aspergillosis, triacetylfusarinine C,
- Publication type
- Journal Article MeSH
In acutely ill patients, particularly in intensive care units or in mixed infections, time to a microbe-specific diagnosis is critical to a successful outcome of therapy. We report the application of evolving technologies involving mass spectrometry to diagnose and monitor a patient's course. As proof of this concept, we studied five patients and used two rat models of mono-infection and coinfection. We report the noninvasive combined monitoring of Aspergillus fumigatus and Pseudomonas aeruginosa infection. The invasive coinfection was detected by monitoring the fungal triacetylfusarinine C and ferricrocin siderophore levels and the bacterial metabolites pyoverdin E, pyochelin, and 2-heptyl-4-quinolone, studied in the urine, endotracheal aspirate, or breath condensate. The coinfection was monitored by mass spectrometry followed by isotopic data filtering. In the rat infection model, detection indicated 100-fold more siderophores in urine compared to sera, indicating the diagnostic potential of urine sampling. The tools utilized in our studies can now be examined in large clinical series, where we could expect the accuracy and speed of diagnosis to be competitive with conventional methods and provide advantages in unraveling the complexities of mixed infections.
- Keywords
- Aspergillus fumigatus, Pseudomonas aeruginosa, coinfection, invasive infection, noninvasive diagnosis, quorum-sensing molecules, siderophores, virulence factor,
- Publication type
- Journal Article MeSH
- Case Reports MeSH
