Evaluation of Serum Mucorales Polymerase Chain Reaction (PCR) for the Diagnosis of Mucormycoses: The MODIMUCOR Prospective Trial

Millon, Laurence; Caillot, Denis; Berceanu, Ana; Bretagne, Stéphane; Lanternier, Fanny; Morio, Florent; Letscher-Bru, Valérie; Dalle, Frédéric; Denis, Blandine; Alanio, Alexandre; Boutoille, David; Bougnoux, Marie‐Elisabeth; Botterel, Françoise; Chouaki, Taïeb; Charbonnier, A; Ader, Florence; Dupont, Damien; Bellanger, Anne‐Pauline; Rocchi, Steffi; Scherer, Émeline; Gbaguidi‐Haore, Houssein; Herbrecht, Raoul

doi:10.1093/cid/ciab1066

Cited by 102 publications

(52 citation statements)

References 36 publications

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“…In addition, our study was grossly underpowered to evaluate whether there are differences among Mucorales in terms of culture positivity from infected lung tissues. Interestingly, a recent study indicated that some Mucorales, such as Rhizimucor species, do not grow well in clinical samples and are better diagnosed by PCR [11]. Lastly, nearly all patients in this study had cytopenia with significant cumulative immune suppression due to their underlying conditions.…”

Section: Discussionmentioning

confidence: 67%

Taking a Closer Look: Clinical and Histopathological Characteristics of Culture-Positive versus Culture-Negative Pulmonary Mucormycosis

Spallone¹,

Moran²,

Wurster³

et al. 2022

Preprint

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Cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared clinical and histological characteristics of culture-positive and culture-negative histology-proven pulmonary mucormycosis cases among cancer patients. Histology specimens were blindly reviewed by a Thoracic Pathologist and graded on four histopathologic features: hyphal quantity, tissue necrosis, tissue invasion, and vascular invasion. Twenty cases with a corresponding fungal culture were identified; five were culture-positive, and 15 culture-negative. Although no statistically significant differences were found, culture-positive patients were more likely to exhibit a high burden of necrosis and have a high burden of hyphae but tended to have less vascular invasion than culture-negative patients. In terms of clinical characteristics, culture-positive patients were more likely to have acute myeloid leukemia (60% vs. 27%, p=0.19), a history of hematopoietic cell transplant (80% vs. 53%, p=0.31), severe lymphopenia (absolute lymphocyte count ≤500/µL, 100% vs. 73%, p=0.36), and monocytopenia (absolute monocyte count ≤100/µL, 60% vs. 20%, p=0.11). Forty-two-day all-cause mortality was comparable between culture-positive and culture-negative patients (60% and 53%, p=0.80). This pilot study represents the first comprehensive histopathological scoring method to examine the relationship between histopathologic features, culture positivity, and clinical features of pulmonary mucormycosis.

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Section: Discussionmentioning

confidence: 67%

Taking a Closer Look: Clinical and Histopathological Characteristics of Culture-Positive versus Culture-Negative Pulmonary Mucormycosis

Spallone¹,

Moran²,

Wurster³

et al. 2022

Preprint

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“…Once the diagnosis is made, quantitative PCR (qPCR) may be used within seven days after treatment initiation to monitor the response to liposomal-amphotericin B. A negative qPCR after seven days of treatment is associated with an 85% lower 30-day mortality rate [37]. Pulmonary findings might be similar to pulmonary aspergillosis, with infiltration, consolidation, nodules, cavitations, atelectasis, effusion, posterior band thickening, hilar or mediastinal adenopathy, or normal appearance [5].…”

Section: Discussionmentioning

confidence: 99%

Disseminated Cunninghamella spp. Endocarditis in a Beta-Thalassemia Patient after Asymptomatic COVID-19 Infection

et al. 2022

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Cunninghamella spp. is a group of fungi belonging to the Mucorales order. Cases of fungal endocarditis are sporadic, but more frequent in immunocompromised patients. COVID-19 (SARS-CoV-2 Infection Disease 2019) infections, prematurity, deferoxamine treatment, iron overload, neutropenia, diabetes, and malignant hemopathies proved to be risk factors for mucormycosis. We present the case of a 7-year-old boy who was treated every three weeks with blood transfusion for major beta-thalassemia, receiving deferoxamine for secondary hemochromatosis. After two weeks with nonspecific respiratory and digestive symptoms, he was admitted for fever, followed by lower limb ischemia and neurological signs. Echocardiography revealed massive endocarditis affecting the mitral and tricuspid valves with embolization phenomena in the brain, lungs, kidney, spleen, and lower limbs. As a particular finding, IgG antibodies for COVID-19 were positive. Emergency cardiac surgery was performed. The mitral valve necessitated replacement with CarboMedics prosthesis. Unfortunately, the patient did not survive. Cunninghamella spp. was confirmed via the PCR analysis of vegetations. Cunninghamella endocarditis in the context of a systemic infection presented as an opportunistic infection affecting a child who had several risk factors. Mucormycosis is challenging to treat, with high mortality. Prophylactic treatment in beta-thalassemia patients with iron-chelator deprivation drugs, such as deferiprone, may help in preventing these particular fungal infections.

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“…Very recently, a French prospective multicenter study (the MODIMUCOR study) which evaluates a Mucorales quantitative PCR in serum for the diagnosis of invasive mucormycosis has been published [ 21 ]. There were 245 patients divided into two cohorts.…”

Section: Advances In Molecular Diagnosismentioning

confidence: 99%

Recent Developments in the Diagnosis of Mucormycosis

Dannaoui

2022

JoF

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Mucormycosis is a potentially fatal infection that presents in different clinical forms and occurs in patients with various risk factors. Recently, the COVID-19 epidemic has been responsible for an increase in the incidence of mucormycosis, particularly in India. As with other invasive filamentous fungal infections, there are no specific clinical or radiological signs, and we have fewer diagnostic tools available than for other invasive fungal infections. Therefore, the diagnosis of Mucormycosis remains difficult. Nevertheless, for optimal management, early and accurate diagnosis is important. According to the latest recommendations, diagnosis is based on direct examination of clinical specimens, and/or histopathology, and culture. There are also molecular tools for direct detection from clinical specimens, but these techniques are moderately recommended. The main problems with these molecular techniques are that, until now, they were not very well standardized; there was a great heterogeneity of DNA targets and methods, which resulted in variable sensitivity. It is in this field that most advances have been made in the last two years. Indeed, recent studies have evaluated the performance and kinetics of Mucorales qPCR in serum and have shown good sensitivity and specificity. Large inter-laboratory evaluations of qPCR in serum have also been performed and have demonstrated good qualitative and quantitative reproducibility. These new results suggest the use of Mucorales qPCR as part of the diagnostic strategy for mucormycosis. One way to achieve better reproducibility could be to use commercial methods. Currently, there are at least three commercial qPCRs for Mucorales (MucorGenius from PathoNostics, MycoGenie from Ademtech, and Fungiplex from Bruker) that can be used to test serum, respiratory samples, or biopsies. However, to date, there has been little evaluation of these methods. Overall, Mucorales PCR in tissue samples, in respiratory samples, and in serum is promising and its addition as a diagnostic tool in the definitions of invasive mucormycosis should be discussed.

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Evaluation of Serum Mucorales Polymerase Chain Reaction (PCR) for the Diagnosis of Mucormycoses: The MODIMUCOR Prospective Trial

Cited by 102 publications

References 36 publications

Taking a Closer Look: Clinical and Histopathological Characteristics of Culture-Positive versus Culture-Negative Pulmonary Mucormycosis

Taking a Closer Look: Clinical and Histopathological Characteristics of Culture-Positive versus Culture-Negative Pulmonary Mucormycosis

Disseminated Cunninghamella spp. Endocarditis in a Beta-Thalassemia Patient after Asymptomatic COVID-19 Infection

Recent Developments in the Diagnosis of Mucormycosis

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