The main objective of this study was to assess the diagnostic performance of a set of three Mucorales quantitative PCR assays in a retrospective multicentre study. Mucormycosis cases were recorded thanks to the French prospective surveillance programme (RESSIF network). The day of sampling of the first histological or mycological positive specimen was defined as day 0 (D0). Detection of circulating DNA was performed on frozen serum samples collected from D-30 to D30, using quantitative PCR assays targeting Rhizomucor, Lichtheimia, Mucor/Rhizopus. Forty-four patients diagnosed with probable (n = 19) or proven (n = 25) mucormycosis were included. Thirty-six of the 44 patients (81%) had at least one PCR-positive serum. The first PCR-positive sample was observed 9 days (range 0-28 days) before diagnosis was made using mycological criteria and at least 2 days (range 0-24 days) before imaging. The identifications provided with the quantitative PCR assays were all concordant with culture and/or PCR-based identification of the causal species. Survival rate at D84 was significantly higher for patients with an initially positive PCR that became negative after treatment initiation than for patients whose PCR remained positive (48% and 4%, respectively; p <10). The median time for complete negativity of PCR was 7 days (range 3-19 days) after initiation of l-AmB treatment. Despite some limitations due to the retrospective design of the study, we showed that Mucorales quantitative PCR could not only confirm the mucormycosis diagnosis when other mycological arguments were present but could also anticipate this diagnosis. Quantification of DNA loads may also be a useful adjunct to treatment monitoring.
I ncidence of coronavirus disease (COVID-19)associated pulmonary aspergillosis (CAPA) in hospital intensive care units (ICUs) is 3.8%-33.3% (1-9). Variations might be explained by differences in patient populations and CAPA defi nitions used, complicating direct comparisons between studies.Diagnosing CAPA is complex because cases frequently lack typical radiologic features and European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) host factors ( 10) and because mycologic evidence is diffi cult to obtain. Serum galactomannan (GM) detection has low sensitivity in CAPA (7,10).The European Confederation of Medical Mycology and International Society for Human and Animal Mycology (ECMM/ISHAM) published consensus criteria for a CAPA defi nition (11). We used these criteria to perform an observational cohort study to assess CAPA incidence in patients with COVID-19 admitted to ICUs during the fi rst wave of the COVID-19 pandemic.
The StudyWe collected partially prospective and partially retrospective data for 823 patients in 2 cohorts. The discovery cohort comprised patients with PCR-confi rmed or clinically presumed COVID-19 admitted to 4 ICUs in the Netherlands and 4 ICUs in Belgium during February 28-May 27, 2020. The validation cohort comprised patients with PCR-confi rmed COVID-19 admitted because of respiratory insuffi ciency to 3 participating ICUs in France during April 7-May 31, 2020 (Appendix Methods, Table 1, https://wwwnc.cdc.gov/EID/ article/27/11/21-1174-App1.pdf).
Trichoderma species are filamentous fungi that were previously considered to be culture contaminants. We report 2 well-documented cases of invasive Trichoderma infections, and we comprehensively review the literature on this topic. Trichoderma species are mainly responsible for continuous ambulatory peritoneal dialysis-associated peritonitis (7 cases) and invasive infections in immunocompromised patients (9 cases) with a hematologic malignancy or solid-organ transplant. Definitive diagnosis is difficult to achieve because of the lack of specific diagnosis tools. Species identification can benefit from a molecular approach. Trichoderma longibrachiatum is the most common species involved in these infections. Regardless of the type of infection, the prognosis was poor, with 8 deaths among 18 cases. This may be partially because of the resistance of these organisms to the majority of available antifungal agents, including amphotericin B. Trichoderma species now should be added to the growing list of emerging filamentous fungal pathogens.
Data on clinical, mycologic characteristics, and outcome of posttraumatic mucormycosis are scarce and often limited to case reports. From the French nationwide “RetroZygo” study, we compared posttraumatic mucormycosis cases with other forms of mucormycosis. We also reviewed reports of posttraumatic mucormycosis in the English-language literature from 1993 to 2013. We included all proven or probable cases for which underlying condition, route of infection, surgical and antifungal treatments, and outcome were detailed. From our cohort, posttraumatic mucormycosis (n = 16) differed significantly from other forms (n = 85) by rarity of underlying disease (31.2% vs 81%, p < 0.0001), frequency of cutaneous localization (87% vs 7%, p < 0.0001), short time before diagnosis (4.5 vs 21 d, p = 0.0002), species involved (Apophysomyces elegans complex and Saksenaea vasiformis), surgical requirement (93.7% vs 47%, p = 0.0006) and better survival (87.5% vs 47.6% at day 90, p = 0.03). We studied 122 cases of posttraumatic mucormycosis through our literature review. Most frequently reported traumas were traffic (37%), domestic accidents (15.1%), or natural disasters (13.4%). Mucormycosis occurred after extensive soft-tissue damage in 47.5% cases, with symptoms occurring a median of 9.5 days after trauma with necrosis being reported in 76.2% cases. Dissemination was found in 9% of patients, and bacterial coinfection in 41%. Nineteen percent of cases occurred in the Middle East or in India where Apophysomyces elegans complex was the predominant species recovered. Awareness of mucormycosis as a cause of posttrauma soft-tissue infection is warranted, especially in cases of soil-contaminated wounds. Survival is higher than in other forms of mucormycosis, but morbidity remains high.
Our study results suggest that BDG levels were increased in neonatal invasive Candida infections (cut-off for BDG positivity > 125 pg/ml). The change in the serum BDG levels may be of value in evaluating the efficacy of antifungal therapy.
A case of fatal aspergillosis due to a TR/Y121F/T289A azole-resistant Aspergillus fumigatus is reported. Environmental investigations at the patient's residence led to the recovery of TR/Y121F/T289A isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis.
Most newborns in the neonatal intensive care unit (NICU) are premature and at risk of invasive fungal infections (IFIs). Invasive yeast infections (IYIs) are the most common fungal infections in this population. These infections are difficult to diagnose because symptoms are nonspecific, and the sensitivity of blood cultures is low. The serum (1,3)-β-D-glucan (BDG) assay provides a reliable marker for the diagnosis of IFIs in adults with haematological malignancies. We assessed the diagnostic performance of this test in neonatal IYIs and its contribution to the monitoring of antifungal treatment. A retrospective study was performed in the NICU of the French University Hospital of Amiens from February 2012 to February 2014. Forty-seven neonates (33 males, 14 females) with a median gestational age of 30 weeks (IQR: 27-31) and median birth weight of 1200 g (IQR: 968-1700) were included and divided into three groups: 21 control neonates (CTRL), 20 neonates with probable IYI (PB), and six with proven IYI (PV). Median BDG levels were significantly higher in the global IYI group (PB + PV): 149 pg/ml (IQR: 85-364) vs. CTRL group: 39 pg/ml (IQR: 20-94) (P < .001). The optimal cut-off was 106 pg/ml (sensitivity 61.5%; specificity 81%). BDG levels decreased with antifungal treatment. BDG was detectable in cerebrospinal fluid, but the interest of this for diagnostic purposes remains unclear. Our results suggest that the BDG assay may be useful for the early identification of IYIs in neonates and for monitoring antifungal therapy efficacy.
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