Most cited article - PubMed ID 31699664
Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium
We analyzed mucormycosis data from the Zygomyco.net registry (2009-2022), encompassing cases from 16 countries. India, Russia and the Czech Republic provided the largest contributions. India reported the highest case number, consistent with its substantially higher incidence compared to that of high-income countries. Among the 382 patients with mucormycosis, 236 (61.8%) were male (male-to-female ratio 1.6). The median age was 48 years [interquartile range (IQR) 32-60]. There were 59 pediatric patients (median age ranging from < 1 month to 19 years). Diabetes mellitus type 2 was the most common underlying condition (39%), with significant geographic variation (> 70% of cases in India and Iran but only 6.9% in Europe). Hematologic malignancies (HM, 31.4%), the second most common underlying condition, were absent in India and Iran. The primary clinical presentations were rhino-orbito-cerebral mucormycosis (ROCM, 36.6%), pulmonary (33.2%) and cutaneous mucormycosis (17.5%). Patients with diabetes mellitus typically developed ROCM (55.9%), while pulmonary infections were more common in those with HM or hematopoietic cell transplantation (HCT) (47.5%, p < 0.001). Rhizopus was the leading fungal genus (58%), followed by Lichtheimia (13.7%) and Mucor (7%), with regional variations. Pulmonary infections in HM patients were linked to L. corymbifera and R. microsporus, while Apophysomyces spp. and Saksenaea spp. were more frequent in Indian healthcare-associated cutaneous cases. Concomitant infections were observed in 8.7% of patients with HM, complicating diagnosis and treatment. In most of them (57.1%), Aspergillus spp. was involved. Improved diagnostic practices, including direct microscopy and cultures, showed higher positivity rates, although PCR remained underutilized. Antifungal therapy, primarily with an amphotericin B formulation, combined with surgery, was the most common therapeutic approach. Overall mortality was high (47.8%), particularly in disseminated or advanced ROCM cases. Multivariable analysis identified older age, advanced ROCM, and HM/HCT as independent mortality risk factors (p < 0.05); whereas localized sinusitis and combined medical and surgical therapy were independently associated with improved outcomes (p < 0.006). This study underscores regional disparities in the mucormycosis epidemiology and species distribution. Improved early detection is needed, particularly in immunocompromised populations with HM. Enhanced surveillance and tailored public health strategies are crucial to address this ongoing global health threat.
- Keywords
- Global registry, Mucorales, Pulmonary mucormycosis, Rhinocerebral mucormycosis, Zygomyconet, Zygomycosis,
- MeSH
- Global Health MeSH
- Child MeSH
- Adult MeSH
- Incidence MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Mucormycosis * epidemiology microbiology drug therapy MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Registries * MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe epidemiology MeSH
UNLABELLED: The aim of this study was to identify parameters influencing DNA extraction and PCR amplification efficiencies in an attempt to standardize Mucorales qPCR. The Fungal PCR Initiative Mucorales Laboratory Working Group distributed two panels of simulated samples to 26 laboratories: Panel A (six sera spiked with Mucorales DNA and one negative control serum) and Panel B (six Mucorales DNA extracts). Panel A underwent DNA extraction in each laboratory according to the local procedure and were sent to a central laboratory for testing using three different qPCR techniques: one in-house qPCR assay and two commercial assays (MucorGenius and Fungiplex). Panel B DNA extracts were PCR amplified in each laboratory using local procedures: nine in-house qPCR assays and two commercial kits (MucorGenius and MycoGENIE). All data were compiled and anonymously analyzed at the central laboratory. For Panel A, a total of six different automated platforms and five manual extraction methods were used. Positive rates were 64%, 70%, and 89%, for the MucorGenius, Fungiplex, and the in-house qPCR assay, respectively. Using a large volume of serum for DNA extraction provided the highest analytical sensitivity (82.5% for 1 mL compared with 62.7% for smaller volumes, P < 0.01). For Panel B, five in-house qPCR assays and two commercial kits had >78% positivity. Using larger PCR input volumes (≥7 µL) was associated with the highest sensitivity at 95.5% compared to 58.3% when lower input volumes were used (P < 0.01). Using larger sample volumes for nucleic acid extraction and DNA template volumes for PCR amplification significantly improves the performance of Mucorales qPCR when testing serum. IMPORTANCE: Mucormycosis is a life-threatening mold infection affecting immunosuppressed patients but also other patients with diabetes or trauma. Better survival is linked to shorter delays in diagnosis and treatment initiation. Detection of Mucorales-free DNA in serum or plasma using quantitative PCR allows a prompt diagnosis and earlier treatment. Several techniques and protocols of quantitative Mucorales PCR are used in Europe, and improving performance remains a common objective of laboratories participating in the fungal PCR Initiative Working Group. This study, which combined results from 26 laboratories in Europe, showed that the main parameters underpinning sensitivity are the preanalytical variables (volume of serum used for DNA extraction and DNA template volume), irrespective of the extraction platforms and qPCR assay/platform.
- Keywords
- Mucorales PCR, interlaboratory assay, mucormycosis, standardization,
- MeSH
- Molecular Diagnostic Techniques * standards methods MeSH
- DNA, Fungal * blood genetics isolation & purification MeSH
- Real-Time Polymerase Chain Reaction * standards methods MeSH
- Humans MeSH
- Mucorales * genetics isolation & purification MeSH
- Mucormycosis * diagnosis microbiology MeSH
- Sensitivity and Specificity MeSH
- Serum * microbiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA, Fungal * MeSH
Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428-e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, "rhinocerebral mucormycosis." A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.
- Keywords
- fungal disease, nomenclature, proposal,
- MeSH
- Fungi * classification pathogenicity MeSH
- Humans MeSH
- Mycoses * microbiology MeSH
- Opportunistic Infections microbiology MeSH
- Terminology as Topic * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Mucormycosis is an opportunistic infection affecting mainly immunocompromised hosts. Infection in immunocompetent patients is rare, but may occur typically in trauma or burn victims. We report on a previously healthy young man suffering devastating trauma from an agricultural accident with the subsequent development of a multifocal mucormycosis. Diagnosis was achieved by cultures obtained from non-healing wounds, some of them even covered by a macroscopic mold formation. Specific treatment was initiated soon after the preliminary results indicated mucormycosis. Aggressive surgical therapy, with concomitant use of systemic posaconazole and topical amphotericin B in a combination treatment, led to the elimination of the fungal infection. The remaining deep tissue defects were consequently reconstructed by a muscle flap and skin graft autotransplantation with a good overall outcome, which would not have been possible without the complete remission of mucormycosis. This case study presents the successful use of a combination treatment with systemic posaconazole and topical amphotericin B and underlines the importance of timely and aggressive surgical therapy.
- Keywords
- amphotericin B, case report, mucormycosis, posaconazole, severe trauma,
- Publication type
- Journal Article MeSH
- Case Reports MeSH
BACKGROUND: Since the novel coronavirus disease (COVID-19) outbreak, the cases of COVID-19 co-infections have been increasingly reported worldwide. Mucormycosis, an opportunistic fungal infection caused by members of the Mucorales order, had been frequently isolated in severely and critically ill COVID-19 patients. METHODS: Initially, the anamnestic, clinical, and paraclinical features of seven COVID-19-associated mucormycosis (CAM) cases from Egypt were thoroughly reported. Subsequently, an extensive review of the literature was carried out to describe the characteristics of CAM cases globally, aiming to explore the potential risk factors of mortality in CAM patients. RESULTS: Out of the seven reported patients in the case series, five (71.4%) were males, six (85.7%) had diabetes mellitus, and three (42.9%) had cardiovascular disease. All patients exhibited various forms of facial deformities under the computed tomography scanning, and two of them tested positive for Mucorales using the polymerase chain reaction (PCR) testing. Liposomal amphotericin B (LAmB) was prescribed to all cases, and none of them died until the end of the follow-up. On reviewing the literature, 191 cases were reported worldwide, of which 74.4% were males, 83.2% were from low-middle income countries, and 51.4% were aged 55 years old or below. Diabetes mellitus (79.1%), chronic hypertension (30%), and renal disease/failure (13.6%) were the most common medical comorbidities, while steroids (64.5%) were the most frequently prescribed medication for COVID-19, followed by Remdesivir (18.2%), antibiotics (12.7%), and Tocilizumab (5.5%). CONCLUSIONS: As the majority of the included studies were observational studies, the obtained evidence needs to be interpreted carefully. Diabetes, steroids, and Remdesivir were not associated with increased mortality risk, thus confirming that steroids used to manage severe and critical COVID-19 patients should not be discontinued. Lung involvement, bilateral manifestation, and Rhizopus isolation were associated with increased mortality risk, thus confirming that proactive screening is imperative, especially for critically ill patients. Finally, surgical management and antimycotic medications, e.g., amphotericin B and posaconazole, were associated with decreased mortality risk, thus confirming their effectiveness.
- Keywords
- COVID-19, Mucorales, Rhizopus, co-infection, cross-infection, mucormycosis, mycoses, review, risk factors, steroids,
- Publication type
- Journal Article MeSH