COVID-19 associated mucormycosis (CAM) in Kashan, Iran: clinical presentations, risk factors, management, and outcomes.

BACKGROUND: This study aimed to estimate the disease burden and describe the clinical presentation, risk factors, and outcome of CAM in a single centre in Iran. METHODS: A case of mucormycosis was defined as one that had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological and molecular examination. RESULTS: We report 30 cases of COVID-19 associated mucormycosis (CAM). The results of this study showed the affected age group in the range of 40-79 years (median = 65.5; IQR = 5) with women (16/30, 53%) affected more than men (14/30, 47%). Among the fungi recovered, Rhizopus oryzae had the highest frequency (79%). Out of the 30 patients, 28 (93%) patients were diabetic with 24 (80%) patients having other co-morbidities. Headache followed by retro-orbital pain, proptosis/ptosis and rapid diminution of vision was a common sequence of symptoms reported by the majority of cases. Use of mechanical ventilation (58% vs. 6%, p = 0.003), O2 required (92% vs. 50%, p = 0.024), and development of renal dysfunction during hospital stay (17% vs. 0%, p = 0.041) was significantly higher in non-survivors than survivors. Temperature (C°), PR (pulse rate), mean levels of serum creatinine, BUN, troponin, and neutrophils were significantly higher in non-survivors (p < 0.05). Besides, Albumin and PO2 were also significantly higher in survivors than non-survivors. CONCLUSION: Despite medical and surgical treatment, the mortality rate among CAM patients is still high. Thus, concerted efforts of revamping surveillance, diagnosis and management, along with public awareness and patient education, are the requisites for managing COVID-19 and mucormycosis.

Pharmacoeconomic evaluation of isavuconazole, posaconazole, and voriconazole for the treatment of invasive mold diseases in hematological patients: initial therapy prior to pathogen differential diagnosis in China.

Background: Invasive mold diseases (IMD) is associated with high mortality and a substantial economic burden. For high-risk patients, fever drive or diagnostic drive therapy is usually initiated prior to the differential diagnosis of the pathogen. This study evaluated the cost-effectiveness of isavuconazole, posaconazole, vs. voriconazole in the treatment of IMD from the perspective of the Chinese healthcare system, informing healthcare decision-making and resource allocation. Methods: A decision analytic model was constructed using TreeAge Pro 2011 software to evaluate the cost-effectiveness of the entire disease course. We assumed that the prevalence of mucormycosis in the patients entering the model was 7.8%. Efficacy, cost, adverse events, and other data included in the model were mainly derived from clinical studies, published literature, and publicly available databases. The primary outcomes of the model output were total cost, quality-adjusted life years (QALYs), life years (Lys), and incremental cost-effectiveness ratio (ICER). The willing-to-pay (WTP) threshold was defined as one to three times China's GDP per capita in 2022. One-way sensitivity analysis and probability sensitivity analysis were used to determine the robustness of the model. At the same time, the cost-effectiveness of three triazole antifungal agents under a broader range of mucormycosis prevalence, when voriconazole was covered by medical insurance reimbursement, and after the price reduction of posaconazole was discussed. Results: Compared with voriconazole, isavuconazole provided an additional 0.38 Lys (9.29 vs. 8.91 LYs) and 0.31 QALYs (7.62 vs. 7.31 QALYs); ICER was $15,702.46/QALY, well-below the WTP threshold ($38,223/QALY). However, posaconazole did not provide a significant economic advantage over voriconazole (9.40 vs. 9.36 Lys; 7.71 vs. 7.68 QALYs; ICER $64,466.57/QALY). One-way sensitivity analysis found that ICER was highly sensitive to the mortality of patients with invasive aspergillus infection. In the probabilistic sensitivity analysis, when the WTP threshold was $38,223/QALY, the probability of isavuconazole being cost-effective was 72.9%. The scenario analysis results indicated that posaconazole would become cost-effective when the price was reduced by 15% or the prevalence of mucormycosis was 14%. Conclusions: Isavuconazole represents a cost-effective initial option for treating IMD in high-risk hematological patients prior to the differential diagnosis of pathogens. It will also be economical when a 15% reduction in posaconazole cost is achieved.

Disease burden and demographic characteristics of mucormycosis: A nationwide population-based study in Taiwan, 2006-2017.

BACKGROUND: Epidemiological knowledge of mucormycosis obtained from national population-based databases is scarce. OBJECTIVES: This study aimed to depict the disease burden and demographics of mucormycosis in Taiwan by using the Taiwan National Health Insurance Research Database (NHIRD) and those of aspergillosis as a comparator. METHODS: Data from patients with either mucormycosis or aspergillosis from 2006 to 2017 identified with the International Classification of Diseases (ICD) codes were extracted from the NHIRD. The incidence, demographics and clinical data of both diseases were analysed. RESULTS: A total of 204 patients with mucormycosis and 2270 patients with aspergillosis who were hospitalised and treated with mould-active antifungals between 2006 and 2017 were identified. The average annual incidence of aspergillosis (0.81 cases per 100,000 population [0.81/100,000]) was 11-fold higher than that of mucormycosis (0.07/100,000). A significant increase in incidence was observed for aspergillosis (from 0.48/100,000 in 2006 to 1.19/100,000 in 2017, p < .0001) but not for mucormycosis (from 0.04/100,000 in 2006 to 0.11/100,000 in 2017, p = .07). The major underlying disease identified was diabetes mellitus (60.8%) for mucormycosis and malignant neoplasms (45.9%) for aspergillosis. The all-cause 90-day mortality rate was similar between mucormycosis and aspergillosis patients (39% vs. 37%, p = .60). For mucormycosis patients, multivariate analysis revealed that posaconazole use was associated with lower in-hospital mortality (aOR 0.38; 95% CI 0.15-0.97; p = .04). CONCLUSIONS: Mucormycosis is an uncommon fungal disease in Taiwan, occurring mostly in diabetic patients. However, the incidence might be underestimated due to limited diagnostics. Continuous surveillance might aid in delineating the evolving features of mucormycosis.

Epidemiology, clinical presentation and management of COVID-19 associated mucormycosis: A single centre experience from Pune, Western India.

BACKGROUND: The second COVID-19 wave in India has been associated with an unprecedented increase in cases of COVID-19 associated mucormycosis (CAM), mainly Rhino-orbito-cerebral mucormycosis (ROCM). METHODS: This retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, India, between 1 April, 2020, and 1 August, 2021, to identify CAM patients and assess their management outcomes. The primary endpoint was incidence of all-cause mortality due to CAM. RESULTS: 59 patients were diagnosed with CAM. Median duration from the first positive COVID-19 RT PCR test to diagnosis of CAM was 17 (IQR: 12,22) days. 90% patients were diabetic with 89% having uncontrolled sugar level (HbA1c >7%). All patients were prescribed steroids during treatment for COVID-19. 56% patients were prescribed steroids for non-hypoxemic, mild COVID-19 (irrational steroid therapy), while in 9%, steroids were prescribed in inappropriately high dose. Patients were treated with a combination of surgical debridement (94%), intravenous liposomal Amphotericin B (91%) and concomitant oral Posaconazole (95.4%). 74.6% patients were discharged after clinical and radiologic recovery while 25.4% died. On relative risk analysis, COVID-19 CT severity index ≥18 (p = .017), presence of orbital symptoms (p = .002), presence of diabetic ketoacidosis (p = .011) and cerebral involvement (p = .0004) were associated with increased risk of death. CONCLUSIONS: CAM is a rapidly progressive, angio-invasive, opportunistic fungal infection, which is fatal if left untreated. Combination of surgical debridement and antifungal therapy leads to clinical and radiologic improvement in majority of cases.

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1.

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

The disease burden of mucormycosis in Japan: results from a systematic literature review and retrospective database study.

OBJECTIVE: To evaluate outcomes, healthcare resource utilization, and costs associated with mucormycosis in inpatient settings in Japan. METHODS: We performed a systematic literature review, followed by a retrospective database study using hospital health claims for patients in Japan hospitalized with a diagnosis of mucormycosis between January 2010 and January 2019. Outcomes assessed included duration of index hospitalization; index stay mortality; hospital readmission within 30, 60, and 90 days after index hospitalization discharge; drug/treatment utilization and patterns; number of patients examined for mucormycosis during the index hospitalization; and index stay inpatient costs. RESULTS: From our systematic literature review of articles describing 133 patients with mucormycosis, mortality in the index hospitalization was 55.6%. From our database study of 126 patients hospitalized for mucormycosis, mortality during the index hospitalization was 35.7% and mean index stay duration was 94 days. Hematologic malignancies were the most common risk factor in the literature review and the most common comorbidity in the database study. During the index stay, 39 patients (31.0%) received liposomal amphotericin B (L-AMB) treatment and 74 patients (58.7%) received other antifungal treatments. Median total inpatient costs for the index hospitalization were equivalent to approximately US$60,945, including US$29,283 in drug costs. CONCLUSIONS: This study investigated the healthcare resource utilization and cost of medical resources caused by mucormycosis in Japan. The drug costs for antifungal treatments comprised about half of total inpatient costs. Mucormycosis leads to high mortality, high healthcare resource utilization, and high costs.

Burden of serious fungal infections in the Netherlands.

BACKGROUND: Fungal diseases have an ever-increasing global disease burden, although regional estimates for specific fungal diseases are often unavailable or dispersed. OBJECTIVES: Here, we report the current annual burden of life-threatening and debilitating fungal diseases in the Netherlands. METHODS: The most recent available epidemiological data, reported incidence and prevalence of fungal diseases were used for calculations. RESULTS: Overall, we estimate that the annual burden of serious invasive fungal infections in the Netherlands totals 3 185 patients, including extrapulmonary or disseminated cryptococcosis (n = 9), pneumocystis pneumonia (n = 740), invasive aspergillosis (n = 1 283), chronic pulmonary aspergillosis (n = 257), invasive Candida infections (n = 684), mucormycosis (n = 15) and Fusarium keratitis (n = 8). Adding the prevalence of recurrent vulvo-vaginal candidiasis (n = 220 043), allergic bronchopulmonary aspergillosis (n = 13 568) and severe asthma with fungal sensitisation (n = 17 695), the total debilitating burden of fungal disease in the Netherlands is 254 491 patients yearly, approximately 1.5% of the country's population. CONCLUSION: We estimated the annual burden of serious fungal infections in the Netherlands at 1.5% of the population based on previously reported modelling of fungal rates for specific populations at risk. With emerging new risk groups and increasing reports on antifungal resistance, surveillance programmes are warranted to obtain more accurate estimates of fungal disease epidemiology and associated morbidity and mortality.

A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India.

OBJECTIVES: To describe the epidemiology, management and outcome of individuals with mucormycosis; and to evaluate the risk factors associated with mortality. METHODS: We conducted a prospective observational study involving consecutive individuals with proven mucormycosis across 12 centres from India. The demographic profile, microbiology, predisposing factors, management and 90-day mortality were recorded; risk factors for mortality were analysed. RESULTS: We included 465 patients. Rhino-orbital mucormycosis was the most common (315/465, 67.7%) presentation followed by pulmonary (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The predisposing factors included diabetes mellitus (342/465, 73.5%), malignancy (42/465, 9.0%), transplant (36/465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most common followed by Apophysomyces variabilis (23/290, 7.9%), and several rare Mucorales. Surgical treatment was performed in 62.2% (289/465) of the participants. Amphotericin B was the primary therapy in 81.9% (381/465), and posaconazole was used as combination therapy in 53 (11.4%) individuals. Antifungal therapy was inappropriate in 7.6% (30/394) of the individuals. The 90-day mortality rate was 52% (242/465). On multivariate analysis, disseminated and rhino-orbital (with cerebral extension) mucormycosis, shorter duration of symptoms, shorter duration of antifungal therapy, and treatment with amphotericin B deoxycholate (versus liposomal) were independent risk factors of mortality. A combined medical and surgical management was associated with a better survival. CONCLUSIONS: Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis. Combined surgical and medical management was associated with better outcomes. Several gaps surfaced in the management of mucormycosis. The rarer Mucorales identified in the study warrant further evaluation.

Managing mucormycosis in a resource-limited setting: challenges and possible solutions.

Mucormycosis is a potentially fatal fungal infection with high prevalence in poor-resource settings. Besides being an extremely expensive disease to treat, the challenges range from lack of experienced mycologists or mycology department to knowledge and availability of treatment regimes.

Healthcare burden of probable and proven invasive mucormycosis: a multi-centre cost-of-illness analysis of patients treated in tertiary care hospitals between 2003 and 2016.

BACKGROUND: Invasive mucormycosis (IM) is a rare invasive fungal infection with a high mortality rate. However, data concerning the clinical and economic burden of IM are scarce. AIM: To evaluate the direct treatment costs and additional expenditures of patients with IM. METHODS: A retrospective cost-of-illness analysis of cases with IM extracted from FungiScope - Global Registry for Emerging Fungal Infections, accessible through the epidemiological research platform www.ClinicalSurveys.net, was undertaken. Results of patients with IM were compared with those of matched patients with similar underlying conditions based on the German Diagnosis Related Group (G-DRG) coding. FINDINGS: Out of 46 patients with probable/proven IM, 31 (67%) patients were male and the median age was 53 years (range 11-88 years). Forty-two patients (92%) had haematological diseases as the most common risk factor. Analysis of cost factors identified antifungal treatment due to IM as the primary cost driver [€22,816, 95% confidence interval (CI) €15,036-32,346], with mean overall direct treatment costs of €53,261 (95% CI €39,660-68,825). Compared with matched patients, patients with IM were treated in hospital for 26.5 additional days (standard deviation 31.8 days; P < 0.001), resulting in mean additional costs of €32,991 (95% CI €21,558-46,613; P < 0.001). Probable IM, as well as absence of chemotherapy, surgical measures due to IM, and antifungal prophylaxis were associated with lower overall costs. Nineteen patients (41.3%) died during hospitalization. CONCLUSION: This study demonstrates the considerable healthcare burden of IM. The choice of antifungal agent for treatment of IM had no impact on overall cost.

Prevalence, clinical and economic burden of mucormycosis-related hospitalizations in the United States: a retrospective study.

BACKGROUND: Mucormycosis is a rare but devastating fungal infection primarily affecting immunocompromised patients such as those with hematological malignancy, bone marrow and solid organ transplantation, and patients with diabetes, and, even more rarely, immunocompetent patients. The objective of this study was to assess the prevalence and burden, both clinical and economic, of mucormycosis among hospitalized patients in the U.S. METHODS: This is a retrospective study using the Premier PerspectiveTM Comparative Database, with more than 560 participating hospitals covering 104 million patients (January 2005-June 2014). All hospitalizations in the database were evaluated for the presence of mucormycosis using either an ICD-9 code of 117.7 or a positive laboratory result for Mucorales. Hospitalizations were further required to have prescriptions of amphotericin B or posaconazole to be considered as mucormycosis-related hospitalizations. The prevalence of mucormycosis-related hospitalizations among all hospital discharges was estimated. Mortality rate at discharge, length of hospital stay, and readmission rates at 1 and 3 months were evaluated among mucormycosis-related hospitalizations. Cost per hospital stay and average per diem cost (inflated to 2014 USD) were reported. RESULTS: The prevalence of mucormycosis-related hospitalizations was estimated as 0.12 per 10,000 discharges during January 2005-June 2014. It increased to 0.16 per 10,000 discharges if the definition of mucormycosis was relaxed to not require the use of amphotericin B or posaconazole. The median length of stay was 17 days, with 23% dead at discharge; readmission rates were high, with 30 and 37% of patients readmitted within one and three months of discharge, respectively. The average cost per hospital stay was $112,419, and the average per diem cost was $4,096. CONCLUSIONS: The study provides a recent estimate of the prevalence and burden of mucormycosis among hospitalized patients. The high clinical and economic burden associated with mucormycosis highlights the importance of establishing active surveillance and optimizing prophylactic and active treatment in susceptible patients.

The burden of mucormycosis in HIV-infected patients: A systematic review.

OBJECTIVES: Mucormycosis is an invasive fungal infection afflicting immunocompromised patients, causing a significant degree of morbidity and mortality. The purpose of the study was to provide a comprehensive analysis describing the epidemiology and outcome of mucormycosis in the scenario of HIV infection. METHODS: We systematically searched PubMed for reports about mucormycosis associated with HIV. Eligible studies describe the predisposing factor, clinical form, treatment, and survival outcome. RESULTS: We included 61 articles from 212 reviewed abstracts, corresponding to 67 cases. Patients were mostly men (68.2%) with a median CD4(+) count of 47 [IQR 17-100] cells/mm(3). Intravenous drug use (50%), neutropenia (29.7%) and corticosteroid use (25%) were the predominant associated factors. The main clinical forms were disseminated (20.9%), renal (19.4%), and rhino-cerebral (17.9%). Rhizopus (45.5%) and Lichtheimia spp (30.3%) were the main fungal isolates. Treatment consisted of antifungal therapy and surgery in 38.8%. Overall mortality rate was 52.2%, and varied with the site of infection: 92.9% for disseminated disease, 62.5% for cerebral disease, 60% for pulmonary infection, and 36.4% for cutaneous infection. Survival was worse for those who did not initiate antifungals (p = .04), who were antiretroviral naïve (p = .01), who were admitted to ICU (p = .003) or had disseminated disease (p = .007). CONCLUSIONS: Mucormycosis is a life-threatening infection in HIV patients and clinician should be aware of this co-infection in the differential diagnosis of HIV opportunistic infections.

Burden of fungal infections in Qatar.

Few estimates of fungal disease frequency have been attempted in the Middle East. We have estimated the burden of fungal infections in Qatar. The aim of the study was to compute and determine the burden of serious fungal infections, in an attempt to estimate fungal disease frequency, which has not previously been attempted in this country. Disease statistics were collected from the Microbiology laboratory database and from 2011 WHO statistics. The data are expressed per 100,000 populations. The reported cases of candidaemia rose to 288 with an estimated rate of 15.4/100,000. A real increase in the burden of candidaemia was found over that previously reported (12.9/100,000) for the years 2004-2009. Candida peritonitis was estimated in 8.02 cases/100,000 population. Recurrent (≥4 year(-1) ) vaginal infections affect at least 32,782 women with a rate of 3506/100,000 inhabitants. Severe asthma with fungal sensitisation affected 1486 people, allergic bronchopulmonary aspergillosis 1126 people and chronic pulmonary aspergillosis 176 people. Rhinosinusitis, mucormycosis and Fusarium infection occurred at rates of 2.31, 1.23, 1.86 cases/100,000 respectively. The estimated rate of invasive aspergillosis was very low (0.6/100,000). Low rates of Cryptococcus meningitis and Pneumocystis pneumonia are attributable to low HIV infection rates. In conclusion, fungal infections are increasingly reported, especially candidaemia. Surveillance and guidelines are needed to optimise care and management of common fungal infections. In addition, a fungal registry system needs development for surveillance.

The burden of serious fungal diseases in Russia.

The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082.

Burden of serious fungal infections in Ukraine.

Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually.

Estimating the burden of mucormycosis infections in France (2005-2007) through a capture-recapture method on laboratory and administrative data.

BACKGROUND: Mucormycoses are rare but severe fungal infections whose incidence is increasing, particularly in immunosuppressed and diabetic patients. Following a retrospective study on the characteristics and outcomes of cases who were identified through two sources of information, we carried out a capture-recapture method to estimate the actual burden of the disease in France, 2005-2007. METHODS: An administrative dataset from the national hospital discharge system and a laboratory dataset from the National Reference Centre for Mycoses and Antifungals were combined to identify patients from 2005 to 2007. We applied capture-recapture equations to estimate the number of cases missed by both sources and to assess the advantages of each dataset, especially in terms of sensitivity. RESULTS: There were 94 mucormycosis cases included in the study: 30 and 31 in each respective source and 33 common to both. Capture-recapture showed that 28 cases were missed (expected total: 122 cases, CI95: 102-142). Each dataset had a sensitivity value below 53%. The merged set yielded a 77% sensitivity (66%-92%). CONCLUSION: This study highlights the importance of combining available sources when analysing rare infectious diseases. The proportion of 23% missed cases might seem acceptable given the scarcity of the disease, for which further knowledge is needed. However this proportion could decrease in the future, through the sensitization of clinicians, pathologists and mycologists together with the improving quality of discharge datasets.