Evaluation of 30 cases of mucormycosis at a university hospital in Iran

Mucormycosis is a deadly invasive fungal infection and mainly affects immunocompromised patients. To investigate the clinical features of patients who developed mucormycosis and to determine the parameters, which influenced the outcome following mycotic infection. The current investigation retrospectively evaluated the demographic characteristics, clinical features, therapeutic data, as well as the outcomes of treatment in all cases of proven and probable mucormycosis diagnosed from 2002 until 2016 in our hospital. A total of thirty cases were recorded. Rhizopus spp. was the predominant pathogen among the identified Mucorales (26.7%). Diabetes mellitus (46.7%) and haematological malignancy (40%), were the most common underlying diseases. With regard to predisposing factors, neutropenia (43.3%) and chemotherapy (40%) were the leading concomitant parameters. The most frequent sites of infection were lung (30%) and sinus (26.7%), whereas disseminated infection was also found in nine of 30 patients (30%). Neutropenia remained the only independent factor associated with mortality (Relative Risk=3.557, 95% CI=1.365‐9.271, P=.009). Diagnostic delay ‐either due to delayed presentation of patients to our centre or insufficient awareness about invasive fungal infection among our clinicians‐ is a likely explanation for such a high mortality rate in our series.     

Chronic rhinocerebral mucormycosis: a rare case report and review of the literature

Rhinocerebral mucormycosis is an invasive infection caused by filamentous fungi of the Mucoraceae family. The rhinocerebral form of the disease represents the most common form and has two distinct clinical entities. The common presentation consists of a rapidly progressive infection with high mortality rate, while the other presentation is that of a chronic infection with lower mortality. In the present paper we report a rare case of chronic rhinocerebral mucormycosis. An 85‐year‐old male with a 6‐month history of purulent and odorous nasal discharge, and sporadic episodes of epistaxis and anosmia, presented to the outpatient department of our clinic. Initial cultures were positive only for Pseudomonas aeruginosa. The patient was unresponsive to ciprofloxacin treatment, developing necrotic areas of the nasal septum suspicious for rhinocerebral mucormycosis. Admission to the ENT clinic followed, with histopathologic evaluation of the vomer bone confirming the diagnosis. The patient was treated with amphotericin B and was discharged 3 weeks later on oral posaconazole therapy. Chronic rhinocerebral mucormycosis may present with atypical symptoms or coinfection with another agent. A high degree of clinical suspicion is required for correct diagnosis and prompt initiation of appropriate treatment.     

Prevalence of the reversed halo sign in neutropenic patients compared with non‐neutropenic patients: Data from a single‐centre study involving 27 patients with pulmonary mucormycosis (2003‐2016)

Pulmonary mucormycosis (PM) is a life‐threatening infection and the diagnosis can be challenging. The objective was to retrospectively explore the value of the RHS in our cohort of 27 patients with mucormycosis and its relation to neutropenia. This was a retrospective study including all patients with a diagnosis of probable or proven invasive PM according to the 2008 EORTC/MSG criteria between September 2003 to April 2016. Fisher's exact test and Mann‐Whitney test, with a P‐value statistically significant under .05 (P<.05), were used to compare neutropenic and non‐neutropenic groups. 27 patients were eligible. The RHS could be identified in 78% of cases in the neutropenic group, and was less common in the non‐neutropenic group (31%) (P<.05). Reticulations inside ground‐glass opacity in case of RHS were present in 13 out of 15 patients (87%). Mucorales DNA detection by PCR on serum provided, a median time to the first PCR‐positive sample of 3 days (?33 to +60 days) before diagnosis was confirmed. Six patients had IPA co‐infection. In conclusion, RHS is more frequent in case of PM in neutropenic patients compare to non‐neutropenic patients. Its presence in immunocompromised patients should be sufficient to promptly start Mucorales‐active antifungal treatment, while its absence especially in non‐neutropenic cases should not be sufficient to exclude the diagnosis.     

Risk factors,clinical presentation and prognosis of mixed candidaemia: a population‐based surveillance in Spain

The low incidence of mixed candidaemia (MC) may have precluded a better knowledge of its clinical presentation. The aim of the study was to analyse the risk factors, clinical presentation and prognosis of MC episodes. A comparison between MC and monomicrobial candidaemia within a prospective programme on candidaemia was performed in 29 hospitals between April 2010 and May 2011. In fifteen episodes of candidaemia corresponding to 15 patients, out of 752, two species of Candida (1.9%) were isolated. MC was more frequent in patients with HIV infection (12%, P = 0.038) and those admitted due to extensive burns (23%, P = 0.012). The Candida species most frequently identified in MC were C. albicans 12 patients (40%), C. glabrata seven patients (23.3%) and C. parapsilosis six patients (20%). Early mortality was higher (nine patients, 60%) in patients with MC than in patients with MMC (223 patients, 30.3%, P = 0.046). In conclusion, MC was was independently associated with increased mortality even after considering other prognostic factors. MC is an infrequent event that is more common in HIV infection and in patients suffering from burns, and is associated with increased mortality.     

Cryptococcus neoformans infection in malignancy

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV‐infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over‐represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.     

Mucormycosis in paediatric patients: demographics, risk factors and outcome of 12 contemporary cases

Mucormycosis is associated with high morbidity and mortality and is perceived as an emerging fungal infection. However, contemporary paediatric data are limited. We present a series of paediatric cases of mucormycosis reported from Germany and Austria collected within a voluntary epidemiological survey through standardised, anonymized case report forms. Twelve cases were reported between January 2004 and December 2008 (six men; mean age: 12.6 years, range: 0.1-17 years). Mucormycosis was proven in nine, and probable in three cases. Isolates included Lichtheimia (syn. Absidia pro parte, Mycocladus) (five), Rhizopus (three) and Mucor (one) species. Infection was limited to soft tissue in three cases, the lung in two cases, and an infected thrombus in one case; rhinocerebral disease was found in three cases, and pulmonary-mediastinal, pulmonary-cerebral and soft tissue-cerebral involvement in one case each. All three patients with isolated soft tissue infection were cured, whereas seven of the remaining patients died (one patient without follow-up). The overall mortality rate was 67%. While these data cannot provide conclusive data on incidence and disease burden of mucormycosis in paediatric patients, they reflect the continuing threat of these infections to immunocompromised patients and the need for improved diagnosis and management.     

Evaluation of 28 cases of mucormycosis

Mucormycosis is a rare but invasive fungal disease with high mortality. The present study aimed to retrospectively investigate the demographic characteristics, as well as the clinical, radiological and laboratory features and the results of treatment, in the patients followed in our hospital because of mucormycosis. The present study retrospectively evaluated 28 cases, which were followed in our hospital because of mucormycosis between January 2002 and July 2013. The clinical form was rhinocerebral in 27 cases (rhinoorbital in 12, nasal in 8 and rhinoorbitocerebral in 7) and disseminated in one case. With regard to predisposing factors, diabetes mellitus (n = 20), haematological malignancy (n = 6) and chronic renal insufficiency (n = 5) were the leading concomitant diseases. Seventeen (61%) of 28 cases showed atypical clinical picture. With regard to the therapeutic outcomes; it was found that 14 (50%) cases died and six cases recovered with sequel. Today, when particularly the prevalence of immunosuppressive diseases and conditions are gradually increasing, the incidence of mucormycosis is also increased. Considering that the majority of our cases had atypical clinical involvement and complications, being familiar with the characteristics of this disease could be life‐saving together with early diagnosis and treatment.     

Invasive infections due to Saprochaete and Geotrichum species: Report of 23 cases from the FungiScope Registry

Saprochaete and Geotrichum spp. are rare emerging fungi causing invasive fungal diseases in immunosuppressed patients and scarce evidence is available for treatment decisions. Among 505 cases of rare IFD from the FungiScope^? registry, we identified 23 cases of invasive infections caused by these fungi reported from 10 countries over a 12‐year period. All cases were adults and previous chemotherapy with associated neutropenia was the most common co‐morbidity. Fungaemia was confirmed in 14 (61%) cases and deep organ involvement included lungs, liver, spleen, central nervous system and kidneys. Fungi were S. capitata (n=14), S. clavata (n=5), G. candidum (n=2) and Geotrichum spp. (n=2). Susceptibility was tested in 16 (70%) isolates. All S. capitata and S. clavata isolates with the exception of one S. capitata (MIC 4 mg/L) isolate had MICs>32 mg/L for caspofungin. For micafungin and anidulafungin, MICs varied between 0.25 and >32 mg/L. One case was diagnosed postmortem, 22 patients received targeted treatment, with voriconazole as the most frequent first line drug. Overall mortality was 65% (n=15). Initial echinocandin treatment was associated with worse outcome at day 30 when compared to treatment with other antifungals (amphotericin B ± flucytosine, voriconazole, fluconazole and itraconazole) (P=.036). Echinocandins are not an option for these infections.     

Cryptococcal meningitis due to Cryptococcus neoformans genotype AFLP1/VNI in Iran: a review of the literature

Cryptococcal meningitis is the most important opportunistic fungal infection with a high mortality in HIV‐patients in less developed regions. Here, we report a case of cryptococcal meningitis in a 49‐year‐old HIV‐positive female due to Cryptococcus neoformans (serotype A, mating‐type alpha, genotype AFLP1/VNI) in Sari, Iran. In vitro antifungal susceptibility tests showed MICs of isavuconazole (0.016 μg ml^?1), voriconazole (0.031 μg ml^?1), posaconazole (0.031 μg ml^?1), itraconazole (0.063 μg ml^?1), amphotericin B (0.125 μg ml^?1) and fluconazole (8 μg ml^?1). Despite immediate antifungal therapy, the patient died 4 days later due to respiratory failure. Cryptococcal infections have been infrequently reported from Iran and therefore we analysed all published cases of cryptococcosis in Iran since the first reported case from 1969.     

Gastrointestinal mucormycosis in immunocompromised hosts

Invasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non‐specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.     

Rhinocerebral mucormycosis,risk factors and the type of oral manifestations in patients referred to a University Hospital in Tabriz,Iran 2007‐2017

Inadequate data are available on the global epidemiology of mucormycosis, mainly derived from the evaluation of specific population groups. Rhinocerebral mucormycosis is an invading and fatal mycosis, particularly among diabetic patients. In the present study, patients hospitalised in Imam Reza Hospital in Tabriz, from 2007 to 2017, were evaluated. The hospital information system (HIS) was used to collect the records of the patients. A total of 42 patients with a diagnosis of mucormycosis were included in the study, 40 cases (95%) of which had a diagnosis of the rhinocerebral form. Of these 40 patients, 21 (52.5%) and 19 (47.5%) were male and female, respectively. Seven cases (17.5%) of rhinocerebral mucormycosis were due to dental procedures. The most predisposing factor in the patients was diabetes with 36 (90%) cases. In our study, the role of tooth extraction in patients with uncontrolled diabetes was identified as an important factor. It may show the important role of dentists in preventing of the disease in diabetic patients.     

Aspergillus tracheobronchitis in critically ill patients with chronic obstructive pulmonary diseases

Aspergillus tracheobronchitis (ATB) is considered as an unusual form of invasive aspergillosis and has a fatal outcome. There is little current information on several aspects of chronic obstructive pulmonary diseases (COPD) complicated by ATB, the frequency of which is expected to increase in the coming years. In a prospective study of invasive bronchial‐pulmonary aspergillosis (IBPA) in a critically ill COPD population, three proven cases of ATB were identified. The three new cases, combined with eight previously reported cases of COPD with ATB over a 30‐year period (1983–2013), were analysed. Among 153 critically ill COPD patients admitted to the ICU, eight cases were complicated by ATB [23.5% of IBPA (8 of 34); and 5.2% of COPD (8 of 153)], and three cases were finally diagnosed as proven ATB by histopathological findings. Among the three new cases reported and the eight published cases, the overall mortality rate was 72.7% (8 of 11 cases), with a median of 11.5 days (range, 7–27 days) between admission to death. The mortality rate was significantly higher in patients with invasive pulmonary aspergillosis (IPA) [100% (8 of 8 patients)] than in patients without parenchyma invasion [0% (0 of 3 patient), P = 0.006]. Seven patients (77.8%) received systemic corticosteroid therapy and three patients (33.3%) inhaled corticosteroids before diagnosis with ATB. Dyspnoea resistant to corticosteroids (77.8%) was the most frequent symptom. The radiological manifestations progressed rapidly in three patients (75%) who had normal chest X‐rays (CXRs) at admission. Pseudomembranous lesions were the most frequent form (54.5%) observed by bronchoscopy. Aspergillus fumigatus was the most frequently isolated pathogen (40%). ATB is an uncommon cause of exacerbation in approximately 5% of critically ill COPD patients admitted to the ICU, and may progress rapidly to IPA with a high mortality rate. Dyspnoea resistant to corticosteroids and appropriate antibiotics with a negative CXR should raise the suspicion of ATB. Early diagnosis of ATB is based on bronchoscopic examination and proven diagnosis maybe safely established with a bronchial mucous biopsy.     

Rhinocerebral Mucormycosis: A Retrospective Study

Mucormycosis is an acute often fatal infection caused by fungi of family mucoracea (Kauffman and Malani Curr Infect Dis Rep 9(6):435–440). The principal pathogens in this family are rhizopus, mucor and absidia species. Mucoracea are found in soil, decaying vegetation and other organic matter. Mucormycosis is a polymorphic disease with diverse clinical manifestation. It is divided into rhinocerebral, pulmonary, cutaneous, cardiac, gastrointestinal and disseminated. Rhinocerebral mucormycosis the most commonest manifestation of mucormycosis is usually a fatal fulminant infection. Rhinocerebral mucormycosis can be further divided into rhino-maxillary and rhino-orbito-cerebral. The disease commonly occur in diabetics who have ketoacidosis but is also seen in severely debilitated or immunosuppressed patients. It has also been reported from otherwise normal individuals. Early diagnosis and treatment is mandatory for a successful management of this infection.     

Does the presence of mediastinal adenopathy confer a risk for disseminated infection in immunocompetent persons with pulmonary coccidioidomycosis?

Pulmonary coccidioidomycosis is caused by inhaling airborne arthroconidia of Coccidioides, a soil‐dwelling fungus endemic to the desert southwestern United States. Although uncommon, disseminated coccidioidal infection can be associated with well‐defined risk factors, such as cell‐mediated immunodeficiency, certain racial heritages (e.g. African or Filipino), male sex, or pregnancy. Before widespread use of computed tomography (CT), the presence or persistence of mediastinal lymphadenopathy was postulated to be a risk factor for disseminated coccidioidal infection. To investigate the use of CT scanning to identify the presence of mediastinal lymphadenopathy in patients with pulmonary coccidioidomycosis, and to correlate such lymphadenopathy with disseminated coccidioidal infection, we performed a retrospective review of patients with pulmonary coccidioidomycosis who were evaluated by chest CT. Two radiologists independently interpreted 150 CT scans from patients with pulmonary coccidioidomycosis. Forty‐nine patients met CT criteria for mediastinal lymphadenopathy, whereas 101 patients did not. Disseminated coccidioidal infection was observed in 5 (10%) of the 49 patients with mediastinal lymphadenopathy and in 6 of the 101 (6%; P = .34) without such adenopathy. Among patients with coccidioidomycosis, patients with mediastinal lymphadenopathy, as assessed by CT, had a higher rate of disseminated infection, but the difference was not statistically significant.     

Acute acalculous cholecystitis due to Fusarium species and review of the literature on fungal cholecystitis

Fungal cholecystitis is an uncommon entity, and no cases of cholecystitis associated with mould infection have been reported. We present a case of acute Fusarium cholecystitis in a cytopenic patient with leukaemia who had disseminated fusariosis. We also review the published cases of fungal cholecystitis, which is most often caused by Candida species. Although it is rare, fungal cholecystitis should be part of the differential diagnosis of acute cholecystitis in high‐risk patients with predisposing factors for opportunistic fungal infections.     

Oral mucormycosis in patients with haematologic malignancies in a bone marrow transplant unit

Mucormycosis is an aggressive and life‐threatening opportunistic fungal infection, which predominantly affects immunocompromised patients. It typically manifests in rhinocerebral, pulmonary or disseminated forms in patients with immunosuppressive conditions. Mucormycosis limited to the oral cavity is rare, and to the best of our knowledge only seven cases have previously been reported in English literature. We present five consecutive cases of oral mucormycosis in patients with leukaemia, and provide a literature review.     

Disseminated histoplasmosis in HIV‐infected patients: determinants of relapse and mortality in a north‐eastern area of Brazil

Many relapses and deaths resulting from disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients have been observed in an endemic area in north‐eastern Brazil. The objective of this study was to evaluate the risk factors associated with the clinical outcomes of DH/AIDS coinfection in patients from the state of Ceará, Brazil. A retrospective cohort of AIDS patients, after their hospital discharge due to first DH episode in the period 2002–2008, was followed until December 31, 2010, to investigate the factors associated with relapse and mortality. A total of 145 patients were evaluated in the study. Thirty patients (23.3%) relapsed and the overall mortality was 30.2%. The following variables were significantly (P < 0.05) associated with relapse and overall mortality (univariate analysis): non‐adherence to highly active antiretroviral therapy (HAART), irregular use of an antifungal, non‐recovery of the CD4+ count and having AIDS before DH; histoplasmosis relapse was also significantly associated with mortality. In the multivariate analysis, non‐adherence to HAART was the independent risk factor that was associated with both relapse (Adj OR = 6.28) and overall mortality (Adj OR = 8.03); efavirenz usage was discovered to be significant only for the overall mortality rate (Adj OR = 4.50). Adherence to HAART was the most important variable that influenced the outcomes in this specific population.     

Efficacy of micafungin in invasive candidiasis caused by common Candida species with special emphasis on non‐albicans Candida species

The incidence of invasive candidiasis caused by non‐albicans Candida (NAC) spp. is increasing. The aim of this analysis was to evaluate the efficacy of micafungin, caspofungin and liposomal amphotericin B in patients with invasive candidiasis and candidaemia caused by different Candida spp. This post hoc analysis used data obtained from two randomised phase III trials was conducted to evaluate the efficacy and safety of micafungin vs. caspofungin and micafungin vs. liposomal amphotericin B. Treatment success, clinical response, mycological response and mortality were evaluated in patients infected with C. albicans and NAC spp. Treatment success rates in patients with either C. albicans or NAC infections were similar. Outcomes were similar for micafungin, caspofungin and liposomal amphotericin B. Candida albicans was the most prevalent pathogen recovered (41.0%), followed by C. tropicalis (17.9%), C. parapsilosis (14.4%), C. glabrata (10.4%), multiple Candida spp. (7.3%) and C. krusei (3.2%). Age, primary diagnosis (i.e. candidaemia or invasive candidiasis), previous corticosteroid therapy and Acute Physiology and Chronic Health Evaluation II score were identified as potential predictors of treatment success and mortality. Micafungin, caspofungin and liposomal amphotericin B exhibit favourable treatment response rates that are comparable for patients infected with different Candida spp.     

Current trends in candidemia and species distribution among adults: Candida glabrata surpasses C. albicans in diabetic patients and abdominal sources

Candidemia rate and species distribution vary according to the type of patients, country of origin and antifungal prophylaxis use. To present current candidemia epidemiological trends. A retrospective examination of candidemia in adults (≥18 years‐old) hospitalised from 2007 to 2015. Cases were identified through the microbiology laboratory. Candida species were distinguished based on colony morphology and VITEK‐2 YBC cards, (bioMerieux, Durham, NC, USA). Patient characteristics, species distribution, source and outcome were assessed. We encountered 275 patients (294 episodes) with candidemia. The rate of candidemia dropped in 2010 (P = 0.003) without further decline. Nearly all cases (97.5%) were healthcare‐associated. C. albicans (n = 118) and C. glabrata (n = 77) proportions varied without a discernable trend. C. glabrata was more common in diabetics [52.9% vs. 32.0% (non‐diabetics); P = 0.004] and abdominal sources [53.3% vs. 35.5% (other sources); P = 0.03], especially gastric/duodenal foci [88.9% vs. 44.1% (other abdominal foci); P = 0.02]. All‐cause 30‐day mortality rate was 43.3% without changes over time or differences between C. albicans and C. glabrata. In conclusion, the candidemia rate remains stable after a decline in 2010. C. albicans remains the most common species but C. glabrata predominates in diabetics and abdominal sources. These findings suggest possible species‐related differences in colonisation dynamics or pathogenicity.