Opportunistic Fungal Infections Research Articles

Bioavailability of a novel sustained-release pellet formulation of 5-flucytosine in healthy-fed participants for use in patients with cryptococcal meningitis.

Cryptococcal meningoencephalitis (CM) is an opportunistic fungal infection and a major cause of death among people living with human immunodeficiency virus in sub-Saharan Africa. 5-flucytosine (5-FC) is a unique, brain-permeable antifungal agent used to reduce mortality from CM and to prevent disease in individuals carrying cryptococcal antigen. 5-FC has a short plasma half-life, requiring 6-hourly oral dosing with an immediate-release (IR) formulation, a significant challenge in hospital and outpatient settings, risking a lack of compliance. We recently reported the relative bioavailability in fasting conditions of a sustained release (SR) oral pellet formulation of 5-FC. In this phase I study, we assessed the safety and pharmacokinetic profiles of the new 5-FC SR formulation in a single dose (2 × 3000 mg), relative to 5-FC IR tablets (Ancotil®; 1500 mg b.i.d.) in healthy participants in fed conditions. This randomized, two-period crossover study was conducted in South Africa to confirm the dose of the identified 5-FC SR formulation for a twice-daily 5-FC regimen in patients. Thirty-six healthy participants were included. All treatments were well tolerated and no serious adverse event was reported. Cmax and AUC(0-t) for the SR formulation (49.2 ± 10.49 μg/mL and 640.4 ± 126.4 h.μg/mL, respectively) were significantly higher than for the IR formulation (36.8 ± 7.61 μg/mL and 456.6 ± 72.8 h.μg/mL, respectively). A physiological based pharmacokinetic model (PBPK) predicted that under fasting conditions, 6000 mg SR pellets would show a good overlap with the IR product (3000 mg b.i.d), thus 6000 mg SR 5-FC b.i.d. in fasting conditions is recommended.

Complete genome sequence of a Circovirus pigeon strain in lymphocyte-depleted bursa of Fabricius of a Common Raven (Corvus corax).

A necropsy was performed on a Common Raven (Corvus corax) presenting an opportunistic fungal respiratory infection and a bursal lymphoid depletion with inclusion bodies, suggestive of a circovirus infection. High-throughput sequencing of circular DNA in the bursa of Fabricius revealed a complete genome sequence of a Circovirus pigeon strain.

Lung adenocarcinoma concurrent with pulmonary cryptococcosis: a case report and literature review

Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F‑FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.

Functional characterization of two survival factor 1 genes in Mucor lusitanicus.

Mucor lusitanicus is a widely used model organism to study various biological processes in the basal fungal group Mucorales. Several members of this group can be agents of mucormycosis, an opportunistic fungal infection, which is associated with high mortality, rapid progression, and wide resistance to the commonly used antifungal agents. Svf1 proteins have so far only been identified in fungi, where they have been involved in pathogenicity and resistance to antifungal agents in many cases. Only a limited number of factors affecting the stress response, antifungal resistance, and virulence of Mucorales fungi have been revealed. Elucidating the function of a fungus-specific protein that may regulate these processes may bring us closer to understanding the pathogenesis of these fungi.

Inflammatory cytokine signalling in vulvovaginal candidiasis: a hot mess driving immunopathology.

Protective immunity to opportunistic fungal infections consists of tightly regulated innate and adaptive immune responses that clear the infection. Immune responses to infections of the vaginal mucosa by Candida species are, however, an exception. In the case of vulvovaginal candidiasis (VVC), the inflammatory response is associated with symptomatic disease, rather than that it results in pathogen clearance. As such VVC can be considered an inflammatory disease, which is a significant public health problem due to its predominance as a female-specific fungal infection. Particularly, women with recurrent VVC (RVVC) suffer from a significant negative impact on their quality of life and mental health. Knowledge of the inflammatory pathogenesis of (R)VVC may guide more effective diagnostic and therapeutic options to improve the quality of life of women with (R)VVC. Here, we review the immunopathogenesis of (R)VVC describing several elements that induce an inflammatory arson, starting with the activation threshold established by vaginal epithelial cells that prevent unnecessary ignition of inflammatory responses, epithelial and inflammasome-dependent immune responses. These inflammatory responses will drive neutrophil recruitment and dysfunctional neutrophil-mediated inflammation. We also review the, sometimes controversial, findings on the involvement of adaptive and systemic responses. Finally, we provide future perspectives on the potential of some unexplored cytokine axes and discuss whether VVC needs to be subdivided into subgroups to improve diagnosis and treatment.

Genetic diversity and antifungal susceptibilities of environmental Cryptococcus neoformans and Cryptococcus gattii species complexes

Cryptococcosis is an opportunistic systemic mycosis caused by Cryptococcus neoformans and C. gattii species complexes and is of increasing global importance. Maintaining continued surveillance of the antifungal susceptibility of environmental C. neoformans and C. gattii isolates is desirable for better managing cryptococcosis by identifying resistant isolates and revealing the emergence of intrinsically resistant species. Relevant research data from Egypt are scarce. Thus, this study aimed to report the genetic diversity of C. neoformans and C. gattii species complexes originating from different environmental sources in Egypt, antifungal susceptibility profiles, antifungal combinations, and correlations of susceptibility with genotypes. A total of 400 environmental samples were collected, 220 from birds and 180 from trees. Cryptococcus spp. were found in 58 (14.5%) of the samples, 44 (75.9%) of the isolates were recovered from birds and 14 (24.1%) from trees. These isolates were genotyped using M13 polymerase chain reaction-fingerprinting and URA5 gene restriction fragment length polymorphism analysis. Of the 31 C. neoformans isolates, 24 (77.4%), 6 (19.4%) and one (4.4%) belonged to VNI, VNII, and VNIII genotypes, respectively. The 27 C. gattii isolates belonged to VGI (70.4%), VGII (18.5%), and VGIII (11.1%) genotypes. Non-wild type C. neoformans and C. gattii isolates that may have acquired resistance to azoles, amphotericin B (AMB), and terbinafine (TRB) were observed. C. gattii VGIII was less susceptible to fluconazole (FCZ) and itraconazole (ITZ) than VGI and VGII. C. neoformans isolates showed higher minimum inhibitory concentrations (MICs) to FCZ, ITZ, and voriconazole (VRZ) than those of C. gattii VGI and VGII. Significant (P < 0.001) correlations were found between the MICs of VRZ and ITZ (r = 0.64) in both C. neoformans and C. gattii isolates, FCZ and TRB in C. neoformans isolates, and FCZ and TRB (r = 0.52) in C. gattii isolates.There is no significant differences in the MICs of TRB in combination with FCZ (P = 0.064) or in combination with AMB (P = 0.543) and that of TRB alone against C. gattii genotypes. By calculating the fractional inhibitory concentration (FIC) index, the combination of FCZ + AMB was synergistic against all tested genotypes. These findings expand our knowledge of ecological niches, genetic diversity, and resistance traits of C. neoformans and C. gattii genotypes in Egypt. Further investigations into how they are related to clinical isolates in the region are warranted.

Candida tropicalis PMT2 Is a Dispensable Gene for Viability but Required for Proper Interaction with the Host.

Candidemia is an opportunistic mycosis with high morbidity and mortality rates. Even though Candida albicans is the main causative agent, other Candida species, such as Candida tropicalis, are relevant etiological agents of candidiasis and candidemia. Compared with C. albicans, there is currently limited information about C. tropicalis' biological aspects, including those related to the cell wall and the interaction with the host. Currently, it is known that its cell wall contains O-linked mannans, and the contribution of these structures to cell fitness has previously been addressed using cells subjected to chemical treatments or in mutants where O-linked mannans and other wall components are affected. Here, we generated a C. tropicalis pmt2∆ null mutant, which was affected in the first step of the O-linked mannosylation pathway. The null mutant was viable, contrasting with C. albicans where this gene is essential. The phenotypical characterization showed that O-linked mannans were required for filamentation; proper cell wall integrity and organization; biofilm formation; protein secretion; and adhesion to extracellular matrix components, in particular to fibronectin; and type I and type II collagen. When interacting with human innate immune cells, it was found that this cell wall structure is dispensable for cytokine production, but mutant cells were more phagocytosed by monocyte-derived macrophages. Furthermore, the null mutant cells showed virulence attenuation in Galleria mellonella larvae. Thus, O-linked mannans are minor components of the cell wall that are involved in different aspects of C. tropicalis' biology.

The underlying factors of occurrence of Mucormycosis in post-COVID-19 patients – A meta-analysis of case histories

Mucormycosis is a life-threatening fungal infection caused by fungi of the order Mucorales. It usually affects people with weakened immune systems, such as those with uncontrolled diabetes, acquired immunodeficiency syndrome, iatrogenic immunosuppression, and hematological malignancies, as well as individuals who have had organ transplants. The type of mucormycosis a person suffers from is often determined by their underlying conditions. The most common types are rhino-cerebral mucormycosis, pulmonary mucormycosis, cutaneous mucormycosis, cerebral mucormycosis, gastrointestinal mucormycosis, and disseminated mucormycosis. The incidence of mucormycosis has been increasing over the years, with an overall mortality rate of 54%. Recent cases have shown a correlation between COVID-19 and mucormycosis. Using anti-inflammatory drugs to combat the cytokine storm associated with COVID-19 can weaken the immune system, making individuals more susceptible to opportunistic fungal infections like mucormycosis. Underlying health conditions further exacerbate the condition. This study reviewing 198 cases of mucormycosis and conducting a meta-analysis found that post-COVID-19 patients most commonly developed rhino-orbital-cerebral mucormycosis, followed by pulmonary and gastrointestinal mucormycosis. The study also identified diabetes as the most common underlying factor contributing to the development of mucormycosis in post-COVID-19 patients, followed by hypertension and obesity. The study also examined the influence of age, affected organs, and the use of certain drugs on the development of mucormycosis. Age was found to be a significant factor in the infection. This meta-analysis is one of the first to compare post-COVID mucormycosis cases with those from the pre-COVID era. The hope is that this study and analysis will help identify the determinants of mucormycosis in post-COVID patients and aid the scientific community in finding a solution to this problem.

Hospitalized COVID-19 Patients with Urinary Tract Infection in Iran: Candida Species Distribution and Antifungal Susceptibility Patterns.

Candida species, typically part of the human skin and mucous membrane flora, can cause opportunistic fungal infections, notably urinary tract infections (UTIs), which are on the rise among hospitalized COVID-19 patients. The lack of understanding of UTIs in this population, coupled with the emergence of multidrug-resistant strains, poses significant challenges for effective treatment and further investigations. In this study, urine samples were collected from 70 COVID-19 patients with UTIs in sterile containers for microbiology examination. After microscopic observation, the isolates were identified both by phenotypic and molecular techniques such as multiplex PCR. Antifungal susceptibility testing (AFST) against fluconazole (Flu), itraconazole (Itr), and amphotericin B (AMB) was performed according to CLSI M27/S4 standard methods, with the frequency of isolates including Candida albicans (n = 20, 51.3%), Candida tropicalis (n = 15, 38.4%), Nakaseomyces glabrata (previously Candida glabrata) (n = 2, 5.1%), Pichia kudriavzevii (previously Candida krusei), and Candida parapsilosis (n = 1, 2.5%). All isolates of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis were sensitive to amphotericin B, while C. kruzei was resistant to AMB. Around 70% of C. albicans isolates were sensitive to Flu; 20% of C. tropicalis were resistant to itraconazole, while 33% were resistant to fluconazole. C. albicans and C. tropicalis were the main causes of candiduria in infected cases and both Flu and AMB showed good results in AFST in these species. Performing drug susceptibility testing for clinical isolates of Candida spp. provided guidance for appropriate management and control, and timely antifungal treatment.

Rapid CD4 cell count determination and Cryptococcus and Histoplasma antigen detection in people living with HIV: Implementation of a package of care strategy in a pilot study, Argentina

ObjectivesDespite advancements in HIV diagnosis and treatment, advanced HIV disease (AHD) is still a significant concern worldwide, especially in countries with a high percentage of undiagnosed cases and late-stage diagnoses. MethodsA prospective pilot study was conducted in Buenos Aires, Argentina to assess the feasibility of implementing a package for people living with HIV, integrating a point-of-care clusters of differentiation (CD4) test, followed by rapid Cryptococcus and Histoplasma antigen (Ag) detection. ResultsA total of 105 people living with HIV were enrolled, during June 2021 to October 2021. The VISITECT CD4 Advanced Disease Lateral Flow Assay (CD4-LFA) (Accubio) classified 98 (93%) patients with AHD. Compared with flow cytometry, the CD4-LFA performed with a high sensitivity (100%) but low specificity (19%) and limited accuracy (47%). In the 98 patients classified with AHD using the CD4-LFA, 16 tested positive for any of the rapid Ag used, including 12 patients positive for the Histoplasma Ag test and four positive for Cryptococcus Ag; all four patients with positive Cryptococcus Ag in sera and were diagnosed with meningitis. In the 30-day follow-up, one death was recorded. ConclusionsThe CD4-LFA correctly classified all patients with CD4 ≤200 cells/µL by flow cytometry, but a high frequency of patients misclassified with AHD was recorded. We also observed a high prevalence of opportunistic fungal infections, as previously observed in the hospital where this pilot study was conducted; however, in contrast with those previous reports, mortality was lower. The study underscores the importance of scaling up comprehensive care strategies and collaborating with governmental and non-governmental partners to enhance access to essential diagnostic tools and treatments for people living with HIV. Further research with larger sample sizes is needed to validate these findings.

A Rare Case of Invasive Thyroid Aspergillosis Revealed on 18F-FDG-PET/CT.

Invasive aspergillosis (IA) represents a common form of fungal infection caused by various species of Aspergillus that most frequently affect immunocompromised patients. Typically, this disease occurs preferentially in high-risk groups including patients infected with the human immunodeficiency virus (HIV), patients with leukemia, patients with autoimmune diseases, and organ transplant patients undergoing medical immunosuppression. Considered the second most common cause of opportunistic fungal infection in humans after Candida albicans, this pathogen predominantly affects the lungs, but it may also spread by a hematogenous route to various organs and have a heterogeneous presentation. Owing to its high iodine levels, high perfusion, and enclosed capsule, the thyroid gland is considered to have a lower susceptibility to microbial invasion, and it is fairly uncommon to find associated infectious nodules. In metabolic imaging, 18F-FDG-PET/CT has become increasingly useful for detecting a wide range of infectious and inflammatory diseases and is already the gold standard for certain indications. According to the literature, no studies of hypermetabolic nodular thyroid aspergillosis on 18F-FDG-PET/CT confirmed on histology have yet been reported. Here, we report the first case of a patient with a heterogeneous presentation of IA and the presence of a hypermetabolic nodule in the thyroid with a surprising result.

COVID-19 as a critical risk factor for osteonecrosis of the jaw: diagnostic challenge and surgical treatment

This case report describes a unique and complex presentation of osteonecrosis of the maxilla, complicated by Aspergillosis and Mucormycosis, developed in an immunocompetent patient recovering from COVID-19. The patient presented with a range of clinical symptoms, including facial pain, rhinorrhea, cacosmia, cough, and radiographic evidence of jaw involvement. Cytological and histological examinations revealed the presence of Aspergillus niger and mucormycosis-like fungal elements. Our report discusses the main diagnostic challenges, the different potential etiopathological hypotheses, and the alternative therapeutic and rehabilitative approaches. This atypical surgical case definitely highlights the need for heightened awareness among healthcare professionals, regarding the potential risk to discover severe opportunistic fungal infections also in COVID-19 patients; this case further sheds light on the importance of a multidisciplinary approach for an effective management of such intricate post-COVID-19 complications.

Inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in susceptible pediatric patients: a case series

BackgroundPulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and timely treatment of pulmonary aspergillosis can play a crucial role in reducing mortality among children admitted with suspected infections.Case presentationThe present study reports three cases of inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in two Iranian pediatric patients under investigation and one Afghan patient. Unfortunately, two of them died. The cases involved patients aged 9, 1.5, and 3 years. They had been diagnosed with pulmonary disorders, presenting nonspecific clinical signs and radiographic images suggestive of pneumonia. The identification of A. flavus was confirmed through DNA sequencing of the calmodulin (CaM) region.ConclusionA. flavus was the most prevalent cause of pulmonary aspergillosis in pediatric patients. Early diagnosis and accurate antifungal treatment of pulmonary aspergillosis could be crucial in reducing the mortality rate and also have significant potential for preventing other complications among children. Moreover, antifungal prophylaxis seems to be essential for enhancing survival in these patients.

A Case Series of Eight Mucormycosis Patients during SARS-CoV-2 –Pandemic

The outbreak of opportunistic fungal infections such as mucormycosis has been a critical issue following coronavirus disease 19 (COVID-19). Mucormycosis is happened by the fungal group Mucorales and commonly affects immunocompromised patients. To date, COVID-19-associated mucormycosis (CAM) is being reported in several countries. It should be noted that CAM has been started in patients approximately within two to three weeks after the onset of COVID-19. However, here, in one case, fungal symptoms appeared after just one week. In patients with mucormycosis due to this enigmatic infection, the sinuses were most commonly affected, followed by the orbit, nose, and finally the brain. All cases received glucocorticoids as a part of viral therapy. Diabetes mellitus (DM) was reported in all but one case in which COVID-19 was detected, without complications, and this may be the sole predisposing agent. Therefore, in this manuscript, we reported eight cases of COVID-19-induced mucormycosis. Although one case experienced evacuation of the right eye, others discharge with promising outcomes after receiving surgical debridement and proper anti-fungal treatment including, amphotericin B, caspofungin, and posaconazole.

Fungal Infections in Hospitalized Patients of Systemic Lupus Erythematosus: A United States Nationwide Cohort Analysis.

Introduction/objective Immunosuppressive therapy is the cornerstone of management in patients with systemic lupus erythematosus (SLE). Patients on immunosuppressive therapy are at increased risk of developing opportunistic fungal infections. We conducted this analysis to describe the epidemiology, including incidence, risk factors, and outcomes, of fungal infections in hospitalized patients with SLE in the United States. Method A retrospective cohort study was performed by analyzing the National Inpatient Sample (NIS) 2016-2020 for all patients with a discharge diagnosis of SLE and fungal infections, including histoplasmosis, pneumocystosis, cryptococcosis, aspergillosis, and blastomycosis, as a primary or secondary diagnosis via ICD-10 (International Classification of Diseases 10th Revision) codes. Frequencies, demographics, and trends were determined and compared between hospitalized patients with SLE and those without SLE. STATA version 17 was used for data analysis. A p-value of ≤0.05 was considered statistically significant. Results In hospitalized SLE patients, there were lower odds of developing fungal infections in females (odds ratio (OR): 0.63 (95% confidence interval (CI): 0.49-0.80)) and higher odds in Hispanic (OR: 1.52 (95% CI: 1.16-1.98) and Asian (OR: 1.78 (95% CI: 1.15-2.75) populations. Steroid use (OR: 1.96 (95% CI: 1.58-2.42)), concomitant HIV infection(OR: 22.39 (95% CI: 16.06-31.22)), and the presence of leukemias (OR: 3.56 (95% CI: 1.67-7.59)) and lymphomas (OR: 3.29 (95% CI: 1.78-6.09)) in hospitalized SLE patients were significant predictors of fungal infection (p < 0.01). There were differences in the incidence of fungal infections based on geographical areas in the US, with blastomycosis being more common in the Midwest. From 2016 to 2020, there was a decline in the incidence rate of hospitalization per 100,000 for non-SLE patientswith fungal infections (10.7 per 100,000 hospitalizations in 2016 versus 9.6 per 100,000 hospitalizations in 2020), whereas this rate remained steady for the SLE cohort (0.1 per 100,000 hospitalizations in 2016 versus 0.2 per 100,000 hospitalizations in 2020). Conclusions Hospitalized patients with SLE are at an increased risk of developing fungal infections, and this risk is increased further in patients who are males, are on steroid therapy, and have HIV or leukemia and lymphomas. Further studies can be done to explain the increased risk of fungal infections associated with these patient characteristics.

Aspergillus oryzae Isolated from Lung Tissue Sample in a Chronic Respiratory Illness Patient from South India

Opportunistic fungal infection by Aspergillus oryzae in patients with chronic respiratory condition is rare in India. A 52-year-old male with a history of diabetes mellitus, chronic smoking, and alcoholism presented with chronic cough, breathlessness, and recurrent blood in sputum. CT imaging revealed features consistent with old pulmonary tuberculosis sequelae and the presence of a right lung lower lobe aspergilloma. The patient underwent a right lower lobectomy, and histopathological examination confirmed severe acute and chronic bronchiolitis with bronchiectasis and organizing pneumonia, indicative of fungal ball formation. Microbiological analysis identified Aspergillus species, possibly A. flavus complex, with sequencing confirming A. oryzae. This case is unique as A. oryzae is typically associated with food fermentation and rarely implicated in invasive lung infections, especially outside regions of traditional exposure, like Japan. The rarity of this presentation underscores the importance of considering unusual pathogens in clinical practice and utilizing advanced diagnostic techniques such as sequencing for accurate identification. The successful outcome of this case, with prolonged antifungal therapy based on microbiological confirmation and clinical follow-up, suggests the importance of personalized treatment strategies. This case report adds to the growing body of evidence on the clinical significance and pathogenic potential of A. oryzae. It underscores the importance of continued vigilance and research in fungal infections.

Screening of Candida spp. in wastewater in Brazil during COVID-19 pandemic: workflow for monitoring fungal pathogens

Fungal diseases are often linked to poverty, which is associated with poor hygiene and sanitation conditions that have been severely worsened by the COVID-19 pandemic. Moreover, COVID-19 patients are treated with Dexamethasone, a corticosteroid that promotes an immunosuppressive profile, making patients more susceptible to opportunistic fungal infections, such as those caused by Candida species. In this study, we analyzed the prevalence of Candida yeasts in wastewater samples collected to track viral genetic material during the COVID-19 pandemic and identified the yeasts using polyphasic taxonomy. Furthermore, we investigated the production of biofilm and hydrolytic enzymes, which are known virulence factors. Our findings revealed that all Candida species could form biofilms and exhibited moderate hydrolytic enzyme activity. We also proposed a workflow for monitoring wastewater using Colony PCR instead of conventional PCR, as this technique is fast, cost-effective, and reliable. This approach enhances the accurate taxonomic identification of yeasts in environmental samples, contributing to environmental monitoring as part of the One Health approach, which preconizes the monitoring of possible emergent pathogenic microorganisms, including fungi.

Current Perspectives on Antifungal Resistance: Focus on Opportunistic Mycoses

Current Perspectives on Antifungal Resistance: Focus on Opportunistic Mycoses

Determinants of Mortality in COVID-19–Associated Opportunistic Fungal Infections

Abstract Background COVID-19–associated mucormycosis (CAM) affected over 50,000 people during the second wave of the pandemic in India. Epidemiological aspects of CAM were reported, but there is a lack of published literature on mortality and its determinants in CAM and other fungal infections. The present study investigated patterns and determinants of mortality in these patients. Methods The retrospective study reviewed case records of 390 patients, with at least 1 year of follow-up, for information related to demographics, epidemiology, clinical features, laboratory investigations, and treatment. The association between categorical variables was studied using the chi-square test of independence and logistic regression between 2 groups of those who survived and those who died during hospitalization or after discharge. Results A total of 157 (40%) patients did not survive; of these, 112 (29%) died during hospitalization and 45 (11%) had postdischarge mortality. The risk of mortality was associated with higher age, use of corticosteroids (odds ratio, 1.38; 95% confidence interval, 0.87–2.16), visual acuity &lt;3/60 at presentation, palate involvement, and abnormal levels of white blood cells and red blood cells. Conclusions The demographic, clinical, laboratory, and microbiological parameters may be predictors of mortality in patients of rhino-orbital-cerebral mucormycosis.

Pulmonary coinfection by Pneumocystis jirovecii and Aspergillus terreus in an ITP patient after corticosteroid therapy: A case report

AbstractPneumocystis jirovecii pneumonia and invasive pulmonary aspergillosis are both life‐threatening opportunistic fungal infections. There are only few reports of coinfection by these two fungi in the literature, and Aspergillus fumigatus is the predominant Aspergillus species in the coinfection. We report here the first case of coinfection by Aspergillus terreus and P. jirovecii pneumonia and caspofungin can be an appropriate choice for salvage treatment of the coinfection. A 51‐year‐old man with a history of immune thrombocytopenia treated with prednisone over 2 months was admitted to emergency intensive care unit for acute respiratory failure and a cavity was found on chest computed tomography. Therefore, his trachea was immediately intubated. The patient was treated with a large spectrum of antibiotic regimen, consisting initially of imipenem/cilastatin, moxifloxacin and fluconazole followed by fluconazole, imipenem/cilastatin, vancomycin, trimethoprim–sulphamethoxazole (TMP‐SMZ) and azithromycin. When the polymerase chain reaction analysis of the bronchoalveolar lavage sample revealed P. jirovecii and A. terreus, all the antibiotics were stopped except TMP‐SMZ, and voriconazole was added. Two weeks later, the patient showed clinical improvement but radiological deterioration. Consequently, caspofungin was started for salvage therapy, then the patient showed gradual clinical improvement. He was discharged with oral voriconazole and TMP‐SMZ. The antifungal treatment was continued for 6 months until complete radiological absorption. In conclusion, early bronchoscopy with bronchoalveolar lavage fluid should be considered in order to diagnose and treat promptly in those treated with corticosteroids combined with immunocompromised and caspofungin could be an appropriate choice for salvage treatment of coinfection by P. jirovecii and A. terreus.