COVID-19-associated mucormycosis presenting to the Emergency Department-an observational study of 70 patients.

BACKGROUND: Mucormycosis (MM) is a deadly opportunistic fungal infection and a large surge in COVID-19-associated mucormycosis (CAM) is occurring in India. AIM: Our aim was to delineate the clinico-epidemiological profile and identify risk factors of CAM patients presenting to the Emergency Department (ED). DESIGN: This was a retrospective, single-centre, observational study. METHODS: We included patients who presented with clinical features or diagnosed MM and who were previously treated for COVID-19 in last 3 months of presentation (recent COVID-19) or currently being treated for COVID-19 (active COVID-19). Information regarding clinical features of CAM, possible risk factors, examination findings, diagnostic workup including imaging and treatment details were collected. RESULTS: Seventy CAM patients (median age: 44.5 years, 60% males) with active (75.7%) or recent COVID-19 (24.3%) who presented to the ED in between 6 May 2021 and 1 June 2021, were included. A median duration of 20 days (interquartile range: 13.5-25) was present between the onset of COVID-19 symptoms and the onset of CAM symptoms. Ninety-three percent patients had at least one risk factor. Most common risk factors were diabetes mellitus (70%) and steroid use for COVID-19 disease (70%). After clinical, microbiological and radiological workup, final diagnosis of rhino-orbital CAM was made in most patients (68.6%). Systemic antifungals were started in the ED and urgent surgical debridement was planned. CONCLUSION: COVID-19 infection along with its medical management have increased patient susceptibility to MM.

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.

Novel synthetic anti-fungal tripeptide effective against Candida krusei.

INTRODUCTION: Candida species are the major fungal pathogens of humans. Among them, Candida krusei have emerged as a notable pathogen with a spectrum of clinical manifestations and is known to develop resistance against azoles mainly fluconazole. Anti-microbial peptides play important roles in the early mucosal defence against infection and are potent anti-fungal agents since they fight against fungal infection as well as have ability to regulate host immune defence system. The aim of the study was to synthesize a small anti fungal peptide. MATERIALS AND METHODS: The series of tripeptides were synthesized and screened for antifungal activity against Candida strains according to CLSI guidelines. Toxicity effect of peptide was tested with human erythrocytes. The mode of action of peptide on fungus was resolved by scanning electron microscopy (SEM) studies Results: The tripeptide FAR showed a prominent anti fungal activity among the series. The minimum inhibitory concentration and minimum fungicidal concentration of tripeptide FAR was found to be 171.25 µg/ml and 685 µg/ml, respectively against Candida krusei . The therapeutic index was 2.9. The haemolytic experiment revealed that this peptide is non-toxic to human cells. The SEM studies showed disruption of cell wall and bleb-like surface changes and irregular cell surface. CONCLUSION: The peptide showed a significant antifungal activity against C. krusei. Thus, it can set a platform for the design of new effective therapeutic agents against C. krusei.

Distribution of different yeasts isolates among trauma patients and comparison of accuracy in identification of yeasts by automated method versus conventional methods for better use in low resource countries.

INTRODUCTION: As most trauma patients require long-term hospital stay and long-term antibiotic therapy, the risk of fungal infections in such patients is steadily increasing. Early diagnosis and rapid treatment is life saving in such critically ill trauma patients. AIMS: To see the distribution of various species of Candida among trauma patients and compare the accuracy, rapid identification and cost effectiveness between VITEK 2, CHROMagar and conventional methods. SETTINGS AND DESIGN: Retrospective laboratory-based surveillance study performed over a period of 52 months (January 2009 to April 2013) at a level I trauma centre in New Delhi, India. MATERIALS AND METHODS: All microbiological samples positive for Candida were processed for microbial identification using standard methods. Identification of Candida was done using chromogenic medium and by automated VITEK 2 Compact system and later confirmed using the conventional method. Time to identification in both was noted and accuracy compared with conventional method. STATISTICAL ANALYSIS: Performed using the SPSS software for Windows (SPSS Inc. Chicago, IL, version 15.0). P values calculated using χ2 test for categorical variables. A P<0.05 was considered significant. RESULTS: Out of 445 yeasts isolates, Candida tropicalis (217, 49%) was the species that was maximally isolated. VITEK 2 was able to correctly identify 354 (79.5%) isolates but could not identify 48 (10.7%) isolates and wrongly identified or showed low discrimination in 43 (9.6%) isolates but CHROM agar correctly identified 381 (85.6%) isolates with 64 (14.4%) misidentification. Highest rate of misidentification was seen in C. tropicalis and C. glabrata (13, 27.1% each) by VITEK 2 and among C. albicans (9, 14%) by CHROMagar. CONCLUSIONS: Though CHROMagar gives identification at a lower cost compared with VITEK 2 and are more accurate, which is useful in low resource countries, its main drawback is the long duration taken for complete identification.

Prevalence and risk factors for allergic bronchopulmonary aspergillosis in Indian children with cystic fibrosis.

OBJECTIVES: Allergic bronchopulmonary aspergillosis (ABPA) is a common complication in patients with cystic fibrosis. This cross-sectional study was planned to determine the prevalence and risk factors for ABPA in Indian children with cystic fibrosis. METHODS: Clinical evaluation, spirometry, chest radiograph, sputum, total IgE, specific IgE for Aspergillus fumigatus, IgG precipitins and skin prick tests were done in 33 CF patients. RESULTS: Prevalence of allergic bronchopulmonary aspergillosis was 18.2% (95% CI 6.9% - 35.4%): allergic bronchopulmonary aspergillosis was higher in patients with low cystic fibrosis score, age >12 years, atopy, and eosinophilia. CONCLUSION: Prevalence of ABPA is higher in Indian children with cystic fibrosis.

A case of dual infection in a paediatric trauma victim of primary cutaneous aspergillosis caused by Aspergillus flavus and Aspergillus terreus.

Aspergillus spp. are widely distributed throughout the environment. They are opportunistic pathogens causing infection at various sites in the body such as lungs, sinuses, eyes, skin, central nervous system etc., Primary cutaneous aspergillosis is an uncommon disease entity. Primary infections usually occur at sites having disruption of the skin and usually occur in burn patients, trauma and surgical patients. A 4-year-old girl who was run over by a truck and suffered extensive de-gloving injury to bilateral lower limbs developed greenish discharge and scaly lesions around the wound margins after 50 days of hospital stay. The skin biopsy demonstrated the presence of thin septate hyphae branching at acute angles and culture demonstrated growth of Aspergillus flavus and Aspergillus terreus. The child was started on voriconazole therapy for 3 weeks and the lesion healed satisfactorily. Subsequent skin biopsy culture was negative for fungi. Prompt diagnosis and management of such cases can salvage the limbs in severe trauma cases.

Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida.

Natural isopropyl cresols have been reported to have antifungal activity. This work is an attempt to examine thymol and carvacrol against 111 fluconazole-sensitive and -resistant Candida isolates. Insight into the mechanism of action was elucidated by flow cytometric analysis, confocal imaging and ergosterol biosynthesis studies. The susceptibility tests for the test compounds were carried out in terms of minimum inhibitory concentrations (MICs), disc diffusion assays and time-kill curves against all Candida isolates by employing standard protocols. Propidium iodide (PI) cell sorting has been investigated by flow cytometric analysis and confocal imaging. Haemolytic activity on human erythrocytes was studied to exclude the possibility of further associated cytotoxicity. Both compounds were found to be effective to varying extents against all isolates, including the resistant strains. In contrast to the fungistatic nature of fluconazole, our compounds were found to exhibit fungicidal nature. Significant impairment of ergosterol biosynthesis was pronouncedly induced by the test entities. Negligible cytoxicity was observed for the same compounds. Furthermore, it was observed that the positional difference of the hydroxyl group in carvacrol slightly changes its antifungal activity. Carvacrol and thymol show strong fungicidal effect against all of the Candida isolates. The mechanisms of action of these natural isopropyl cresols appear to originate from the inhibition of ergosterol biosynthesis and the disruption of membrane integrity.

Multiple osseous involvements in a case of disseminated cryptococcosis.

Osseous involvement occurs in 5-10% of patients with disseminated cryptococcosis. We are reporting an unusual case of disseminated cryptococcosis involving the sternum and lumbar vertebra with the formation of psoas abscess with pulmonary tuberculosis. The patient presented with fever for 3 months. A diagnosis of pulmonary tuberculosis was made on thoracic contrast-enhanced computerized tomography and she was put on antituberculosis treatment. She was immunocompetent with negative human immunodeficiency virus. She conceived subsequently and had complaints of backache and swelling over the sternum. Magnetic resonance imaging showed destruction of L5 vertebra with psoas abscess. Vertebral cryptococcosis may mimic tuberculosis and malignancy. She had a bad obstetric history and experienced five, first-trimester spontaneous abortions in each successive year since 2001. This pregnancy again resulted in spontaneous abortion. Cryptococcus neoformans was isolated from two different sites: pus-involving the sternum and ultrasound-guided psoas abscess aspirate. Serum latex agglutination test for cryptococcal capsular polysaccharide antigen was positive. The diagnosis of cryptococcosis was delayed because the patient was diagnosed as a case of pulmonary tuberculosis, wherein clinical signs, symptoms and radiological findings in both the conditions are similar. Amphotericin B was started but she developed varicella infection and expired due to cardiac failure.

Candida rugosa: a possible emerging cause of candidaemia in trauma patients.

INTRODUCTION: Candida rugosa appears to be emerging as a distinctive cause of candidaemia in recent years. Candidaemia due to this species is important to recognise because of its decreased susceptibility to azoles. MATERIALS AND METHODS: We retrospectively evaluated a cluster of C. rugosa candidaemia occurring in critically ill trauma patients from a level I trauma centre of India. During the period from July 2008 to September 2009, a total of 28 blood samples from 19 patients were found to be positive for C. rugosa. Genetic relatedness among 17 C. rugosa isolates were characterised by the random amplified polymorphic DNA (RAPD) assay using M13 primers. These isolates were also characterised for their susceptibility to four antifungal agents, amphotericin B, fluconazole, flucytosine and voriconazole. RESULTS: In our study, 21% of C. rugosa isolates were resistant to fluconazole, whereas 100% susceptibility to amphotericin B, flucytosine and voriconazole was noted. Thirteen out of the 19 patients (68.4%) with C. rugosa candidaemia died. Of these, six had received antifungal therapy after confirmation of fungaemia. DISCUSSION: Prior to this cluster, C. rugosa had never been identified as a cause of infection at our centre. Due to the retrospective nature of the evaluation of these cases, the source of this possible outbreak could not be traced. Nevertheless, to the best of our knowledge, this is the largest cluster of cases of C. rugosa candidaemia reported from a single institution in the English literature.

Primary cutaneous aspergillosis due to Aspergillus niger in an immunocompetent patient.

Primary cutaneous aspergillosis is a rare entity, usually caused by A. fumigatus and A. flavus . Here, we present such a case, manifested by ulceration due to A. niger, which remained undiagnosed for a prolonged period. The immunological status was intact, although the patient had associated severe fungal infection. Recurrence of the lesion occurred despite repeated anti-fungal therapies. Anti fungal testing was done based on the broth dilution (M-38A, NCCLS, USA) method. The culture isolate was found to be sensitive to fluconazole and amphotericin B. Continuation of antifungal therapy improved the symptoms, reducing the size of the lesion.

Basidiobolomycosis: a rare case report.

We report a rare case of basidiobolomycosis seen in an 11-year-old girl from North-Eastern part of India. She presented with complaints of bilateral nasal block and nasal discharge for seven-eight months. CT scan of sinuses revealed polypoidal mass in all the sinuses with extradural extension. The tissue biopsy examined histopathologically and microbiologically, revealed Basidiobolus ranarum.

Brain abscess caused by Cladophialophora Bantiana in an immunocompetent host: need for a novel cost-effective antifungal agent.

We report a 53-year-old male who presented with headache, tremor and memory disturbance. Radiological evaluation was suggestive of brain abscess. He underwent gross total excision of the cerebral abscess. The histopathological examination and pus culture was suggestive of brain abscess caused by Cladophialophora bantiana. Authors report a rare case of biopsy and culture proven Cladophialophora bantiana brain abscess in an immunocompetent host. The authors review the relevant literature and current treatment options while emphasizing the need for a cost-effective novel antifungal drug to salvage a subset of patients suffering from this rare but increasingly frequent condition.

Fungal panniculitis in renal transplant recipients.

Panniculitis may result due to various etiologies. In post-transplant immunosuppressed patients infection is the foremost cause of panniculitis. We present 2 cases of fungal panniculitis in renal transplant recipients. The first patient presented with non-tender firm erythematous plaques on the left thigh. Biopsy showed panniculitis with cryptococci. Subsequent investigations revealed the presence of cryptococcal antigens in the blood, urine, and bronchoalveolar lavage fluid. There was no evidence of cryptococcal meningitis. The second patient complained of subcutaneous nodules on the trunk and right thigh. Biopsy of one of the nodules showed panniculitis with histoplasma. This patient had been treated earlier (inadequately) for disseminated histoplasmosis. Both the cases responded well to conventional amphotericin B therapy. Their renal functions remained stable.

Epidemiology of candidemia in a tertiary care centre of north India: 5-year study.

BACKGROUND: To determine the distribution of species of Candida and the risk factors associated with candidemia in Indian population for which we conducted a retrospective study for 5 years in a tertiary care centre of North India. MATERIALS AND METHODS: Blood samples from 7,297 patients aged from 3 days to 85 years, suspected with candidemia, were collected and tested for Candida. The susceptibility patterns toward fluconazole for the year 2005 isolates were tested by micro-dilution assay as described in the CLSI (M27A-2 method). RESULTS: Most of the episodes have been caused by species other than C. albicans. Non-albicans candidemia was 79%-80% in both female and male populations. The most frequent species isolated from 275 patients in 5 years (January 2001-December 2005) was C. tropicalis (35.3%), followed by C. albicans (21.5%), C. parapsilosis (20%), C. glabrata (17.5%), C. krusei (3.3%), C. haemulonii (1.5%), and C. guilliermondii (1%). C. parapsilosis was the predominant in the fifth year of the study (2004-2005). Dose-dependent susceptibility to fluconazole was observed in 5% (n = 3) of the strains. Antifungal resistance was found in 11.7% (n = 7), which includes only C. glabrata. CONCLUSION: These results were comparable to those derived from other regions of India. C. tropicalis has been reported as the predominant species involved in the cases of candidemia. But in 2005 it has moved toward C. parapsilosis. No true antifungal resistance is reported. Further epidemiological surveillance is needed.

Invasive dermatophytosis with lymph node involvement in an immunocompetent patient.

A 23-year-old man presented with annular and arcuate, hyperpigmented, itchy, scaly plaques over the trunk and lower extremities for 5 years progressing to verrucous papules and nodules for the last 1.5 years. He also had nontender, inguinal and axillary lymphadenopathy. Skin and lymph node biopsies showed granulomatous inflammation and special stains demonstrated long septate hyphae. Tissue cultures grew Trichophyton verrucosum. The patient was treated with itraconazole 100 mg twice daily for 8 months, resulting in complete clearance of the lesions.

The first major outbreak of dengue hemorrhagic fever in Delhi, India.

India An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHS/DSS) occurred in 1996 in India in and near Delhi. The cause was confirmed as dengue virus type 2, by virus cultivation and indirect immunofluorescence with type-specific monoclonal antibodies. This is the largest such outbreak reported from India, indicating a serious resurgence of dengue virus infection.