Disseminated phaeohyphomycosis due to Cladophialophora bantiana in an immunocompetent child.

A 3-year-old boy presented with acute headache, vomiting and right focal clonic seizures without history of fever, joint pain or altered sensorium. Neuroimaging showed multifocal contrast enhancing lesions with significant perilesional edema. CECT chest and abdomen showed multiple variable sized nodules in the lungs and hypodense lesion in liver with mesenteric lymphadenopathy. There was persistent eosinophilia with maximum upto 35 %. Liver biopsy and brain biopsy revealed Cladophialophora bantiana. He was treated with IV liposomal amphotericin and voriconazole for 6 weeks with repeat neuroimaging showing more than 50 % resolution of the intracranial lesions. He was transitioned to oral combination of flucytosine and voriconazole. At 14 months follow-up, he remained symptom free with complete radiological resolution of the lesions and no eosinophilia. High suspicion, an aggressive approach in obtaining microbiological diagnosis and timely combination antifungal therapy may give satisfactory outcome without surgery.

Pan-Indian Clinical Registry of Invasive Fungal Infections Among Patients in the Intensive Care Unit: Protocol for a Multicentric Prospective Study.

BACKGROUND: Fungal infections are now a great public health threat, especially in those with underlying risk factors such as neutropenia, diabetes, high-dose steroid treatment, cancer chemotherapy, prolonged intensive care unit stay, and so on, which can lead to mycoses with higher mortality rates. The rates of these infections have been steadily increasing over the past 2 decades due to the increasing population of patients who are immunocompromised. However, the data regarding the exact burden of such infection are still not available from India. Therefore, this registry was initiated to collate systematic data on invasive fungal infections (IFIs) across the country. OBJECTIVE: The primary aim of this study is to create a multicenter digital clinical registry and monitor trends of IFIs and emerging fungal diseases, as well as early signals of any potential fungal outbreak in any region. The registry will also capture information on the antifungal resistance patterns and the contribution of fungal infections on overall morbidity and inpatient mortality across various conditions. METHODS: This multicenter, prospective, noninterventional observational study will be conducted by the Indian Council of Medical Research through a web-based data collection method from 8 Advanced Mycology Diagnostic and Research Centers across the country. Data on age, gender, clinical signs and symptoms, date of admission, date of discharge or death, diagnostic tests performed, identified pathogen details, antifungal susceptibility testing, outcome, and so on will be obtained from hospital records. Descriptive and multivariate statistical methods will be applied to investigate clinical manifestations, risk variables, and treatment outcomes. RESULTS: These Advanced Mycology Diagnostic and Research Centers are expected to find the hidden cases of fungal infections in the intensive care unit setting. The study will facilitate the enhancement of the precision of fungal infection diagnosis and prompt treatment modalities in response to antifungal drug sensitivity tests. This registry will improve our understanding of IFIs, support evidence-based clinical decision-making ability, and encourage public health policies and actions. CONCLUSIONS: Fungal diseases are a neglected public health problem. Fewer diagnostic facilities, scanty published data, and increased vulnerable patient groups make the situation worse. This is the first systematic clinical registry of IFIs in India. Data generated from this registry will increase our understanding related to the diagnosis, treatment, and prevention of fungal diseases in India by addressing pertinent gaps in mycology. This initiative will ensure a visible impact on public health in the country. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54672.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Lodderomyces elongisporus fungemia in a patient with previous cardiac surgery: Case report and review of literature.

Lodderomyces elongisporus is a rare cause of invasive fungal infections. Most phenotypic tests that are routinely used for identification of yeasts fail to identify this organism. However, chromogenic media for yeasts, MALDI-TOF MS and DNA sequencing can be used for correct identification. We report a case of fungemia complicated by infective endocarditis and intracerebral bleeding in a pediatric patient with previous cardiac surgery.

The Role of Serum Galactomannan Assay as a Potential Surrogate Biomarker for Fungal Microinvasion in Allergic Fungal Rhinosinusitis.

We conducted this study to determine if serum galactomannan (GM) can be used as a marker to implicate the invasiveness of allergic fungal rhinosinusitis (AFRS), and correlate this value with the aggressiveness of disease documented via computed tomography (CT). All paranasal CT scans done for AFRS patients prospectively over a five-year period (2015-2019) were included. An indigenous 20-point score was used to document the extent of bone erosion seen on CT, wherein a higher score meant a greater extent of bone erosion. It was then correlated with serum GM scores. The median CT scores of galactomannan-positive (GM+) patients were compared with the median CT scores of galactomannan-negative (GM-) patients 3 using Mann-Whitney U test. The patients were divided into five groups based on the extent of disease-No bone erosion, erosion of only sinus wall/orbit, 3 erosion of orbit and skull base, erosion of only skull base and lateral extension of disease into infratemporal fossa (ITF). Subgroup analysis was conducted over mean GM values in these groups using ANOVA test. p-value < 0.05 was considered significant. Statistical analysis was performed using SPSS version 25.0. A total of 92 patients were included (56 males, 36 females). No statistically significant difference was found (p-value = 0.42) between the CT scores of galactomannan-positive (GM+) group and galactomannan-negative (GM-) group. The mean GM scores amongst the five sub-groups did not show a statistically significant difference. Serum galactomannan values correlate poorly with aggressiveness of disease quantified on non-contrast CT of paranasal sinuses.

Cryptococcal antigenemia in people living with HIV and AIDS.

AIM: To assess the prevalence of cryptococcal antigenemia among people living with HIV/AIDS (PLHA) with CD4 ≤100/mm3. DESIGN: This observational study was performed on PLHA with laboratory-confirmed CD4 ≤100/mm3. All PLHA were recruited irrespective of their duration of HIV diagnosis, antiretroviral therapy (ART) naïve, or ART failure. METHODS: The prevalence of cryptococcal antigen (CrAg) was assessed in 102 PLHA, with CD4 ≤100/mm3, using a latex agglutination test on serum samples. All the subjects were followed up for 3 months. RESULTS: Amongst 102 PLHA, 62 (60.8%) and 40 (39.2%) patients were ART-naïve and ART failures, respectively, with 2.9% (n = 3) having clinical features of meningitis and 6.8% (n = 7) patients being asymptomatic CrAg-positive. At the 3 month follow-up, total mortality was 10.8%, of which 33.3% and 8.8% were among CrAg-positive and negative patients (p = 0.05). Mortality in asymptomatic and meningitis symptomatic CrAg-positive patients was 1.03% (n = 1) and 2.06% (n = 2), respectively. Of note, five patients were lost to follow-up. CONCLUSION: Cryptococcal antigenemia is common among patients with CD4 ≤100/mm3 who were either ART naïve or had treatment failure. Asymptomatic patients who underwent pre-emptive therapy demonstrated good clinical outcomes.

Therapeutic Drug Monitoring of Voriconazole in Children with Hematologic Malignancy and Invasive Fungal Infections: An RCT from a Tertiary Care Centre in India.

INTRODUCTION: Voriconazole is a triazole anti-fungal with non-linear kinetics and a narrow therapeutic range. The objective of our study was to monitor the voriconazole serum levels in children with hematological malignancy and clinically suspected invasive fungal infections. METHODS: The study was a prospective, randomized controlled trial conducted from June 2016 to December 2017. All children who had haematologic malignancies with clinically suspected invasive fungal infections and received voriconazole as the only anti-fungal were included in the study. The children were randomly allotted into two groups; one was the group that underwent TDM, and the other, TDM, was not done. Bioassay was the method employed for TDM. The trough levels were evaluated on a sample obtained on the fifth day of starting the drug. The institute's ethics committee approved the study. RESULT: A total of 30 children were included in the study: 15 in the TDM group and 15 in the non-TDM group. The most common underlying malignancy was AML. Neutropenia due to chemotherapy sessions was these patients' most common risk factor. A favorable outcome was seen in 13/15 (86.7%) in the TDM group and 11/15 in the non-TDM group (73.3%). CONCLUSION: Only five out of 15 (33.3%) children had voriconazole serum levels within the therapeutic range. Alterations in dose had to be done in the remaining to achieve the recommended serum levels. Thus, we recommend TDM for all children of hematologic malignancy receiving voriconazole for better management. Our findings also revealed that children with AML had lower than recommended levels of voriconazole on TDM evaluation, whereas those with ALL had normal to elevated levels of voriconazole.

Experience on rhino-orbital mucormycosis from a tertiary care hospital in the first wave of COVID-19: An Indian perspective.

Background: To highlight the clinical presentations and management outcomes of rhino-orbital mucormycosis during first wave of COVID-19 pandemic in North India. Methods: A retrospective observational study. 15 patients with mucormycosis (orbital disease) who presented during short span of 3 months (October-December 2020) in a tertiary-care referral institution were analysed. Results: At presentation, 13 of 15 patients had uncontrolled diabetes. Four had history of COVID-19 infection. All patients had advanced orbital disease with sinusitis; cavernous sinus involvement was in nine and intracranial spread in three patients. Liposomal amphotericin-B was started and prompt orbital exenteration with sinus surgery was performed in 12 patients. All 12 patients survived with an average follow-up of 4.8 months. Conclusion: In the present series, cases with orbital spread of mucormycosis were mostly found in non-COVID uncontrolled diabetics. Exenteration was done in 80% of cases with advanced orbital disease. Prevention and early detection of infection at the stage of sino-nasal involvement might help to prevent spread and/or halt the orbital disease.

The association of Candida and antifungal therapy with pro-inflammatory cytokines in oral leukoplakia.

OBJECTIVES: To study the association of Candida and antifungal therapy with pro-inflammatory cytokines (PIC) in oral leukoplakia (OL). MATERIALS AND METHODS: A prospective observational study where immunocompetent adult subjects with OL (30 homogenous (HL), 30 non-homogenous (NHL)) and 30 age and sex-matched healthy controls (C) with no predisposing factors for oral Candida infection were recruited. Sterile cotton swabs and ophthalmic sponges were used to sample the lesion surface in OL and buccal mucosa in C, for direct microscopy and culture for Candida and to determine levels of PIC (IL-6, IL-8. IL-17, TNF-α) by ELISA, respectively. Sampling for PIC was repeated at same sites in OL, 2 weeks after antifungal therapy. RESULTS: Candida was associated with 55.3% of NHL, 23.3% of HL and 13.3% of C. The oral secretary levels of PIC were raised in NHL as compared to HL and C. The levels of IL-6, IL-8, TNF-α (p<0.001) and IL-17 (p<0.01) were significantly raised in Candida positive NHL while IL-6 (p<0.05) and TNF-α (p<0.01) were significantly raised in Candida positive HL before antifungal treatment. After antifungal treatment, there was significant reduction in PIC in Candida positive NHL and HL. CONCLUSIONS: Candida infection contributes to the inflammatory milieu in Candida associated OL which increases the risk of carcinogenesis. Antifungal therapy reduces the PIC in Candida associated OL. CLINICAL RELEVANCE: Identification and elimination of predisposing factors for Candida infection, like cessation of harmful habits, maintenance of oral/denture hygiene, surveillance for Candida and antifungal therapy at intervals, are recommended in OL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04712929.

Therapeutic implications of candida phenotypes, virulence factors and antifungal sensitivity in Oral leukoplakia.

OBJECTIVES: To determine the association of Candida phenotypes, virulence factors, antifungal sensitivity and clinical response to Fluconazole in Oral leukoplakia (OL). METHODS: Sterile swabs were obtained from oral lesions in immunocompetent subjects [30 Homogenous (HOL), 31 Non- Homogenous (NHOL] and normal buccal mucosa in 30 age and sex-matched healthy controls (C). Candida phenotypes, virulence factors (Secreted Aspartyl Proteinase (SAP), Phospholipase (PL), Biofilm formation (BF) and antifungal sensitivity were determined. Clinical features (Size, Erythema, thickness, oral burning sensation (VAS scores) before and after Fluconazole therapy in OL were recorded by two calibrated observers. RESULTS: Candida was associated with OL (p â€‹< â€‹0.01). Candida albicans was the most common phenotype sensitive to Fluconazole. SAP, PL and BF activity was significantly high in NHOL. Strong positive correlation was seen between SAP, and PL activity and pre-treatment VAS scores in NHOL. There was significant reduction in VAS scores, size of lesion [HOL (p â€‹< â€‹0.001) NHOL (p â€‹< â€‹0.05)], erythematous areas (67.8%) in NHOL and thickness of lesions (42.6%) in both types OL after Fluconazole therapy with substantial inter-observer agreement. Non albicans candida (NAC) species had similar virulence profiles but resistant to Fluconazole and showed minimal clinical improvement. CONCLUSIONS: Virulence activity of Candida in OL increases severity of lesions. Fluconazole is effective against virulent Candida albicans, causes clinical improvement and down-staging from high -risk NHOL to low-risk HOL which can reduce risk of malignant transformation. Detection of highly virulent NAC infection and antifungal sensitivity is recommended in OL recalcitrant to Fluconazole therapy.

Epidemiology and Antifungal Susceptibility Patterns of Invasive Fungal Infections (IFIs) in India: A Prospective Observational Study.

The epidemiology of invasive fungal infections (IFI) is ever evolving. The aim of the present study was to analyze the clinical, microbiological, susceptibility, and outcome data of IFI in Indian patients to identify determinants of infection and 30-day mortality. Proven and probable/putative IFI (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group and AspICU criteria) from April 2017 to December 2018 were evaluated in a prospective observational study. All recruited patients were antifungal naïve (n = 3300). There were 253 episodes of IFI (7.6%) with 134 (52.9%) proven and 119 (47%) probable/putative infections. There were four major clusters of infection: invasive candidiasis (IC) (n = 53, 20.9%), cryptococcosis (n = 34, 13.4%), invasive aspergillosis (IA) (n = 103, 40.7%), and mucormycosis (n = 62, 24.5%). The significant risk factors were high particulate efficiency air (HEPA) room admission, ICU admission, prolonged exposure to corticosteroids, diabetes mellitus, chronic liver disease (CLD), acquired immunodeficiency syndrome (AIDS), coronary arterial disease (CAD), trauma, and multiorgan involvement (p < 0.5; odds ratio: >1). The all-cause 30-day mortality was 43.4% (n = 110). It varied by fungal group: 52.8% (28/53) in IC, 58.8% (20/34) in cryptococcosis, 39.8% (41/103) in IA, and 33.9% (21/62) in mucormycosis. HEPA room, ICU admission for IC; HEPA rooms, diabetes mellitus for cryptococcosis; hematological malignancies, chronic kidney disease (CKD), sepsis, galactomannan antigen index value ≥1 for IA and nodules; and ground glass opacities on radiology for mucormycosis were significant predictors of death (odds ratio >1). High minimum inhibitory concentration (MIC) values for azoles were observed in C. albicans, C. parapsilosis, C. glabrata, A. fumigatus, A. flavus, R. arrhizus, R. microsporus, and M. circinelloides. For echinocandin, high MIC values were seen in C. tropicalis, C. guillermondii, C. glabrata, and A. fumigatus. This study highlights the shift in epidemiology and also raises concern of high MICs to azoles among our isolates. It warrants regular surveillance, which can provide the local clinically correlated microbiological data to clinicians and which might aid in guiding patient treatment.

Development of a Sensitive and Specific Novel qPCR Assay for Simultaneous Detection and Differentiation of Mucormycosis and Aspergillosis by Melting Curve Analysis.

Molecular diagnostic assays can expedite the diagnosis of fungal infections, and subsequently help in early interventions and appropriate management of patients. The aim of this study was to develop a single set of primers for a real-time quantitative polymerase chain reaction (qPCR) assay to detect and identify commonly reported, clinically relevant molds i.e., Aspergillus spp, Mucorales and Fusarium spp., up to genus level by melting curve analysis. This assay was evaluated in whole blood from patients with suspected invasive aspergillosis (IA), and in tissue biopsy, bronchoalveolar lavage (BAL) fluid and other site-specific samples from patients with suspected invasive mucormycosis (IM). The limit of detection (LoD) was determined as 10 copies/µl for all three molds. The mean coefficient of variation (CV) across all sets of intra- and inter-assay data was 0.63% (ranging from 0.42 to 1.56%), showing high reproducibility of the assay. Sensitivity and specificity of the assay were 93.3 and 97.1% respectively for diagnosis of IA, and 99.29 and 83.84% respectively for diagnosis of IM. Fusarium was not detected in any of the clinical samples included and the few laboratory confirmed cases of fusariosis did not meet the inclusion criteria of the study. Hence no ROC curve or cutoff value could be generated for the same. This newly developed qPCR assay therefore appears to be a promising tool in detection of IA and IM.

Role of Voriconazole in the Management of Invasive Central Nervous System Aspergillosis: A Case Series from a Tertiary Care Centre in India.

Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy.

Aetiological agents for pulmonary exacerbations in children with cystic fibrosis: An observational study from a tertiary care centre in northern India.

Background & objectives: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF). The infection occurs with a unique spectrum of bacterial pathogens that are usually acquired in an age-dependent fashion. The objective of this study was to find out the aetiological agents in respiratory specimens from children with CF during pulmonary exacerbation and relate with demographic variables. Methods: In this observational study, airway secretions from children (n=104) with CF presenting with pulmonary exacerbations were collected and tested for bacteria, fungi, mycobacteria and viral pathogens using appropriate laboratory techniques. The frequencies of isolation of various organisms were calculated and associated with various demographic profiles. Results: Bacteria were isolated in 37 (35.5%) and viral RNA in 27 (29.3%) children. Pseudomonas was the most common bacteria grown in 31 (29.8%) followed by Burkholderia cepacia complex (Bcc) in three (2.8%) patients. Among viruses, Rhinovirus was the most common, identified in 16 (17.4%) samples followed by coronavirus in four (4.3%). Fungi and mycobacteria were isolated from 23 (22.1%) and four (3.8%) children, respectively. Aspergillus flavus was the most common fungus isolated in 13 (12.5%) children. Interpretation & conclusions: Pseudomonas was the most common organism isolated during exacerbation. Non-tuberculous mycobacteria were not isolated, whereas infection with Bcc and Mycobacterium tuberculosis was observed, which could probably have a role in CF morbidity. Polymicrobial infections were associated with severe exacerbations.

Mucor menace in an immunocompetent young male after dental manipulation.

Fungal rhino-orbital sinusitis due to mucormycetes is a rapidly progressive condition with high mortality, rarely seen in immunocompetent individuals. A 26-year-old immunocompetent male presented with rhino-orbital mucormycosis after a history of dental manipulation. The patient was successfully managed with a combination of surgery, amphotericin B, and posaconazole. Here, we highlight the delay in diagnosis and challenges faced in the management.

A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment.

Mucormycosis due to Mucorales is reported at large numbers in uncontrolled diabetics across India, but systematic multicenter epidemiological study has not been published yet. The present prospective study was conducted at four major tertiary care centers of India (two in north and two in south India) during 2013-2015 to compare the epidemiology, treatment strategies and outcome of mucormycosis between the two regions. Molecular techniques were employed to confirm the identity of the isolates or to identify the agent in biopsy samples. A total of 388 proven/probable mucormycosis cases were reported during the study period with overall mortality at 46.7%. Uncontrolled diabetes (n = 172, 56.8%) and trauma (n = 31, 10.2%) were the common risk factors. Overall, Rhizopus arrhizus (n = 124, 51.9%) was the predominant agent identified, followed by Rhizopus microsporus (n = 30, 12.6%), Apophysomyces variabilis (n = 22, 9.2%) and Rhizopus homothallicus (n = 6, 2.5%). On multivariate analysis, the mortality was significantly associated with gastrointestinal (OR: 18.70, P = .005) and pulmonary infections (OR: 3.03, P = .015). While comparing the two regions, majority (82.7%) cases were recorded from north India; uncontrolled diabetes (n = 157, P = .0001) and post-tubercular mucormycosis (n = 21, P = .006) were significantly associated with north Indian cases. No significant difference was noted among the species of Mucorales identified and treatment strategies between the two regions. The mortality rate was significantly higher in north Indian patients (50.5%) compared to 32.1% in south India (P = .016). The study highlights higher number of mucormycosis cases in uncontrolled diabetics of north India and emergence of R. microsporus and R. homothallicus across India causing the disease.

Efficacy of Posaconazole Prophylaxis in Patients with Acute Myeloid Leukemia Undergoing Induction Chemotherapy: An Observational Study in Resource Limited Settings.

Large randomized controlled trials have shown significant decrease in incidence of invasive fungal infection in acute myeloid leukemia patients with Posaconazole prophylaxis. However, very less is known about value of Posaconazole prophylaxis in resource limited settings. This observational cohort study evaluated the incidence of fungal infection in patients with hematological malignancies undergoing induction chemotherapy with Posaconazole as antifungal prophylaxis and was compared with historical controls who received Fluconazole as fungal prophylaxis. The study was conducted from Oct 2013 to July 2015 in Department of Hematology of a tertiary care center. Fifty-three patients of acute myeloid leukemia on Posaconazole as fungal prophylaxis and 53 historical controls on Fluconazole as fungal prophylaxis were included for final analysis. Baseline characteristics were well matched between groups. Patients on Fluconazole were more likely to experience breakthrough IFDs (28.3 and 11.3%; p = 0.028) than in patients receiving Posaconazole prophylaxis. No significant difference was observed in overall, attributable mortality or in shift to first line antifungal. Both Posaconazole and Fluconazole were well tolerated with no major adverse effects requiring discontinuation of the drug. Minor side effects were seen in 39 and 47% patients in study and control group respectively. Vomiting and nausea were the commonest side effects seen in both study and control group (26 vs. 34% and 38 vs. 40% of patients, respectively). The results of our study in patients with acute myeloid leukemia provide evidence that Posaconazole prophylaxis significantly decreases the incidence of fungal infection and is well tolerated.

Prevalence and Predictors of Invasive Fungal Infections in Children with Persistent Febrile Neutropenia Treated for Acute Leukemia - A Prospective Study.

OBJECTIVE: To ascertain the prevalence of invasive fungal infections (IFI), predictors of IFI, identify etiological species and outcome (mortality/discharge) in persistent febrile neutropenia in children with acute leukemia. METHODS: It was a prospective, observational study conducted from January 2013 through June 2014 in a tertiary care centre in New Delhi. Children between 1 and 12 y of age, on chemotherapy for acute leukemia with persistent febrile neutropenia (> 96 h) were enrolled. These children were not on any antifungal prophylaxis. Diagnosis of IFI was based on European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. Prevalence and outcome was reported in mean ± 95% CI form and etiological species were presented in the form of the frequency distribution. RESULTS: Three hundred nineteen episodes involving 187 children of febrile neutropenia were screened and 74 were enrolled. Prevalence of IFI was 22.97% (13.99-34.21). Positive cases were further classified into proven 3(17.6%), probable 11(64.8%) and possible 3(17.6%) according to EORTC/MSG criteria. On multivariate analysis, abnormal CXR and clinical sinusitis were important predictors of IFI. Most common fungi isolated was Aspergillus sp. followed by Candida sp. Mortality rate was 9.45% (3.89-18.52). CONCLUSIONS: Thus, prevalence of IFI is very high in children with persistent febrile neutropenia who are not on antifungal prophylaxis. Abnormal chest x- ray and clinical sinusitis are important predictors of IFI.

Two cases of Osteoarticular Mucor menace: A diagnostic and management conundrum.

Mucormycosis is an uncommon aggressive fungal infection usually seen in immunocompromised hosts or patients with burns and trauma. The common presentations include rhino-orbital-cerebral and pulmonary involvement. Osteoarticular involvement is a rare presentation of this disease. We present two cases of osteoarticular mucormycosis of pelvis and long bones of the lower limb, one in a patient with burn injury and other one in a patient with chronic granulomatous disease, hitherto a rarely reported association. Delayed diagnosis in a setting where tuberculosis is a common cause of chronic osteomyelitis, challenges in medical and surgical management of these patients are discussed in this report.