Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

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.

Dengue and Other Viral Hemorrhagic Fevers.

How to cite this article: Shastri PS, Taneja S. Dengue and Other Viral Hemorrhagic Fevers. Indian J Crit Care Med 2021;25(Suppl 2):S130-S133.

Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India.

During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.

A prospective 3 year study of clinical spectrum and outcome of dengue fever in ICU from a tertiary care hospital in North India.

BACKGROUND AND AIMS: The incidence of specific complications and adverse outcomes in dengue patients needing admission to intensive care units (ICU) may be quite variable in different regions of India presumably because of different strains of dengue virus or due to re infection. METHODS: Patients admitted with acute febrile illness (AFI) with either positive IgM antibody or NS1 antigen for dengue were enrolled. Data were collected for 3 years (2015-2017). A total of 313 patients with acute febrile illness were admitted in the study period (2252 total ICU admissions). A total of 137 (43.76%) cases were serologically proven as dengue fever. RESULTS: Median age (IQR) of study population was 36.0 (26.0-52.0) years. Liver (65.7%) was the main organ involved followed by acute kidney Injury (AKI) (18.6%). Dengue Shock Syndrome (DSS) was found in 18.6% of cases. Fifty-two patients died and the crude mortality was 38.0%. On multivariate analysis APACHE Score <10, thrombocytopenia, hepatic dysfunction, AKI and dengue shock syndrome (DSS) were associated with the risk of mortality. CONCLUSION: This study in ICU patients showed high mortality in relatively younger patients. Liver (in the form of raised Bilirubin) was the most common organ dysfunction. The need to recognise early warning signs for ICU admission is highlighted.

Candida auris candidaemia in an intensive care unit - Prospective observational study to evaluate epidemiology, risk factors, and outcome.

PURPOSE: To determine the prevalence of Candida auris candidaemia in our ICU patients and its molecular epidemiology. METHODS: A prospective observational study was conducted on candidaemia in our ICU patients over 18 months during 2016-2017. Demographics, underlying disease, risk factors, antifungal therapy and outcome were studied. Risk factors of C. auris and non-auris candidaemia were compared. RESULTS: During the study period, among 108 candidaemia cases recorded, the incidence was 6.75/1000 ICU bed days. C. auris topped the list (n = 42, 39.9%), followed by C. tropicalis (34.3%), and C. parapsilosis (15.7%). On bivariate analysis prior antibiotic therapy, long central line days, mechanical ventilation and length of ICU stay were significant risk factors for C. auris candidaemia compared to non-auris candidaemia. Multivariate analysis showed underlying respiratory and neurological diseases as significantly associated with risk of C. auris candidaemia. Fluconazole, amphotericin B, and caspofungin resistance were noted in 97.0%, 93.7% and 3% of C. auris isolates respectively. CONCLUSION: Longer duration of central line days, prior antibiotic use, mechanical ventilation and prolonged ICU stay were important risk factors associated with C. auris candidaemia along with underlying respiratory or neurological disease. The isolates are non-clonal in origin, but they belong to a single clade.

Fulminant Histoplasmosis Presenting as Pyrexia of Unknown Origin in Immunocompetent Adult Diabetic Patient.

Opportunistic infections are commonly seen in immunocompromised individuals such as those suffering from HIV infection, organ transplant recipients and connective tissue disorders. Histoplasmosis is one of the fungal opportunistic infections which is usually seen in immunosuppressed individuals but can also be seen in immunocompetent patients with frequent involvement of adrenal glands. We present a case of adult diabetic patient presenting as pyrexia of unknown origin in which bone marrow aspiration and biopsy lead to diagnosis of histoplasmosis without adrenal involvement. How to cite this article: Shastri P, Gupta P. Fulminant Histoplasmosis Presenting as Pyrexia of Unknown Origin in Immunocompetent Adult Diabetic Patient. Indian J Crit Care Med 2019;23(4):193-195.

Epidemiology and clinical outcomes of invasive mould infections in Indian intensive care units (FISF study).

BACKGROUND AND AIM: Due to limited data on invasive mould infections (IMIs) in the intensive care units (ICUs) of developing countries, we ascertain epidemiology and management of IMIs at 11 ICUs across India. METHODS: Consecutive patients with proven or probable/putative IMIs were enrolled during the study period. Subjects were categorized into classical (neutropenia, malignancy, transplant recipients on immunosuppression) and non-classical (chronic obstructive pulmonary disease, diabetes, liver disease and glucocorticoids) risk groups. We analyzed the demographic, laboratory variables and outcomes of these patients. RESULTS: 398 patients with IMIs (96 proven, 302 probable) were identified, amounting to a prevalence of 9.5 cases/1000 ICU admissions. The mean ±â€¯SD age of the participants was 45.6 ±â€¯21.9 years. The mean ±â€¯SD APACHE II score was 14.3 ±â€¯11.4. The IMIs were diagnosed at a median of 4 days after ICU admission. There were 145 and 253 subjects with classical and non-classical risk groups, respectively. Although Aspergillus spp. were the commonest (82.1%) isolates, Mucorales were detected in 14.4% subjects. A high APACHE II score and IMI due to mucormycosis were significant predictors of mortality. CONCLUSIONS: The study highlights the distinct epidemiology of IMIs in India ICUs with high burden, new susceptible patient groups and considerable number of non-Aspergillus mould infections. [clinicaltrials.gov: NCT02683642].

A Rare Case of Combined Pulmonary Cryptococcosis and Cryptococcal Meningitis in Renal Allograft Recipient.

Invasive cryptococcosis is the third most common invasive fungal infection among organ transplant recipients.1 The most frequently encountered clinical manifestation is cryptococcal meningoencephalitis (CM) which may be easily missed because of varying clinical presentations. 1-year mortality is estimated at 20-30% even with long-term consolidated antifungal therapy. Here we report a case of combined pulmonary and cryptococcal meningitis in a renal allograft recipient. This case illustrates the difficulty of estimating the real extent of the disease when only clinical features are considered. The patient presented with nonspecific symptoms. Chest computed tomography (CT) scans revealed multiple pulmonary nodular shadows. The CT-guided biopsy of the pulmonary nodule clinched the diagnosis of pulmonary cryptococcosis (PC). The central nervous system (CNS) cryptococcosis was proved by positive culture and crypto-LA antigen in the cerebrospinal fluid (CSF). HOW TO CITE THIS ARTICLE: Shastri PS, Kumar R, Gupta P. A Rare Case of Combined Pulmonary Cryptococcosis and Cryptococcal Meningitis in Renal Allograft Recipient. Indian J Crit Care Med 2019;23(12):587-589.

Tropical Fevers in Indian Intensive Care Units: A Prospective Multicenter Study.

BACKGROUND AND AIMS: Infections in tropics often present as undifferentiated fevers with organ failures. We conducted this nationwide study to identify the prevalence, profile, resource utilization, and outcome of tropical fevers in Indian Intensive Care Units (ICUs). MATERIALS AND METHODS: This was a multicenter prospective observational study done in 34 ICUs across India (July 2013-September 2014). Critically ill adults and children with nonlocalizing fever >48 h and onset < 14 days with any of the following: thrombocytopenia/rash, respiratory distress, renal failure, encephalopathy, jaundice, or multiorgan failure were enrolled consecutively. RESULTS: Of 456 cases enrolled, 173 were children <12 years. More than half of the participants (58.7%) presented in postmonsoon months (August-October). Thrombocytopenia/rash was the most common presentation (60%) followed by respiratory distress (46%), encephalopathy (28.5%), renal failure (23.5%), jaundice (20%), and multiorgan failure (19%). An etiology could be established in 365 (80.5%) cases. Dengue (n = 105.23%) was the most common followed by scrub typhus (n = 83.18%), encephalitis/meningitis (n = 44.9.6%), malaria (n = 37.8%), and bacterial sepsis (n = 32.7%). Nearly, half (35% invasive; 12% noninvasive) received mechanical ventilation, a quarter (23.4%) required vasoactive therapy in first 24 h and 9% received renal replacement therapy. Median (interquartile range) ICU and hospital length of stay were 4 (3-7) and 7 (5-11.3) days. At 28 days, 76.2% survived without disability, 4.4% had some disability, and 18.4% died. Mortality was higher (27% vs. 15%) in patients with undiagnosed etiology (P < 0.01). On multivariate analysis, multiorgan dysfunction syndrome at admission (odds ratio [95% confidence interval]-2.8 [1.8-6.6]), day 1 Sequential Organ Failure Assessment score (1.2 [1.0-1.3]), and the need for invasive ventilation (8.3 [3.4-20]) were the only independent predictors of unfavorable outcome. CONCLUSIONS: Dengue, scrub typhus, encephalitis, and malaria are the major tropical fevers in Indian ICUs. The data support a syndromic approach, point of care tests, and empiric antimicrobial therapy recommended by Indian Society of Critical Care Medicine in 2014.

Comparative study of dopamine and norepinephrine in the management of septic shock.

OBJECTIVE: The objective was to compare the ability of norepinephrine and dopamine in reversing the hemodynamic and metabolic abnormalities of septic shock using Edwards Vigileo Monitor with Flotrac Sensor. DESIGN: Prospective randomized control study. METHODS: Fifty consecutive patients presenting with hyperdynamic septic shock who fulfilled the inclusion criteria were randomly allocated to either group I or group II. The goal of therapy was to achieve and maintain for 6 hours, all of the following - systolic blood pressure (SBP) >90 mmHg, systemic vascular resistance index (SVRI) >1800 dynes.s/cm(5)m(2), cardiac index (CI) >4.0 lt/min/m(2), index of oxygen delivery >550 ml/min/m(2), index of oxygen uptake >150 ml/min/m(2). The patients in group I were started on dopamine infusion at 10 µg/kg/min which was increased by 2.5 µg/kg/min, every 15 minutes till the goals were achieved. The patients in group II received norepinephrine infusion started at a dose of 0.5 µg/kg/min with a dose increment of 0.25 µg/kg/min, every 15 minutes till the goals were achieved. RESULTS: Post-treatment heart rate showed an increase in the mean value in group I patients and a decrease in group II patients. The post-treatment mean SBP and SVRI in group II was significantly higher than that in group I. Patients in group I showed a significantly higher increase in post-treatment CI and index of oxygen delivery compared to patients in group II. Nineteen out of 25 patients responded to the treatment in group II while only 10 out of 25 responded in group I. CONCLUSION: Norepinephrine was more useful in reversing the hemodynamic and metabolic abnormalities of hyperdynamic septic shock compared to dopamine.