Characteristics, outcome and risk factors for mortality of paediatric patients with ICU-acquired candidemia in India: A multicentre prospective study.

BACKGROUND: The epidemiology, clinical profile and outcome of paediatric candidemia vary considerably by age, healthcare settings and prevalent Candida species. Despite these differences, few comprehensive studies are undertaken. This nationwide study addresses this knowledge gap. METHODS: 487 children who contracted ICU-acquired candidemia at 23 Indian tertiary care centres were assessed for 398 variables spanning demography, clinical characteristics, microbiology, treatment and outcome. RESULTS: Both neonates (5.0 days; range = 3.0-9.5) and non-neonatal children (7.0 days; range = 3.0-13.0) developed candidemia early after ICU admission. Majority of neonates were premature (63.7%) with low birthweight (57.1%). Perinatal asphyxia (7.3%), pneumonia (8.2%), congenital heart disease (8.4%) and invasive procedures were common comorbidities, and antibiotic use (94.1%) was widespread. C tropicalis (24.7%) and C albicans (20.7%) dominated both age groups. Antifungal treatment (66.5%) and removal of central catheters (44.8%) lagged behind. Overall resistance was low; however, emergence of resistant C krusei and C auris needs attention. The 30-day crude mortality was 27.8% (neonates) and 29.4% (non-neonates). Logistic regression identified admission to public sector ICUs (OR = 5.64), mechanical ventilation (OR = 2.82), corticosteroid therapy (OR = 8.89) and antifungal therapy (OR = 0.22) as independent predictors of 30-day crude mortality in neonates. Similarly, admission to public sector ICUs (OR = 3.62), mechanical ventilation (OR = 3.13), exposure to carbapenems (OR = 2.18) and azole antifungal therapy (OR = 0.48) were independent predictors for non-neonates. CONCLUSIONS: Our findings reveal a distinct epidemiology, including early infection with a different spectrum of Candida species, calling for appropriate intervention strategies to reduce candidemia morbidity and mortality. Independent factors identified in our regression models can help tackle these challenges.

Candida auris candidaemia in Indian ICUs: analysis of risk factors.

Objectives: To identify the risk factors associated with Candida auris candidaemia, as this fungus now poses a global threat. Methods: We performed a subgroup analysis of a previously reported study of 27 Indian ICUs. The clinical data of candidaemia cases due to C. auris and other Candida species were compared to determine significant risk factors associated with C. auris infection. Results: Of the 1400 candidaemia cases reported earlier, 74 (5.3%) from 19 of 27 ICUs were due to C. auris . The duration of ICU stay prior to candidaemia diagnosis was significantly longer in patients with C. auris candidaemia (median 25, IQR 12-45 days) compared with the non- auris group (median 15, IQR 9-28, P < 0.001). Based on logistic regression modelling, admission to north Indian ICUs [OR 2.1 (1.2-3.8); P = 0.012], public-sector hospital [OR 2.2 (1.2-3.9); P = 0.006], underlying respiratory illness [OR 2.1 (1.3-3.6); P = 0.002], vascular surgery [OR 2.3 (1.00-5.36); P = 0.048], prior antifungal exposure [OR 2.8 (1.6-4.8); P < 0.001] and low APACHE II score [OR 0.8 (0.8-0.9); P = 0.007] were significantly associated with C. auris candidaemia. The majority (45/51, 88.2%) of the isolates were clonal. A considerable number of isolates were resistant to fluconazole ( n = 43, 58.1%), amphotericin B ( n = 10, 13.5%) and caspofungin ( n = 7, 9.5%). Conclusions: Although C. auris infection has been observed across India, the number of cases is higher in public-sector hospitals in the north of the country. Longer stay in ICU, underlying respiratory illness, vascular surgery, medical intervention and antifungal exposure are the major risk factors for acquiring C. auris infection even among patients showing lower levels of morbidity.

Role of (1-3)-Β-D-Glucan Test in the Diagnosis of Invasive Fungal Infections among High-Risk Patients in a Tertiary Care Hospital.

Background Invasive fungal infections (IFI) are associated with high mortality. Serum fungal biomarkers offer an advantage over the traditional methods in early diagnosis and better clinical outcomes. The aim of the study was to evaluate the role of (1-3)-ß-D-glucan (BDG) assay in the patients suspected of IFI. Materials and Methods This prospective study was conducted in the Department of Microbiology, Dayanand Medical College and Hospital, Ludhiana, over a period of 1 year. A total of 862 serum samples were received from patients suspected of IFI, for the BDG test (Fungitell, Associates of Cape Cod Inc., USA). The test was performed as per kit protocol. Appropriate samples were processed for KOH fungal smear and fungal culture. Blood culture was done by Bactec (Biomerieux). Statistical Analysis Results were analyzed using descriptive statistical methods. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated at different cutoffs. In addition, the receiver operating characteristic (ROC) curve using SPSS 21.00 software was calculated and the diagnostic accuracy was shown by the area under the ROC curve (AUC). Results Among 862 patients, 546 (63.3%) were males. The predominant age group (25.6%) was between 61 and 70 years. The most common risk factor (54.8%) was prolonged intensive care unit stay. Out of the total samples, 455 (52.8%) samples were found positive for BDG. Fungal elements were seen in 48 (10.5%) KOH smears and fungal growth was obtained in 81 (17.8%) cultures. Comparison of BDG assay and culture at different cutoffs yielded AUC-0.823. Sensitivity (100%), specificity (51.3%), accuracy (55.6%), PPV (15.8%), and NPV (100%) were observed at the kit cutoff of 80 pg/mL. Optimum sensitivity and specificity of 79.2% and 70.3%, respectively, were observed at a cutoff of 142.4pg/mL. A significant correlation was observed between BDG positivity and piperacillin-tazobactam use and dialysis. Among BDG positive patients, 38(8.4%) succumbed to death. Conclusion Detection of BDG helps in the early diagnosis of IFI in critically ill patients. As the assay has a high NPV, a negative test can be used to stop the empirical antifungal drugs. The use of a higher cutoff can be useful to avoid false-positive results.

Clinical spectrum and outcome of pulmonary nocardiosis: 5-year experience.

BACKGROUND: Pulmonary nocardiosis is a rare but a life-threatening infection caused by Nocardia spp. The diagnosis is often missed and delayed resulting in delay in appropriate treatment and thus higher mortality. AIM: In this study, we aim to evaluate the clinical spectrum and outcome of patients with pulmonary nocardiosis. METHODS: A retrospective, 5-year (2009-2014) review of demographic profile, risk factors, clinical manifestations, imaging findings, treatment, and outcome of patients with pulmonary nocardiosis admitted to a tertiary care hospital. RESULTS: The median age of the study subjects was 54 years (range, 16-76) and majority of them (75%) were males. The risk factors for pulmonary nocardiosis identified in our study were long-term steroid use (55.6%), chronic lung disease (52.8%), diabetes (27.8%), and solid-organ transplantation (22.2%). All the patients were symptomatic, and the most common symptoms were cough (91.7%), fever (78%), and expectoration (72%). Almost two-third of the patients were initially misdiagnosed and the alternative diagnosis included pulmonary tuberculosis (n = 7), community-acquired pneumonia (n = 5), lung abscess (n = 4), invasive fungal infection (n = 3), lung cancer (n = 2), and Wegener's granulomatosis (n = 2). The most common radiographic features were consolidation (77.8%) and nodules (56%). The mortality rate for indoor patients was 33% despite treatment. Higher mortality rate was observed among those who had brain abscess (100.0%), HIV positivity (100%), need for mechanical ventilation (87.5%), solid-organ transplantation (50%), and elderly (age > 60 years) patients (43%). CONCLUSION: The diagnosis of pulmonary nocardiosis is often missed and delayed resulting in delay in appropriate treatment and thus high mortality. A lower threshold for diagnosing pulmonary nocardiosis needs to be exercised, in chest symptomatic patients with underlying chronic lung diseases or systemic immunosuppression, for the early diagnosis, and treatment of this uncommon but potentially lethal disease. Despite treatment mortality remains high, especially in those with brain abscess, HIV positivity, need for mechanical ventilation, solid-organ transplantation, and elderly.

Post-operative Abdominal Wall Mucormycosis-a Case Series.

Mucormycosis is caused by saprophtytic fungi which cause acute invasive zygomycosis. It clinically presents with necrosis, and on histopathology, acute and chronic infiltrates are seen. It rarely infects a healthy host, but is devastating in an immunocompromised host. We studied five cases with post-operative abdominal wall mucormycosis, three females and two males. Three patients were post-operative while the other two had mucormycosis following trauma and infection was found in sutured wound. All were initially diagnosed as cases of necrotizing fasciitis. Two patients eventually survived after intensive medical therapy and extensive debridements.

Incidence, characteristics and outcome of ICU-acquired candidemia in India.

PURPOSE: A systematic epidemiological study on intensive care unit (ICU)-acquired candidemia across India. METHOD: A prospective, nationwide, multicentric, observational study was conducted at 27 Indian ICUs. Consecutive patients who acquired candidemia after ICU admission were enrolled during April 2011 through September 2012. Clinical and laboratory variables of these patients were recorded. The present study is an analysis of data specific for adult patients. RESULTS: Among 1,400 ICU-acquired candidemia cases (overall incidence of 6.51 cases/1,000 ICU admission), 65.2 % were adult. Though the study confirmed the already known risk factors for candidemia, the acquisition occurred early after admission to ICU (median 8 days; interquartile range 4-15 days), even infecting patients with lower APACHE II score at admission (median 17.0; mean ± SD 17.2 ± 5.9; interquartile range 14-20). The important finding of the study was the vast spectrum of agents (31 Candida species) causing candidemia and a high rate of isolation of Candida tropicalis (41.6 %). Azole and multidrug resistance were seen in 11.8 and 1.9 % of isolates. Public sector hospitals reported a significantly higher presence of the relatively resistant C. auris (8.2 vs. 3.9 %; p = 0.008) and C. rugosa (5.6 vs. 1.5 %; p = 0.001). The 30-day crude and attributable mortality rates of candidemia patients were 44.7 and 19.6 %, respectively. Logistic regression analysis revealed significant independent predictors of mortality including admission to public sector hospital, APACHE II score at admission, underlying renal failure, central venous catheterization and steroid therapy. CONCLUSION: The study highlighted a high burden of candidemia in Indian ICUs, early onset after ICU admission, higher risk despite less severe physiology score at admission and a vast spectrum of agents causing the disease with predominance of C. tropicalis.

Prevalence of metalo- ß-lactamase-producing (MBL) Acinetobacter species in a tertiary care hospital.

BACKGROUND AND OBJECTIVES: Acinetobacter causes a wide variety of illness in debilitated and hospitalized patients. Carbapenem resistance in Acinetobacter is an emerging problem and is a cause of concern as many nosocomial infections with Acinetobacter are resistant to most other antibiotics. The present study was aimed to study metallo-ß-lactamase (MBL) production in Acinetobacter species. MATERIALS AND METHODS: During one year prospective study, all isolates of Acinetobacter obtained from various clinical samples like respiratory, pus, blood and others were included. Antimicrobial susceptibility testing was done by standard Kirby Bauer disk diffusion method. Metallo ß-lactamase (MBL) detection was done by imipenem-EDTA combined disk method. RESULTS: Among 1017 isolates, 964 were A. baumannii, 48 were A. lwoffii and 5 were A. hemolyticus. Out of these, majority of the isolates were obtained from respiratory samples, followed by pus. A .baumannii showed high level of resistance to cephalosporins, cotrimoxazole and piperacillin. A .lwoffii and A. hemolyticus showed lesser resistance to all antibiotics. Imipenem resistance was observed in 389 (40.3 %) isolates of A.baumannii and MBL activity was seen in 80.3% of isolates. MBL positive isolates of A. baumannii showed higher resistance as compared to MBL negative isolates. CONCLUSION: This study demonstrated that multidrug resistant strains of Acinetobacter are common in tertiary care hospitals. Unwarranted and unrestricted usage of antibiotics is associated with emergence of resistance in nosocomial pathogens. Regular monitoring and documentation of carbapenem resistant is crucial in developing strategies to control infection due to these bacteria.

Cerebral Phaeohyphomycosis due to Cladophialophora bantiana - A Case Report and Review of Literature from India.

Cerebral phaeohyphomycosis is a rare disease caused by dematiaceous fungi. It has poor prognosis irrespective of the immune status of the patient. Cladophialophora bantiana is the most commonly isolated species. We report a case of multiple brain abscesses caused by C. bantiana in an immune competent patient. The diagnosis was based on CT scan of head, direct examination and culture of the aspirate from the abscess. Despite complete surgical resection of the abscesses and antifungal therapy with amphotericin B and voriconazole the patient could not be saved. All the cases of cerebral phaeohyphomycosis due to this rare neurotropic fungus reported from India between 1962 and 2009 have also been reviewed.

Identificación de las especies de Candida en las infecciones sanguíneas / Characterization of Candida species in blood stream infections

Introducción: La candidemia se convirtió en una infección importante del torrente sanguíneo que se asocia frecuentemente con índices elevados de mortalidad y morbilidad. Las especies de Candida generan del 70% al 80% de las infecciones micóticas invasivas del torrente sanguíneo y son la cuarta causa más frecuente de infecciones hospitalarias del torrente sanguíneo. La identificación de las especies de Candida es importante, ya que las especies no albicans son cada vez más numerosas y resistentes a las drogas antimicóticas. El objetivo del estudio fue aislar e identificar diferentes especies de Candida asociadas con candidemia y analizar su patrón de susceptibilidad a los antimicóticos. Materiales y métodos: Los pacientes con sospecha de infecciones del torrente sanguíneo (ITS) fueron reclutados durante un período de un año para el estudio prospectivo. Se analizaron las características demográficas, la duración de la internación y los factores de riesgo asociados y la evolución clínica. El análisis de las muestras de sangre tuvo lugar mediante el sistema automatizado BacTAlert. La identificación y la susceptibilidad antimicótica de las levaduras fueron realizadas mediante el uso de dispositivo VITEK-2. Resultados: Las especies de Candida fueron aisladas en 30 de los 3146 cultivos recibidos (0.9%). La mayoría de los casos de candidemia tuvieron lugar en hombres (66%). Los factores de riesgo más frecuentes fueron el uso de antibióticos de amplio espectro, la vía central y la ventilación mecánica. Entre las levaduras aisladas, las especies de Candida no albicans fueron predominantes (60%), en comparación con la especie C. albicans (40%). La especie albicans presentó una susceptibilidad del 100% a los azoles y la anfotericina, en tanto que las especies no albicans fueron resistentes. De los 30 pacientes mencionados, 5 fallecieron. Conclusión: La prevalencia de Candida no albicans fue mayor en comparación con la prevalencia de Candida albicans. Las especies no albicans fueron más resistentes a los antimicóticos. En consecuencia, los pacientes internados deberían ser evaluados para identificar la candidemia.

Introduction: Candidemia has become an important bloodstream infection that is frequently associated with high rates of mortality and morbidity. Candida species account for 70-80% of invasive bloodstream fungal infections and represent the fourth most common nosocomial bloodstream infections. The identification of Candida species is important as the number of non albicans Candida species is increasing and they are becoming more resistant to antifungal drugs. The aim of the study was to isolate and identify various Candida species associated with candidemia and to study their antifungal susceptibility pattern. Materials and methods: Patients suspected of having BSI were enrolled on a one-year prospective study. Patient's demographic details, duration of hospital stay, associated risk factors and outcome were studied. Blood samples were analyzed by BacTAlert automated system. Identification and antifungal susceptibility testing of yeasts was done using VITEK-2 compact system. Results: Of 3146 blood cultures received, Candida species were isolated in 30 samples (0.9%). The majority of candidemia cases were in males (66%). The most common risk factors were use of broad spectrum antibiotics, central line and mechanical ventilation. Among the yeast isolates, non albicans Candida species were predominant (60%) compared to C. albicans (40%). Candida albicans showed 100% susceptibility to azoles and amphotericin whereas non albicans Candida species showed resistance. Of these 30 patients, 5 patients died. Conclusion: Prevalence of non albicans Candida was greater than C. albicans and cases were more resistant to antifungal drugs. Therefore surveillance for candidemia should be carried out in hospitalized patients.

Liver function tests in patients with dengue viral infection.

To assess the frequency and degree of hepatic dysfunction in patients with dengue infection, records of214 serologically confirmed cases of dengue infection with available biochemical liver tests, admittedto our tertiary-care institute, were analysed. Patients were classified as classical dengue fever (DF) –81.3%, dengue haemorrhagic fever (DHF) – 13.6% and dengue shock syndrome (DSS) – 5.1%. Themean age was 31.6 years (male:female = 3.3:1). Deranged total bilirubin, aspartate aminotransferase(AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin and prothrombin timeindex (PTI) [international normalized ratio (INR)] was present in 19.5% (29/143), 97.7% (209/214),93.9% (199/214), 32.6% (47/144), 29.1% (44/151) and 15.5% (22/156) patients respectively. Themean (± SE) total bilirubin, AST, ALT, ALP, albumin and INR values were 0.93 ± 0.09 mg/dl, 353.7 ±49.6 U/L, 218.6 ± 27.2 U/L, 135.2 ± 6.5 U/L, 3.2 ± 0.04 g/dl and 1.2 ± 0.03 respectively. The meanvalue of AST was significantly higher than ALT. The degree of rise of AST and ALP was significantly morein DHF and DSS, as compared to DF; but the frequency of rise was similar in all groups. Mean serumbilirubin, ALT and ALP values were significantly higher in patients with haemorrhage as compared tothose without haemorrhage, in patients with secondary dengue infection as compared to primary infection, and in non-survivors. Hepatic dysfunction was very common in all forms of dengue infection,with AST rising significantly more than ALT. Serum bilirubin, ALT and ALP were significantly higher inpatients with DSS, haemorrhage, sequential infection and non-survivors. While preferentially high AST may serve as an early indicator of dengue infection, high bilirubin, ALT and ALP may act as poorprognostic markers.