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Coronavirus disease-2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a new disease characterized by secondary Aspergillus mold infection in patients with COVID-19. It primarily affects patients with COVID-19 in critical state with acute respiratory distress syndrome, requiring intensive care and mechanical ventilation. CAPA has a higher mortality rate than COVID-19, posing a serious threat to affected individuals. COVID-19 is a potential risk factor for CAPA and has already claimed a massive death toll worldwide since its outbreak in December 2019. Its second wave is currently progressing towards a peak, while the third wave of this devastating pandemic is expected to follow. Therefore, an early and accurate diagnosis of CAPA is of utmost importance for effective clinical management of this highly fatal disease. However, there are no uniform criteria for diagnosing CAPA in an intensive care setting. Therefore, based on a review of existing information and our own experience, we have proposed new criteria in the form of practice guidelines for diagnosing CAPA, focusing on the points relevant for intensivists and pulmonary and critical care physicians. The main highlights of these guidelines include the role of CAPA-appropriate test specimens, clinical risk factors, computed tomography of the thorax, and non-culture-based indirect and direct mycological evidence for diagnosing CAPA in the intensive care unit. These guidelines classify the diagnosis of CAPA into suspected, possible, and probable categories to facilitate clinical decision-making. We hope that these practice guidelines will adequately address the diagnostic challenges of CAPA, providing an easy-to-use and practical algorithm to clinicians for rapid diagnosis and clinical management of the disease. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to conduct external validation of risk prediction scores for invasive candidiasis. Methods: We conducted a prospective observational study in a 12-bedded adult medical/surgical Intensive Care Unit (ICU) to evaluate Candida score >3, colonization index (CI) >0.5, corrected CI >0.4 (CCI), and Ostrosky's clinical prediction rule (CPR). Patients' characteristics and risk factors for invasive candidiasis were noted. Patients were divided into two groups; invasive candidiasis and no-invasive candidiasis. Results: Of 198 patients, 17 developed invasive candidiasis. Discriminatory power (area under receiver operator curve [AUROC]) for Candida score, CI, CCI, and CPR were 0.66, 0.67, 0.63, and 0.62, respectively. A large number of patients in the no-invasive candidiasis group (114 out of 181) were exposed to antifungal agents during their stay in ICU. Subgroup analysis was carried out after excluding such patients from no-invasive candidiasis group. AUROC of Candida score, CI, CCI, and CPR were 0.7, 0.7, 0.65, and 0.72, respectively, and positive predictive values (PPVs) were in the range of 25%-47%, along with negative predictive values (NPVs) in the range of 84%-96% in the subgroup analysis. Conclusion: Currently available risk prediction scores have good NPV but poor PPV. They are useful for selecting patients who are not likely to benefit from antifungal therapy. [ABSTRACT FROM AUTHOR]

Objectives To study outcomes with voriconazole therapy in immunocompetent individuals following maximal safe endoscopic resection in invasive aspergillosis of the anterior skull base. Design Retrospective study of patients with chronic invasive aspergillosis including symptomatology, extent of disease, and response to voriconazole following maximal safe resection in immunocompetent individuals. Setting Tertiary care superspeciality referral center. Participants Ten consecutive patients of invasive aspergillosis of anterior skull base managed over a period of 2 years. Main Outcome Measures Symptom resolution with systemic voriconazole and radiologic evaluation following systemic antifungals as per predefined protocol. Conclusions Maximal safe resection via transnasal endoscopic route followed by systemic antifungals provides excellent outcomes in invasive skull base aspergillosis. Although liver and renal functions, besides visual acuity, need serial monitoring, voriconazole is well tolerated by our patients. [ABSTRACT FROM AUTHOR]

Background: Invasive candidiasis (IC) is associated with increased morbidity in severe acute pancreatitis (SAP). There is limited information regarding the predisposing factors, Candida species distribution and in vitro susceptibility. Methodology: Current data have been derived from a larger prospective nonintervention study conducted on 200 critically ill patients which was done to study the antifungal prescription practices, collect epidemiological data, and perform an external validation of risk prediction models for IC under senior research associateship program of Council of Scientific and Industrial Research New Delhi. Of these critically ill patients, thirty had SAP and were included for analysis. Results: There were 23 males and 7 females. Out of eight patients (27%) who developed IC, three had isolated candidemia, two had isolated deep-seated candidiasis while three had both candidemia and deep-seated candidiasis. SAP patients with IC had a longer duration of Intensive Care Unit stay, hospital stay, days on mechanical ventilation and duration of shock. Mortality was not different between SAP patients with or without IC. Conclusion: There is a high rate of Candida infection in SAP. More studies are needed to generate epidemiological data and develop antifungal stewardship in this subset of high-risk population. [ABSTRACT FROM AUTHOR]

Use of antifungal agents has increased over past few decades.A number of risk factors such as immunosuppression, broad spectrum antibiotics, dialysis, pancreatitis, surgery, etc., have been linked with the increased risk of invasive candidiasis. Though there are various guidelines available for the use of antifungal therapy, local/regional epidemiology plays an important role in determining the appropriate choice of agent in situations where the offending organism is not known (i.e. empirical, prophylactic or preemptive therapy). Developing countries like India need to generate their own epidemiological data to facilitate appropriate use of antifungal therapy. In this article, the authors have highlighted the need for region-specific policies/guidelines for treatment of invasive candidiasis. Currently available Indian literature on candidemia epidemiology has also been summarized here. [ABSTRACT FROM AUTHOR]

We present two cases of renal zygomycosis caused by Apophysomyces elegans and Mycocladus corymbifer in previously healthy immunocompetent males and an overview of the disease in India. In both cases a percutaneous nephrostomy (PCN) was performed and the etiologic agents were identified by direct microscopy and culture. Amphotericin B was administered and both patients recovered completely. A review of the literature revealed 42 cases of renal zygomycosis in India. The majority of them were from the Postgraduate Institute of Medical Education and Research, Chandigarh, in North India. In contrast to cases from the developed world where transplant recipients and patients with hematological malignancies seem to be most vulnerable to zygomycosis, the most common risk factor in India is uncontrolled diabetes mellitus. However, renal zygomycosis is an exception and the patients in both of our cases had no identifiable underlying disorder and recovered successfully without nephrectomy. It is important to emphasize that treatment of A. elegans must be aggressive and lipid formulations of antifungals are typically favored due to their limited side effects profile and ability of the clinician to use higher doses. A high index of clinical suspicion and knowledge of the varied manifestations in diagnosing this condition cannot be overemphasized. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Invasive Candidiasis," by B. J. Kullberg et al that was published in a 2015 issue.

Introduction: Oropharyngeal candidiasis (OPC) is the most common opportunistic fungal infection reported in human immunodeficiency virus (HIV) positive patients worldwide. This prospective study was undertaken to investigate OPC and Candida colonization (CC) and their correlation with CD4+ cell counts and antiretroviral therapy (ART) in HIV-positive patients. Methodology: In total, 190 HIV-positive patients were enrolled for study in three groups as follows: Group A, 90 patients without ART; Group B, 100 patients undergoing treatment with ART; and Group C, 75 HIV-negative control patients. All HIV patients underwent clinical examination and were subjected to CD4+ cell counts. Swabs were collected from the oral cavity of all individuals and plated on Sabouraud's dextrose agar. Identification of Candida species was performed by conventional methods. Results: Candida species were isolated in 84/190 (44.2%) and 20/75 (26.6%) of the HIV-positive subjects and controls respectively (p<0.01). OPC was noted in 21/190 (11%) of the HIV-positive patients. Candida albicans was the most frequently isolated species. Patients with CD4+ cell counts ≤ 200 cells/mm³ were significantly (p<0.001) more frequently colonized (37/63; 58.7%) and infected (18/21; 85.7 %) with Candida species. Candida species was seen in patients with CC and OPC with CD4+cell counts between 201 and 500 (21/63; 33.4% vs 3/21; 14.3%) and > 500 cell/mm³ (5/63; 7.9% versus 0/21 0%) respectively. Conclusion: OPC and Candida colonization occur more frequently in HIV-positive patients with CD4+ cell counts ≤200 cell/mm³. ART significantly reduces OPC. C. albicans is the most frequently isolated species in both OPC and colonization, suggesting endogenous infection. [ABSTRACT FROM AUTHOR]

Background: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients., Methods: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes., Results: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection., Conclusions: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The etiology, presentation and mortality of patients with primary adrenal insufficiency (PAI) in developing countries may differ from economically developed nations. However, information in this regard is scanty. The aim of this study was to determine the etiology and compare the clinical characteristics and mortality in infectious and autoimmune causes of PAI in Indian patients. All eligible (n = 89) patients (ages 15-83 years) diagnosed with PAI between 2006 and 2019 were studied. Patients were followed for a median duration of 5.9 (range 0.1-15.7) years. Eighty-six subjects underwent an abdominal computerized tomography scan or ultrasonography, and adrenal biopsy was performed in 60 patients. The most frequent etiologies of PAI were adrenal histoplasmosis (AH, 45%), adrenal tuberculosis (AT, 15%), autoimmunity (AI, 25%) and primary lymphoma (6%). Forty-two percent of patients presented with an acute adrenal crisis. AH and AT could not be differentiated on the basis of clinical features, except for a greater frequency of hepatomegaly-splenomegaly and type 2 diabetes mellitus (63% vs 15%, P < 0.01) in the former. Patients with an autoimmune etiology had a higher frequency of 21-hydroxylase antibodies (41% vs 3%) and autoimmune thyroid disease (46% vs 5%) vs those with infectious etiologies. Mortality was significantly higher in AH (45%) compared with AT (8%) or AI (5%) (P = 0.001). Causes of death included adrenal crises, progressive AH and unexplained acute events occurring at home. In conclusion, infections, especially AH, were the most frequent cause of PAI in north India. Despite appropriate therapy, AH had very high mortality as compared with AT and AI.

Competing Interests: None

Background and Objectives: Resistance in Salmonella enterica var Typhi (S. Typhi) to chloramphenicol, amoxicillin and co-trimoxazole has posed a challenge to treatment of typhoid fever. Ciprofloxacin has been the empirical therapy of choice, but the recent increase in minimum inhibitory concentration (MIC) to ciprofloxacin in S. Typhi, not detectable by disc diffusion (DD) tests, may result in delayed response and serious complications. Nalidixic acid (NA) resistance has been used as an indirect evidence of increased ciprofloxacin MIC in S. Typhi. We evaluated the predictive value of NA resistance for fluoroquinolone resistance in clinical isolates of S. Typhi., Methods: A total of 70 clinical isolates of S. Typhi were tested for antimicrobial susceptibility according to the National Committee for Clinical Laboratory Standards (NCCLS) method. MIC to fluoroquinolones was carried out by the agar dilution method., Results: Thirteen (18.6 %) isolates were resistant to amoxicillin, chloramphenicol and cotrimoxazole; all were sensitive to ciprofloxacin and cefotaxime. Fifty (71.4%) were resistant to NA. Nineteen (27.1 %) isolates were resistant to ciprofloxacin by MIC tests. The MIC for ciprofloxacin was 0.03-4 microg/ml for NA(S) and 0.25-4 microg/ml for NA(R) isolates. NA susceptibility showed a predictive value of 95 per cent for ciprofloxacin susceptibility while NA resistance had a predictive value of 36 per cent for ciprofloxacin resistance. Thirty isolates studied were sensitive to gatifloxacin; MIC values were 0.03-0.5 microg/ml for NA(S) and 0.25-0.5 microg/ml for NA(R) isolates., Interpretation and Conclusion: NA susceptibility was a good marker for fluoroquinolone susceptibility but NA resistance had a poor predictive value for ciprofloxacin resistance. NA resistant isolates should be tested for ciprofloxacin MIC before deciding a change in therapeutic regimen. Higher MIC for gatifloxacin was also noticed in NA resistant isolates.

Though Chromobacterium violaceum is a common inhabitant of soil and water in tropical and sub-tropical regions, human infections are rare but when they do occur result in high mortality. Since the first case from Malaysia in 1927, about 150 cases have been reported in world literature. Till date 6 cases have been reported from southern and eastern parts of India. We report here a case of C. violaceum septicaemia, probably the first case from north India. The patient, a 6 and a half year old boy was admitted with high fever. The patient had anaemia, neutrophilic leucocytosis and bilateral chest infiltrates. Routine and bacteriological investigations were carried out to establish the aetiological diagnosis. C. violaceum was isolated in pure culture from blood and pus. The patient was successfully treated with ciprofloxacin and amikacin. This is probably the first documented case report of C. violaceum infection from north India and the only Indian case with septicaemia which survived.