Epidemiology and outcomes of infections during extracorporeal membrane oxygenation in adult patients with COVID-19 ARDS- A single center study.

BACKGROUND: There is a scarcity of data regarding nosocomial infections in patients with COVID-19 treated with ECMO. This observational study from India aims to describe the epidemiology and microbiology of infections in patients with COVID-19 associated ECMO. METHODS: This is an ambi-directional observational study of COVID-19 ECMO patients admitted from April 2021 to June 2022 in a tertiary care hospital. The total number of sepsis episodes for each patient was recorded and were categorized as bloodstream infections (BSI), pneumonias, skin and soft tissue infections (SSTI), invasive candidiasis (IC), catheter associated urinary tract infection (CAUTI), intra-abdominal infections (IAI), and Clostridioides difficile infections. Details regarding each infection including the microbiological profile and outcomes were recorded. RESULTS: 29 patients who received ECMO for COVID-19 pneumonia during the study period were identified. Of the 29 patients, there were a total of 185 septic episodes. The incidence of septic episodes was 72.4 per 1000 ECMO days. Of the 185 sepsis events, 82 (44.3%) were BSI, 72 (39%) were pneumonia, 19 (10.3%) were SSTI, 7 (3.8%) were CAUTI and 5 (2.7%) were IAIs. Of these 29 patients, 16 (55.2%) patients were discharged and 13 (44.8%) died. CONCLUSIONS: The most common infections in our patients were bloodstream infections followed by pneumonia. High rates of gram negative infections, including those caused by carbapenem resistant bacteria, reflect the Indian critical care unit epidemiology in general. Despite these high infection rates with antimicrobial resistant set of micro-organisms, we had a successful outcome in 55.2% of patients.

Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Bacteremia Caused by Enterobacteriaceae.

Introduction and background: Rapid molecular diagnostics to predict carbapenem resistance well before the availability of routine drug sensitivity testing (DST) can serve as an antimicrobial stewardship tool in the context of high rates of Carbapenem-resistant Enterobacteriaceae (CRE). Materials and methods: A retrospective observational study of patients more than 18 years of age on whom Xpert Carba-R (FDA approved for rectal swab specimen) was done on gram-negative bacteria (GNB) flagged blood culture samples, in an Indian intensive care unit between January 2015 and November 2018. We analyzed the performance of Xpert Carba-R in comparison with routine DST. Results: A total of 164 GNBs were isolated from 160 patients. Klebsiella pneumoniae and Escherichia coli were the predominant isolates. Carba-R was positive in 35.36% of samples and 45.34% were carbapenem-resistant (CR) on routine DST. The distribution of the CR gene was: Oxacillinase (OXA) (50%), NDM (32.7%) followed by OXA and NDM co-expression (15.51%). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of Carba-R were 90.74, 93.15, 13.25, 0.10, 83.58 and 96.31% for Enterobacteriaceae. The median time to obtain the Carba-R report was 30 hours 34 minutes vs 74 hours and 20 minutes for routine DST. Based on the Carba-R report, 9.72% of patients had escalation and 27.08% had de-escalation of antibiotics. Conclusion: Xpert Carba-R serves as a rapid diagnostic tool for predicting carbapenem resistance in intensive care unit patients with bacteremia caused by Enterobacteriaceae. How to cite this article: Rajendran S, Gopalakrishnan R, Tarigopula A, Kumar DS, Nambi PS, Sethuraman N, et al. Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Bacteremia Caused by Enterobacteriaceae. Indian J Crit Care Med 2023;27(9):655-662.

Active surveillance for carbapenem resistant enterobacteriaceae (CRE) using stool cultures as a method to decrease CRE infections in the pediatric intensive care unit (PICU).

BACKGROUND: The incidence of Carbapenem Resistant Enterobacteriaceae (CRE) infections is increasing worldwide. Due to dearth of alternative antibiotics, prevention of infection transmission is a part of CRE infection management strategy. Early detection of CRE by active surveillance coupled with contact isolation is much more appropriate compared to contact isolation upon receipt of routine cultures dictated by the patient's clinical condition. OBJECTIVES: To determine whether active CRE surveillance will decrease CRE infection rates in the Pediatric Intensive Care Unit (PICU). METHODS: Retrospective observational study done in the 10-bed PICU of a tertiary care teaching children's hospital from July 2013 to June 2015. Rectal swabs for CRE were sent from all PICU patients except stable post-operative patients. Contact isolation precautions were followed for rectal swab positive patients. CRE colonization and infection rates were calculated and compared. RESULTS: Total of 1262 rectal swabs were sent from 1022 patients. CRE colonization rate was 19.5%. Post intervention, ICU acquired CRE colonization decreased by 36% and ICU acquired CRE infection rates decreased by 100%, both showed significant decrease (p â€‹< â€‹0.0001). CONCLUSION: Active CRE surveillance and institution of contact isolation in appropriate situations is helpful in decreasing CRE colonization and infection rates in the PICU.

Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation.

Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing 'fit-for-use' diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Thr@ee-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings. Interpretation & conclusions: Diagnostics developed using these TPPs will facilitate utilization of invested resources leading to development of the products that have potential to ease the economic burden on patient and save lives.

Erysipelothrix Bacteremia; is Endocarditis a Rule?

Erysipelothrix rhusiopathiae is a Gram-positive bacillus, a zoonotic pathogen rarely causing human infections ranging from localized skin infections to invasive infections such as endocarditis. In this report, we present two cases of Erysipelothrix bacteremia. The first case is a native valve tricuspid endocarditis, which is a highly unusual valve to be involved. The second case is bacteremia, probably secondary to a minor skin breach, which did not involve heart valves. Erysipelothrix bacteremia is considered highly associated with infective endocarditis and a high mortality rate, which could be a bias due to underreporting of Erysipelothrix bacteremia without endocarditis. Erysipelothrix is intrinsically resistant to vancomycin, the first-line agent for Gram-positive bacteremia. Both the patients in this report were treated successfully with ceftriaxone.

Not so uncommon, yet neglected 'Severe Streptococcus pyogenes infections at a tertiary care center in south India.

Streptococcus pyogenes (SP) causes uncomplicated infections of throat & skin to severe life-threatening invasive diseases and poststreptococcal sequelae. Despite being common, it hasn't been studied much in recent times. Data of 93 adult patients >18 years, culture proven (SP) infections from 2016 to 2019 was studied in south India. Irrespective of comorbidities, SSTI were most common followed by surgical site infections& bacteremia. Isolates were susceptible to penicillin, cephalosporins but 23% were resistant to clindamycin. Timely surgical interventions and appropriate antibiotics reduced morbidity& limb salvage by 9 times. Larger studies, worldwide, to see the current trend of SP need to be conducted.

Post-COVID multisystem inflammatory syndrome in adults: a study from a tertiary care hospital in south India.

Background & objectives: There are limited data from India on the post-COVID multisystem inflammatory syndrome in adults (MIS-A). The objective of the present study was to evaluate the clinical profile of patients with MIS-A admitted to a tertiary care centre in southern India. Methods: This single-centre retrospective study was conducted from November 2020 to July 2021, and included patients aged >18 yr admitted to the hospital as per the inclusion and exclusion criteria. Results: Nine patients (5 male, mean age 40±13 yr) met the criteria for MIS-A. Five patients had proven COVID-19 infection or contact history 36.8±11.8 days back. All patients were positive for SARS-CoV-2 IgG antibody, negative for COVID-19 PCR, and had negative blood, urine and sputum cultures. All patients had fever and gastrointestinal (GI) symptoms, and five patients had left ventricular dysfunction. All patients had neutrophilic leucocytosis at presentation and elevated biomarkers such as C-reactive protein serum procalcitonin, D-dimer and ferritin. The majority of the patients (7/9 i.e. 77.78%) were treated with intravenous hydrocortisone (50-100 mg q6h-q8h). Six patients recovered completely whereas three patients expired. Interpretation & conclusions: Fever and GI symptoms were the most common presentation of MIS-A. Elevated serum procalcitonin may not be useful in differentiating bacterial sepsis from MIS-A. Most patients responded to corticosteroids.

Safety and Feasibility of Antibiotic De-escalation in Critically Ill Children With Sepsis - A Prospective Analytical Study From a Pediatric ICU.

Introduction: De-escalation is the key to balance judicious antibiotic usage for life-threatening infections and reducing the emergence of antibiotic resistance caused by antibiotic overuse. Robust evidence is lacking regarding the safety of antibiotic de-escalation in culture negative sepsis. Materials and Methods: Children admitted to the PICU during the first 6 months of 2019 with suspected infection were included. Based on the clinical condition, cultures and septic markers, antibiotics were de-escalated or continued at 48-72 h. Outcome data like worsening of primary infection, acquisition of hospital acquired infection, level of ICU support and mortality were captured. Results: Among the 360 admissions, 247 (68.6%) children received antibiotics. After excluding 92 children, 155 children with 162 episodes of sepsis were included in the study. Thirty four episodes were not eligible for de-escalation. Among the eligible group of 128 episodes, antibiotics were de-escalated in 95 (74.2%) and continued in 33 (25.8%). The primary infection worsened in 5 (5.2%) children in the de-escalation group and in 1 (3%) in non de-escalation group [Hazard ratio: 2.12 (95%CI: 0.39-11.46)]. There were no significant differences in rates of hospital acquired infection, mortality or length of ICU stay amongst the groups. Blood cultures and assessment of clinical recovery played a major role in de-escalation of antibiotics and the clinician's hesitation to de-escalate in critically ill culture negative children was the main reason for not de-escalating among eligible children. Conclusion: Antibiotic de-escalation appears to be a safe strategy to apply in criticallly ill children, even in those with negative cultures.

Can urinary histoplasma antigen test improve the diagnosis of histoplasmosis in a tuberculosis endemic region?

BACKGROUND: Many patients with histoplasmosis are treated with anti-tubercular therapy (ATT) in tuberculosis endemic regions as diagnosis of histoplasmosis requires invasive sampling. We sought to study the utility of urinary Histoplasma antigen detection test. METHODS: Case records of patients with a diagnosis of histoplasmosis prior to (Period A) and after (Period B) introduction of urinary Histoplasma antigen detection test were analysed in this single centre retrospective study. RESULTS: Thirty-seven patients (18 in Period A, and 19 patients in Period B) were studied. There was nearly a threefold increase in diagnoses (from 0.39 cases to 1.18 cases per month) after the introduction of antigen test. Nine patients (24.3%) were immunocompromised (6 had HIV infection and 3 were on steroids), and 28 (75.6%) were immunocompetent. Empirical ATT had been given to 10 patients prior to histoplasmosis diagnosis. Invasive tissue sampling was required in only two patients in Period B to confirm the diagnosis. Immunocompromised patients were younger, were more likely to have skin and mucosal findings, anaemia and leucopenia as compared to immune-competent patients. CONCLUSION: This study emphasises that histoplasmosis cases may be missed and patients may receive ATT unnecessarily. Histoplasma antigen increased the diagnostic yield by almost threefold in our study.

Melioidosis mimicking tuberculous vertebral osteitis: Case report and review of literature.

Whitmore's disease or melioidosis is an infectious disease caused by Burkholderia pseudomallei. The reported cases are but the tip of the iceberg. This pathogenic saprophyte is commonly found in wet soil and water. An accidental or occupational exposure (in field workers, farmers, gardeners or villagers) to B. pseudomallei contaminated soil or pooled water is the primary source of infection. Neurosurgeons need to consider this as a possible rare cause of back pain and possible neurological deterioration. A diabetic type 2 rice farmer with severe lumbago and fever, misdiagnosed as vertebral tuberculous osteitis based on his radiological findings, was confirmed to harbour Burkholderia Pseudomallei, which was diagnosed using laboratory cultures. He made a remarkable recovery with antibiotic therapy. The empiric anti-tuberculous (ATT) drugs were stopped. The rare differential diagnosis of melioidosis should be thought of in diabetic patients with a psoas abscess and vertebral osteitis, especially in rice farmers from endemic regions that includes India.

Experience with ß-D-Glucan Assay in the Management of Critically ill Patients with High Risk of Invasive Candidiasis: An Observational Study.

BACKGROUND: The (1,3)-ß-D-glucan assay (BDG) is recommended for the early diagnosis of invasive candidiasis (IC). METHODS: Records of 154 critically ill adults with suspected IC, on whom BDG was done, were analyzed. Patients were divided into three groups: Group A (confirmed IC), Group B (alternative diagnosis or cause of severe sepsis), and Group C (high candidal score and positive BDG [>80 pg/mL] but without a confirmed diagnosis of IC). RESULTS: Mean BDG levels were significantly higher in Group A (n = 32) as compared to Group B (n = 60) and Group C (n = 62) (448.75 ± 88.30 vs. 144.46 ± 82.49 vs. 292.90 ± 137.0 pg/mL; P < 0.001). Discontinuation of empiric antifungal therapy based on a value <80 resulted in cost savings of 14,000 INR per day per patient. CONCLUSION: A BDG value of <80 pg/ml facilitates early discontinuation of empirical antifungal therapy, with considerable cost savings.

Profile of Infective Endocarditis: At a Tertiary Care Referral Centre.

BACKGROUND: Infective endocarditis (IE) remains a serious challenge with a persistently high morbidity and mortality despite the availability of improved diagnostic and treatment amenities in the developing world. Data on the clinical and microbiological profile of IE in India is still limited. The emergence of modern risk factors such as hospitalization and device insertion has changed the epidemiology of the disease in the western world, whereas in India and other parts of the developing world the situation is more complex because of the concomitant burden of rheumatic heart disease and congenital heart defects. We therefore attempted to describe the changing epidemiology of the disease in a cohort of patients with definite IE admitted to a tertiary care centre. METHODS: 145 cases were identified as IE during the period January 2010-December 2015 (6 years) of which 120 'definite' cases of IE according to the modifies Dukes' criteria were analysed. RESULTS: The mean age of patients was 53 years ± 15 years (age range 18 to 79 years) with a male preponderance of 72%. Native valve disease was seen in 103 cases and 17 cases had prosthetic valve infections. IE was classified as community acquired in 87 (72.5%) cases and healthcare associated in 33(27.5%) events. Predisposing factors contributing to healthcare associated events included hemodialysis in 8.3%, recent surgical intervention which included urological instrumentation with urosepsis and gastrointestinal procedures in 5.8% events. Postpartum IE was seen in 1.7% cases. There was evidence of remote abscess, prior bacteraemia or septic foci in the preceding 3 months of presentation with IE in 8.3% of patients and 3.3% patients underwent prior dental procedure. Prior structural heart disease was present in 47.5% of cases of which Rheumatic heart disease (RHD) was seen in 15%. A previous episode of infective endocarditis was observed in significantly more patients with PVE (29.4%) than with NVE (1.9%). Blood cultures were negative in 50 (41.7%) of cases of whom 60% had received antibiotics prior to admission. Nine of 17 patients with PVE (52.9%) were culture negative. In the 70(58.3% of all patients) patients with positive blood cultures, Streptococcus sp were the commonest bacteria isolated in 15.8%, of which Viridans group Streptococci (VGS) was seen in majority of the cases (13.3%) followed by Staphylococcus sp (14.2%) with methicillin resistant staphylococcus was seen in 3.3% and Enterococcus sp in 13.3%. Gram negative bacteraemia were seen in 8.3%. In addition, ESBL E coli constituted 4% of our culture positive cases, perhaps representing a complication of this common community acquired bacteraemia and increasing resistance in E coli. Tissue / valve cultures in patients who underwent surgery was positive in four cases, 3 of whom where blood culture negative The mortality rate was higher among PVE (33%) compared to 10% in NVE. The most common cause of death in IE was usually congestive cardiac failure. CONCLUSIONS: Thought Rheumatic heart disease continues to be the most common predisposing factor, degenerative heart diseases and healthcare associated IE are also gradually increasing. Use of antibiotics prior to sending blood cultures remains a significant cause of culture negativity. Viridans streptococci continue to be the commonest pathogen and though ESBL E coli constituted a significant minority it could expound the changing epidemiology and risk factors for Gramnegative endocarditis especially non-HACEK group necessitating an updated review of this subject.

Carbapenem-resistant enterobacteriaceae screening: A core infection control measure for critical care unit in India?

BACKGROUND: Infection/colonization due to carbapenem-resistant enterobacteriaceae (CRE) are emerging as an important challenge, particularly in high risk patients due to widespread use of Carbapenems. Therefore, preventing both CRE infections and their transmission has become an important infection control objective. AIMS AND OBJECTIVE: Determine the proportion of asymptomatic carriers of CRE among patients admitted to our critical care unit (CCU) from the community and other health care facilities. Enumerate risk factors and guide implementation of infection control interventions. METHODS: This prospective surveillance study was done in a 24 bed CCU of a tertiary care hospital, at Chennai, India between August2017 through December 2017. Patients were screened based on a composed questionnaire framed from Centers for Diseases Control and Prevention CRE tool-kit. Two rectal swabs were collected from each patient. They were processed in microbiology laboratory. RESULTS: A total of 102 patients were included. CRE colonization were identified in 8 (7.8%) of the total samples. Among 8 CRE colonized patients 3 (37.5%) patients developed systemic infection. Patients who were exposed to high end antibiotic and past history of surgery had significant association with CRE colonization of (P = 0.0029) and (P = 0.0167) respectively. CONCLUSION: Overall CRE colonization rates among our CCU patients were found to be low. Risk factors associated with CRE colonization were high end antibiotic exposure and surgery in past 90 days. Hence rectal screening should be a risk factor-based active surveillance. Association of systemic infection among CRE colonizers was more significant. This study led us to modify our infection control practices in CCU.

Listeria in Adults - Truly Rare or Rarely Diagnosed in India?

Listeria monocytogenes is a facultative anaerobic intracellular Gram positive rod causing infection in pregnant women, extremes of age and immune-compromised hosts. In clinical specimens, the organisms may be gram-variable: laboratory misidentification of L. monocytogenes isolates as diphtheroids, streptococci, or enterococci is not uncommon and the isolation of a diphtheroid from blood or CSF should always alert the clinician to the possibility that the organism may be L. monocytogenes. The disease has rarely been reported in India in non-pregnant adults. We herein report four cases of L. monocytogenes infection in immune-compromised adults.

A Study of 24 Patients with Colistin-Resistant Gram-negative Isolates in a Tertiary Care Hospital in South India.

BACKGROUND: As the use of colistin to treat carbapenem-resistant Gram-negative infections increases, colistin resistance is being increasingly reported in Indian hospitals. MATERIALS AND METHODS: Retrospective chart review of clinical data from patients with colistin-resistant isolates (minimum inhibitory concentration >2 mcg/ml). Clinical profile, outcome, and antibiotics that were used for treatment were analyzed. RESULTS: Twenty-four colistin-resistant isolates were reported over 18 months (January 2014-June 2015). A history of previous hospitalization within 3 months was present in all the patients. An invasive device was used in 22 (91.67%) patients. Urine was the most common source of the isolate, followed by blood and respiratory samples. Klebsiella pneumoniae constituted 87.5% of all isolates. Sixteen (66.6%) were considered to have true infection, whereas eight (33.3%) were considered to represent colonization. Susceptibility of these isolates to other drugs tested was tigecycline in 75%, chloramphenicol 62.5%, amikacin 29.17%, co-trimoxazole 12.5%, and fosfomycin (sensitive in all 4 isolates tested). Antibiotics that were used for treatment were combinations among the following antimicrobials-tigecycline, chloramphenicol, fosfomycin, amikacin, ciprofloxacin, co-trimoxazole, and sulbactam. Among eight patients who were considered to have colonization, there were no deaths. Bacteremic patients had a significantly higher risk of death compared to all nonbacteremic patients (P = 0.014). CONCLUSIONS: Colistin resistance among Gram-negative bacteria, especially K. pneumoniae, is emerging in Indian hospitals. At least one-third of isolates represented colonization only rather than true infection and did not require treatment. Among patients with true infection, only 25% had a satisfactory outcome and survived to discharge. Fosfomycin, tigecycline, and chloramphenicol may be options for combination therapy.

Successful Use of High-dose Daptomycin in a Child With Staphylococcus aureus Endocarditis.

We report the successful use of daptomycin in a child with methicillin-resistant Staphylococcus aureus endocarditis with persistent bacteremia and clinical deterioration, despite treatment with vancomycin and rifampicin. She had acute kidney injury, requiring daptomycin dosage adjustment.

Antimicrobial susceptibility of Salmonella enterica serovars in a tertiary care hospital in southern India.

BACKGROUND & OBJECTIVES: Salmonella enterica serovars Typhi and Paratyphi are predominantly known to cause enteric fever. Multidrug resistance in S. Tphi and S. Paratyphi has emerged as a cause of concern. This study was done to evaluate status in antimicrobial susceptibility patterns of Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi obtained from blood culture in a tertiary care hospital in south India. METHODS: Blood isolates of Salmonella species over a two year period between May 2009 and June 2011 were studied. A total of 322 isolates of Salmonella species were tested for antimicrobial susceptibility by Kirby-Bauer disc diffusion method. The MIC of ciprofloxacin was obtained by E-test, and azithromycin MIC was confirmed by agar dilution method for a limited number of isolates. RESULTS: Of the total of 322 isolates studied, 186 (57.8%) were S. Typhi, 134 (41.6%) were S. Paratyphi A, and two were S. Paratyphi B. Of these, 44(13.66%) were resistant to ciprofloxacin (MIC <0.50 µg/ml) and 296 (91.9%) were nalidixic acid resistant. Of these 296 nalidixic acid resistant isolates, 278 (94%) were susceptible to ciprofloxacin by MIC criteria (<0.5 µg/ml). Of the 262 isolates tested for azithromycin sensitivity, only 120 (46%) were susceptible, whereas 81 (31%) were resistant and 55 (21%) showed intermediate susceptibility. Of the isolates, 322 (90%) were susceptible to ampicillin and (95%) were susceptible to co-trimoxazole. However, all the isolates were susceptible to chloramphenicol and ceftriaxone. INTERPRETATION & CONCLUSIONS: Nalidixic acid resistance screening is not a reliable surrogate indicator of ciprofloxacin resistance. Ciprofloxacin MIC should to be routinely done. Azithromycin resistance appears to be emerging. However, isolates showed a high degree of susceptibility to ampicillin, co-trimoxazole and chloramphenicol. Thus, antibiotics like ampicillin and co-trimoxazole may once again be useful for the management of enteric fever in southern India.

Histoplasmosis in India: truly uncommon or uncommonly recognised?

OBJECTIVES: To study the clinical profile of patients with proven histoplasmosis who had presented to a tertiary care referral centre. METHODS: We retrospectively analysed the medical records of 24 patients diagnosed to have histoplasmosis between January 2002 and April 2011. Histoplasmosis was diagnosed when compatible intracellular organisms were seen on biopsy and/or when Histoplasma capsulatum was grown in culture. RESULTS: Twenty four patients were diagnosed to have histoplasmosis of whom 23 were male. Diabetes and HIV infection was the most common co-morbid conditions. Subacute progressive disseminated histoplasmosis (PDH) (22 patients) was the most common clinical presentation. Ten patients had received 2-3 months of empiric anti-tuberculous therapy (ATT) with no response prior to the diagnosis of histoplasmosis. Fever, weight loss, hepato-splenomegaly, oral ulcers and lymphadenopathy were the most common clinical features. Bilateral adrenal enlargement was detected by imaging in 15 patients and adrenal insufficiency was noted in 4 patients. Itraconazole alone was used for treatment in 20 patients while 3 patients were treated with amphotericin B initially, followed by itraconazole. Response to therapy was excellent in 20 patients. CONCLUSIONS: Histoplasmosis is an under-recognized disease in India and should be considered in the differential diagnosis of male patients with prolonged fever, adrenal enlargement, hepato-splenomegaly, oral ulcers and granulomatous disease on histopathology without response to ATT. When tissue biopsy specimens show granulomas, fungal stains should be routinely performed. Treatment with itraconazole leads to an excellent outcome in most patients.