Good survival rate, moderate overall and good respirator quality of life, near normal pulmonary functions, and good return to work despite catastrophic economic costs 6 months following recovery from Acute Respiratory Distress Syndrome.

Introduction: Long-term quality of life, return to work, economic consequences following Acute Respiratory Distress Syndrome (ARDS) are not well described in India. This study was aimed to address the question. Methods: A prospective cohort study of 109 ARDS survivors were followed up for a minimum of 6 months following discharge. Quality of life was assessed using the SF-36 questionnaire. Respiratory quality was assessed using the St Georges Respiratory Questionnaire. Time to return to work was documented. Costs-direct medical, as well as indirect were documented up to 6 months. Results: At 6 months, 6/109 (5.5%) had expired. Low energy/vitality and general heath were noted in the SF-36 scores at 6 months; overall a moderate quality of life. Pulmonary function tests had mostly normalized. Six-min walk distance was 77% of predicted. Respiratory quality of life was good. It took at the median of 111 days to go back Interquartile range (55-193.5) to work with 88% of previously employed going back to work. There were no significant differences in the severity of ARDS and any of these outcomes at 6 months. The average total cost from the societal perspective was ₹ 231,450 (standard deviation 146,430-, 387,300). There was a significant difference between the 3-ARDS severity groups and costs (P < 0.01). There were no independent predictors of return to work. Conclusion: ARDS survivors have low 6-month mortality. Pulmonary physiology and exercise capacity was mostly normal. Overall, quality of life is average was moderate, while respiratory quality of life was good. Return to work was excellent, while cost of care falls under a catastrophic heath expense.

Clinical Profile and Outcome of Critically Ill Patients with Tuberculosis.

AIM AND OBJECTIVE: Although studies have described the clinical profile of patients admitted to the intensive care unit (ICU) with tuberculosis, it is unclear if the type of tuberculosis (pulmonary, extrapulmonary, or disseminated) impacts outcome. MATRIALS AND METHODS: Demographic data, microbiology, treatment, and outcomes over 5 years (2012-16) were obtained from electronic records. Patients were categorized as pulmonary, extrapulmonary, or disseminated tuberculosis. Comparisons were done using t test and Fisher's exact test as appropriate. Predictors of outcome were explored using bivariate and multivariate logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Of the 428 ICU admissions with suspected tuberculosis, 212 (121 male) patients with mean (standard deviation) age of 41.9 (16.7) years and APACHE-II score of 20.8 (6.6) were diagnosed as pulmonary (n = 55) and extrapulmonary (n = 52) or disseminated tuberculosis (n = 105). In 50.5%, the diagnosis of tuberculosis was established during the current ICU admission when they presented with organ dysfunction. Overall, microbiological confirmation was possible in 75.5%; 14 (10.3%) isolates were Rifampicin resistant. ICU admission was required primarily for ventilation (n = 176; 83%) and hemodynamic instability (n = 67; 32%). Hospital mortality was 50%. Outcomes were similar in the three groups except for longer duration of stay (p value = 0.04) in disseminated tuberculosis. On multivariate logistic regression analysis, pulmonary tuberculosis (OR 2.83; 95% CI 1.15-6.95) and vasoactive treatment (OR 15.8; 95% CI 6.4-39.2) were independently associated with death; need for ventilation predicted mortality perfectly. CONCLUSION: In this cohort of patients admitted to ICU with tuberculosis, 50% were newly diagnosed during ICU admission. Pulmonary site of involvement and need for organ support are independent risk factors for death. HOW TO CITE THIS ARTICLE: Thomas L, Chacko B, Jupudi S, Mathuram A, George T, Gunasekaran K, et al. Clinical Profile and Outcome of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2021;25(1):21-28.

Tuberculous ARDS is associated with worse outcome when compared with non-tuberculous infectious ARDS.

BACKGROUND: Patients with tuberculosis (TB) developing acute respiratory distress syndrome (ARDS) may have a higher mortality when compared with ARDS of other infectious etiology. METHODOLOGY: In this single-centre retrospective cohort study spanning 5-years (2012 to 2016), TB-ARDS patients were age and gender matched (1:2) with non-TB infectious ARDS and followed up until death or hospital discharge. Clinical profile, treatment and outcomes were compared using t-test and Chi-square as appropriate. Mortality predictors were explored using Conditional Poisson regression analysis and expressed as relative risk (RR) with 95% confidence interval (CI). RESULTS: Of the 516 ARDS patients, 74 TB-ARDS and 148 non-TB infectious ARDS patients were included. Although admission APACHE-II (21.4 ± 7.1 vs. 17.6 ± 6.8, p < 0.001), incidence of shock (36.5% vs. 19.1%, p = 0.005) and mortality (59.5% vs. 29.7%, p < 0.001) were significantly higher in TB-ARDS than non-TB etiology, overall ICU length of stay and nosocomial infections were similar in both groups. On regression analysis, after adjusting for confounders, TB-ARDS (RR 1.82; 95% CI 1.13-2.92) and need for inotropes (RR 3.49; 95% CI 1.44-8.46) were independently associated with death. CONCLUSION: Patients with TB-ARDS presented sicker and had higher mortality when compared with ARDS due to non-TB infectious etiology.

Clinical spectrum, aetiology and predictors of acute febrile encephalopathy at a tertiary hospital in south India - A prospective observational study.

Acute febrile encephalopathy is a common syndrome in the tropics with high mortality encountered by emergency physicians. In order to study the aetiology of acute febrile encephalopathy and its mortality and functional outcome over one year, data on all patients >18 years of age with short duration of fever (<14 days) and altered mental status were collected and followed up until one month after discharge. Non-infectious aetiology, found in 29%, portends a poor outcome.

Performance of molecular and serologic tests for the diagnosis of scrub typhus.

Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its non-specific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluates the diagnostic performance of various tests. The present study aims at assessing the accuracy of various rapid diagnostic tests, serologic tests, and nucleic acid amplification methods on well-characterized patient samples. Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood, eschar or tissue were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative real time PCR using 47kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil-Felix test(WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT).Among the 316 participants, 158 had confirmed scrub typhus (cases) and 158 were controls. ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies had excellent discriminative potential with sensitivities and specificities of 92%, 94% and 92%, 92% respectively. The sensitivity and specificity of IFA were found to be 95% and 74% respectively. IgM serology had a false positivity rate of 8% with other acute febrile illnesses such as dengue, leptospirosis and spotted fever due to the nonspecific binding of the pentavalent IgM. LAMP assay had 91.7% sensitivity and 77.2% specificity while qPCR provided excellent sensitivity (97%) and perfect specificity. In conclusion, ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies have excellent sensitivity and specificity while the accuracy of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories particularly for diagnosis of early disease with less than 7 days duration. This study provides a comprehensive evaluation of all currently available diagnostic tests for scrub typhus.

A Hospital-Based Nonconcurrent Cohort Study on Factors Associated with in-Hospital Mortality in Patients with Laboratory Confirmed Influenza.

BACKGROUND AND AIM: Influenza is a disease with varied clinical presentation and varied mortality reported in existing literature. The study aimed to determine the factors associated with mortality in patients hospitalized with influenza infection. MATERIALS AND METHODS: This was a 5-year nonconcurrent cohort study done in a tertiary care center in Southern India. Patients with laboratory confirmed influenza infection diagnosed between January 2013 and October 2018 were recruited into the study. RESULTS: A total of 130 patients were recruited. Diabetes (45.4%) and chronic obstructive pulmonary disease (COPD) (26.1%) were the most common comorbid illnesses. Thirty-one patients (23.8%) required admission to the intensive care unit (ICU) and 58 patients required ventilation (noninvasive/mechanical ventilation [MV] - 44.6%). Influenza A was the most common isolated strain (46.9%). Univariate analysis demonstrated that a high pneumonia severity index (P < 0.0001), CURB 65 > 2 (P < 0.0001), MV dependency (P < 0.0001), need for ICU stay (P < 0.0001), low PF ratio (P < 0.0001), COPD (P = 0.021), secondary bacterial pneumonia (P < 0.0001), acute respiratory distress syndrome (P = 0.0004), and acute kidney injury (P = 0.0006) were the significant factors associated with in-hospital mortality. Multivariate analysis demonstrated that new onset/worsening renal dysfunction was the only factor significantly associated with in-hospital mortality in patients admitted with influenza. CONCLUSIONS: Our study showed a mortality of 12.3% (n= 16) and new onset/worsening renal dysfunction was the only patient factor associated with mortality. Early recognition of complications and appropriate treatment may reduce mortality in patients admitted with severe influenza. We recommend influenza vaccination for at-risk populations to reduce severity and mortality.

A fatal case of levamisole induced bone marrow failure.

A 20-year-old college student presented with high grade, intermittent fever for 10 days associated with blood stained loose stools after taking tablet levamisole for 17 days for vitiligo vulgaris. He was febrile, had a toxic appearance and appeared pale. Investigations showed neutropaenia with thrombocytopaenia. Blood cultures were sterile and stool cultures did not grow any enteric pathogens. His bone marrow examination was suggestive of an aplastic anaemia. He was administered empirical antibiotics, granulocyte colony stimulating factor and platelet transfusions. However, his fever and blood stained stools persisted. A repeat bone marrow examination after 2 weeks still revealed a hypoplastic marrow. Hence, a diagnosis of a levamisole induced bone marrow failure was made. While being worked up for an allogeneic stem cell transplantation, he developed neutropaenic enterocolitis and refractory septic shock with carbapenem resistant Klebsiella pneumoniae and succumbed to his illness.

Will ceftazidime/avibactam plus aztreonam be effective for NDM and OXA-48-Like producing organisms: Lessons learnt from In vitro study.

Introduction: Carbapenem resistance (CR) in Klebsiella pneumoniae is mainly mediated by bla NDM and bla OXA-48 carbapenemases. Newer Food and Drug Administration-approved antimicrobial ceftazidime/avibactam (C/A) has a potent activity against bla OXA-48-like producers. However, its activity is limited in organisms co-producing bla NDM and bla OXA-48-like. Addition of aztreonam (ATM) to C/A potentially expands the spectrum of coverage for carbapenemase co-producers. With this, we aimed to determine the synergistic activity of combination of C/A plus ATM against bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like producing CR Klebsiella pneumoniae (CRKp). Materials and Methods: A total of 12 isolates of CRKp-harbouring genes encoding bla NDM and bla OXA-48-like were tested. Minimum inhibitory concentrations (MICs) were determined for several antimicrobial agents, including C/A (0.5-8 µg/ml) by broth microdilution method. Checkerboard assay was performed for the combination of C/A plus ATM at varying concentrations. Fold differences in the MIC of C/A with and without addition of ATM were determined to infer synergistic effects. Results: MIC of C/A and ATM ranged from 0.5 to >8 µg/ml and 64 to 2048 µg/ml, respectively. Two isolates were susceptible to C/A with MIC of 0.5 and 1 µg/ml, while others were resistant with MIC of >8 µg/ml. Synergistic effects of >8-fold MIC difference in C/A MIC were noted with addition of ATM at 4 µg/ml. This was observed for all CRKp with profiles of bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48-like genes, which was a promising effect. Notably, all five of the colistin-resistant CRKp were inhibited with >8-fold MIC difference in the combination of C/A plus ATM at 4 µg/ml. Conclusion: With the increasing burden of CRKp, the use of C/A with ATM combination seems to be very promising, especially for bla NDM, bla OXA-48-like and co-producers of bla NDM + bla OXA-48like carbapenemases.

Direct cost of illness for dengue in hospitalized children and adults at a referral hospital in India.

OBJECTIVES: To describe the direct cost of illness in pediatric and adult inpatients at a referral hospital in India. METHODS: Inpatients who tested positive for dengue were identified in the hospital records of a single private non-profit hospital over a period of 1 year and line-listed. Hospital discharge bills were obtained for pediatric and adult patients and the median costs by severity of illness for bed and treatment were estimated. Costs were also converted to US dollars (1 USD=64.6 Indian rupees (INR)). RESULTS: The median and interquartile range (IQR) direct costs for pediatric dengue without warning signs, dengue with warning signs, and severe dengue were 179.80 (IQR 85.51-428.51) USD, 145.06 (IQR 90.89-321.86) USD, and 933.51 (IQR 400.50-1117.43) USD, respectively. The median and IQR direct costs for adult dengue without warning signs, dengue with warning signs, and severe dengue were 312.75 (IQR 174.55-531.03) USD, 287.22 (IQR 210.96-389.34) USD, and 720.39 (IQR 389.23-1035.51) USD, respectively. CONCLUSIONS: Children and adults with dengue incur high costs when hospitalized for dengue. Since most medical costs in India are out-of-pocket expenses, these illnesses can impact households.

Visceral leishmaniasis with haemophagocytic lymphohistiocytosis.

A 27-year-old man presented with high-grade intermittent fever for 4 months, generalised fatigue for 2 months, intermittent gum bleeds for 1 month and loss of weight of 15 kg. He appeared cachectic with generalised wasting, had pallor and features of reticuloendothelial system proliferation. His liver span was 17 cm. He had massive splenomegaly. His cardiovascular, respiratory and neurological examination were normal. He was diagnosed to have visceral leishmaniasis (VL) based on bone marrow (BM) examination that showed Leishmania donovani (LD) bodies and was treated with liposomal amphotericin (LA). During the course of therapy, he developed bleeding from various mucosal and venepuncture sites. His further evaluation, which included a repeat BM aspirate, showed haemophagocytes. Final diagnosis made was VL with secondary haemophagocytic lymphohistiocytosis. He was continued on LA with intravenous hydrocortisone. He developed refractory distributive shock with multiorgan dysfunction and succumbed to his illness.

Risk Factors for Acquiring Scrub Typhus among the Adults.

BACKGROUND: Behavioral and geographical factors may play a role in the acquisition of scrub typhus infection. In this prospective case-control study, we studied the factors associated with infection. PATIENTS AND METHODS: Consecutive adult patients admitted with scrub typhus infection over 10 months were recruited. For every case, a geographical control from the same area and a gender-matched clinical control admitted with acute febrile illness were enrolled. The risk factors, which included sanitation, environment, activity, and protective measures, were compared between cases and controls using univariable and multivariable conditional logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The study cohort (n = 225; 132 female) aged 44 ± 17 years comprised of 75 cases and 150 controls from mid to low socioeconomic background. When compared with clinical controls, on univariable conditional regression analysis, cases were more likely to be involved in farming or gardening and less likely to have a toilet within the house. On multivariate regression analysis, only involvement in farming or gardening was associated with infection (OR: 4.2, 95% CI: 1.5-11.5). When compared with geographical controls, on univariable conditional regression analysis, cases were less likely to change undergarments or clothes before sleeping (OR: 3.5, 95% CI: 1.3-9.5) and more likely to have rodents in their house (OR: 2.5, 95% CI: 1-6.4) and rest on grass/mud without a mat (OR: 2.4, 95% CI: 1.1-5.3). On multivariate regression analysis, not changing undergarments or clothes tended to be associated with infection (OR: 2.7, 95% CI: 0.98-7.3). CONCLUSION: Certain behavioral factors predisposed our cohort to develop scrub typhus infection. Lifestyle changes may reduce the burden of scrub typhus in South India.

Mycobacterial blood culture as the only means of diagnosis of disseminated tuberculosis in advanced HIV infection.

The diagnosis of disseminated tuberculosis (TB) in advanced HIV infection is often delayed because of difficulty in obtaining suitable specimens for culture. A total of 32 such patients from South India with positive mycobacterial blood cultures were studied over ten years. Almost all (90%) had a febrile illness and the majority (68.7%) had clinical lung involvement, but only 27.3% had positive sputum smears. Liver biopsy yielded a positive diagnosis in only 1/7. Cytopenia was almost universal (96.9%). Bone marrow cultures were, however, positive in 54.8%, of whom one-quarter grew atypical mycobacteria. Mycobacterial blood culture is therefore a useful adjunct test to diagnose TB in advanced HIV.

Renal cell carcinoma presenting as a cutaneous horn and nodules on the gingiva and scalp.

A 63-year-old man presented with a pulsatile cutaneous horn on the nose and multiple angiomatous nodules on the gingiva and scalp, which appeared over 2 months. He had severe hypercalcaemia, lytic lesions in multiple bones and acute kidney injury. Excision biopsy from the gingival nodule showed a clear cell neoplasm. The bone marrow showed atypical cells with similar morphology. Imaging showed a 7 cmx7.5 cm mass at the upper pole of the left kidney with metastases to the bones, liver and lung. Immunohistochemistry was consistent with metastatic renal cell carcinoma. Renal cell carcinoma presenting as a cutaneous horn is extremely rare and to the best of our knowledge only one other case was found in the literature. There was visible regression in the size of the cutaneous horn and nodules following initiation of pazopanib therapy. However, he succumbed to his illness a month later.

Scrub typhus in pregnancy: Maternal and fetal outcomes.

Scrub typhus is an important unrecognized cause for undifferentiated acute febrile illness in India associated with poor fetal outcomes. Maternal and fetal outcomes among pregnant patients with scrub typhus presenting to a tertiary care university teaching hospital from January 2010 to July 2012 were studied. Scrub typhus was diagnosed by clinical criteria along with scrub ELISA positivity or an eschar. In total, 33 of 738 patients (4.5%) who were diagnosed with scrub typhus were pregnant; 57.6% were in the third trimester, 27.3% in the second, and only 15.2% in the first trimester; 69.7% required admission to intensive care. Mortality was low (3%, n = 1) compared to 12.2% mortality reported previously. All patients were treated with Azithromycin. Poor fetal outcome was observed in 51.5% of these pregnancies with fetal loss occurring in 42.4% and preterm childbirth in 9.1%. Scrub typhus complicating pregnancy is associated with a poor fetal outcome despite treatment with Azithromycin. A majority require intensive care treatment for survival.

Cost-utility in medical intensive care patients. Rationalizing ongoing care and timing of discharge from intensive care.

RATIONALE: Intensive care unit (ICU) treatment costs pose special challenges in developing countries. OBJECTIVES: To determine the prognostic value of the "utility" score and evaluate the relationship of willingness to pay assessment to utility score during ICU admission. METHODS: We performed a prospective study spanning 12 months in a 24-bed medical ICU in India. Treatment cost was estimated by direct measurement. Global utility score was assessed daily by healthcare providers on a Likert scale (0-1 in increments of 0.1, with 0 indicating death/severe disability and 1 indicating cure/perfect health). The sensitivity, specificity, and likelihood ratios of utility in predicting ICU mortality was calculated. Receiver operating characteristic curves were generated to compare Day 2 utility with APACHE II. The caregiver's willingness to pay for treatment was assessed on alternate days using the bidding method by presenting a cost bid. Based on the response ("yes" or "no"), bids were increased or decreased in a prespecified manner until a final bid value was reached. Simultaneously, treating doctors were asked how much institutional funds they would be willing to spend for treatment. MEASUREMENTS AND MAIN RESULTS: Primary diagnosis in 499 patients included infection (26%) and poisoning (21%). The mean (SD) APACHE II score was 13.9 (5.8); 86% were ventilated. ICU stay was 7.8 (5.5) days. ICU mortality was 23.9% (95% confidence interval, 20.3-27.8). Survival without disability was 8.3% (2/24) for Day 2 utility score ≤0.3 and 95.8% (53/56) for Day 5 score >0.8 (P < 0.001). The likelihood ratio to predict mortality increased as utility values decreased and was highest (5.85) for utility 0.2. Area under the receiver operating characteristic curves for utility and APACHE II were similar. Willingness to pay by the caregiver was 53% of treatment cost and was not influenced by utility. Willingness to pay by ICU doctors showed an inverted U-shaped relationship with utility. CONCLUSIONS: Utility scores help prognosticate, with Day 2 score ≤0.3 associated with poor outcome and ≥0.8 Day 5 score with survival. The caregiver's willingness to pay was inadequate to meet treatment cost. ICU doctors were willing to spend more for moderate utility scores than for very high or low utility values. Further prospective studies are needed to optimize the utilization of scarce ICU resources by identifying patients for appropriate step-down care using utility and willingness to pay.

Cytomegalovirus reactivation in drug induced hypersensitivity syndrome.

Drug induced hypersensitivity syndrome has been reported to a variety of drugs. Reactivation of herpes viruses is associated with relapse of symptoms even as late as five weeks after stopping the inciting drug. We report here a case of drug hypersensitivity with CMV reactivation which was treated successfully.

Salmonella typhi rib osteomyelitis with abscess mimicking a 'cold abscess'.

Salmonella enterica serovar typhi (Salmonella typhi) causing typhoid fever is common in many parts of the world particularly in developing countries. Extra-intestinal manifestations such as osteomyelitis are rare in immunocompetent individuals. We report a case of Salmonella typhi osteomyelitis of a rib with overlying abscess mimicking a 'cold abscess', treatment outcomes and discuss relevant literature.

Rhino-orbital-cerebral infection by Syncephalastrum racemosusm.

Invasive rhino-sinusitis infection has been known to be caused by zygomycetes commonly belonging to the genera Rhizopus, Mucor and Rhizomucor. We report a middle aged diabetic gentleman who had invasive rhino-orbital-cerebral infection with Syncephalastrum racemosum. This genera belonging to zygomycetes group of fungi which usually causes skin and soft tissue infection but invasive infection with this fungus is rarely known.