Colistin (Polymyxin E) Use in Abdominal Solid Organ Transplant Recipients.

Background: Patients undergoing solid organ transplantation are at a higher risk of multi-drug resistant (MDR) bacterial infections especially during the immediate post operative period. Objective: To audit the usage, dosage appropriateness and safety of colistin use in abdominal solid organ transplant recipients to treat immediate post-transplant bacterial infections. Methods: After completion of 1000 abdominal solid organ transplants at our institute, data of the transplant recipients who received colistin between October 2010 and December 2019 was extracted from the hospital health information system. Data of all microbiological culture isolates, the minimum inhibitory concentration (MIC) of colistin, appropriateness of colistin dosing and nephrotoxicity associated with colistin use was assessed. Results: Of the 1170 (732 liver and 438 renal) solid organ transplant recipients, 82 (66 liver and 16 renal) received colistin to treat posttransplant MDR bacterial infections. Nearly 60% received colistin as definitive therapy and 87.81% received colistin as combination. Mean duration of colistin therapy was found to be higher in renal than liver transplant recipients. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Colistin in combination with meropenem (36.4%) was the most commonly used dual therapy. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Overall in-hospital mortality of patients who received colistin was 43.9%. Renal impairment occurred in 28.8% of liver transplant recipients. Conclusion: Infection necessitating colistin use increases mortality by three folds in liver transplant recipients and by five percentage points in renal transplant recipients.

Epidemiology of Community-Acquired Sepsis: Data from an E-Sepsis Registry of a Tertiary Care Center in South India.

The study aims to characterize community-acquired sepsis patients admitted to our 1300-bedded tertiary care hospital in South India from the Surviving Sepsis Campaign (SSC) guideline-compliant e-sepsis registry stratified by focus of infection. The prospective observational study recruited 1009 adult sepsis patients presenting to the emergency department at the center based on Sepsis-2 criteria for a period of three years. Of the patients, 41% were between 61 and 80 years with a mean age of 57.37 ± 13.5%. A total of 13.5% (136) was under septic shock and in-hospital mortality for the study cohort was 25%. The 3 h and 6 h bundle compliance rates observed were 37% and 49%, respectively, without significant survival benefits. Predictors of mortality among patients with bloodstream infections were septic shock (p = 0.01, OR 2.4, 95% CI 1.23-4.79) and neutrophil-to-lymphocyte ratio (p = 0.008, OR 1.01, 95% CI 1.009-1.066). The presence of Acinetobacter (p = 0.005, OR 4.07, 95% CI 1.37-12.09), Candida non-albicans (p = 0.001, OR16.02, 95% CI 3.0-84.2) and septic shock (p = 0.071, OR 2.5, 95% CI 0.97-6.6) were significant predictors of mortality in patients with community-acquired pneumonia. The registry has proven to be a key data source detailing regional microbial etiology and clinical outcomes of adult sepsis patients, enabling comprehensive evaluation of regional community-acquired sepsis to tailor institutional sepsis treatment protocols.

A comparison of clinical outcomes between vaccinated and vaccine-naive patients of COVID-19, in four tertiary care hospitals of Kerala, South India.

THE PROBLEM CONSIDERED: This multi-centric study analyzed data of COVID-19 patients and compared differences in symptomatology, management, and outcomes between vaccinated and vaccine-naive patients. METHODS: All COVID-19 positive individuals treated as an in-or out-patient from the 1stMarch to 15th May 2021 in four selected study sites were considered for the study. Treatment details, symptoms, and clinical course were obtained from hospital records. Chi-square was used to test the association of socio-demographic and treatment variables with the vaccination status and binary logistic regression were used to obtain the odds ratio with a 95% confidence interval. RESULTS: The analysis was of 1446 patients after exclusion of 156 with missing data of which males were 57.3% and females 42.7%. 346 were vaccinated; 189 received one dose and 157 both doses. Hospitalization was more in vaccinated (38.2% vs 27.4%); ICU admissions were less in vaccinated (3.5% vs 7.1%). More vaccinated were symptomatic (OR = 1.5); half less likely to be on non-invasive ventilation (OR = 0.5) while vaccine naive patients had 4.21 times the risk of death. CONCLUSION: Severe infection, duration of hospital stays, need for ventilation and death were significantly less among vaccinated when compared with vaccine naive patients.

Clinical efficacy and pharmacokinetics of colistimethate sodium and colistin in critically ill patients in an Indian hospital with high endemic rates of multidrug-resistant Gram-negative bacterial infections: A prospective observational study.

BACKGROUND: Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing. AIM: To evaluate the pharmacokinetics of colistimethate sodium and colistin in critically ill patients and correlate with clinical efficacy and renal function. MATERIALS AND METHODS: Twenty critically ill adult patients with colistin-susceptible multidrug-resistant (MDR) infections and normal renal function treated with intravenous colistimethate sodium - at a 9 million units (270 mg CBA) loading dose followed by maintenance (MD) of 3 million units t.i.d, 24 hours later - were evaluated for clinical cure (CC) at the end of therapy. Patient characteristics and plasma colistin levels at 0, 0.5, 1, 2, 4, 8 and 12 hours after the loading dose and at 1, 2 and 8 hours after the eighth and ninth infusion of MD were evaluated. Colistimethate sodium and colistin levels were measured by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). RESULTS: Among the 20 patients who were evaluated, 60% had pneumonia. Predominant pathogens were Klebsiella pneumoniae and Acinetobacter spp. Clinical cure was 50% (10/20). Mean peak loading dose concentrations were 3 ± 1.1 mg/L (1.75-5.14) and 2.37 ± 1.2 mg/L (1.52-5.54) for 'cure' and 'failure' groups, respectively (p = 0.13), while mean steady-state (Cssavg) concentrations were 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in 'cure' and 'failure' groups, respectively (p = 0.19). Nephrotoxicity was 5% on day 7 of therapy. However, bacteriological cure could not be correlated with PK/PD. CONCLUSIONS: Subtherapeutic Cssavg with clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing.

Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/µl) in adult dengue - Results of a pilot study.

Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11-43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/µL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/µL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/µL was 2 days (IQR 2-3) compared to 3 days (IQR 2-4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred-mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies. Trial registration Name of the registry: Clinical Trials Registry-India (CTRI) Registration No.: CTRI-REF/2017/02/013314.

Waiting for Godot: A cross sectional survey based analysis of the hydroxychloroquine prophylaxis strategy against COVID-19 in India.

Background: India currently has the second largest burden of infections due to COVID-19. Health Care Worker (HCW) shortages are endemic to Indian healthcare. It should therefore be a huge priority to protect this precious resource as a critical component of the systemic response to this pandemic. Advisories from the Indian Council of Medical Research (ICMR) have focused on using hydroxychloroquine prophylaxis against COVID-19 in at risk HCW. This prophylaxis strategy has no evidence. In further jeopardy there appear to insubstantial attempts to build this evidence as well. In this connection, we commissioned a survey within our Institution to estimate the penetration of hydroxychloroquine (HCQ) use and use this to statistically model the impact of current ongoing studies in India. We also briefly review the literature on HCQ prophylaxis for COVID-19. Design and methods: A structured survey designed using RedCAP application was disseminated among healthcare professionals employed at an academic referral tertiary care centre via online social media platforms. The survey was kept open for the entire month of June 2020. The survey was additionally used to statistically model the size of studies required to comprehensively address the efficacy of HCQ in this setting. Results: 522 responses were received, of which 4 were incomplete. The ICMR strategy of 4 or more doses of HCQ was complete only in 15% of HCW in our survey. The majority of respondents were doctors (238, 46%). Amongst all category of responders, only 12% (n=63) received the full course. A majority of those who initiated the chemoprophylaxis with HCQ turned out to be medical professionals (59/63) with neither nurse nor other categories of healthcare workers accessing the medication. The respondents of our institutional survey did not report any life-threatening side effects. Presuming efficacy as per ICMR modelling for new registry trial on the lines of the published case control study, equal allocation between cases and controls and assuming a RR of 1.3.6, the power of such a study would be very low for n=2000 for event rates from 2.5-12.5%. Conclusion: We report the low penetration of HCQ chemoprophylaxis among the healthcare workers of our institution. We highlight the inherent drawbacks in the study design of current national COVID related trial based on the statistical modelling of our survey results and published literature, and thereby emphasis the need of evidence-based strategies contributing to research policy at national level.

Myocardial injury after noncardiac surgery-incidence and predictors from a prospective observational cohort study at an Indian tertiary care centre.

Asymptomatic myocardial injury following noncardiac surgery (MINS) is an independent predictor of 30-day mortality and may go unrecognized based on standard diagnostic definition for myocardial infarction (MI). Given lack of published research on MINS in India, our study aims to determine incidence of MINS in patients undergoing noncardiac surgery at our tertiary care hospital, and evaluate the clinical characteristics including 30-day outcome.The prospective observational study included patients >65 years or >45 years with either hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), cerebrovascular accident (CVA), or peripheral arterial disease undergoing noncardiac surgery. MINS was peak troponin level of ≥0.03 ng/dL at 12-hour or 24-hour postoperative. All patients were followed for 30 days postoperatively. Predictors of MINS and mortality were analyzed using multivariate logistic regression. Patients categorized based on peak troponin cut-off values determined by receiver operating characteristic curve were analyzed by Kaplan-Meir test to compare the survival of patients between the groups.Among 1075 patients screened during 34-month period, the incidence of MINS was 17.5% (188/1075). Patients with DM, CAD, or who underwent peripheral nerve block anaesthesia were 1.5 (P < .01), 2 (P < .001), and 12 (P < .001) times, respectively, more likely to develop MINS than others. Patients with heart rates ≥96 bpm before induction of anesthesia were significantly associated with MINS (P = .005) and mortality (P = .02). The 30-day mortality in MINS cohort was 11.7% (22/188, 95% CI 7.5%-17.2%) vs 2.5% (23/887, 95% CI 1.7%-3.9%) in patients without MINS (P < .001). ECG changes (P = .002), peak troponin values >1 ng/mL (P = .01) were significantly associated with mortality. A peak troponin cut-off of >0.152 ng/mL predicted mortality among MINS patients at 72% sensitivity and 58% specificity. Lack of antithrombotic therapy following MINS was independent predictor of mortality (P < .001), with decreased mortality in patients who took post-op ASA (Aspirin) or Clopidogrel. Mortality among MINS patients with post-op ASA intake is 6.7% vs 12.1% among MINS patients without post-op ASA intake. Mortality among MINS patients with post-op Clopidogrel intake is 10.5% vs 11.8% among MINS patients without post-op Clopidogrel intake.A higher (17.5%, 95% CI 15-19%) incidence of MINS was observed in our patient cohort with significant association with 30-day mortality. Serial postoperative monitoring of troponin following noncardiac surgery as standard of care, would identify "at risk" patients translating to improved outcomes.

A Quality Improvement Initiative to Reduce "Out-of-ICU" Cardiopulmonary Arrests in a Tertiary Care Hospital in India: A 2-Year Learning Experience.

QUALITY PROBLEM OR ISSUE: To assess impact of medical emergency team (MET) in reducing "out-of-ICU" cardiopulmonary arrests and identify barriers to its optimal utilization. INITIAL ASSESSMENT: Frequently observed critical clinical signs and laboratory values of "out-of-ICU" crashes were used to develop Amrita Early Warning Criteria. CHOICE OF SOLUTION: A physician-led MET was established to respond to code MET, activated by a primary nurse. IMPLEMENTATION: Rates of "out-of-ICU" cardiopulmonary arrests per 1000 admissions were compared in pre-MET (2013-2014) and post-MET periods (2014-2016) along with disposition following MET and mortality. Descriptive statistics and logistic regression were used for comparative analysis. EVALUATION: For continued quality improvement, a Likert agreement scale questionnaire collated the nurse's feedback on MET. 386 Code MET were recorded with an activation rate of 18.8 per 1000 inpatients for 2014-2016. Common MET triggers were desaturation (53%), seizure (10%), and syncope (9%). Seventy-one percent of activations were attended within 5 minutes, with 45% reported during nurse's night shift hours. Medical emergency team interventions resulted in 59% being shifted to ICU. In the "post-MET" period, "Cold Blue" dose reduced from 6.9 in 2013-2014 to 2.6 (P = .0002) in 2014-2015 and 3.2 (P = .01) in 2015-2016. Ninety-three percent of the Code Blues with prior MET calls were "delayed MET" and 28% of the Code Blues without prior MET activation were "missed MET." Nurse's feedback revealed that 46% lacked knowledge of correct MET activation process while 31% expressed a fear of reprisal for inappropriate activation. LESSONS LEARNED: Although MET intervention was successful in significantly reducing "out-of-ICU" Code Blues, focused training of nurses is required for continued quality improvement.

Assessment of 2013 AHA/ACC ASCVD risk scores with behavioral characteristics of an urban cohort in India: Preliminary analysis of Noncommunicable disease Initiatives and Research at AMrita (NIRAM) study.

Cardiovascular diseases (CVDs) are the leading cause of death and disability in India. Early and sustained exposure to behavioral risk factors leads to development of CVDs.The aim of this study was to determine the baseline risk of a "hard CVD event" in subjects attending comprehensive health clinic and assess behavioral characteristics in "at risk" population.Using WHO STEPwise approach to Surveillance modified questionnaire, prevalence of noncommunicable diseases (NCDs) and risk factors was estimated in this cross-sectional study of 4507 subjects. Baseline cardiovascular risk was determined using Framingham risk score (FRS) and American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) algorithms. Modifiable behavior associated with high CVD risk was assessed. Among 40 to 59-year olds, ASCVD risk tool derived both a 10-year and lifetime risk score, which were used to stratify the cohort into 3 risk groups, namely, a high 10-year and high lifetime, a low 10-year and high lifetime, and a low 10-year and low lifetime risks.Dyslipidemia (30.6%), hypertension (25.5%), diabetes mellitus (20%), and obstructive airway disorders (17.6%) were most prevalent NCDs in our cohort. The ASCVD score stratified 26.1% subjects into high 10-yr and 59.5% into high lifetime risk while FRS classified 17.2% into high 10-year risk. Compared with FRS, the ASCVD risk estimator identified a larger proportion of subjects "at risk" of developing CVD. A high prevalence of alcohol use (38.4%), decreased intake of fruits and vegetables (96.2%) and low physical activity (58%) were observed in "at risk" population. Logistic regression analysis showed that in 40 to 59-year group, regular and occasional drinkers were 8.5- and 3.1-fold more likely to be in high 10-year and high lifetime ASCVD risk category than in low 10-year and low lifetime risk group. Similarly, regular drinkers and occasional drinkers were 2.1 and 1.3 times more likely to be in low 10-year and high lifetime risk than in low 10-year and low lifetime risk category. Subjects with inadequate intake of fruits and vegetables were 1.59 times more likely to be in low 10-year and high lifetime risk than the lower 10-year and lifetime risk group. Obese participants were 2.3-fold more likely to be in low 10-year and high lifetime risk.Identification of "at risk" subjects from seemingly healthy population will allow sustainable primary prevention strategies to reduce CVD.

Long term outcome of medical and surgical co-management of craniospinal aspergillosis in an immunocompromised patient.

35 yr old steroid dependent lady with Pulmonary TB underwent debridement of epidural abscess & posterior stabilization for paraparesis. With histopathology and cultures showing Aspergillus fumigatus, voricanozole was started. By the fourth week, she developed persistent fever, and altered mental status. Brain MRI and CSF study including multiplex PCR evaluation confirmed cerebral aspergillosis. Voricanozole was changed to intravenous lipid complex Amphotericin B to achieve sustained clinical and radiological response after six months of therapy.