Association of Physicians of India Expert Recommendations on Oral Fluid, Electrolytes, and Energy Management during Transition Care and Discharge for Hospitalized Patients with Nondiarrheal Illnesses.

Acute nondiarrheal illnesses (NDIs) involve overt or subclinical dehydration, requiring rehydration and electrolyte repletion. Dehydration is frequently under-recognized and under-managed, both in outpatient departments (OPDs) and inpatient departments (IPDs). Postadmission dehydration is associated with longer hospital stays and higher inhospital mortality rates. Recognizing and understanding dehydration in hospitalized patients is necessary due to the adverse outcomes associated with this condition. In this article, we aimed to develop practical consensus recommendations on the role of oral fluid, electrolyte, and energy (FEE) management in hospitalized patients with FEE deficits in NDI. The modified Delphi consensus methodology was utilized to reach a consensus. A scientific committee comprising eight experts from India formed the panel. Relevant clinical questions within three major domains were formulated for presentation and discussion: (1) burden and factors contributing to dehydration in hospitalized patients; (2) assessment of fluid and electrolyte losses and increased energy requirements in hospitalized patients; and (3) management of FEE deficits in hospitalized patients [at admission, during intravenous (IV) therapy, IV to oral de-escalation, and discharge]. The consensus level was classified into agreement (mean score ≥4), no consensus (mean score <4), and exclusion (mean score <4 after the third round of discussion). The questions that lacked agreement were discussed during the virtual meeting. The experts agreed that the most common factors contributing to dehydration in patients with NDI hospitalized in IPDs include decreased oral fluid intake, increased fluid loss due to the illness, insensible fluid loss, and a lack of awareness among doctors about dehydration, which can result in poor fluid intake. Time constraints, discontinuity of care, lack of awareness of the principles of fluid balance, lack of formal procedures for enforcing hydration schemes, and lack of adequate training are most often barriers to the assessment of hydration status in hospital settings. Experts used hydration biomarkers, such as changes in body weight, serum, or plasma osmolality; fluid intake; and fluid balance charts; along with urine output, frequency, quantity, and color, to determine hydration status in hospital settings. Experts agreed that appropriate FEE supplementation in the form of ready-to-drink (RTD) fluids can restore FEE deficits and shorten the length of hospital stays in hospitalized patients at admission, during de-escalation from IV to oral therapy, and at discharge. RTD electrolyte solutions with known concentrations of electrolytes and energy are good choices to avoid taste fatigue and replenish FEE in hospitalized patients during transition care and at discharge.

Efficacy and Safety of Oral and IV Levonadifloxacin Therapy in Management of Bacterial Infections: Findings of a Prospective, Observational, Multi-center, Post-marketing Surveillance Study.

Background Antimicrobial resistance by bacteria poses a substantial threat to morbidity and mortality worldwide, and treatment of resistant infections is a challenge for the treating clinician. Levonadifloxacin is a novel broad-spectrum agent belonging to the benzoquinolizine subclass of quinolone, which can be used by both oral and intravenous administration for the treatment of infections caused by gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). Patients and methods This prescription event monitoring study captured data from 1266 patients receiving levonadifloxacin (oral and/or IV) in a real-world setting to assess the safety and efficacy in the treatment of various bacterial infections. The duration of the study was 18 months. Study outcomes were clinical success and microbial success at the end of therapy. Global assessments were done for safety and efficacy at the end of therapy using a 5-point Likert scale (excellent, very good, good, satisfactory, and poor). Results The mean (median) duration of therapy was 7.2 (7.0) days, with a median time to clinical improvement of four days. Oral therapy was administered to 224 patients; 940 received IV, and 102 received IV followed by oral therapy. Patients were prescribed levonadifloxacin for gram-positive infections, skin and soft tissue infections, diabetic foot infections, septicemia, catheter-related blood-stream infections, bone and joint infections, febrile neutropenia, and respiratory infections, including COVID-19 pneumonia. The clinical cure on the eighth day was 95.7%, whereas the microbial success on the eighth day was 93.3% (n=60). For different types of infections, the clinical success rates ranged from 85.2% to 100%. There were only 30 treatment-emergent adverse events reported in 29 patients. Overall, about 95.6% of patients rated the efficacy as good to excellent, whereas only 3.8% of patients rated it satisfactory; for safety, 95.7% of patients rated it as good to excellent, with only 3.9% of patients rated it as satisfactory. Conclusions The excellent safety and efficacy profile of levonadifloxacin, when administered as an oral or intravenous therapy, makes it a desirable treatment modality for the management of various bacterial infections, including those caused by resistant pathogens such as MRSA and quinolone-resistant Staphylococcus aureus (QRSA). Features of levonadifloxacin, such as availability in both IV and oral form, minimal drug-drug interactions, lack of the need to adjust dosages in renal and hepatically impaired patients along with a broad spectrum of coverage, make it a suitable agent that meets several unmet clinical needs of physicians.

Effectiveness of Ceftazidime-Avibactam in Gram-Negative Nosocomial Pneumonia: A Real-World Study in India.

BACKGROUND AND OBJECTIVE: The incidences of nosocomial pneumonia in intensive care units (ICUs) in India have been reported to range from 9% to 58% and are associated with a mortality rate of 30-70%. Ceftazidime-avibactam has activity against OXA-48-like carbapenem-resistant Enterobacterales (CRE) and has a safer adverse effect profile as compared to the nephrotoxic colistin. The current study aimed to assess the effectiveness and usage pattern of ceftazidime-avibactam in gram-negative hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in real-world settings in India. METHODS: Electronic medical records of hospitalized patients in three prominent medical centers in India (Fortis Memorial Research Centre, Gurugram, S L Raheja Hospital, Mumbai, and Fortis Hospital, Anandapur, Kolkata) with nosocomial pneumonia and documented gram-negative Klebsiella pneumoniae (KP)-confirmed infection were collected. This study assessed the effectiveness, usage pattern of ceftazidime-avibactam, and clinical and microbiological cure rates. RESULTS: Among the 116 patients included, 78.45% (91/116) showed clinical cure. Microbiological cure was observed in nine out of 13 (69.23%) patients. In the subset analysis, a clinical cure rate of 84.85% (28/33) and microbiological recovery rate of 62.50% (5/8) were observed when ceftazidime-avibactam was initiated within 72 hours of diagnosis. Ceftazidime-avibactam was administered for a mean (±SD) duration of 7.79 ± 4.43 days, with improvement in signs and symptoms reported among 91.38% (106/116). Ceftazidime-avibactam showed a susceptibility of 56% (28/56) in the study. CONCLUSION: The current study showed a better clinical and microbiological cure rate with a safer tolerability profile of ceftazidime-avibactam in carbapenem-resistant KP nosocomial pneumonia and VAP. This study has further demonstrated that ceftazidime-avibactam may be used as one of the viable treatment choices in carbapenem-resistant KP with favorable clinical outcomes.

Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral).

PURPOSE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.

Relationship of End Expiratory Lung Volume, Compliance, and Plateau Pressure in Acute Respiratory Distress Syndrome.

COVID-19 ARDS (acute respiratory distress syndrome), caused by SARS-CoV-2, involves a decrease in the end expiratory lung volume (EELV), compliance, and hypoxemia. The authors retrospectively analysed the relationship between the EELV, Plateau pressure (Pplat), and compliance of the respiratory system in a group of 21 mechanically ventilated COVID ARDS patients with moderate to severe hypoxia who were subjected to a recruitment manoeuvre. Further, these parameters were studied after dividing them into two groups as Group 1 of clinically non-recruitable and Group 2 of clinically recruitable patients. There was relationship between EELV, compliance, and Pplat among those patients who were clinically recruited versus those who were not in a homogeneous group of COVID ARDS patients. In Group 1, the statistical value of EELV and compliance were r = 0.395, p>0.05, EELV and Pplat were r = 0.021, p>0.05, and compliance and Pplat were r = -0.848, p<0.001. In Group 2, the statistical values of EELV and compliance were (r = 0.605, p<0.001), EELV and Pplat were r = -0.391, p<0.05, compliance and Pplat were r = -0.848, p<0.001. The additional information gained after understanding this relationship can help to optimise ventilator settings. Key Words: COVID, ARDS, End expiratory lung volume, Plateau pressure, Compliance, Recruitment, Ventilation.

Therapeutic Drug Monitoring of Isavuconazole: Lessons Learnt from a Real-life Setting in a Tertiary Care Center in India.

Introduction: Isavuconazole is an emerging therapeutic option for invasive infections caused by molds, especially aspergillosis and mucormycosis. Isavuconazole has predictable pharmacokinetics and good bioavailability. These attributes have led to some doubts regarding the need for therapeutic drug monitoring (TDM). There are no data from India regarding TDM for isavuconazole. Methods: A retrospective analysis of 50 patients who received oral isavuconazole for therapeutic purposes. Plasma isavuconazole levels were measured using a reversed phase high-performance liquid chromatography (HPLC) and UV detector with acetonitrile (ACN) as protein precipitating solvent. Results: Of the 50 cases, 5 (10.0%) patients had subtherapeutic levels, while 45 (90.0%) had therapeutic levels. Higher body weight and solid organ transplantation (SOT) were significantly associated with subtherapeutic levels of isavuconazole (p-value < 0.05 for all). Receipt of a SOT was the only independent and statistically significant factor which was associated with subtherapeutic levels of isavuconazole (p-value < 0.05). Conclusion: Our study reemphasizes the need of TDM for isavuconazole and adds to the growing evidence for the need to obtain drug levels. Factors associated with subtherapeutic levels of isavuconazole need to be assessed in larger studies to help identify those patients who are at risk of having subtherapeutic drug levels. How to cite this article: Prayag PS, Soman RN, Panchakshari SP, Ajapuje PS, Mahale NP, Dhupad S, et al. Therapeutic Drug Monitoring of Isavuconazole: Lessons Learnt from a Real-life Setting in a Tertiary Care Center in India. Indian J Crit Care Med 2023;27(4):260-264.

A retrospective review of a 2-year strong antimicrobial stewardship program in a tertiary care institute in Mumbai.

BACKGROUND INFORMATION: Many institutes have implemented a strict antimicrobial stewardship (AMS) program in the postantibiotic era. AIM: To investigate how the resistance pattern changes after implementation of a stringent AMS programme. METHODOLOGY: It employs a defined daily dose methodology (DDD). The formulae listed below are used to compute this for two periods: October 2015 to October 2017 (Period 1) and October 2017 to October 2019 (Period 2) (Period 2). DDD = Antibiotics used in total (g) per year The length of stay was determined using the data from the hospital's information system (HIS). The patterns of resistance to the limited antibiotics are vancomycin, linezolid, tigecycline, and colistin. In both Periods 1 and 2, skin and soft-tissue infections, urinary tract infections, bloodstream infections, and respiratory tract infections were studied in both periods. RESULTS: In the year from October 2015 to October 2017, 4569 patients received limited antibiotics out of a total of 14,544 admissions. The average length of stay was 7.48 days in Period 1, however, it was reduced to 3.96 days in Period 2 out of 15,199 patients. In vitro isolate sensitivities to vancomycin, linezolid, tigecycline, and colistin were increased. CONCLUSION: Some of the most common antibiotics were used less frequently. This appears to be linked to a shorter stay in the hospital and increased antibiotic susceptibility.

Energy expenditure in COVID-19 mechanically ventilated patients: A comparison of three methods of energy estimation.

BACKGROUND: Indirect calorimetry (IC) is the gold standard for measuring resting energy expenditure. Energy expenditure (EE) estimated by ventilator-derived carbon dioxide consumption (EEVCO2 ) has also been proposed. In the absence of IC, predictive weight-based equations have been recommended to estimate daily energy requirements. This study aims to compare simple predictive weight-based equations with those estimated by EEVCO2 and IC in mechanically ventilated patients of COVID-19. METHODS: Retrospective study of a cohort of critically ill adult patients with COVID-19 requiring mechanical ventilation and artificial nutrition to compare energy estimations by three methods through the calculation of bias and precision agreement, reliability, and accuracy rates. RESULTS: In 58 mechanically ventilated patients, a total of 117 paired measurements were obtained. The mean estimated energy derived from weight-based calculations was 2576 ± 469 kcal/24 h, as compared with 1507 ± 499 kcal/24 h when EE was estimated by IC, resulting in a significant bias of 1069 kcal/day (95% CI [-2158 to 18.7 kcal]; P < 0.001). Similarly, estimated mean EEVCO2 was 1388 ± 467 kcal/24 h when compared with estimation of EE from IC. A significant bias of only 118 kcal/day (95% CI [-187 to 422 kcal]; P < 0.001), compared by the Bland-Altman plot, was noted. CONCLUSION: The energy estimated with EEVCO2 correlated better with IC values than energy derived from weight-based calculations. Our data suggest that the use of simple predictive equations may potentially lead to overfeeding in mechanically ventilated patients with COVID-19.

Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia.

PURPOSE: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. METHODS: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. RESULTS: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). CONCLUSION: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

Smart secretion management to protect nurses from COVID19 and other infectious diseases.

BACKGROUND: COVID-19 has been linked to over 40 million infections and 1.1 million deaths in 210 countries as of October 19, 2020. This highly contagious communicable disease has put not only infected individuals but other patients and frontline workers like nurses at risk in hospitals, especially in Intensive Care units (ICUs). There is a need for minimizing patient contact, improving hand hygiene practices, and optimizing healthcare provider time, especially nurses. Globally it is estimated that nearly a million health care providers have been infected with COVID-19 as of the end of October 2020. METHODS: This retrospective service evaluation documents the experience of health care providers in a COVID-19 ICU in India that was used to implement new protocols for secretion management and oral hygiene. Patient chart information and staff feedback were utilized. INTERVENTION: This pilot study captures the practical benefits of using VAPCare, an automated, closed-loop system for oral secretion removal. RESULTS: Six patients were included in this small-scale study; three patients following the current standard of care for suctioning and oral hygiene and three receiving the new VAPCare and Lumen device protocol. With the new device protocol, the number of infected secretion interactions by a nurse was 50% lower, and nursing time spent on oral hygiene and secretion management 70% less than seen with the current standard of care. The number of disposable gloves used with VAPCare and Lumen was reduced by over 50%. All 10 nurses and six doctors gave positive feedback on device usage. The department recommended updating protocols to prioritize the use of the new secretion management system for patients with COVID19 and other highly contagious conditions. CONCLUSION: The findings are an early indication that using VAPCare for patients could help protect infected patients, other ICU patients, and health care workers.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. METHODS: This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. DISCUSSION: This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

In Vitro activity of a Novel Benzoquinolizine Antibiotic, Levonadifloxacin (WCK 771) against Blood Stream Gram-Positive Isolates from a Tertiary Care Hospital.

Background Blood stream infections (BSIs) due to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality ranging from 10 to 60%. The current anti-MRSA agents have limitations with regards to safety and tolerability profile which limits their prolonged usage. Levonadifloxacin and its oral prodrug alalevonadifloxacin, a novel benzoquinolizine antibiotic, have recently been approved for acute bacterial skin and skin structure infections including diabetic foot infections and concurrent bacteremia in India. Methods The present study assessed the potency of levonadifloxacin, a novel benzoquinolizine antibiotic, against Gram-positive blood stream clinical isolates ( n = 31) collected from January to June 2019 at a tertiary care hospital in Mumbai, India. The susceptibility of isolates to antibacterial agents was defined following the Clinical and Laboratory Standard Institute interpretive criteria (M100 E29). Results High prevalence of MRSA (62.5%), quinolone-resistant Staphylococcus aureus (QRSA) (87.5%), and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) (82.35%) were observed among bacteremic isolates. Levonadifloxacin demonstrated potent activity against MRSA, QRSA, and MR-CoNS strains with significantly lower minimum inhibitory concentration MIC 50/90 values of 0.5/1 mg/L as compared with levofloxacin (8/32 mg/L) and moxifloxacin (2/8 mg/L). Conclusion Potent bactericidal activity coupled with low MICs support usage of levonadifloxacin for the management of BSIs caused by multidrug resistant Gram-positive bacteria.

CT Scan Findings of Five Mildly Symptomatic COVID Patients from India.

The outbreak of the SARS-Cov-2 (Severe Acute Respiratory Syndrome - Coronavirus 2) viral pandemic which started at Wuhan China has spread to 200 countries and have resulted in a huge loss to mankind and the global economy. Computerised Tomographic (CT) scan may play an important role in the diagnosis and management of the COVID -19-the disease caused by the SARS-Cov-2. This modality might help in triaging this extremely contagious disease and thus help serve in reducing the outbreak. We present five cases that presented to the hospital with mild symptoms, where the CT scan findings were disproportionate to the symptoms thus leading to effective triage. This resulted in effective disposition in isolation ward and thus helped to protect the healthcare workers from contraction of the disease. This is especially important as the definitive diagnosis via RT-PCR (Reverse Transcriptase - Polymerase Chain Reaction) would take almost 24 hours in the present time in India. Key Words: CT scan, COVID- 19, Triage, SARS-Cov-2.

Thromboelastography Profile of Patients with COVID-19 Admitted to Intensive Care Unit: A Single-center Retrospective Study from India.

Coronavirus disease (COVID-19) causes thromboinflammation resulting in a high incidence of venous thromboembolism (VTE) events, which occur in significant numbers despite giving standard thromboprophylaxis with low-molecular-weight heparins. Various markers and tests have been evaluated and found to have a strong association with the worse prognosis of the disease. Common coagulation markers like D-dimer and fibrinogen give more of a static picture of coagulation, whereas viscoelastic tests like thromboelastography (TEG) provide an understanding of the coagulation function and help in better interpretation. We conducted a retrospective analysis of TEG values of 32 patients with COVID-19 admitted to the intensive care unit (ICU). Hypercoagulation as defined by TEG-coagulation index (CI) higher than the upper limit of the normal reference range (NRR) is found in 62.5% of the patients. There is also a clear representation of hypercoagulability as reflected by TEG-R, TEG-K, and TEG-LY30 values lower than or toward the lower limit of NRR, and TEG-ANGLE, TEG-MA, and TEG-CI values higher than or toward the upper limit of NRR which is more pronounced in severe forms of the disease, both in comparison to NRRs and other non-COVID ICU patients. Findings are similar to that of earlier studies in patients with COVID-19 except for the LY30, which is retained in the majority of our patients. Thromboelastography can be a useful tool to understand and screen for COVID-19-related hypercoagulability and may help predict VTE events. The potential of TEG to determine the optimal anticoagulant therapy needs to be evaluated in larger prospective studies. How to cite this article: Saseedharan S, Talla VB, Chiluka A. Thromboelastography Profile of Patients with COVID-19 Admitted to Intensive Care Unit: A Single-center Retrospective Study from India. Indian J Crit Care Med 2020;24(12):1218-1222.

Microbiological profile and antibiotic susceptibility pattern of Gram-positive isolates at a tertiary care hospital.

OBJECTIVES: Gram-positive infections such as those by Staphylococcus aureus have contributed to the disease burden by increasing the morbidity and mortality rates in India. This study aims to determine the prevalence and the antibiotic susceptibility pattern of Gram-positive pathogens at a tertiary care hospital, Mumbai, Maharashtra, India. MATERIALS AND METHODS: This retrospective cross-sectional study was carried out from January, 2015 to December, 2017, at a tertiary care hospital in Mumbai, India. The clinical isolates were cultured, and identification was done using Vitek 2 culture system. The antibiotic susceptibility testing was done as per the Clinical Laboratory Standard Institute guidelines. RESULTS: Out of 2132 (29%) Gram-positive isolates, S. aureus (49%) was the most common encountered pathogen, followed by Enterococcus spp. (24.5%) and coagulase-negative Staphylococcus (16%). Majority of the S. aureus were observed in patients with skin and soft-tissue infections (61.2%) followed by those suffering from respiratory (41%) and bloodstream infections (35%). Among the infections caused by S. aureus, the prevalence of methicillin resistance was 30%. While the MRSA isolates showed lower sensitivity toward co-trimoxazole (39%), clindamycin (30%), erythromycin (23%), and ciprofloxacin (10%), they showed higher susceptibility to linezolid (98%), vancomycin (98%), and teicoplanin (98%). All the isolates were found to be sensitive to daptomycin and tigecycline. While vancomycin-resistant enterococci (VRE) formed 7.5%, the linezolid-resistant enterococcus species was as high as 4.1%. CONCLUSION: The study showed a high prevalence of MRSA and VRE, thereby emphasizing the increasing antimicrobial resistance pattern of the Gram-positive pathogens. Therefore, there is an urgent need for novel antimicrobial stewardship to restrict the ongoing resistance rate among the isolates.