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.

Proceedings of the expert consensus group meeting on herpes zoster disease burden and prevention in India: An opinion paper.

Herpes zoster (HZ) is a debilitating viral infection causing a dermatomal vesicular rash. Many known risk factors exist in India and adults >50 years of age may be especially susceptible to HZ. However, HZ is not a notifiable disease in India and data on incidence and disease burden is lacking. An Expert Consensus Group meeting was conducted with experts from relevant specialties to discuss HZ disease, its local epidemiology, and suggestions for implementing HZ vaccination in the Indian healthcare system. Currently, there is lack of patient awareness, poor reporting practices and general negligence in the treatment of the disease. HZ patients generally approach their general physicians or specialists for diagnosis, which is usually based on patient history and clinical symptoms. Recombinant zoster vaccine (RZV) has >90% efficacy and is recommended in adults ≥50 years of age to prevent HZ in the United States. Despite RZV being approved for use, it is not yet available in India. India has a growing elderly population with known risk factors for HZ like immunosuppression, and co-morbidities like diabetes and cardiovascular disease. This indicates the need for a targeted immunization program in India. Meeting also emphasized adult vaccine availability and accessibility in the country.

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.

Hospital-based antimicrobial stewardship, India.

Objective: To establish a framework for implementing antimicrobial stewardship in Indian tertiary care hospitals, and identify challenges and enablers for implementation. Methods: Over 2018-2021 the Indian Council of Medical Research followed a systematic approach to establish a framework for implementation of antimicrobial stewardship in Indian hospitals. We selected 20 Indian tertiary care hospitals to study the feasibility of implementing a stewardship programme. Based on a questionnaire to lead physicians before and after the intervention, we assessed progress using a set of process and outcome indicators. In a qualitative survey we identified enablers and barriers to implementation of antimicrobial stewardship. Findings: We found an improvement in various antimicrobial stewardship implementation indicators in the hospitals after the intervention. All 20 hospitals conducted monthly point prevalence analysis of cultures compared with three hospitals before the intervention. The number of hospitals that initiated formulary restrictions increased from two to 12 hospitals and the number of hospitals that started practising prescription audit and feedback increased from six to 16 hospitals. Respondents in 15 hospitals expressed their willingness to expand the coverage of antimicrobial stewardship implementation to other wards and intensive care units. Six hospitals were willing to recruit the permanent staff needed for antimicrobial stewardship activities. Conclusion: Antimicrobial stewardship can be implemented in Indian tertiary hospitals with reasonable success, subject to institutional support, availability of trained manpower and willingness of hospitals to support antimicrobial stewardship-related educational and training activities.

Infections caused by Aeromonas species in hospitalized patients: A case series.

The Aeromonads are ubiquitous Gram-negative bacilli that cause community acquired, and healthcare associated infections. In this retrospective study we analysed clinical and microbiological characteristics of thirty-six culture proven Aeromonas infections. The most common species isolated was A.hydrophila. Clinical presentation included syndromes like skin and soft tissue infections (SSTI), urinary tract infections, and central line associated bloodstream infections (CLABSI). Most of the isolates were sensitive to aminoglycosides [97.2%], followed by 3 rd generation cephalosporins, quinolones and carbapenems. Overall mortality was 13.88% (5 out of 36 patients). A high index of suspicion is required for diagnosis and better outcomes.

Dietary Effect of Padina boergesenii on Growth, Immune Response, and Disease Resistance Against Pseudomonas aeruginosa in Cirrhinus mrigala.

In the aquatic environment, seaweeds have the potential to be renewable resources. The current study was designed to assess the impact of seaweed Padina boergesenii incorporated into a basal diet at various concentrations. The phytoconstituents of the seaweeds were characterised by gas chromatography-mass spectrometry. Diets were designed to include elevated levels of 0.5%, 2.5%, 4.5%, and 6.5% of seaweed meal. Significant differences in Cirrhinus mrigala fed with P. boergesenii incorporated into the basal diet for 45 days. The growth parameters (weight gain, specific growth rate), biochemical constituents, and immunological assays were observed. The extract fraction demonstrated effective inhibitory activity against Pseudomonas aeruginosa. As a result, this research suggests that extracts of the seaweed P. boergesenii contain potential bioactive compounds with significant antibiotic activity.

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.

Clinical Profile of Non-neutropenic Patients with Invasive Candidiasis: A Retrospective Study in a Tertiary Care Center.

Introduction: Invasive candidiasis (IC) is a major cause of morbidity and mortality in critically ill patients in the intensive care unit (ICU). In this study, we aim to analyze the clinical profile, species distribution, and susceptibility pattern of patients with IC. Methods: Case records of non-neutropenic patients ≥18 years of age with IC between January 2016 and June 2019 at a tertiary care referral hospital were analyzed. IC was defined as either candidemia or isolation of Candida species from a sterile site (such as CSF; ascitic, pleural, or pericardial fluid; or pus or tissue from an intraoperative sample) in a patient with clinical signs and symptoms of infection. Results: A total of 114 patients were analyzed, out of which 105 (92.1%) patients had bloodstream infection (BSI) due to Candida and 9 (7.9%) had IC identified from a sterile site. Central line-associated blood stream infection (27 patients, 23.6%) and a gastrointestinal source (30 patients, 26.3%) were the most common presumed sources for candidemia. The commonest species was Candida tropicalis 42 (36.8%), followed by Candida glabrata 20 (17.5%). Serum beta-D-glucan (BDG) was done only in 32 patients of the 114 (35.3%); among those who were tested, 5 (15.6%) had a BDG value of less than 80 pg/mL despite having Candida BSI. Fluconazole sensitivity was 69.5% overall. At 14 days after diagnosis of IC, 49.1% had recovered, with the remainder having an unfavorable outcome (32.4% had died and 18.4% had left against medical advice). Clinical significance: IC is a major concern in Indian ICUs, with a satisfactory outcome in only half of our patients. Serum BDG is a valuable test to diagnose blood culture-negative IC, but more studies are needed to determine its role in the exclusion of IC, as we had a small minority of patients with negative tests despite proven IC. Conclusion: We recommend sending two sets of blood cultures and serum BDG assay for all suspected patients. Initiating empiric antifungal therapy with an echinocandin is advisable, in view of increasing azole resistance and the emergence of Candida auris, with de-escalation to fluconazole for sensitive isolates after clinical stability and blood culture clearance. How to cite this article: Sridharan S, Gopalakrishnan R, Nambi PS, Kumar S, Sethuraman N, Ramasubramanian V. Indian J Crit Care Med 2021;25(3):267-272.

A technique for quantifying the sensitivity of dosimetric tool gamma with 2D detector array in pretreatment IMRT plans by segment deletion method.

OBJECTIVES: Motivation of this study is to check the sensitivity of dosimetric tool gamma with 2D detector array combination when unexpected errors occur while transferring intensity-modulated radiation therapy treatment plans from planning system to treatment unit. METHODS: This study consists of 17 head and neck cancer patient's treatment plans. Nine types of verification plans are created for all 17 clinically approved treatment plans by consecutively deleting different segments (up to eight) one by one from each field of the plan. Decrement factor (χ) is introduced in our study which illustrated the degree of decay of gamma passing rate when intentional errors are introduced. We analyzed the data by two different methods-one without selecting the region of interest (ROI) in dose distributions and the other by selecting the region of interest. RESULTS: By linear regression, the absolute value of slopes is 0.025, 0.024 and 0.015 without ROI and 0.030, 0.027 and 0.015 with ROI for 2%/2 mm, 3%/3 mm and 5%/5 mm criteria, respectively. The higher absolute value of the fitted slope indicates the higher sensitivity of this method to identify erroneous plan in treatment unit. The threshold value for 2%/2 mm equivalent to 95% passing criteria in 3%/3 mm used in clinical practice is obtained as 83.44%. CONCLUSIONS: The 2D detector array with dosimetric tool gamma is less sensitive in detecting errors when unprecedented errors of segment deletion occur within the treatment plans.

Talaromyces marneffei Outside Endemic Areas in India: an Emerging Infection with Atypical Clinical Presentations and Review of Published Reports from India.

Talaromycosis is a disseminated disease caused by Talaromyces (Penicillium) marneffei, mainly seen in acquired immunodeficiency syndrome (AIDS) patients. Its distribution is restricted to southeast Asian countries; a small pocket of endemicity exists in the northeast Indian state of Manipur. Here, we present a series of five cases presenting to our tertiary care hospital, originating from non-endemic states neighboring Manipur. In addition to the geographical distinction, a variety of unique features were noted in our cases, including human immunodeficiency virus (HIV)-negative hosts, the absence of typical skin lesions, presentation as pneumonia and generalized lymphadenopathy. Our series highlights the importance of distinguishing this disease from histoplasmosis and tuberculosis, both endemic in India.

Policy document on antimicrobial stewardship practices in India.

Antimicrobial resistance (AMR) in India has become a great threat because of high rate of infectious diseases. One of the key contributing factors is high antibiotic use due to poor prescription practices, self-medication, over-the-counter sale of drugs and lack of awareness. Antimicrobial stewardship programme (AMSP) have been proved to be successful in restraining sale and use of antibiotics to a large extent in many countries. An AMSP programme for a hospital is imperative for rational and evidence-based antimicrobial therapy. The ultimate aim is to improve patient outcomes, reduce emergence of bacterial resistance and ensure longevity of the existing antimicrobials. The primary goal of AMSP is to encourage cautious use of available antibiotics by training the healthcare workers and creating awareness. This article describes the strategies and recommendations for formulation of AMSP policy for India.

Variations in antibiotic use across India: multi-centre study through Global Point Prevalence survey.

The aim of the study was to assess antimicrobial prescribing patterns, and variation in practice, in India. A point prevalence survey (PPS) was conducted in October to December 2017 in 16 tertiary care hospitals across India. The survey included all inpatients receiving an antimicrobial on the day of PPS and collected data were analysed using a web-based application of the University of Antwerp. In all, 1750 patients were surveyed, of whom 1005 were receiving a total of 1578 antimicrobials. Among the antimicrobials prescribed, 26.87% were for community-acquired infections; 19.20% for hospital-acquired infections; 17.24% for medical prophylaxis; 28.70% for surgical prophylaxis; and 7.99% for other or undetermined reasons. Antibiotic prescribing quality indicators, such as reason in notes and post-prescription review score, were low. This PPS showed widespread antibiotic usage, underlining the need for antibiotic stewardship to promote evidence-based practice.

Newer ß-Lactam/ß-Lactamase inhibitor for multidrug-resistant gram-negative infections: Challenges, implications and surveillance strategy for India.

Antimicrobial resistance (AMR) is a major public health concern across the globe, and it is increasing at an alarming rate. Multiple classes of antimicrobials have been used for the treatment of infectious diseases. Rise in the AMR limits its use and hence the prerequisite for the newer agents to combat drug resistance. Among the infections caused by Gram-negative organisms, beta-lactams are one of the most commonly used agents. However, the presence of diverse beta-lactamases hinders its use for therapy. To overcome these enzymes, beta-lactamase inhibitors are being discovered. The aim of this document is to address the burden of AMR in India and interventions to fight against this battle. This document addresses and summarises the following: The current scenario of AMR in India (antimicrobial susceptibility, resistance mechanisms and molecular epidemiology of common pathogens); contentious issues in the use of beta-lactam/beta-lactamase inhibitor as an carbapenem sparing agent; role of newer beta-lactam/beta-lactamase inhibitor agents with its appropriateness to Indian scenario and; the Indian Council of Medical Research interventions to combat drug resistance in terms of surveillance and infection control as a national response to AMR. This document evidences the need for improved national surveillance system and country-specific newer agents to fight against the AMR.

Efficacy and Cost Comparison of Ertapenem as Outpatient Parenteral Antimicrobial Therapy in Acute Pyelonephritis due to Extended-spectrum Beta-lactamase-producing Enterobacteriaceae.

Outpatient parenteral antimicrobial therapy (OPAT) programs are becoming an increasingly popular trend in clinical practice as they offer several benefits to both patients and health-care setups. While OPAT is an established clinical practice in the Western world, the concept itself is alien to patients in India as they prefer the security of hospitals to receive antibiotics over OPAT. We evaluated the clinical response and cost comparison of ertapenem under OPAT versus inpatient settings in patients with extended-spectrum beta-lactamase (ESBL)-positive acute pyelonephritis (APN) given the increasing importance of optimizing both hospital beds and overall cost of patient care in India. APN was chosen as the indication to be studied as it is one of the common complicated urinary tract infections treated in our OPAT unit requiring 10-14 days of parenteral therapy with an agent active against various Gram-negative bacilli and multidrug-resistant organisms. One hundred patients were retrospectively studied based on whether antibiotics were administered during hospital stay alone (hospital only), during both hospital stay, and also as OPAT post discharge (hospital/OPAT) or as OPAT alone (OPAT only). Response to ertapenem and cost of treatment in inpatient versus OPAT settings were compared using Pearson's Chi-square or Fisher's exact test for categorical variables. ANOVA (or Kruskal-Wallis) was used for continuous variables. Baseline urine cultures were ESBL positive with 98% prevalence of Gram-negative bacilli (GNB). Colony counts were ≥100,000 in 74% patients. Only ertapenem, imipenem, and meropenem showed 100% sensitivity to ESBL-positive GNB in baseline urine culture and sensitivity reports. Ertapenem showed 100% sensitivity and complete clinical resolution for 96% patients with APN due to ESBL Enterobacteriaceae. It was administered as OPAT in 90% patients and significantly reduced overall treatment costs.

Utility of multiplex polymerase chain reaction (PCR) in diarrhea-An Indian perspective.

BACKGROUND: Infective diarrhea causes morbidity worldwide. Polymerase chain reaction (PCR)-based pathogen diagnostics of diarrheal stool specimens are shown to be highly sensitive and rapid as opposed to conventional diagnostics. METHODS: We analyzed the performance of FilmArray gastrointestinal (GI) panel, one such multiplex PCR test, on stool specimens in patients presenting with diarrhea to our hospital from March 2016 to September 2017 and compared the results with conventional diagnostic tests. RESULTS: A total of 106 patients were included. The panel detected at least one target in 54 out of 106 patients (50.9%) with results available on the same day. Multiple targets were detected in 26 out of 54 patients who tested positive (48.1%). Bacteria as an isolated etiology for diarrhea was present in 34 patients (62.9%), viruses (16.7%, nine patients), parasites (7.4%, four patients), and multiple pathogens in seven patients (12.9%). Enteroaggregative Escherichia coli (EAEC) was the commonest pathogen detected (in 23, 24% patients). Conventional diagnostic investigations, undertaken in 68/106 (64.1%) patients were positive in 12 (17.65%) as compared to 54/106 (50.9%) (p < 0.0001). Conventional  investigations detected a pathogen not included in the study panel in 11 of 52 patients (21.1%). CONCLUSION: FilmArray multiplex PCR panel detects a wide array of GI pathogens including viruses and co-infections at a shorter time with more sensitivity compared to conventional diagnostics. Henceforth, it may facilitate treatment decisions, isolation policy, and antimicrobial stewardship in patients with diarrhea requiring hospitalization.

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.