Candidaemia and Central Line-Associated Candidaemia in a Network of Indian ICUs: Impact of COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Candidaemia is a potentially life-threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare-associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID-19 had on the rates and associated mortality of candidaemia. METHODS: This study included adult patients from 67 Indian ICUs in the AIIMS-HAI surveillance network that conducted BSI surveillance in COVID-19 and non-COVID-19 ICUs during and before the COVID-19 pandemic periods. Hospitals identified healthcare-associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. RESULTS: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID-19 ICUs (2.52/1000 patient days) was significantly higher than in non-COVID-19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID-19 ICUs (4.53/1000 central line days) was also significantly higher than in non-COVID-19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID-19 ICUs associated with candidaemia (61%) was higher than that in non-COVID-19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. CONCLUSION: Patients in ICUs with COVID-19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country.

Gram-Negative Colonization and Bacterial Translocation Drive Neonatal Sepsis in the Indian Setting.

BACKGROUND: The gut microbiota, comprising billions of microorganisms, plays a pivotal role in health and disease. This study aims to investigate the effect of sepsis on gut microbiome of neonates admitted to the Neonatal Intensive Care Unit. METHODS: A prospective cohort study was carried out in the NICU of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Preterm neonates with birth weight < 1500 g and gestational age < 37 weeks were recruited, excluding those with congenital gastrointestinal anomalies, necrotizing enterocolitis, or blood culture-negative infections. The study population was divided into three groups: healthy neonates (Group A), neonates with drug-sensitive GNB sepsis (Group B), and neonates with pan drug-resistant GNB sepsis (Group C). Stool samples were collected aseptically, snapped in liquid nitrogen, and stored at -80°C for extraction of DNA and microbiome analysis. RESULTS: The gut microbiota of healthy neonates (Group A) was dominated by Proteobacteria (24.04%), Actinobacteria (27.13%), Firmicutes (12.74%), and Bacteroidetes (3%). Predominant genera included Bifidobacterium (55.17%), Enterobacter (12.55%), Enterococcus (50.69%), Streptococcus (7.92%), and Bacteroides (3.58%).Groups B and C, the microbiota exhibited higher Proteobacteria abundance (57.16% and 66.58%, respectively) and reduced diversity of beneficial bacteria. Notably, the presence of sepsis was associated with an increase in pathogenic bacteria and a decrease in beneficial commensal bacteria. CONCLUSION: Neonates with sepsis exhibited significant gut microbiome dysbiosis, characterized by increased Proteobacteria and reduced beneficial bacteria diversity. These findings highlight the potential of microbiome profiling as a diagnostic tool and underscore the importance of gut microbiota modulation in managing neonatal sepsis.

Comparative evaluation of Vitek®2 and broth microdilution method for colistin susceptibility testing of Gram-negative isolates from intensive care unit in a tertiary care hospital.

INTRODUCTION: Colistin is the last resort treatment against resistant Gram-negative bacteria, necessitating reliable and rapid means for sensitivity testing of colistin. Automated systems like VITEK®2 are adopted to determine the minimum inhibitory concentration (MIC) due to easy usage. Broth microdilution (BMD) for colistin MIC was suggested by EUCAST and CLSI. OBJECTIVE: To compare and evaluate colistin MIC by BMD and VITEK®2 against Gram-negative organisms from the ICU in a tertiary care hospital. METHOD: Clinically significant organisms isolated from ICU patients were included. MIC was determined using BMD and VITEK®2. Very major error (VME), major error (ME), essential agreement (EA), categorical agreement (CA), positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity were analysed. RESULT: 533 isolates were obtained from blood (435,81.60%), respiratory samples (57,10.70%), pus and exudates (20,3.80%), urine (18,3.40%), and CSF (3,0.60%). The Enterobacterales were K. pneumoniae (185,34.70%) E. coli (73,13.70%) and E. cloacae (26,4.90%) while non-fermenters were A. baumannii (209,39.20%) and P. aeruginosa (40,7.50%). The VITEK®2 sensitivity was >99%; specificity ranged from 14.28 to 52.94%. PPV was 93.81% while NPV was 93.75%. VME ranged from 47 to 100% between isolates. ME was up to 20%. The highest VME was obtained in E. coli (100%). The total EA and CA observed were 68.5% and 99.79% respectively. CONCLUSION: Automated system VITEK®2 failed to detect the resistance in 32 (60%) isolates. The obtained VME and ME values were >3%, which is unacceptable as per the standard guidelines. EA of ≥90% wasn't obtained. Sensitivity for VITEK®2 was >99%, but had low specificity (14.28%). Hence, VITEK®2 is not reliable for colistin susceptibility testing.

MIST (Modified Intubating Sequence for Transmissibility) Bundle for Infectious Diseases with Aerosol Hazard.

The current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has magnified the risk to healthcare providers when inititiating airway management, and safe tracheal intubation has become of paramount importance. Mitigation of risk to frontline providers requires airway management to be an orchestrated exercise based on training and purposeful simulation. Role allocation and closed-loop communication form the foundation of this exercise. We describe a methodical, 10-step approach from decision-making and meticulous drug and equipment choices to donning of personal protective equipment, and procedural concerns. This bundled approach will help reduce unplanned actions, which in turn may reduce the risk of aerosol transmission during airway management in resource-limited settings.

Design, synthesis, in silico and in vitro evaluation of novel diphenyl ether derivatives as potential antitubercular agents.

Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the fatty acid synthesis cycle of genus Mycobacterium. To select and validate a protein crystal structure of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis for designing inhibitors using molecular modelling, a cross-docking and correlation study was performed. A series of novel 1-(3-(3-hydroxy-4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) ethan-1-ones were synthesized from this model and screened for their antitubercular activity against M. tuberculosis H37Rv. Compound PYN-8 showed good antitubercular activity on M. tuberculosis H37Rv (MIC = 4-7 µM) and Mycobacterium bovis (% inhibition at 10 µM = 95.91%). Cytotoxicity of all the synthesized derivatives was assessed using various cell lines, and they were found to be safe. Structure of PYN-8 was also confirmed by single-crystal X-ray diffraction. The molecular modelling studies also corroborated the biological activity of the compounds. Further, in silico findings revealed that all these tested compounds exhibited good ADME properties and drug likeness and thus may be considered as potential candidates for further drug development.

Diagnostic utility of in-house loop-mediated isothermal amplification and real-time PCR targeting virB gene for direct detection of Brucella melitensis from clinical specimens.

AIMS: In this present study, the utility of a newly developed loop-mediated isothermal amplification (LAMP) and real-time PCR assays designed to amplify the virB gene region of Brucella melitensis was evaluated from human clinical specimens. METHODS AND RESULTS: Fifty-four culture-confirmed cases of brucellosis and 54 culture negative but clinically suspected cases of brucellosis were included in the study. Whole blood, serum and other nonblood specimens were collected and subjected to blood culture using automatic blood culture system, serological tests, LAMP assay and real-time PCR. Overall sensitivities of LAMP and real-time PCR assays were 67·5 and 68·3% respectively. For nonblood clinical specimens, we noticed a marked increase in the sensitivities of LAMP (88·9%) and real-time PCR (100%) assays. CONCLUSIONS: Performance of LAMP and real-time PCR was not satisfactory for whole-blood specimens because of the low abundance of bacteria or DNA. On the other hand, using nonblood specimens, both the assays showed higher sensitivity and specificity which makes them a good alternative for the rapid diagnosis of human brucellosis. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed LAMP and real-time PCR assays are a specific and rapid diagnostic tool for direct and early detection of Brucella in clinical specimens.

Assessment of core capacities for antimicrobial stewardship practices in indian hospitals: Report from a multicentric initiative of global health security agenda.

Introduction: Antimicrobial-resistant HAI (Healthcare associated infection) are a global challenge due to their impact on patient outcome. Implementation of antimicrobial stewardship programmes (AMSP) is needed at institutional and national levels. Assessment of core capacities for AMSP is an important starting point to initiate nationwide AMSP. We conducted an assessment of the core capacities for AMSP in a network of Indian hospitals, which are part of the Global Health Security Agenda-funded work on capacity building for AMR-HAIs. Subjects and Methods: The Centers for Disease Control and Prevention's core assessment checklist was modified as per inputs received from the Indian network. The assessment tool was filled by twenty hospitals as a self-administered questionnaire. The results were entered into a database. The cumulative score for each question was generated as average percentage. The scores generated by the database were then used for analysis. Results and Conclusion: The hospitals included a mix of public and private sector hospitals. The network average of positive responses for leadership support was 45%, for accountability; the score was 53% and for key support for AMSP, 58%. Policies to support optimal antibiotic use were present in 59% of respondents, policies for procurement were present in 79% and broad interventions to improve antibiotic use were scored as 33%. A score of 52% was generated for prescription-specific interventions to improve antibiotic use. Written policies for antibiotic use for hospitalised patients and outpatients were present on an average in 72% and 48% conditions, respectively. Presence of process measures and outcome measures was scored at 40% and 49%, respectively, and feedback and education got a score of 53% and 40%, respectively. Thus, Indian hospitals can start with low-hanging fruits such as developing prescription policies, restricting the usage of high antibiotics, enforcing education and ultimately providing the much-needed leadership support.

Antibiotic prophylaxis in organophosphorus poisoning: A study of health and economic outcomes.

Objective: Organophosphorus poisoning (OPP) is a major concern for developing countries. There are no guidelines for the prophylactic use of antibiotics in the management of OPP which in such critical cases might add to the economic burden of the patients as well as antibiotic resistance. We compared the health and economic outcomes in patients prescribed with prophylactic antibiotics with respect to the patients not prescribed with any antibiotics. Methods: A retrospective observational study was carried out for two years for patients admitted to ICU with OPP. Patients were graded for severity of OPP, and divided into two groups based on prophylactic prescription and no prescription of antibiotics. The length of stay (LOS), hospitalization cost and outcomes were measured and compared between the two groups using statistical tests. Results: Out of the 254 patients observed, 108 were prescribed with prophylactic antibiotics and 94 were not prescribed with any antibiotic. There was a significant difference between LOS, cost of treatment and outcomes in the two groups (p < 0.001). When antibiotics were not prescribed, the odds of improvement was 1.854 times higher compared to those who received prophylactic antibiotics although after adjusting for severity of poisoning, significance was lost. On an average, 2-3 antibiotics were prescribed to every patient in the first group. Conclusion: OPP is an important health concern where issues of antibiotic misuse and overuse are practiced. Our study suggested that systemic antibiotic prophylaxis did not offer any advantage over non-use of any antibiotics in patients with OPP.

Melioidosis: Reinfection going incognito as relapse.

Melioidosis has recently gained importance as an emerging disease in India. Recurrent melioidosis has been reported from different parts of the world and can be due to relapse or reinfection. Distinction between relapse and reinfection is important for epidemiology, investigation and management. Here, we present the data regarding rate of recurrence and utility of multilocus sequence typing (MLST) in differentiating relapse form reinfection amongst melioidosis patients from a tertiary care hospital in South India. Amongst the 31 patients who survived and underwent follow-up, 4 (13%) presented with recurrence. Three cases (75%) were identified as reinfection and one (25%) as relapse based on MLST. Re-exposure to environmental Burkholderia pseudomallei amongst patients with melioidosis in endemic areas is likely. In such a scenario, more often than not, recurrence of melioidosis can be attributed to reinfection.