Unraveling Sepsis Epidemiology in a Low- and Middle-Income Intensive Care Setting Reveals the Alarming Burden of Tropical Infections and Antimicrobial Resistance: A Prospective Observational Study (MARS-India).

BACKGROUND: Our study addresses the sepsis research gap in lower middle-income countries, notably India. Here, we investigate community-acquired sepsis comprehensively and explore the impact of tropical microbiology on aetiology and outcomes. METHODS: MARS-India was a prospective observational study from Dec-2018 to Sep-2022 in a tertiary-care hospital in South India. Adult patients within 24hrs of ICU admission meeting the Sepsis 3.0 definition were enrolled, with 6-months follow-up (http://clinicaltrials.gov number NCT03727243). RESULTS: Over 4000 patients were screened on ICU admission, with 1000 unique patients meeting the inclusion criteria. Median age was 55 years (IQR: 44-65) with a male preponderance (66%). Almost half the cohort resided in villages (46.5%) and 74.6% worked in the primary sector. Mortality in-hospital was 24.1%. Overall, ∼54% had confirmed microbiological diagnosis. Over 18% had a viral cause of sepsis. Surprisingly, we identified leptospirosis (10.6%), scrub typhus (4.1%), dengue (3.7%) and Kyasanur forest disease (1.6%) as notables causes of sepsis. All these infections showed seasonal variation around the monsoon. In community-acquired infections we observed substantial resistance to 3rd generation cephalosporins and carbapenems. CONCLUSIONS: In India, sepsis disproportionally affects a younger and lower socio-economic demographic, yielding high mortality. Tropical and viral sepsis carry a significant burden. Analyzing local data, we pinpoint priorities for public health and resources, offering valuable insights for global sepsis research.

Diagnostic Potential of Serum Interleukin-6 in Predicting Bacteremia in Adult Patients with Sepsis: A Prospective Observational Study.

Background: This study aimed to assess the potential of serum interleukin-6 (IL-6) as a diagnostic marker in predicting bacteremia and to determine its association with severity and outcome among sepsis patients. Materials and methods: A prospective observational study was conducted, comprising a cohort of 118 patients admitted to the ICU with suspected sepsis from January 2019 to April 2020. Results: Among the 108 patients analyzed, 60 (55.6%) were bacteremic and 48 (44.4%) were nonbacteremic. Of 60 patients with bacteremia, 13 (21.6%) had sepsis and 47 (78.3%) had septic shock. In predicting bacteremia, the area under the curve (AUC) for IL-6 was 0.512 [95% CI, 0.400-0.623]. The AUC for IL-6 in differentiating sepsis from septic shock was 0.724 [95% CI, 0.625-0.823]. The sensitivity and specificity for predicting bacteremia for IL-6 were 66% and 67%, respectively (p < 0.001). Multivariate analysis revealed that C-reactive protein (CRP) (p = 0.04) and APACHE II score (p = 0.025) were significant predictors of bacteremia, whereas lactate (p = 0.04), and APACHE II score (p < 0.001) were significant predictors of sepsis severity. Patients with elevated levels of procalcitonin PCT (p = 0.024), APACHE II (p = 0.003), and SOFA (p = 0.002) scores had significantly higher mortality rates. Conclusion: C-reactive protein and APACHE II score, lactate and APACHE II score, and PCT, SOFA, and APACHE II scores performed better in predicting bacteremia, sepsis severity, and clinical outcome, respectively compared with IL-6. How to cite this article: Reddy PRV, Cherukuri M, Eshwara VK, Kudru CU, Prabhu RVK. Diagnostic Potential of Serum Interleukin-6 in Predicting Bacteremia in Adult Patients with Sepsis: A Prospective Observational Study. Indian J Crit Care Med 2024;28(7):637-644.

Optimization and validation of indirect ELISA using truncated TssB protein for the serodiagnosis of glanders amongst equines.

OBJECTIVE: To express truncated TssB protein of Burkholderia mallei and to evaluate its diagnostic efficacy for serological detection of glanders among equines. MATERIALS AND METHODS: In an attempt to develop recombinant protein based enzyme-linked immunosorbent assay (ELISA), N-terminal 200 amino acid sequences of B. mallei TssB protein-a type 6 secretory effector protein--were expressed in prokaryotic expression system. Diagnostic potential of recombinant TssB protein was evaluated in indirect ELISA using a panel of glanders positive (n = 49), negative (n = 30), and field serum samples (n = 1811). Cross-reactivity of the assay was assessed with equine disease control serum and human melioidosis positive serum. RESULTS: In comparison to CFT, diagnostic sensitivity and specificity of ELISA were 99.7% and 100%, respectively. CONCLUSIONS: The indirect ELISA method using the truncated TssB offered safer and more rapid and efficient means of serodiagnosis of glanders in equines. These data highlight the use of TssB as potential diagnostic antigen for serological diagnosis of glanders.

A self-reported survey on the implementation of infection prevention and control elements in Indian hospitals, part of a HAI surveillance network: Results from 23 hospitals conducting a standardized IPC assessment.

BACKGROUND: Healthcare-associated infections (HAIs) are one of the most common adverse events in patient care that account for substantial morbidity and mortality. We evaluate the existing Infection Prevention and Control (IPC) practices in hospitals participating in the nationally representative HAI Surveillance network. METHODS: This cross-sectional survey was conducted in 23 hospitals across 22 states of India from October-2015 to September-2018 in the HAI surveillance network. The World Health Organization (WHO) IPC core components assessment tool for health-care facility level (IPCAT-H) was adapted from IPC assessment tool developed by US Centers for Disease Control and Prevention (US CDC) under the Epidemiology and Laboratory Capacity (ELC) Infection Control Assessment and Response (ICAR) Program. Mann-Whitney U test was used to calculate the significant difference between scores (P < .05). RESULTS: Amongst the participating hospitals, 7 were private sectors and 16 were public health care facilities. Infection IPCAT-H average score per multimodal strategy was less than 50% for programmed IPC activities (45.7); implementation of health care workers (HCWs) immunization programme (43.5%); monitoring and evaluation component (38.30%). CONCLUSIONS: There is potential for improvement in Human Resources, Surveillance of HAIs as well as Monitoring and Evaluation components.

Synthesis, Biological Evaluation and Molecular Dynamics Simulation Studies of Novel Diphenyl Ethers.

BACKGROUND: The well-known antibacterial agent Triclosan (TCL) that targets bacterial enoylacyl protein reductase has been described to inhibit human fatty acid synthase (FASN) via the enoylacyl reductase domain. A Literature survey indicates that TCL is selectively toxic to cancer cells and furthermore might indeed reduce cancer incidence in vivo. A recent study found that TCL inhibits FASN by acting as an allosteric protein-protein interface (PPI) inhibitor. It induces dimer orientation changes that effect in a downstream reorientation of catalytic residues in the NADPH binding site proposing TCL as a viable scaffold to design a superior molecule that might have more inhibitory potential. This unveils tons of potential interaction space to take advantage of future inhibitor design. OBJECTIVES: Synthesis of TCL mimicking novel diphenyl ether derivatives, biological evaluation as potential antiproliferative agents and molecular docking and molecular dynamics simulation studies. METHODS: A series of novel N-(1-(3-hydroxy-4-phenoxyphenyl)-3-oxo-3-phenylpropyl)acetamides (3a-n) and N-(3(3-hydroxy-4phenoxyphenyl)-3-oxo-1-phenylpropyl) acetamides (6a-n) were designed, synthesized, characterized and evaluated against HepG2, A-549, MCF-7 and Vero cell lines. The induction of antiproliferative activity of selected compounds (3d and 6c) was done by AO/EB (acridine orange/ethidium bromide) nuclear staining method, DNA fragmentation study, and cell cycle analysis was performed by flow cytometry. Molecular docking and dynamics simulation study was also performed. RESULTS: Among the tested compounds, compound 3d was most active (IC50 13.76 ± 0.43 µM) against A-549 cell line. Compounds 3d and 3g were found to be moderately active with IC50 30.56 ± 1.1 µM and 25.05 ± 0.8 µM respectively against MCF-7 cell line. Morphological analysis of A-549 cells treated with 3d and 6c clearly demonstrated the reduction of cell viability and induction of apoptosis. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Further, cell cycle analysis by flow cytometry confirmed that compounds 3d and 6c significantly arrested the cell cycle at the G0/G1 phase. Molecular docking study demonstrated that these compounds exhibit high affinity for the human fatty acid synthase (hFASN) target. Molecular dynamics simulation study of the most active compound 3d was performed for calculating binding free energies using Molecular Mechanics-Generalized Born Surface Area (MM/GBSA). CONCLUSION: Compound 3d (IC50 13.76 ± 0.43 µM) has been identified as a potential lead molecule for anticancer activity against A-549 cells followed by 3l, 6c, and 3g. Thus, the design of diphenyl ether derivatives with enhanced affinity to the binding site of hER may lead to the discovery of potential anticancer agents.

Screening of vulvovaginal infections during pregnancy in resource constrained settings: Implications on preterm delivery.

The present study was undertaken to evaluate the efficacy of clinical and microbiological investigations available in limited resource settings for an effective diagnosis of vaginal infections/abnormal vaginal microbiota among pregnant women. As an outcome of the study we intended to find the association of various vaginal infections during pregnancy with preterm delivery. Pregnant women presenting for routine antenatal care at an antenatal clinic in south India were enrolled in the study. Each participant underwent clinical and microbiological examinations for the diagnosis of vaginal infections such as bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and trichomoniasis. In addition, Gram's stained high-vaginal smears were evaluated for the presence of partial BV and vaginitis. Diagnostic accuracies of clinical diagnosis for the aforementioned infections was determined in comparison with gold standard microbiological diagnosis. Proportion of women with vulvovaginal infections were estimated using descriptive statistics and incidence risk ratio for preterm delivery with each form of the infection was estimated using univariate analysis. A total of 790 pregnant women were recruited in the study. Positive predictive values of clinical diagnosis for BV, VVC and Trichomoniasis in comparison with reference method were 72.7, 33.5 and 37.6% respectively. Partial BV (3.2%) and vaginitis due to mixed bacterial etiology (9.4%) were per exclusionem diagnosed using the microbiological smear examination. Microbiological diagnosis of BV and vaginitis were found to have a statistically significant association with preterm delivery. Effective diagnosis of vaginal infections/abnormal vaginal microbiota associated with preterm delivery can be achieved by the adjunct of microbiological smear examination of the vaginal smears to the clinical examination in limited resource settings.

Pediatric melioidosis in Southern India.

Melioidosis in children is increasingly detected from the coastal region of Southern India during monsoon. We present 11 cases of melioidosis, ranging from localized to disseminated, treated successfully, barring one death. It calls for awareness and upgrading laboratory facilities for better diagnosis and management of pediatric melioidosis.

Microbial quality of well water from rural and urban households in Karnataka, India: a cross-sectional study.

OBJECTIVE: The objective of this study was to evaluate the microbial quality of the well water used as a drinking source in urban and rural households. METHODS: A total of 80 household well water samples were analyzed by the multiple fermentation tube method to determine the presumptive coliform count/most probable number of coliforms, and the isolates were identified using standard procedures, followed by susceptibility testing. RESULTS: Fecal indicator organisms, including Escherichia coli and Enterococcus spp. were isolated from 22 (27.5%) samples, and the majority (92.5%) of the water sources were contaminated with coliforms. A total of 170 bacterial isolates were obtained, including coliforms (70%), Enterococcus spp. (1.8%) and saprophytes (28.2%). A significant number of isolates were multi-drug resistant, which is a cause of concern. A comparison of the microbial quality of the water between urban and rural households revealed no significant differences. CONCLUSION: It might be prudent to monitor the bacteriological quality of well water at the source in addition to resistance profiles of the isolates.