Respiratory tract viral infections associated sepsis in patients with underlying liver disease: Viral sepsis an entity to look forward!

BACKGROUND: Sepsis remains a global health burden associated with significant morbidity and mortality. Bacteria are known to be the predominant pathogens in sepsis; however, viral etiologies in sepsis are still under diagnosed. Respiratory viral pathogens have been previously linked to sepsis, but the knowledge of incidence, disease burden and mortality of viral-induced sepsis remains limited. This study aimed at understanding the role of respiratory viral infections in the causation of sepsis in liver disease patients. METHODS: In this retrospective study, the clinical records of liver disease patients with influenza-like illness, whose requests for respiratory viral testing were received from January 2019 to December 2022, were reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics, Utah, USA). RESULTS: Of 1391 patients tested, a respiratory viral etiology was detected in 23%. The occurrence of sepsis was seen in 35%. Among these, isolated viral etiology with no other bacterial/fungal coinfection was found in 55% of patients. Rhinovirus/Enterovirus was found as the most common underlying viral etiology (23.4%). The sepsis prevalence was higher among patients with associated comorbidities (45%) and decompensated cirrhosis (84%). On multi-variable analysis, no factor was found independently associated with sepsis-related mortality. CONCLUSION: This study underlines the importance of isolated viral etiology in causation of sepsis among liver disease patients. Patients with comorbidities, older age and decompensated cirrhosis are at an increased risk of developing sepsis and are associated with poorer outcomes. Accurate and timely identification of the viral etiology in sepsis would prevent the misuse of antibiotics and improve overall patient care.

Cryptococcosis among HIV negative liver disease patients: Epidemiology, underlying conditions, antifungal susceptibility profile from tertiary care hepatobiliary center.

PURPOSE: Cryptococcus neoformans is an encapsulated yeast. It is a significant pathogen among immunocompromised people with HIV & Non-HIV vulnerable populations. These conditions include cancer, corticosteroid usage, immunosuppression following sarcoidosis, organ transplantation, immunosuppressive medication, and liver cirrhosis. In cirrhotic, it accounts for 6-21% of systemic infections. METHODS: The retrospective study was conducted in tertiary care hepatobiliary center in New Delhi, India. Samples of blood, cerebrospinal fluid (CSF), urine, body fluids, and serum were processed for gram stain, India ink, fungal culture and identification, and cryptococcal antigen. Antifungal susceptibility was assessed using the micro-broth dilution technique. RESULTS: 30 patients with cryptococcal infection were analysed, and 40 isolates from various samples were recovered. Out of 40 samples, C. neoformans was isolated from blood (62.5%), urine (15%), ascitic fluid (10%), MiniBAL (5%), bone marrow, CSF, and pleural fluid in one sample each. India ink positivity was 56% and all samples were positive for Cryptococcal antigen. Alcoholic liver disease & Hepatitis B & C associated chronic liver disease were seen in 43% & 20% of patients. Other underlying conditions were diabetes mellitus (20%), TB (10%), autoimmune hepatitis (6.6%), autoimmune disease (autoimmune hemolytic anemia, Sjogren syndrome) (6.6%), sarcoidosis (3.3%), hepatocellular carcinoma (3.3%). 7.5%, 5%, 2.5%, 7.5%, and 2.5% of C. neoformans strains were the non-wild type to fluconazole, 5-fluorocytosine, amphotericin B, posaconazole, and itraconazole respectively, but all strains were wildtype to voriconazole. CONCLUSION: According to the study liver conditions are a significant risk factor for cryptococcal infection. Therefore, cryptococcal isolation and antifungal susceptibility testing, as well as appropriate antifungal drug use, should be studied and paid attention too.

Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial.

BACKGROUND: Severe alcoholic hepatitis (SAH) has high 90-day mortality. Prednisolone therapy has shown modest survival benefits over placebo at 28 but not 90 days. Fecal microbial transplantation (FMT) has shown promise in these patients. We compared the efficacy and safety of the two therapies in SAH patients. METHODS: Steroid eligible SAH patients were randomized in an open-label study to prednisolone (n = 60) 40 mg/day for 28 days (assessed at day-7 for continuation) or healthy donor FMT (n = 60) through naso-duodenal tube, daily for seven days. Primary outcome of study was day-90 survival. RESULTS: Patients in prednisolone and FMT arms were comparable at baseline (discriminant function score 65 ± 16.2 and 68 ± 14, MELD score 17.1 and 16.5, respectively). Of 120 patients, 112 [prednisolone-57; FMT-55] completed trial. As per intention-to-treat analysis, 90-day survival was achieved by 56.6% (34/60) patients in prednisolone and 75% (45/60) in FMT group (p = 0.044, FMT HR = 0.528, 95%CI 0.279-0.998). Secondary outcome of 28-day survival [78.33% (47/60) and 88.33% (53/60) (p = 0.243, FMT HR = 0.535, 95%CI 0.213-1.34)] with comparable severity scores over time between both arms. Infections accounted for 11 (19.3%) and 2 (3.6%) deaths in prednisolone and FMT groups, respectively (p = 0.01). Path-tracing showed a slow establishment of microbiota and alpha diversity (Shannon index) improvement by day-28 (p = 0.029). FMT resulted in 23 new taxa by day-28, reduction from baseline in pathogenic taxa [Campylobacter (19-fold, p = 0.035), anaerobes (Parcubacteria, Weisella and Leuconostocaceae)], and increase of Alphaproteobacteria [~ sevenfold, p = 0.047] and Thaumarcheota (known ammonia oxidizer, p = 0.06). Lachnospiraceae (p = 0.008), Prevotella and Viellonella communities in gut favored survival (p < 0.05). CONCLUSION: In severe alcoholic hepatitis, FMT is safe and improves 90-day survival and reduces infections by favorably modulating microbial communities. It can be a useful alternative to prednisolone therapy.

Randomized control trial on perioperative antibiotic prophylaxis in live liver donors: Are three doses enough?

INTRODUCTION: The duration of perioperative antibiotic prophylaxis following live liver donor hepatectomy (LDH) is not known. METHODS: This is a double-blind equivalence trial. All consecutive LDH were randomized into: group A (three doses) and group B (nine doses) of perioperative antibiotics (piperacillin + tazobactam - 4.5 g intravenous) at fixed 8 hourly intervals. Primary end point was incidence of infective complications as per CDC (Centers for Disease Control and Prevention) criteria. Secondary end points were liver function tests, total leukocyte count, international normalized ratio, hospital stay, morbidity, and cost analysis. RESULTS: One hundred and twenty-six LDHs were enrolled. A total of 19.8% (n = 25) experienced postoperative complications, 11 (17.7%) in group A and 14 (21.9%) in group B (P = .561). Infective complications were seen in 11 donors (8.1%), five in group A and six in group B (P = .79). A total of 8.1% of donors required continuation/up-gradation of antibiotics in group A and 9.4% in group B. Return to soft diet was delayed in group B (P = .039). Median hospital stay and cost were similar. CONCLUSION: Three doses of perioperative antibiotic are equally effective in preventing infective complications.

Vaccine Breakthrough Infections by SARS-CoV-2 Variants after ChAdOx1 nCoV-19 Vaccination in Healthcare Workers.

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

Difficult-to-treat ascitic fluid infection is a predictor of transplant-free survival in childhood decompensated chronic liver disease.

OBJECTIVE: To study the clinico-bacteriological profile of ascitic fluid infection (AFI) and its impact on outcome in childhood chronic liver disease (CLD). METHODS: It was a retrospective study on pediatric CLD patients requiring an ascitic tap. Logistic regression was performed to study the predictive factors for AFI. RESULTS: Two hundred and fifty-two (30.9%) of 814 children with CLD underwent ascitic tap on suspicion of AFI of whom 79 (31.3%) had AFI, culture negative neutrocytic ascites being the commonest. Younger age (p = 0.002), male gender (p = 0.007), new onset/rapid increase in ascites (p = 0.032), fever (p = 0.012), and blood total leukocyte count (TLC) (p = 0.001) were found to be independently associated with AFI. Twenty-three children had positive ascitic fluid culture: 15 Gram negative; 11 (52.3%) were multidrug resistant organism. Hepatic encephalopathy (HE) (p = 0.001), Model for End-stage Liver Disease/Pediatric End-stage Liver Disease (MELD/PELD) (p < 0.0005), and difficult-to-treat AFI (p = 0.007) were found to be independently associated with death and or LT. CONCLUSION: Children with ascites should undergo a diagnostic paracentesis in presence of fever, increasing or new-onset ascites, and/or increased TLC. Death or liver transplant are more likely due to advanced liver disease (high PELD /HE) and in those with difficult-to-treat AFI.

Comparative Evaluation of Echinococcus Serology with Cytology for the Diagnosis of Hepatic Hydatid Disease.

Objectives The purpose of this study is to determine the diagnostic efficacy of enzyme-linked immunosorbent assay (ELISA) in radiologically confirmed liver mass lesions for the diagnosis of hepatic hydatid disease (HHD) and to compare the diagnostic performance of ELISA with fine needle aspiration cytology (FNAC) (taken as standard) for HHD diagnosis. Materials and Methods This retrospective study included blood samples of 223 patients with radiologically confirmed liver mass lesions in which immunoglobulin G (IgG) anti- Echinococcus antibodies were tested using a commercial IgG ELISA (RIDASCREEN, R-Biopharm AG, Darmstadt, Germany). Results of ELISA, ultrasonography, FNAC, and liver function tests were obtained from the hospital information system. ELISA results were compared with those of FNAC to analyze the diagnostic efficacy of ELISA for HHD diagnosis. Statistical Analysis Comparison of the results obtained from ELISA was performed with respect to FNAC results (taken as standard) to analyze the diagnostic efficacy of ELISA for HHD detection. Data has been represented as median (range) or in frequencies. Wilson score was used to assess 95% confidence interval of diagnostic parameters. The analysis was performed using SPSS Version 22.0 (IBM Corp.) and Open Epi (version 3.01). Results Out of 223 cases with liver mass lesions, Echinococcus IgG was reactive in 62 (28%) cases and FNAC was positive in 16 (7.2%) cases. Since two cases were FNAC-positive but IgG-nonreactive, total HHD cases were 64 (28.7%). Echinococcus IgG reactive cases were seen more in the extremes of age group, that is, 1 to 10 years and 81 to 90 years. Taking FNAC as the standard, the sensitivity, specificity, positive predictive value, and negative predictive value of ELISA were 87.5, 76.8, 22.6, and 98.7%, respectively. Cytology-positive cases demonstrated a mean ELISA optical density/cut-off (OD/CO) of 4.2 ± 3 standard deviation. Conclusion ELISA in radiologically confirmed liver mass cases is highly sensitive in detecting HHD and hence should be used along with ultrasonography for the screening of HHD followed by confirmation with cytology even in cases with a higher OD/CO of ELISA.

Incidence, Microbiological Profile, and Impact of Preventive Measures on Central Line-associated Bloodstream Infection in Liver Care Intensive Care Unit.

AIMS AND OBJECTIVES: Central line-associated bloodstream infection (CLABSI) is among one of the preventable healthcare-associated infections (HAIs). The data for the CLABSI rate in liver care intensive care unit (LCICU) patients are scarce, so the present study was conducted to ascertain the CLABSI rate, the microbiological profile, and the impact of preventive measures for reduction of infection. MATERIALS AND METHODS: This is a prospective observational study done on LCICU patients during the period of January 2017-December 2018. We followed up patients on the central venous catheter for the development of CLABSI as a part of routine surveillance of HAIs. The impact of introduction and implementation of the CLABSI bundle to reduce the CLABSI rate was analyzed and the microbiological profile of infection was determined. RESULTS: During the study period, the total number of patients admitted in LCICU were 1,336 (648 in 2017 and 688 in 2018) and a total of 995 central lines were inserted for various indications. A total of 57 patients were meeting the CLABSI criteria among 7,324 central line catheter days of surveillance. In year 2017, rate of CLABSI was 11.78/1,000 catheter days and after implementation of the bundle in 2018 the rate reduced to 3.99/1,000 catheter days. Gram-negative organisms (86%) predominated with Pseudomonas aeruginosa being the most common pathogen (19.3%). Out of 49 isolates of gram-negative bacilli (GNB), 40 (81.6%) were multidrug resistant (MDR) and 9 (18.4%) were pan-drug resistant. CONCLUSION: We found significant reduction in the CLABSI rate after implementation of the bundle of care. Gram-negative bacilli were the most common pathogen in our study and antimicrobial resistance was very high, which suggest hospital environment as a source of infection. CLINICAL SIGNIFICANCE: Knowledge of the microbiological profile and the preventive strategy of CLABSI is essential for prevention and timely initiation of the most appropriate anti-infective therapy, if it happens. HOW TO CITE THIS ARTICLE: Khodare A, Kale P, Pindi G, Joy L, Khillan V. Incidence, Microbiological Profile, and Impact of Preventive Measures on Central Line-associated Bloodstream Infection in Liver Care Intensive Care Unit. Indian J Crit Care Med 2020;24(1):17-22.

Novel association of Streptococcus gallolyticus subspecies pasteurianus and hepatocelluar carcinoma: opening new frontiers.

BACKGROUND: Streptococcus gallolyticus subsp. gallolyticus bacteremia is associated with colorectal malignancies. There is limited data regarding the association of Streptococcus gallolyticus subsp. pasteurianus with malignancies. We aimed to study the pattern of isolation of Streptococcus gallolyticus and analysis of risk factors in patients with hepatobiliary diseases. We also planned to evaluate its association with hepatocellular malignancy. METHODS: We analyzed clinical and laboratory data of 68 cases of Streptococcus gallolyticus infections (77 isolates) from January 2013 to December 2017. These included blood (58), ascitic fluid (15), bile (2) and pleural fluid (2). We analyzed the risk factors in patients developing malignancy with Streptococcus gallolyticus infections. RESULTS: Amongst the 68 patients studied, eight (11.76%) had confirmed malignancies, hepatocellular carcinoma (HCC) (5), rectal adenocarcinoma (1), pancreatic carcinoma (1) and uterine tumors (1). Simultaneous isolation of S. gallolyticus subsp. pasteurianus from blood and ascitic fluid in eight patients (11.8%, p = .01) was significantly associated with the occurrence of HCC. Streptococcus gallolyticus infection with HCC was associated with younger age (median 55 years), lymphocytosis and elevated gamma-glutamyl transferase (GGT). CONCLUSIONS: This study provides a novel insight into the association of Streptococcus gallolyticus subspecies pasteurianus with HCC. The isolation of the organism from blood and ascitic fluid should prompt the clinicians to search for evidence of HCC actively.

Resurgence of Global Opportunistic Multidrug-resistant Stenotrophomonas maltophilia.

CONTEXT: Stenotrophomonas maltophilia is a known nosocomial pathogen which is intrinsically resistant to multiple antibiotics. In India, S. maltophilia infection has only few case reports. AIM: To determine the incidence of S. maltophilia infection from clinical isolates based on the specimen type, antibiotic susceptibility pattern, and impact on outcome. SETTINGS AND DESIGN: One-year retrospective study was done at a tertiary liver care center. METHODS: Patients with S. maltophilia isolation in clinical samples were selected. Serial levels of serum procalcitonin and total leukocyte count were recorded. Environmental surveillance was done from the wards of S. maltophilia isolation as part of routine practice. STATISTICAL ANALYSIS: Continuous data were compared using Kruskal-Wallis test/Mann-Whitney test. The categorical data were compared by Chi-square/Fisher's exact test, wherever necessary. Besides this, an appropriate analysis like survival was carried out at the time of data analysis. RESULTS: One hundred isolates were obtained from eighty patients of six wards. The greatest number (44/100, 44%) were from the Liver Coma Intensive Care Unit and the lowest (3/100) from the day care. Isolation from the respiratory samples was 1.32% and bloodstream infection 0.6%. Of 100 isolates, 12 (12%) were resistant to both trimethoprim-sulfamethoxazole and levofloxacin. CONCLUSION: S. maltophilia was effectively isolated from the hospital environment, with two of hand impression and three of water samples' positive. Patients with respiratory infection had most S. maltophilia isolates. Antibiotic susceptibility revealed more resistance than reported in this region.