Case Series: Efficacy of Polyclonal Intravenous Immunoglobulin for Refractory Clostridioides difficile Infection.

BACKGROUND: Intravenous immunoglobulin (IVIg) for Clostridioides difficile infection (CDI) no longer features in treatment guidelines. However, IVIg is still used by some clinicians for severe or recurrent CDI (rCDI) cases. The main objective of this study was to investigate the efficacy of IVIg and to identify possible predictors of disease resolution post IVIg administration for patients with CDI. METHODS: This retrospective observational cohort study of patients ≥2 years old hospitalised with severe, relapsing, or rCDI treated with IVIg therapy was performed in a large UK tertiary hospital between April 2018 and March 2023. Scanned electronic notes from patient admissions and clinical reporting systems were used to collect relevant data. RESULTS: In total, 20/978 patients diagnosed with CDI over the 5-year study were treated with IVIg. Twelve (60%) had hospital-onset CDI. Eleven of the twenty patients (55%) responded to treatment, with a mean of 8.6 (SD 10.7) days to disease resolution. Sixteen (80%) patients were treated for severe CDI and four (20%) for rCDI (n = 3) and relapsing CDI (n = 1). There were no statistically significant differences in possible independent predictors of disease resolution post IVIg administration between groups. There was an average of 6.2 (4.9) days to IVIg administration after diagnosis with no difference between responders and non-responders (p = 0.88) and no further significant difference in additional indicators. Four (36%) of the responders were immunosuppressed compared to just one (11%) of the non-responders (p = 0.15). Six of the responders (two with recurrent and four with severe CDI) improved rapidly within 2 days, and three of these were immunosuppressed. CONCLUSION: We observed disease resolution post IVIg therapy in over 50% of patients with refractory CDI. Our data also support a potential enhanced effect of IVIg in immunosuppressed individuals. Thus, the role of IVIg for CDI treatment, particularly in the immunosuppressed, warrants future case-control studies coupled to mechanistic investigations to improve care for this ongoing significant healthcare-associated infection.

Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update.

The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-ß accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.

Population infection estimation from wastewater surveillance for SARS-CoV-2 in Nagpur, India during the second pandemic wave.

Wastewater-based epidemiology (WBE) has emerged as an effective environmental surveillance tool for predicting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease outbreaks in high-income countries (HICs) with centralized sewage infrastructure. However, few studies have applied WBE alongside epidemic disease modelling to estimate the prevalence of SARS-CoV-2 in low-resource settings. This study aimed to explore the feasibility of collecting untreated wastewater samples from rural and urban catchment areas of Nagpur district, to detect and quantify SARS-CoV-2 using real-time qPCR, to compare geographic differences in viral loads, and to integrate the wastewater data into a modified Susceptible-Exposed-Infectious-Confirmed Positives-Recovered (SEIPR) model. Of the 983 wastewater samples analyzed for SARS-CoV-2 RNA, we detected significantly higher sample positivity rates, 43.7% (95% confidence interval (CI) 40.1, 47.4) and 30.4% (95% CI 24.66, 36.66), and higher viral loads for the urban compared with rural samples, respectively. The Basic reproductive number, R0, positively correlated with population density and negatively correlated with humidity, a proxy for rainfall and dilution of waste in the sewers. The SEIPR model estimated the rate of unreported coronavirus disease 2019 (COVID-19) cases at the start of the wave as 13.97 [95% CI (10.17, 17.0)] times that of confirmed cases, representing a material difference in cases and healthcare resource burden. Wastewater surveillance might prove to be a more reliable way to prepare for surges in COVID-19 cases during future waves for authorities.