Clinical efficacy of IgM-enriched immunoglobulin as adjunctive therapy in neonatal and pediatric sepsis: a systematic review and meta-analysis.

Background: Sepsis is a major cause of mortality and morbidity globally, with around one-quarter of all sepsis-related deaths occurring in children under the age of 5. We conducted a meta-analysis and systematic review of the literature to evaluate the clinical effectiveness of an IgM-enriched immunoglobulin preparation in pediatrics patients and neonates with sepsis. Methods: Systematic searches of PubMed, the Cochrane Library and Embase databases were performed in November 2022, with no date limitations, to identify studies in which IgM-enriched immunoglobulin was used as adjunctive therapy in neonatal and pediatric patients with sepsis. Results: In total, 15 studies fulfilled the eligibility criteria, 13 neonatal studies and 2 pediatric studies. Pooled estimates from all studies indicated that mortality rates were significantly lower in patients who received treatment with the IgM-enriched immunoglobulin compared with controls (OR 0.41; 95% CI 0.32-0.55). Further analyses in neonatal studies, alone, showed a significant benefit with longer treatment durations (>3 days) vs. the recommended treatment duration (3 days) (OR 0.32; 95% CI 0.22-0.47) vs. (OR 0.61; 95% CI 0.41-0.92). Treatment with IgM-enriched immunoglobulin was associated with a lower mortality risk compared with controls in prospective studies vs. retrospective analyses (OR 0.37; 95% CI 0.27-0.51) vs. (OR 0.73; 95% CI 0.41-1.30). Conclusions: This systematic review suggests that adjunctive treatment with IgM-enriched immunoglobulin may reduce the risk of mortality in neonatal and pediatric populations. However, large randomized controlled trials are required to further substantiate and evaluate these findings.

IgM-enriched immunoglobulin in COVID-19: Case series of 15 severely ill SARS-CoV-2-infected patients.

The healthcare system in Iran, like most around the world, is managing thousands of patients hospitalised with COVID-19. In Iran, in-hospital mortality is in the region of 25%, rising to 50-60% in patients admitted to intensive care. Hyperinflammation, characterised by cytokine storm, appears to be a hallmark of severe COVID-19 and to date only the anti-inflammatory drug dexamethasone has been shown to reduce mortality in those hospitalised with the disease. There is a sound scientific rationale behind the use of IgM-enriched immunoglobulin in the management of patients with severe COVID-19. It has been used successfully in the management of hyperinflammation in patients with sepsis and has led to improved radiographic scores in patients with severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Recently the successful treatment of a patient with COVID-19 with IgM-enriched immunoglobulin was reported. Here we report the outcome of a further 15 patients hospitalised with COVID-19 treated with IgM-enriched immunoglobulin. Improvements in computed tomography (CT) score were observed in nine patients, indicating that further clinical studies into the use of IgM-enriched immunoglobulin in the treatment of severe COVID-19 are warranted.

The clinical efficacy of intravenous IgM-enriched immunoglobulin (pentaglobin) in sepsis or septic shock: a meta-analysis with trial sequential analysis.

BACKGROUND: Sepsis is characterized by a complex immune response. This meta-analysis evaluated the clinical effectiveness of intravenous IgM-enriched immunoglobulin (IVIgGM) in patients with sepsis and septic shock. METHODS: Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 to update the 2013 edition of the Cochrane review by two investigators, who independently selected studies, extracted relevant data, and evaluated study quality. Data were subjected to a meta-analysis and trial sequential analysis (TSA) for the primary and secondary outcomes. Level of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. RESULTS: Nineteen studies comprising 1530 patients were included in this meta-analysis. Pooled analyses showed that the use of IVIgGM reduced the mortality risk of septic patients (relative risk 0.60; 95% confidence interval [CI] 0.52-0.69, I2 = 0%). TSA showed that IVIgGM had a significant effect on mortality. Additionally, the meta-analysis suggested that use of IVIgGM shortened length of mechanical ventilation (mean difference - 3.16 days; 95% CI - 5.71 to - 0.61 days) and did not shorten length of stay in the intensive care unit (mean difference - 0.38 days; 95% CI - 3.55 to 2.80 days). The GRADE scale showed that the certainty of the body of evidence was low for both benefits and IVIgGM. CONCLUSION: Administration of IVIgGM to adult septic patients may be associated with reduced mortality. Treatment effects tended to be smaller or less consistent when including only those studies deemed adequate for each indicator. The available evidence is not clearly sufficient to support the widespread use of IVIgGM in the treatment of sepsis. Trial registration PROSPERO registration number: CRD42018084120. Registered on 11 February 2018.

Septic shock from descending necrotizing mediastinitis - combined treatment with IgM-enriched immunoglobulin preparation and direct polymyxin B hemoperfusion: a case report.

BACKGROUND: Descending necrotizing mediastinitis is a common and progressive polymicrobial infection involving the neck and chest with a high death rate (10 to 40%). From a microbiological point of view, descending necrotizing mediastinitis is sustained by Gram-positive bacteria (43-62%), anaerobes (46-78%), and, rarely, Gram-negative bacteria. Data collected during the Antibiotic Resistance-Istituto Superiore di Sanità project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance. In particular, 32.9% of Klebsiella pneumoniae isolates were resistant to carbapenem, 33.6% of Staphylococcus aureus to methicillin, and 28.7% and 43.9% of Escherichia coli isolates to third-generation cephalosporins and fluoroquinolones, respectively. CASE PRESENTATION: We describe the case of a 38-year-old white man with septic shock due to descending necrotizing mediastinitis sustained by multidrug-resistant Gram-negative and Gram-positive bacteria treated after surgery with an IgM-enriched immunoglobulin preparation and polymyxin B hemoperfusion therapy. CONCLUSION: Despite the contrasting data on the use of immunoglobulins and polymyxin B hemoperfusion in septic shock and the lack of literature in cases of acute mediastinitis caused by both Gram-negative and Gram-positive multidrug-resistant bacteria, we obtained an improvement in clinical conditions and the survival of our patient, against all odds.

The use of IgM-enriched immunoglobulin in adult patients with sepsis.

The administration of intravenous immunoglobulins (IVIG) is one of the adjunct therapies investigated and applied to sepsis patients, with the first studies being published nearly four decades ago. Intravenous immunoglobulin preparations have several mechanisms of action e.g. antigen neutralization, Fc-receptor blockade on phagocytic cells, modulation of cytokine responses and modulation of immune cell functions. The currently available evidence suggesting the use of intravenous immunoglobulins in sepsis is weak, but results from recent trials and systematic metanalyses seem more promising for the use of intravenous IgM-enriched immunoglobulins (IVIgGM) in septic patients. Nevertheless, the results of studies examining its value are contradicting. The purpose of this review is to summarize and present, clearly and thoroughly, the currently available data regarding established and future potential clinical uses of IVIgGM in patients with sepsis.