Evaluation of Parenteral Vitamin C's Effectiveness in Critically Ill Patients: A Systematic Review and Critical Appraisal.

Vitamin C, a key nutrient with potent antioxidant and immunomodulatory properties, has been explored for its therapeutic potential in treating severe infections, particularly sepsis. This systematic review aims to evaluate the effectiveness of parenteral vitamin C in improving clinical outcomes in patients with severe infections. A comprehensive search of several databases, including PubMed, EMBASE, and the Cochrane Library, was conducted for studies published between January 2000 and June 2024. Included were randomized controlled trials, observational studies, and case reports that examined the use of parenteral vitamin C in adult patients with severe infections. Data extracted included study design, sample size, intervention specifics, and clinical outcomes. Quality was assessed using tools appropriate to each study design, such as the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale. The review included nine studies with diverse methodologies. While individual studies reported benefits such as improved immune function and reduced oxidative stress, larger systematic reviews and meta-analyses did not demonstrate a significant reduction in mortality. The results indicate that while parenteral vitamin C may improve certain biochemical and physiological parameters, these improvements do not consistently translate into enhanced survival or substantial clinical benefits. Parenteral vitamin C shows potential in modulating immune response and reducing oxidative damage in severe infections. However, its impact on key clinical outcomes like mortality and long-term recovery remains uncertain. This review highlights the need for further high-quality, randomized controlled trials to clarify vitamin C's role in managing severe infections and define optimal therapeutic protocols.

A population-based multigenerational family co-aggregation study of severe infections and obsessive-compulsive disorder.

BACKGROUND: Postinfectious autoimmune processes have been proposed as potential causal factors for obsessive-compulsive disorder (OCD). This large population-based study aimed to clarify the co-aggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness. METHODS: We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until 2020. Each individual was linked to their first- and second-degree relatives, including monozygotic (MZ) and dizygotic (DZ) twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient units were retrieved from the Swedish National Patient Register. We compared the risk of OCD in relatives of probands with severe infections to those of probands without severe infections. Cox proportional hazard regression models, incorporating time-varying exposures, were used to estimate hazard ratios (HRs). Dose-response associations were examined using logistic regression models. RESULTS: Relatives of probands with severe infections exhibited a higher risk of OCD, increasing with genetic relatedness, with HRs (95% CI) ranging from 1.46 (1.07-1.98) in MZ twins to 1.10 (1.09-1.11) in cousins. The results remained robust after adjusting for severe infections among relatives, OCD in probands, and comorbid autoimmune disorders in both probands and relatives. A dose-response association was observed between the number of infections in the probands and their odds of OCD, as well as in their relatives. CONCLUSIONS: The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.

Severe infections in systemic necrotizing vasculitis.

Infections in patients with systemic vasculitis represent one of the main causes of mortality. Corticosteroid use, immunosuppressive therapy, age, associated organic involvement and dialysis dependence are risk factors of infection. OBJECTIVES: To determine the prevalence of severe infection and associated factors in patients diagnosed with ANCA-associated vasculitis (AAV) and Polyarteritis Nodosa (PAN). METHODS: retrospective study was conduced in a single rheumatology center (2000-2018). We included patients diagnosed with AAV (Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (PAM) and Polyarteritis nodosa (PAN). Serious infectious events requiring hospitalisation or prolonged antibiotic/antiviral treatment, recurrent infection of Herpes Zoster Virus or opportunistic infections were evaluated. Sites of infection, isolated microorganisms and mortality related were analyzed. RESULTS: 105 patients were analyzed, follow-up time median 18 m, 58.7% were women and median age was 52 years. Types of vasculitis: 41.9% PAM, 16.2% EPGA, 40% GPA, 1.9% PAN. Constitutional, pulmonary, renal and otorhinolaryngology manifestations were the most frequent. PREVALENCE OF INFECTION: 34.2%, with a median of 3 months from diagnosis of vasculitis to the infectious event. Low respiratory tract (42.8%), sepsis (31.4%), and urinary tract (14.3%) were the most common sites of infections. Bacterial aetiology was the most prevalent (67.7%). Mortality at the first event was 14.3% and a 72.2% of patients were in the induction phase of treatment. Infectious events were significantly associated with age > 65 years (p = 0.030), presence of lung (p = 0.016) and renal involvement (p = 0.001), BVASv3 > 15, mortality (p = 0.0002). CONCLUSIONS: The prevalence of infection was 34.2%. Lower airway infections, septicemia and urinary tract infections were the most prevalent. Infections were associated with renal and pulmonary involvement, age older than 65 years and score BVAS > 15. Severe infections were associated with mortality, especially in elderly patients.

Genetic polymorphisms of TLR1, TLR2, TLR3 and TLR4 in patients with recurrent or severe infections.

Toll-like receptors (TLRs) play an important role in innate immunity. Previous studies have shown that single nucleotide polymorphisms (SNPs) in the genes coding for these innate immune molecules can affect susceptibility to and the outcome of certain diseases. The aim of the present study was to examine the clinical relevance of well-studied TLR1-4 SNPs in individuals who are prone to infections. Four functional SNPs, TLR1 rs5743618 (1805C > A, Ser602Ile), TLR2 rs5743708 (2258G > A, Arg753Gln), TLR3 rs3775291 (1234C > T, Leu412Phe) and TLR4 rs4986790 (896A > G, Asp299Gly), were analysed in 155 patients with recurrent respiratory infections (n = 84), severe infections (n = 15) or common variable immunodeficiency (n = 56), and in 262 healthy controls, using the High Resolution Melting Analysis method. Polymorphisms of TLR2 rs5743708 (odds ratio [OR] 3.16; 95% confidence interval [CI] 1.45-6.83, p = .004, ap = .016) and TLR4 rs4986790 (OR 1.8; 95% CI 1.05-3.12, p = .028, ap = .112) were more frequent in patients with recurrent or severe infections than in controls. Interestingly, seven patients were found to carry both variant genotypes of TLR2 and TLR4, whereas none of the control group carried such genotypes (p  ≤ .0001). Moreover, TLR2 polymorphism was associated with increased risk for acute otitis media episodes (OR, 3.02; 95% CI 1.41-6.47; p = .012). This study indicates that children and adults who are more prone to recurrent or severe respiratory infections carry one or both variant types of TLR2 and TLR4 more often than control subjects. Genetic variations of TLRs help explain why some children are more susceptible to respiratory infections.

Neutralizing anti-IFN-γ IgG was increased in patients with systemic lupus erythematosus and associated with susceptibility to infection.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complicated autoimmune disease, in which infection is a leading cause of death. Some SLE patients clinically presented with recurrent and refractory infections, which manifested as adult-onset immunodeficiency syndrome due to the production of anti-interferon-γ (anti-IFN-γ) autoantibodies. This study aimed to investigate the role of anti-IFN-γ autoantibodies concerning severe infections in SLE patients. METHODS: We detected serum levels of anti-IFN-γ IgG/IgM isotypes in SLE patients with severe infections (n = 55), SLE patients without severe infections (n = 120), rheumatoid arthritis (n = 24), ankylosing spondylitis (n = 24), and healthy controls (n = 60). The relationship between anti-IFN-γ autoantibodies and clinical characteristics and laboratory parameters were analyzed. We further evaluated the neutralizing ability of anti-IFN-γ IgG. RESULTS: The level of anti-IFN-γ IgG was significantly elevated in SLE patients with severe infections compared with the other groups (all p < 0.01), and the positive rates of anti-IFN-γ IgG in SLE patients with and without severe infections were 29.1% and 10.8%, respectively. Further analysis indicated that the levels of anti-IFN-γ IgG were positively associated with the SLEDAI score (r = 0.6420, p < 0.001), and it could predict the susceptibility to severe infections in SLE patients. Moreover, the inhibition and function assay showed that purified IgG from anti-IFN-γ IgG-positive SLE patients could neutralize IFN-γ, and further impair IFN-γ-induced STAT1 phosphorylation. CONCLUSIONS: The neutralizing anti-IFN-γ IgG might increase the susceptibility to infection in SLE patients, which has important implications for the treatment. Key Points • The role of anti-IFN-γ autoantibodies concerning severe infections in SLE patients remains unknown. • The results of this study reveals that anti-IFN-γ IgG levels were significantly elevated in SLE patients with severe infections. • This study suggests that neutralizing anti-IFN-γ IgG might increase the susceptibility to infection in SLE patients.

Severe Rickettsia typhi Infections, Costa Rica.

Murine typhus is a febrile, fleaborne disease caused by infection with Rickettsia typhi bacteria. Cases can range from mild and nonspecific to fatal. We report 2 cases of murine typhus in Costa Rica, confirming the presence and circulation of R. typhi causing severe disease in the country.

Alternative Antimicrobial Irrigation Strategies for the Treatment of Infections in Children: A Review of the Existing Literature.

As a synergistic treatment approach with systemic antimicrobial therapy or a systemic antibiotic-sparing strategy, the local administration of antimicrobial agents has been proposed as an alternative route for complicated infections. With the rationale of concentrating the active principle in the desired target site, avoiding potentially toxic systemic levels and bypassing anatomical and physiological barriers, local irrigation or infusion of antibiotics may effectively shorten the antimicrobial therapy course and reduce both infection-related and systemic therapy-related complications. Although evidence from the adult population supports its use in selected patients with an acceptable safety profile, data specifically focused on the pediatric population are limited. To provide a rapid and easily accessible tool for clinical practice, we synthesized the most relevant evidence on the use of local antimicrobial agents in common severe infections in children: meningitis, mediastinitis, pleural infections, recurrent urinary infections, and peritonitis. A literature search was performed using predefined combined keywords through an electronic research database (PubMed). Described molecules, dosages, routes, treated age groups, and related efficacy have been summarized for prompt application to clinical practice. It should, however, be noted that the evidence for the pediatric population remains limited, and the local administration of several molecules remains off-label. A careful multidisciplinary and patient-tailored evaluation, as well as a rational use of available guidelines, should always be the basis of clinical decision making in settings where local administration of antibiotics may be considered.

Impact of SARS-CoV-2 Omicron and Delta variants in patients requiring intensive care unit (ICU) admission for COVID-19, Northern Italy, December 2021 to January 2022.

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic.

Association between hypogammaglobulinaemia and severe infections during induction therapy in ANCA-associated vasculitis: from J-CANVAS study.

OBJECTIVES: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. METHODS: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. RESULTS: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. CONCLUSION: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

Predictors of hypogammaglobulinemia in ANCA-associated vasculitis after a rituximab-based induction: a multicentre study.

OBJECTIVES: Rituximab has become the cornerstone of induction treatment in ANCA-associated vasculitis (AAV). B-cell depletion may increase the risk of hypogammaglobulinemia, potentially leading to severe infections. This study aims to assess factors associated with hypogammaglobulinemia in AAV patients treated with rituximab. METHODS: This retrospective cohort study included AAV patients treated with rituximab induction in 14 European centres. Severe adverse events (SAEs) were defined as episodes requiring hospitalization or intravenous antibiotics, malignancies, or death. Linear and logistic regression were used to identify predictors of IgG levels and of the risk of hypogammaglobulinemia, defined as IgG ≤7 g/l at 6 months. RESULTS: The study included 227 patients. IgG levels at 6 months were lower than baseline (P < 0.001). Patients requiring intravenous antibiotics during the first 6 months had lower IgG levels at 6 months (P = 0.004). Age [ß (95% CI): -0.23 (-0.38, -0.08) per 10 years, P = 0.003], oral glucocorticoid dose at induction [ß (95% CI): -0.37 (-0.51, -0.24) per sqrt-transformed mg prednisone, P < 0.001] and concomitant use of intravenous glucocorticoid pulses [ß (95% CI): -0.88 (-1.73, -0.02), P = 0.044] were associated with IgG levels at 6 months. Hypogammaglobulinemia was identified in 97 (42.7%) patients. In multivariable logistic regression, factors associated with the risk of hypogammaglobulinemia were age [OR (95% CI): 1.46 (1.15, 1.86) per 10 years, P = 0.002] and oral glucocorticoid dose at induction [OR (95% CI): 1.52 (1.23, 1.89) per 10 mg prednisone, P < 0.001]. CONCLUSIONS: In AAV patients treated with rituximab, hypogammaglobulinemia at 6 months after induction is common, and lower IgG levels are associated with serious infections. The risk of hypogammaglobulinemia in these patients increases with age and higher glucocorticoid doses.

Characterization of sepsis inflammatory endotypes using circulatory proteins in patients with severe infection: a prospective cohort study.

BACKGROUND: Sepsis is a heterogeneous syndrome due to a variable range of dysregulated processes in the host immune response. Efforts are made to stratify patients for personalized immune-based treatments and better prognostic prediction. Using gene expression data, different inflammatory profiles have been identified. However, it remains unknown whether these endotypes mirror inflammatory proteome profiling, which would be more feasible to assess in clinical practice. We aim to identify different inflammatory endotypes based on circulating proteins in a cohort of moderately ill patients with severe infection (Sepsis-2 criteria). METHODS: In this prospective study, 92 inflammatory plasma markers were profiled using a targeted proteome platform and compared between patients with severe infection (Sepsis-2 criteria) and healthy controls. To identify endotypes with different inflammatory profiles, we performed hierarchical clustering of patients based on the differentially expressed proteins, followed by clinical and demographic characterization of the observed endotypes. RESULTS: In a cohort of 167 patients with severe infection and 192 healthy individuals, we found 62 differentially expressed proteins. Inflammatory proteins such as TNFSF14, OSM, CCL23, IL-6, and HGF were upregulated, while TRANCE, DNER and SCF were downregulated in patients. Unsupervised clustering identified two different inflammatory profiles. One endotype showed significantly higher inflammatory protein abundance, and patients with this endotype were older and showed lower lymphocyte counts compared to the low inflammatory endotype. CONCLUSIONS: By identifying endotypes based on inflammatory proteins in moderately ill patients with severe infection, our study suggests that inflammatory proteome profiling can be useful for patient stratification.

Severe Staphylococcus aureus infections in children: Case reports and management of positive Panton-Valentine leucocidin cases.

Background: Staphylococcus aureus is a well-known bacterium associated with carriage and responsible for different types of infections. The Panton-Valentine leucocidin (PVL) is a key virulence factor causing tissue necrosis. PVL can, however, be present in both benign and life-threatening infections. Case reports and management: We present three pediatric severe infections occurring over a period of only three weeks, in February 2021, and caused by genetically unrelated methicillin-sensitive Staphylococcus aureus producing PVL in a tertiary children's hospital in Belgium. The first one presented with necrotizing pneumonia, the second one with a neck abscess extended to the mediastinum, and the last one had sacral osteomyelitis complicated by endocarditis. The management of these infections is mostly based on expert opinions. The most appropriate treatment seems to be the combination of early surgical drainage of infected collections with an antibiotic regimen associating two antibiotics; beta-lactams and either clindamycin or linezolid. Human immunoglobulins also appear to be useful as adjunctive therapy. Conclusion: PVL-producing Staphylococcus aureus is associated with life-threatening infections in children. Prompt management is needed including surgery and appropriate antibiotic regimens.

Combined Immune Defect in B-Cell Lymphoproliferative Disorders Is Associated with Severe Infection and Cancer Progression.

B cell chronic lymphoproliferative diseases (B-CLPD) are associated with secondary antibody deficiency and other innate and adaptive immune defects, whose impact on infectious risk has not been systematically addressed. We performed an immunological analysis of a cohort of 83 B-CLPD patients with recurrent and/or severe infections to ascertain the clinical relevance of the immune deficiency expression. B-cell defects were present in all patients. Patients with combined immune defect had a 3.69-fold higher risk for severe infection (p = 0.001) than those with predominantly antibody defect. Interestingly, by Kaplan-Meier analysis, combined immune defect showed an earlier progression of cancer with a hazard ratio of 3.21, than predominantly antibody defect (p = 0.005). When B-CLPD were classified in low-degree, high-degree, and plasma cell dyscrasias, risk of severe disease and cancer progression significantly diverged in combined immune defect, compared with predominantly antibody defect (p = 0.001). Remarkably, an underlying primary immunodeficiency (PID) was suspected in 12 patients (14%), due to prior history of infections, autoimmune and granulomatous conditions, atypical or variegated course and compatible biological data. This first proposed SID classification might have relevant clinical implications, in terms of predicting severe infections and cancer progression, and might be applied to different B-CLPD entities.

Corticosteroids Use and Incidence of Severe Infections in People Living with HIV Compared to a Matched Population.

BACKGROUND: People living with HIV (PLWH) have been shown to have an increased risk of autoimmune diseases. Corticosteroids are the cornerstone of autoimmune diseases treatment, but their use is associated with an increased risk of infections. It is unclear how HIV status affects the risk of infection associated with corticosteroids use. METHODS: We conducted a retrospective cohort study from 1991 to 2011, using a medico-administrative database from Quebec. Medical billing codes were used to identify PLWH, and we matched them on age, sex, and index date with up to 4 HIV-negative controls. The exposure of interest was the use of corticosteroids, defined as a systemic corticosteroid dispensation lasting at least 20 days. The outcome of interest was hospitalization for severe infection. Crude and adjusted incidence rates ratios of infection were obtained using a random effect Poisson model, and results were stratified by HIV status. RESULTS: In total, 4798 PLWH were matched to 17 644 HIV-negative controls, among which 1083 (22.6%) PLWH and 1854 (10.5%) HIV-negative controls received at least one course of corticosteroid. The mean duration of corticosteroids use was 4 ± 4.4 months in PLWH and 1.6 ± 5.5 months in HIV-negative controls. The incidence rate ratio (IRR) for infections associated with corticosteroids use was 2.49[1.71-3.60] in PLWH and 1.32[0.71-2.47] in HIV-negative controls (P value for interaction 0.18). The most frequent infections were pulmonary infections (50.4%), followed by urinary tract infections (26%) and opportunistic infections (10.5%). CONCLUSION: Although our interaction term did not reach significance, the increased risk of infection associated with corticosteroids use was more pronounced in PLWH. However, further research with contemporary data is warranted to confirm if the risk associated with corticosteroids use remains high in PLWH with well-controlled HIV infection.

Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis.

We systematically reviewed the efficacy and safety of an extended or continuous infusion (EI/CI) versus short-term infusion (STI) of carbapenems in children with severe infections. Databases, including PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, WanFang Data, and SinoMed, were systematically searched from their inceptions to 10 August 2020, for all types of studies (such as randomized controlled trials (RCTs), retrospective studies, and pharmacokinetic or population pharmacokinetic (PK/PPK) studies) comparing EI/CI versus STI in children with severe infection. There was no limitation on language, and a manual search was also conducted. The data were screened, evaluated, extracted, and reviewed by two researchers independently. Quantitative (meta-analysis) or qualitative analyses of the included studies were performed. Twenty studies (including two RCTs, one case series, six case reports, and 11 PK/PPK studies) were included in this review (CRD42020162845). The RCTs' quality evaluation results revealed a risk of selection and concealment bias. Qualitative analysis of RCTs demonstrated that, compared with STI, an EI (3 to 4 h) of meropenem in late-onset neonatal sepsis could improve the clinical effectiveness and microbial clearance rates, and reduce the rates of mortality; however, the differences in the incidence of other adverse events were not statistically significant. Retrospective studies showed that children undergoing an EI of meropenem experienced satisfactory clinical improvement. In addition, the results of the PK/PPK study showed that an EI (3 or 4 h)/CI of carbapenems in severely infected children was associated with a more satisfactory goal achievement rate (probability of target attainment) and a cumulative fraction of response than STI therapy. In summary, the EI/CI of carbapenems in children with severe infection has a relatively sufficient PK or pharmacodynamic (PD) basis and satisfactory efficacy and safety. However, due to the limited quantity and quality of studies, the EI/CI therapy should not be used routinely in severely infected children. This conclusion should be further verified by more high-quality controlled clinical trials or observational studies based on PK/PD theories.

Novel Cephalosporins in Septic Subjects and Severe Infections: Present Findings and Future Perspective.

In past decade, cephalosporins have developed significantly, and data regarding novel cephalosporins (i.e., ceftobiprole, ceftaroline, ceftolozane/tazobactam, ceftazidime/avibactam, and cefiderocol) within septic and bacteremic subjects are rising. These compounds generally offer very promising in vitro microbiological susceptibility, although the variability among gram-negative and -positive strains of different cohorts is noticed in the literature. We require further pharmacological data to measure the best dose in order to prevent sub-therapeutic drug levels in critically ill patients. These new compounds in theory are the sparing solution in the Enterobacteriales infection group for different antimicrobial classes such as aminoglycosides notably within endovascular and GNB-bacteremias, as well as colistin and carbapenem-sparing strategies, favoring good safety profile molecules. Moreover, new cephalosporins are the basis for the actual indications to open up new and exciting prospects for serious infections in the future. In future, patients will be addressed with the desirable approach to sepsis and serious infections in terms of their clinical situation, inherent features of the host, the sensitivity profile, and local epidemiology, for which evidence of the use of new cephalosporin in the treatment of severe infections will fill the remaining gaps.

Severe infections in patients with ANCA-associated vasculitis treated with rituximab.

OBJECTIVES: Rituximab (RTX) is an anti-CD20 antibody that selectively depletes B cells and has emerged as a therapy for ANCA-associated vasculitis (AAV) during the past decade. This study sought to quantify and determine potential risk factors for severe infections in AAV patients treated with RTX at rheumatology clinics in Mexico City, Mexico and Lund, Sweden. METHODS: The study consisted of a retrospective case-record review (2005-15) with standardized data collection related to the occurrence of severe infection in 46 patients with AAV in Mexico City (n = 20) and Lund (n = 26) treated with RTX during their disease course. Median duration of follow-up from first RTX dose to death or end of study was 26 months. RESULTS: Eleven (24%) patients suffered a total of 18 severe infections (infection rate of 11.5/100 patient-years). Thirteen of the 18 infections (72%) occurred within the first year of treatment. Risk factors for severe infection were older age at RTX initiation and absence of ENT involvement at diagnosis. In multivariate analyses, age at RTX infusion was the only independent factor predicting severe infection. Four patients (9%) died during follow-up, all as a result of infection. CONCLUSION: Severe infections are common following RTX treatment, and mortality due to infection is a major concern. Most severe infections occur within the first year of RTX treatment. The negative correlation of ENT involvement with severe infection might reflect granulomatosis with polyangiitis phenotype heterogeneity. Older age at time of RTX treatment independently predicts severe infections.

Pre-hospital antibiotic therapy preceded by blood cultures in a physician-manned mobile emergency care unit.

BACKGROUND: Rapid recognition and antibiotic treatment, preferably preceded by blood cultures (BCs), is a mainstay in sepsis therapy. The objective of this investigation was to determine if pre-hospital BCs were feasible and drawn with an acceptably low level of contamination and to investigate whether pre-hospital antibiotics were administered on correct indications. METHODS: We performed a register-based study in a pre-hospital physician-manned mobile emergency care unit (MECU) operating in a mixed urban/rural area in Denmark. All patients who received pre-hospital antibiotics by the MECU from November 2013 to October 2018 were reviewed. Outcome measures were characterisation of microbial findings and subsequent in-hospital confirmation of the pre-hospital indication for antibiotics. RESULTS: One-hundred-and-nineteen patients received antibiotics pre-hospitally. Six were excluded. One-hundred-and-thirteen patients were included in the study. BCs were drawn in 107 of the 113 patients (94.7% [88.8%-98.0%]). We found a true pathogen of sepsis in 29 (27.1% [19.0%-36.6%]) of these 107 patients. Nine (8.4% [3.9%-15.4%]) patients had contaminated pre-hospital BCs. Forty-nine of all patients (36.3% [27.4%-45.9%]) had causative pathogens in either their BCs or other samples confirming the pre-hospital tentative diagnosis. Eighty-two (72.6% [63.4%-80.5%]) patients received antibiotic therapy in-hospitally, while 27 (23.9% [16.4%-32.8%]) were assigned an in-hospital diagnosis not associated with infection. Four (3.5% [1.0%-8.8%]) patients died in hospital before a diagnosis was established. CONCLUSIONS: Pre-hospital administration of antibiotics preceded by BCs is feasible, although with somewhat high blood culture contamination rates. Antibiotics are administered on reasonable indications.