Biomarkers in infection and sepsis: Can they really indicate final outcome?

Infectious diseases are among the most common reasons for admission to hospital and can easily lead to sepsis. Sepsis is globally associated with increased mortality, and although biomarkers could help clinicians in the early diagnosis of sepsis and immediate onset of antibiotics, there are always questions to be answered about their usefulness in the prognosis of infectious diseases. This article reviews some of the available biomarkers used in infectious diseases and sepsis in order to evaluate their utility to predict mortality and unfavourable outcome. Several studies present the pros and cons of each compound, but it is obvious that the ideal biomarker, with high sensitivity and specificity, cost effectiveness and with definite cut-off ranges and time of blood sampling, is yet to be found. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved

Oral minocycline plus rifampicin versus oral linezolid for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: the AIDA open label, randomized, controlled Phase 4 trialResearch in context

Summary: Background: The need for oral, cost-effective treatment for complicated skin and skin structure infections (cSSSIs) due to methicillin-resistant Staphylococcus aureus (MRSA) was addressed by the non-inferiority comparisons of oral minocycline plus rifampicin with linezolid. Methods: In the AIDA multicenter, open label, randomized, controlled clinical trial, hospitalized adults with cSSSI and documented MRSA were randomly assigned at a 2:1 ratio to either oral 600 mg rifampicin qd plus 100 mg minocycline bid or oral 600 mg linezolid bid for 10 days. The primary endpoint was the clinical cure rate in the clinically evaluable (CE) population at the test-of-cure visit (14 days). Non-inferiority was confirmed if the lower confidence limit (CI) did not fall below the accepted error margin of 15%. The study is registered with EudraCT number 2014-001276-56. Findings: 123 patients recruited between November 2014 and January 2017 were randomly assigned to treatment (81 patients to minocycline plus rifampicin and 42 patients to linezolid). Cure rates were 78.% (46/59, 90% CI 67.3–86.5) and 68.6% (24/35, 90% CI 53.4–81.3), respectively (P = 0.337). The percent difference in cure rates was 9.4% (90% CI −7.2 to 26.8%). Minocycline plus rifampicin combination was deemed non-inferior to linezolid as the lower CI was −7.2% i.e. smaller than the accepted error margin of −15%. Although statistically not significant, the overall rate of adverse events was higher in the linezolid group (47.6%, 20/42 versus 38.3%, 31/81). Interpretation: Oral minocycline plus rifampicin was non-inferior to oral linezolid treatment providing alternative oral treatment for cSSSI. Funding: The EU Seventh Research Framework Programme

NF-kappa-B essential modulator (NEMO) gene polymorphism in an adult woman with systemic lupus erythematosus and recurrent non-tuberculous mycobacterial disseminated infections

Infections are among the most serious complications in patients with systemic lupus erythematosus (SLE), with bacterial and viral infections being the most common. Non-tuberculous mycobacterial (NTM) infections are quite rare and are typically seen in older patients with SLE with longstanding disease duration treated with corticosteroids. Here, we describe a 39-year-old woman with SLE and an unusual pattern of recurrent NTM disseminated infections. After excluding the presence of autoantibodies against interferon-γ, whole exome sequencing revealed a homozygous polymorphism in the NF-kappa-B essential modulator (NEMO) gene. Primary immunodeficiencies should be included in the differential diagnosis of patients with recurrent opportunistic infections, even in those with iatrogenic immunosuppression

Real-Life Effectiveness and Safety of Baricitinib as Adjunctive to Standard-of-Care Treatment in Hospitalized Patients With Severe Coronavirus Disease 2019

Background. Therapeutic options for hospitalized patients with severe coronavirus disease 2019 (sCOVID-19) are limited. Preliminary data have shown promising results with baricitinib, but real-life experience is lacking. We assessed the safety and effectiveness of add-on baricitinib to standard-of-care (SOC) including dexamethasone in hospitalized patients with sCOVID-19. Methods. This study is a 2-center, observational, retrospective cohort study of patients with sCOVID-19, comparing outcomes and serious events between patients treated with SOC versus those treated with SOC and baricitinib combination. Results. We included 369 patients with sCOVID-19 (males 66.1%; mean age 65.2 years; median symptom duration 6 days). The SOC was administered in 47.7% and combination in 52.3%. Patients treated with the combination reached the composite outcome (intensive care unit [ICU] admission or death) less frequently compared with SOC (22.3% vs 36.9%, P = .002). Mortality rate was lower with the combination in the total cohort (14.7% vs 26.6%, P = .005), and ICU admission was lower in patients with severe acute respiratory distress syndrome (29.7% vs 44.8%, P = .03). By multivariable analysis, age (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.36-2.44, per 10-year increase), partial pressure of oxygen/fraction of inspired oxygen ratio (OR = 0.60, 95% CI = .52-0.68, per 10 units increase), and use of high-flow nasal cannula (OR = 0.34; 95% CI, .16-0.74) were associated with the composite outcome, whereas baricitinib use was marginally not associated with the composite outcome (OR = 0.52; 95% CI, .26-1.03). However, baricitinib use was found to be significant after inverse-probability weighted regression (OR = 0.93; 95% CI, .87-0.99). No difference in serious events was noted between treatment groups. Conclusions. In real-life settings, addition of baricitinib to SOC in patients hospitalized with sCOVID-19 is associated with decreased mortality without concerning safety signals