Improved Outcome with Early Rifampicin Combination Treatment in Methicillin-Sensitive Staphylococcus aureus Bacteraemia with a Deep Infection Focus - A Retrospective Cohort Study

Introduction Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection. Methods Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality. Results Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin >= 14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy >= 14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy >= 14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p Conclusion Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.Peer reviewe

Inflammation parameters predict fatal outcome in male COVID-19 patients in a low case-fatality area - a population-based registry study

Background Male sex predicts case-fatality in SARS-CoV-2 (COVID-19) - a phenomenon linked to systemic inflammation. We compared sex-related associations of inflammation parameters and outcome in a population-based setting with low case-fatality prior to wide use of immunosuppressives. Methods A population-based quality registry with laboratory-confirmed COVID-19 cases of specialized hospitals of the Capital Province of Finland were analysed to compare inflammatory parameters by sex during the first COVID-19 wave February-June 2020. Results Altogether, 585 hospitalized patients (54% males) were included. Males required more often intensive care unit (ICU) treatment (26.9 vs. 17.5%) and had higher 90-d case-fatality (14.9 vs. 7.8%) compared with females. Highest association with case-fatality in males was seen for high neutrophil counts (median; interquartile range) (8.70; 7.10-9.10 vs. 5.60; 3.90-7.80) (E9/l), low monocyte (0.50; 0.20-1.50 vs. 0.70; 0.50-0.90) (E9/l) and lymphocyte (0.90; 0.70-1.40 vs. 1.50; 1.10-2.00) (E9/l) counts, and high levels of d-dimer (3.80; 1.80-5.30 vs. 1.10; 0.60-2.75) (mg/l) and C-reactive protein (CRP) (190; 85.5-290 vs. 77.0; 49.0-94.0) (mg/l). In females, low lymphocyte (0.95; interquartile range 0.60-1.28 vs. 1.50; 1.10-2.00) (E9/l) and thrombocyte counts (196; 132-285 vs. 325; 244-464) (E9/l) and high CRP values (95.0; 62.0-256 vs. 66.0; 42.5-89.0) (mg/l) were associated with case-fatality. In multivariable analysis for males, lymphocyte cut-off 0.85 (E9/l) (OR 0.02; 95% CI 0.002-0.260), d-dimer cut-off 1.15 (mg/l) (OR 7.29; 1.01-52.6) and CRP cut-off 110 (mg/l) (OR 15.4; 1.87-127) were independently associated with case-fatality. In female multivariable analysis, CRP cut-off 81 (mg/l) (OR 7.32; 1.44-37.2) was the only inflammatory parameter associated with case-fatality. Conclusions COVID-19 results in higher inflammation parameter levels in male vs. female patients irrespective of outcome. This study suggests that low lymphocyte, high d-dimer and high CRP cut-off values may serve as potential markers for risk stratification in male patients.Peer reviewe

Comparable Effectiveness of First Week Treatment with Anti-Staphylococcal Penicillin versus Cephalosporin in Methicillin-Sensitive Staphylococcus aureus Bacteremia : A Propensity-Score Adjusted Retrospective Study

The objective was to compare the prognostic impact of first week treatment with anti-staphylococcal penicillin (ASP) versus cephalosporin in methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB). Altogether 580 patients were retrospectively followed and categorized according to first week treatment; 84% (488) received ASP (cloxacillin) and 16% (92) cephalosporin (cefuroxime or ceftriaxone). SAB management was optimized with formal bedside infectious disease specialist consultation in 88%, deep infection foci diagnosed in 77% and adjunctive rifampicin therapy given to 61% of patients. The total case fatality in 580 patients was 12% at 28 days and 18% at 90 days. When comparing effectiveness of first week ASP versus cephalosporin treatment there were no significant differences in 28-days (11% vs. 12%, OR; 1.05, 95% CI, 0.53-2.09) or 90-days (17% vs. 21% OR; 1.25, 95% CI, 0.72-2.19) outcome. In univariate analysis no prognostic impact of either first week ASP or cephalosporin treatment was observed for 28-days (OR; 0.96, 95% CI, 0.48-1.90 and OR; 1.05, 95% CI, 0.53-2.09) or 90-days (OR; 0.80, 95% CI, 0.46-1.39 and OR; 1.25, 95% CI, 0.72-2.19) outcome. Propensity-score adjusted Cox proportional regression analysis for first week treatment with cephalosporin demonstrated no significant prognostic impact at 28-days (HR 1.54, 95% CI 0.72-3.23) or 90-days (HR 1.56, 95% CI 0.88-2.86). In conclusion: There is a comparable effectiveness with respect to 28- and 90-days outcome for first week treatment with ASP versus cephalosporin in MS-SAB. The results indicate that the difference in prognostic impact between first week ASP and cephalosporin may be nonsignificant in patient cohorts with SAB management optimized by infectious disease specialist consultation.Peer reviewe

Women report more symptoms and impaired quality of life : a survey of Finnish COVID-19 survivors

Background The long-term sequelae after COVID-19 are not yet fully known. Our aim was to evaluate subjective symptoms and quality of life in Finnish hospitalized COVID-19 patients at six months follow-up. Methods Hospitalised adult patients with laboratory-confirmed SARS-CoV-2 infection from March to June 2020 were recruited. We conducted a survey on demographics and comorbidities, ten specific symptoms, and a RAND-36 quality of life questionnaire six months after hospital discharge. We collected clinical data manually from medical records. Results 101 patients (54 male) out of 246 invited completed the survey. Their median age was 60 years, and the mean hospital length of stay was 15 d. Most patients (90%) experienced symptoms, the most common of which were tiredness (88%), fatigue (79%), sleeping problems (76%), and dyspnoea (70%). In regard to gender, women showed a shorter time of hospitalization (p = .048) and lower peak flow of supplementary oxygen (p = .043). Women reported more frequently dyspnoea, fatigue, tiredness, sleeping problems, and mood problems (p = .008-.033), and a lower quality of life in seven of eight dimensions (p < .001-.015). Five explanatory variables for the reduced quality of life were identified in multivariate analysis: age, female sex, BMI, sleep apnoea, and duration of mechanical ventilation. Of the patients who worked full-time before COVID-19, 11% had not returned to work. Conclusions Most patients experienced symptoms six months after hospital discharge. Women reported more symptoms and a lower quality of life than men. These findings highlight the differences in recovery between men and women and call for active rehabilitation of COVID-19 patients.Peer reviewe

High Cell-Free DNA Predicts Fatal Outcome among Staphylococcus aureus Bacteraemia Patients with Intensive Care Unit Treatment

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Unexpectedly High Prevalence of Common Variable Immunodeficiency in Finland

Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. Prevalence varies greatly between countries and studies. Most diagnostic criteria include hypogammaglobulinemia and impaired vaccine response. Aim: To evaluate the minimum prevalence as well as the clinical and immunological phenotypes of CVID in Southern Finland. Methods: We performed a cross-sectional study to assess all adult CVID patients followed up in three hospital districts in Southern and South-Eastern Finland between April 2007 and August 2015. CVID diagnosis was based, with a minor modification, on the ESID/PAGID criteria for primary CVID. Antipolysaccharide responses to Pneumovax (R) were defined as impaired only if 50% or more of the serotypes did not reach a level of 0.35 mu g/mL after vaccination. We further characterized the patients' B cell phenotypes and complications associated with CVID. Results: In total, 9 patients were excluded due to potential secondary causes before diagnosis. ESID/PAGID criteria were met by 132 patients (males 52%), of whom, 106 had "probable" and 26 "possible CVID." Based on the population statistics in the three hospital districts, the minimum adult prevalence per 100,000 inhabitants in Finland for all CVID ("probable CVID," respectively) patients was 6.9 (5.5). In the highest prevalence district (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from frequent complications. Ten patients died during follow-up. Of probable CVID patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell loss from peripheral blood during follow-up was seen in as many as 16% of "Xprobable CVID" patients. Patients with possible CVID displayed somewhat milder clinical and laboratory phenotypes than probable CVID patients. We also confirm that large granular lymphocyte lymphoproliferation is a CVID-associated complication. Conclusion: The prevalence of CVID in Finland appears the highest recorded, likely reflecting the genetic isolation and potential founder effects in the Finnish population. Studies to discover potential gene variants responsible for the high prevalence in Finland thus seem warranted. Increased awareness of CVID among physicians would likely lead to earlier diagnosis and improved quality of care.Peer reviewe

Complement C4 Deficiency - A Plausible Risk Factor for Non-Tuberculous Mycobacteria (NTM) Infection in Apparently Immunocompetent Patients

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