Staphylococcus aureus bacteremia in alcoholics.

BACKGROUND: Alcoholism associates with increased Staphylococcus aureus bacteremia incidence and mortality. The objective was to compare disease progression, treatment and prognosis of Staphylococcus aureus bacteremia in alcoholics versus non-alcoholics. METHODS: The study design was a multicenter retrospective analysis of methicillin-sensitive Staphylococcus aureus bacteremia with 90-day follow-up. Patients were stratified as alcoholics or non-alcoholics based on electronic health record data. Altogether 617 Staphylococcus aureus bacteremia patients were included of which 83 (13%) were alcoholics. RESULTS: Alcoholics, versus non-alcoholics, were younger, typically male and more commonly had community-acquired Staphylococcus aureus bacteremia. No differences in McCabe´s classification of underlying conditions was observed. Higher illness severity at blood culture sampling, including severe sepsis (25% vs. 7%) and intensive care unit admission (39% vs. 17%), was seen in alcoholics versus non-alcoholics. Clinical management, including infectious disease specialist (IDS) consultations and radiology, were provided equally. Alcoholics, versus non-alcoholics, had more pneumonia (49% vs. 35%) and fewer cases of endocarditis (7% vs. 16%). Mortality in alcoholics versus non-alcoholics was significantly higher at 14, 28 and 90 days (14% vs. 7%, 24% vs. 11% and 31% vs. 17%), respectively. Considering all prognostic parameters, male sex (OR 0.19, p = 0.021) and formal IDS consultation (OR 0.19, p = 0.029) were independent predictors of reduced mortality, whereas ultimately or rapidly fatal comorbidity in McCabe´s classification (OR 12.34, p < 0.001) was an independent predictor of mortality in alcoholics. CONCLUSIONS: Alcoholism deteriorates Staphylococcus aureus bacteremia prognosis, and our results suggests that this is predominantly through illness severity at bacteremia onset. Three quarters of Staphylococcus aureus bacteremia patients we studied had identified deep infection foci, and of them alcoholics had significantly less endocarditis but nearly half of them had pneumonia.

Incidence and outcome of hospital-acquired COVID-19 infections in secondary and tertiary care hospitals in the era of COVID-19 vaccinations.

Objective: Hospital-acquired (HA) COVID-19 infections are known to increase morbidity and mortality. The aim of this study was to investigate the incidence and outcome of HA COVID-19 in different specialties across the wards in 18 hospitals belonging to the Helsinki University Hospital (HUH) responsible for secondary and tertiary care of a population of 1.8 million. Design: Retrospective population-based cohort study. Setting: Secondary and tertiary care hospitals. Patients: Inpatients with HA COVID-19 infection. Methods: The HA COVID-19 infections with patient characteristics were retrospectively searched from HUH patient database from 1st October 2021 to 31st March 2022. All positive SARS-CoV-2 nucleic acid amplification tests (NAATs) from any ward were reviewed. The COVID-19 infection was classified as HA if a notification of HA infection was done or SARS-CoV-2 NAAT was positive ≥6 days after hospital admission or medical records revealed a known exposure for COVID-19 during hospital stay. Results: 177 HA COVID-19 infections were retrieved with an incidence of 0.55 per 1000 patient days. Of these patients, 71 (40%) were treated in medicine, 52 (29%) in operative, and 54 (31%) in psychiatric wards, leading to incidences of 0.51, 0.39, and 1.10 per 1,000 patient days, respectively. In association with COVID-19, 16 (23%) in medicine, 3 (6%) in operative, and 1 (2%) patient in psychiatric wards deceased. Of the deceased patients, 16 (80%) had received at least one COVID-19 vaccine. Conclusions: Hospital-acquired COVID-19 infections in omicron era were related to high mortality, especially among patients in medicine wards who also had good vaccination coverage.

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.

Association between first language and SARS-CoV-2 infection rates, hospitalization, intensive care admissions and death in Finland: a population-based observational cohort study.

OBJECTIVES: Motivated by reports of increased risk of coronavirus disease 2019 (COVID-19) in ethnic minorities of high-income countries, we explored whether patients with a foreign first language are at an increased risk of COVID-19 infections, more serious presentations, or worse outcomes. METHODS: In a retrospective observational population-based quality registry study covering a population of 1.7 million, we studied the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), admissions to specialist healthcare and the intensive care unit (ICU), and all-cause case fatality in different language groups between 27th February and 3rd August 2020 in Southern Finland. A first language other than Finnish, Swedish or Sámi served as a surrogate marker for a foreign ethnic background. RESULTS: In total, 124 240 individuals were tested, and among the 118 300 (95%) whose first language could be determined, 4005 (3.4%) were COVID-19-positive, 623 (0.5%) were admitted to specialized hospitals, and 147 (0.1%) were admitted to the ICU; 254 (0.2%) died. Those with a foreign first language had lower testing rates (348, 95%CI 340-355 versus 758, 95%CI 753-762 per 10 000, p < 0.0001), higher incidence (36, 95%CI 33-38 versus 22, 95%CI 21-23 per 10 000, p < 0.0001), and higher positivity rates (103, 95%CI 96-109 versus 29, 95%CI 28-30 per 1000, p < 0.0001). There was no significant difference in ICU admissions, disease severity at ICU admission, or ICU outcomes. Case fatality by 90 days was 7.7% in domestic cases and 1.2% in those with a foreign first language, explained by demographics (age- and sex-adjusted HR 0.49, 95%CI 0.21-1.15). CONCLUSIONS: The population with a foreign first language was at an increased risk for testing positive for SARS-CoV-2, but when hospitalized they had outcomes similar to those in the native, domestic language population. This suggests that special attention should be paid to the prevention and control of infectious diseases among language minorities.

Infectious diseases specialist consultation in Staphylococcus lugdunensis bacteremia.

BACKGROUND: Commensal coagulase negative Staphylococcus lugdunensis may cause severe bacteremia (SLB) and complications. Treatment of SLB is not fully established and we wanted to evaluate if infectious diseases specialist consultation (IDSC) would improve management and prognosis. METHODS: Multicenter retrospective study of SLB patients followed for 1 year. Patients were stratified according to bedside (formal), telephone (informal) or lack of IDSC within 7 days of SLB diagnosis. RESULTS: Altogether, 104 SLB patients were identified: 24% received formal bedside and 52% informal telephone IDSC whereas 24% were managed without any IDSC. No differences in demographics, underlying conditions or severity of illness were observed between the groups. Patients with bedside IDSC, compared to telephone IDSC or lack of IDSC, had transthoracic echocardiography more often performed (odds ratio [OR] 4.00; 95% confidence interval [CI] 1.31-12.2; p = 0.012) and (OR 16.0; 95% CI, 4.00-63.9; P<0.001). Bedside IDSC was associated with more deep infections diagnosed compared to telephone IDSC (OR, 7.44; 95% CI, 2.58-21.4; p<0.001) or lack of IDSC (OR, 9.56; 95% CI, 2.43-37.7; p = 0.001). The overall mortality was 7%, 10% and 17% at 28 days, 90 days and 1 year, respectively. Considering all prognostic parameters, patients with IDSC, compared to lack of IDSC, had lower 90 days and 1 year mortality (OR, 0.11; 95% CI, 0.02-0.51; p = 0.005) and (OR, 0.22; 95% CI, 0.07-0.67; p = 0.007). CONCLUSION: IDSC may improve management and outcome of Staphylococcus lugdunensis bacteremia.

Male predominance in disease severity and mortality in a low Covid-19 epidemic and low case-fatality area - a population-based registry study.

BACKGROUND: Men reportedly suffer from a more severe disease and higher mortality during the global SARS-CoV-2 (Covid-19) pandemic. We analysed sex differences in a low epidemic area with low overall mortality in Covid-19 in a population based setting with patients treated in specialized healthcare. METHODS: We entered all hospitalized laboratory-confirmed Covid-19 cases of all specialized healthcare hospitals of the Capital Province of Finland, into a population-based quality registry and described demographics, severity and case-fatality by sex of the first Covid-19 wave February-June 2020. RESULTS: Altogether 5471 patients (49% male) were identified. Patients hospitalized in the specialist healthcare (N = 585, 54% male, OR 1.25; 95% CI 1.05-1.48) were of the same age. Men had less asthma and thyroid insufficiency and more coronary artery disease compared to women. Mean time from symptom onset to diagnosis was at least one day longer for men (p=.005). Men required intensive care unit (ICU) more often (27% vs. 17%) with longer lengths-of-stays at ICU. Male sex associated with significantly higher case-fatality at 90-days (15% vs. 8%) and all excess male deaths occurring after three weeks from onset. Men with fatal outcomes had delays in both Covid-19 testing and hospital admission after a positive test. The delays in patients with the most severe and fatal outcomes differed markedly by sex. In multivariable analysis, male sex associated independently with case-fatality (OR 2.37; 95% CI 1.22-4.59). CONCLUSIONS: Male sex associated with higher disease severity and case-fatality. Late presentation of male fatal cases could represent different treatment-seeking behaviour or disease progression by sex.

Matrix metalloproteinase MMP-8, TIMP-1 and MMP-8/TIMP-1 ratio in plasma in methicillin-sensitive Staphylococcus aureus bacteremia.

BACKGROUND: Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been shown to predict prognosis in sepsis. However, MMP-8 and TIMP-1 in Staphylococcus aureus bacteremia (SAB) lacks evaluation and their role in the pathogenesis of SAB is unclear. METHODS: MMP-8 and TIMP-1 and MMP-8/TIMP-1 molar ratio were determined at days 3, 5 and 28 from positive blood cultures in patients with methicillin-sensitive SAB and the connection to disease severity and early mortality was determined. RESULTS: Altogether 395 SAB patients were included. Patients with severe sepsis or infection focus presented higher MMP-8 levels at day 3 and 5 (p<0.01). Higher day 3 and 5 MMP-8 levels were associated to mortality at day 14 and 28 (p<0.01) and day 90 (p<0.05). Day 3 MMP-8 cut-off value of 203 ng/ml predicted death within 14 days with an area under the curve (AUC) of 0.70 (95% CI 0.57-0.82) (p<0.01). Day 5 MMP-8 cut-off value of 239 ng/ml predicted death within 14 days with an AUC of 0.76 (95% CI 0.65-0.87) (p<0.001). The results for MMP-8/TIMP-1 resembled that of MMP-8. TIMP-1 had no prognostic impact. In Cox regression analysis day 3 or 5 MMP-8 or day 3 MMP-8/TIMP-1 had no prognostic impact whereas day 5 MMP-8/TIMP-1 predicted mortality within 14 days (HR, 4.71; CI, 95% 1.67-13.3; p<0.01). CONCLUSION: MMP-8 and MMP-8/TIMP-1 ratio were high 3-5 days after MS-SAB diagnosis in patients with an infection focus, severe sepsis or mortality within 14 days suggesting that matrix metalloproteinase activation might play a role in severe SAB.

Changes in hemostasis parameters in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia complicated by endocarditis or thromboembolic events: a prospective gender-age adjusted cohort study.

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB) - a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender-age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p < 0.05), elevated antithrombin III at day 90 (p < 0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p < 0.05), and enhanced thrombin-antithrombin complex at day 4 (p < 0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin-antithrombin complex at day 4 (p < 0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p < 0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D-dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS-SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.

Formal Infectious Diseases Specialist Consultation Improves Long-term Outcome of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

BACKGROUND: Formal infectious diseases specialist (IDS) consultation has been shown to improve short-term outcomes in Staphylococcus aureus bacteremia (SAB), but its effect on long-term outcomes lacks evaluation. METHODS: This retrospective study followed 367 methicillin-sensitive (MS) SAB patients for 10 years. The impact of formal IDS consultation on risk for new bacteremia and outcome during long-term follow-up was evaluated. Patients who died within 90 days were excluded to avoid interference from early deceased patients. RESULTS: Three hundred four (83%) patients had formal IDS consultation, whereas 63 (17%) received informal or no IDS consultation. Formal consultation, compared with informal or lack of consultation, was associated with a reduced risk of new bacteremia caused by any pathogen within 1 year (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.18-0.84; P = .014; 8% vs 17%) and within 3 years (OR, 0.39; 95% CI, 0.19-0.80; P = .010; 9% vs 21%), whereas a trend toward lower risk was observed within 10 years (OR, 0.56; 95% CI, 0.29-1.08; P = .079; 16% vs 25%). Formal consultation, compared with informal or lack of consultation, improved outcomes at 1 year (OR, 0.16; 95% CI, 0.06-0.44; P < .001; 3% vs 14%), at 3 years (OR, 0.19; 95% CI, 0.09-0.42; P < .001; 5% vs 22%), and at 10 years (OR, 0.43; 95% CI, 0.24-0.74; P = .002; 27% vs 46%). Considering all prognostic parameters, formal consultation improved outcomes (HR, 0.42; 95% CI, 0.27-0.65; P < .001) and lowered risk for any new bacteremia (OR, 0.45; 95% CI, 0.23-0.88; P = .02) during 10 years of follow-up. CONCLUSIONS: MS-SAB management by formal IDS consultation, compared with informal or lack of IDS consultation, reduces risk for new bacteremia episodes and improves long-term prognosis up to 10 years.

Microbiological Etiology and Treatment of Complicated Skin and Skin Structure Infections in Diabetic and Nondiabetic Patients in a Population-Based Study.

BACKGROUND: Diabetes is a major risk factor for skin and skin structure infection (SSSI), and the global burden of diabetics with SSSI is enormous. The more complex microbiology of diabetic foot infection (DFI) is well established, but it is not known whether microbiological etiology differs between diabetics and nondiabetics in other disease entities under the umbrella of complicated SSSI (cSSSI). METHODS: This retrospective, population-based study included patients with cSSSI, and it was conducted in 2 Nordic cities with a low prevalence of antimicrobial resistance. In analyses, patients (N = 460) were separated into 3 groups: diabetics (n = 119), nondiabetics (n = 271), and patients with DFI (n = 70). RESULTS: After exclusion of patients with DFI, there was no difference in the microbiological etiology or initial antimicrobial treatment of cSSSI between diabetics and nondiabetics. Gram-positive bacteria encountered 70% of isolations in diabetics and 69% in nondiabetics, and the empirical treatment covered initial pathogens in 81% and 86% of patients, respectively. However, diabetes was the only background characteristic in the propensity score-adjusted analysis associated with broad-spectrum antimicrobial use and longer antibiotic treatment duration. Patients with DFI had Gram-negative and polymicrobial infection more often than nondiabetics. CONCLUSIONS: These observations suggest that diabetics without DFI are not different in the causative agents of cSSSI, although they are more exposed to antimicrobial therapy of inappropriate extended spectrum and long duration. Broad-spectrum coverage was clearly needed only in DFI. A clear opportunity for antimicrobial stewardship was detected in the rapidly growing population of diabetic patients with cSSSI.

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 non-significant in patient cohorts with SAB management optimized by infectious disease specialist consultation.

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<0.01) during 90 days follow-up. 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.

High cell-free DNA predicts fatal outcome among Staphylococcus aureus bacteraemia patients with intensive care unit treatment.

INTRODUCTION: Among patients with bacteraemia or sepsis the plasma cell-free DNA (cf-DNA) biomarker has prognostic value and Pitt bacteraemia scores predict outcome. We evaluated the prognostic value of plasma cf-DNA in patients with Staphylococcus aureus bacteraemia (SAB) treated in the ICU or in the general ward. METHODS: 418 adult patients with positive blood culture for S. aureus were prospectively followed for 90 days. SAB patients were grouped according to ICU treatment: 99 patients were treated in ICU within 7 days of documented SAB whereas 319 patients were managed outside ICU. Pitt bacteraemia scores were assessed at hospital arrival and cf-DNA was measured at days 3 and 5 from positive blood culture. RESULTS: SAB patients with high Pitt bacteraemia scores and ICU treatment presented higher cf-DNA values as compared to SAB patients with low Pitt bacteraemia scores and non-ICU treatment at both days 3 and 5. Among ICU patients cf-DNA >1.99 µg/ml at day 3 predicted death with a sensitivity of 67% and a specificity of 77% and had an AUC in receiver operating characteristic analysis of 0.71 (p<0.01). The cut-off cf-DNA >1.99 µg/ml value demonstrated a strong association to high Pitt bacteraemia scores (≥ 4 points) (p<0.000). After controlling for all prognostic markers, Pitt bacteraemia scores ≥ 4 points at hospital admission (OR 4.47, p<0.000) and day 3 cf-DNA (OR 3.56, p<0.001) were the strongest factors significantly predicting outcome in ICU patients. cf-DNA at day 5 did not predict fatal outcome. CONCLUSION: High cf-DNA concentrations were observed among patients with high Pitt bacteraemia scores and ICU treatment. Pitt bacteraemia scores (≥ 4 points) and cf-DNA at day 3 from positive blood culture predicted death among SAB patients in ICU and were found to be independent prognostic markers. cf-DNA had no prognostic value among non-ICU patients.