Low incidence of severe bacterial infections in hospitalised patients with COVID-19: A population-based registry study.

BACKGROUND: Bacterial infections complicating COVID-19 are rare but present a challenging clinical entity. The aim of this study was to evaluate the incidence, aetiology and outcome of severe laboratory-verified bacterial infections in hospitalised patients with COVID-19. METHODS: All laboratory-confirmed patients with COVID-19 admitted to specialised healthcare hospitals in the Capital Province of Finland during the first wave of COVID-19 between 27 February and 21 June 2020 were retrospectively studied. We gathered the blood and respiratory tract culture reports of these patients and analysed their association with 90-day case-fatality using multivariable regression analysis. RESULTS: A severe bacterial infection was diagnosed in 40/585 (6.8%) patients with COVID-19. The range of bacteria was diverse, and the most common bacterial findings in respiratory samples were gram-negative, and in blood cultures gram-positive bacteria. Patients with severe bacterial infection had longer hospital stay (mean 31; SD 20 days) compared to patients without (mean 9; SD 9 days; p < 0.001). Case-fatality was higher with bacterial infection (15% vs 11%), but the difference was not statistically significant (OR 1.38 CI95% 0.56-3.41). CONCLUSIONS: Severe bacterial infection complicating COVID-19 was a rare occurrence in our cohort. Our results are in line with the current understanding that antibiotic treatment for hospitalised COVID-19 patients should only be reserved for situations where a bacterial infection is strongly suspected. The ever-evolving landscape of the pandemic and recent advances in immunomodulatory treatment of COVID-19 patients underline the need for continuous vigilance concerning the possibility and frequency of nosocomial bacterial infections.

Comparison of patient characteristics, clinical management, infectious specialist consultation, and outcome in men and women with methicillin-sensitive Staphylococcus aureus bacteremia: a propensity-score adjusted retrospective study.

BACKGROUND: Sex-related treatment inequalities are suggested to explain outcome differences between men and women in Staphylococcus aureus bacteremia (SAB). We compared patient characteristics, clinical management, infectious specialist consultation (ISC) and outcome in men and women with SAB. METHODS: Multicenter retrospective study of methicillin-sensitive (MS-) SAB patients categorized according to sex and ISC consultation provided within 7 days of diagnosis. RESULTS: Altogether 617 SAB patients were included in the analysis: 62% males and 38% females. Male sex was associated less often to nosocomial bacteremia (OR 0.69, 95% CI 0.50-0.96, p = 0.029) and more often to alcoholism (OR 2.25, 95% CI 1.31-3.87, p = 0.003). No sex-related differences were seen in basic or immunologic laboratory tests, illness severity, intensive care unit treatment or thromboembolic events. ISC was provided to most patients (94%) irrespective of sex. No differences were seen in clinical management of men or women: Transthoracic or -esophageal echocardiography (61% vs. 65%), deep infection (77% vs. 72%), infection removal (30% vs. 27%) and anti-staphylococcal antibiotics as first-line treatment (54% vs. 51%). However, male sex was connected to more frequent adjunctive rifampicin treatment (52% vs. 41%, p = 0.025). No difference in 28- or 90-day mortality (13% vs. 13% and 18% vs. 20%) or SAB relapse (0% vs. 1%) was observed between men and women. Propensity-score adjusted Cox proportional analysis gave no connection of sex to mortality within 90 days. CONCLUSION: Patient characteristics, clinical management, ISC guidance, bacteremia relapse, and outcome did not differ in men and women with MS-SAB.

Methicillin-sensitive Staphylococcus aureus bacteremia in aged patients: the importance of formal infectious specialist consultation.

BACKGROUND: Infectious specialist consultations (ISC) provide ever more evidence for improved outcome in Staphylococcus aureus bacteremia (SAB). Most ISC are formal (bedside). However, the impact of ISC on clinical management and prognosis lacks evaluation in aged patients with SAB. METHODS: Multicenter retrospective analysis of methicillin-sensitive (MS) SAB. Patients were stratified according to age ≥ 60 years (sub-analyses for ≥ 75 years and females) and formal (bedside) ISC given within 7 days of SAB diagnosis. The impact on management and outcome of formal ISC was explored. Statistics were performed with univariate analysis, Cox proportional hazards regression model analysis, including propensity-score adjustment, and graphic Kaplan-Meier interpretation. RESULTS: Altogether 617 patients were identified and 520 (84%) had formal ISC. Presence of formal ISC resulted in equivalent clinical management regardless of age over or under 60 years: localization and eradication of infection foci (80 vs. 82% and 34 vs. 36%) and use of anti-staphylococcal antibiotics (65 vs. 61%). Patients aged ≥ 60 years managed without formal ISC, compared to those with formal ISC, had less infection foci diagnosed (53 vs. 80%, p < 0.001). Lack of formal ISC in patients aged ≥ 60 years resulted in no infection eradication and absence of first-line anti-staphylococcal antibiotics. Formal ISC, compared to absence of formal ISC, lowered mortality at 90 days in patients aged ≥ 60 years (24 vs. 47%, p = 0.004). In Cox proportional regression, before and after propensity-score adjustment, formal ISC was a strong positive prognostic parameter in patients aged ≥ 60 years (HR 0.45; p = 0.004 and HR 0.44; p = 0.021), in patients aged ≥ 75 years (HR 0.18; p = 0.001 and HR 0.11; p = 0.003) and in female patients aged ≥ 75 years (HR 0.13; p = 0.005). CONCLUSION: Formal ISC ensures proper active clinical management irrespective of age and improve prognosis in aged patients with MS-SAB.

Correction to: Methicillin-sensitive Staphylococcus aureus bacteremia in aged patients: the importance of formal infectious specialist consultation.

[This corrects the article DOI: 10.1007/s41999-018-0038-2.].

Prognostic impact of hyperglycemia at onset of methicillin-sensitive Staphylococcus aureus bacteraemia.

Previous reports have associated hyperglycemia to poor outcome among aged and comorbid Staphylococcus aureus bacteraemia (SAB) patients. However, the prognostic impact of hyperglycemia in SAB irrespective of age and underlying conditions including a diagnosis of diabetes has received little attention. The objective here was to evaluate the prognostic relevance of hyperglycemia at onset of methicillin-sensitive SAB (MS-SAB). It was a retrospective study of MS-SAB patients. Blood glucose was measured within 24 h of positive blood cultures. The patient cohort was analyzed en bloc and by categorization according to age, underlying conditions and a diagnosis of diabetes. Altogether 161 patients were identified. High initial blood glucose levels were observed among diabetics (p < 0.001), patients with deep infections (p < 0.05) and poor outcome at 28- or 90-days (p < 0.05). Receiver operating characteristics presented the glucose cut-off level of 7.2 mmol/L as a significant predictor of mortality with an area under the curve of 0.63 (95% CI 0.52-0.75, p < 0.05). Blood glucose ≥7.2 mmol/L connected to higher 28- (9 vs. 20%, p < 0.05) and 90-day (14 vs. 29%, p < 0.01) mortality. In Cox proportional hazard regression the blood glucose cut-off value of 7.2 mmol/L significantly predicted 90-day mortality (HR, 2.12; 95% CI, 1.01-4.46; p < 0.05). Among young and healthy non-diabetics the negative prognostic impact of high glucose was further accentuated (HR 7.46, p < 0.05). High glucose levels had no prognostic impact among diabetics. Hyperglycemia at SAB onset may associate to poor outcome. The negative prognostic impact is accentuated among young and healthy non-diabetics.

Factors associated with time to clinical stability in complicated skin and skin structure infections.

OBJECTIVES: Factors associated with the time to clinical stability in patients with complicated skin and skin structure infection (cSSSI) were analysed in a retrospective population-based study. METHODS: All hospitalized patients (n=402) with cSSSI in two Nordic cities during a 4-year period were included. Patient, disease, and treatment related factors were analysed in relation to early (0-3 days) or late (≥4 days) clinical stability. Clinical stability was assessed as improvement of infection related local and systemic signs. Furthermore, the effect of antimicrobial and other treatment on achievement of clinical stability was studied. RESULTS: Clinical stability was reached within 0-3 days by 59% (239/402) of patients. In multivariable analysis later clinical stability was associated with admission to ICU (OR 10.1, 95% CI 4.01-25.3), posttraumatic wound infection (OR 3.17, 95% CI 1.31-7.69), bacteraemia (OR 3.09, 95% CI 1.36-7.02), surgical intervention after diagnosis (OR 2.64, 95% CI 1.36-5.11), diabetes (OR 2.33, 95% CI 1.28-4.25), and initial broad-spectrum antibiotic therapy (OR 3.03, 95% CI 1.43-6.40). Early stabilization within 3 days was associated with previous hospitalization (OR 0.47, 95% CI 0.22-0.99) and empirical antimicrobial therapy covering the initial pathogens (OR 0.38, 95% CI 0.18-0.80). Patients with clinical stability within 3 days were less likely to have treatment modifications and antimicrobial changes and had shorter hospital stay and antimicrobial treatment than those who stabilized later. CONCLUSIONS: This study suggests that late treatment response depends on several baseline characteristics of patients and disease related factors other than treatment related factors.

Thrombocytopaenia during methicillin-sensitive Staphylococcus aureus bacteraemia.

The prognostic impact of thrombocytopaenia in Staphylococcus aureus bacteraemia (SAB) has previously been determined at bacteraemia onset only and relevant pre-bacteraemic thrombocytopaenia predisposing parameters have not been accounted for. We evaluated the prognostic impact of low thrombocyte count in SAB excluding pre-bacteraemic factors potentially causing thrombocytopaenia. This was a multicentre retrospective analysis of methicillin-sensitive SAB (MS-SAB) patients. Thrombocyte count was determined at blood culture collection and at days 3 and 7. Thrombocytopaenia was defined as a thrombocyte count less than 150 ×109/L. Patients with chronic alcoholism, liver diseases and haematologic malignancies were excluded. Altogether, 495 patients were identified. Thrombocytopaenia at blood culture and at day 3 associated to endocarditis (p < 0.05 and p < 0.01) and defervescence (p < 0.001 and p < 0.01). Mortality at 90 days was higher for patients with thrombocytopaenia at blood culture collection (26 vs. 16%, p < 0.05), at day 3 (32 vs. 13%, p < 0.01) and at day 7 (50 vs. 14%, p < 0.001). In receiver operating characteristic analyses, thrombocytopaenia predicted a poor outcome at blood culture collection (p < 0.05), at day 3 (p < 0.001) and at day 7 (p < 0.001). When accounting for all prognostic parameters, thrombocytopaenia at day 3 [hazard ratio (HR), 1.83; p = 0.05] demonstrated a trend towards poor outcome, whereas thrombocytopaenia at day 7 (HR, 3.64; p < 0.001) associated to poor outcome. Thrombocytopaenia at blood culture collection was not a prognostic parameter when all prognostic factors were taken into account. However, thrombocytopaenia at day 3 indicated a poor outcome and thrombocytopaenia at day 7 was a significant independent negative prognostic marker that has not been previously reported in SAB.

Should all adjunctive corticosteroid therapy be avoided in the management of hemodynamically stabile Staphylococcus aureus bacteremia?

The purpose of this study was to examine the prognostic impact of corticosteroids in hemodynamically stabile Staphylococcus aureus bacteremia (SAB). There were 361 hemodynamically stabile methicillin-sensitive SAB patients with prospective follow-up and grouping according to time-point, dose and indication for corticosteroid therapy. To enable analyses without external interfering corticosteroid therapy all patients with corticosteroid therapy equivalent to prednisone >10 mg/day for ≥1 month prior to positive blood culture results were excluded. Twenty-five percent (92) of patients received corticosteroid therapy of which 11 % (40) had therapy initiated within 1 week (early initiation) and 9 % (31) had therapy initiated 2-4 weeks after (delayed initiation) positive blood culture. Twenty-one patients (6 %) had corticosteroid initiated after 4 weeks and were not included in the analyses. A total of 55 % (51/92) received a weekly prednisone dose >100 mg. Patients with early initiated corticosteroid therapy had higher mortality compared to patients treated without corticosteroid therapy at 28 days (20 % vs. 7 %) (OR, 3.11; 95%CI, 1.27-7.65; p < 0.05) and at 90 days (30 % vs. 10 %) (OR, 4.01; 95%CI, 1.82-8.81; p < 0.001). Considering all prognostic markers, early initiated corticosteroid therapy predicted 28-day (HR, 3.75; 95%CI, 1.60-8.79; p = 0.002) and 90-day (HR, 3.10; 95%CI, 1.50-6.39; p = 0.002) mortality in Cox proportional hazards regression analysis. When including only patients receiving early initiated corticosteroid therapy with prednisone ≥100 mg/week the negative prognostic impact on 28-day mortality was accentuated (HR 4.8, p = 0.001). Corticosteroid therapy initiation after 1 week of positive blood cultures had no independent prognostic impact. Early initiation of corticosteroid therapy may be associate to increased mortality in hemodynamically stabile SAB.

Telephone consultation cannot replace bedside infectious disease consultation in the management of Staphylococcus aureus Bacteremia.

BACKGROUND: Infectious disease specialist (IDS) consultation improves the outcome of Staphylococcus aureus bacteremia (SAB). Although telephone consultations constitute a substantial part of IDS consultations, their impact on treatment outcome lacks evaluation. METHODS: We retrospectively followed 342 SAB episodes with 90-day follow-up, excluding 5 methicillin-resistant S. aureus SAB cases. Patients were grouped according to bedside, telephone, or no IDS consultation within the first week. Patients with fatal outcome within 3 days after onset of SAB were excluded to allow for the possibility of death occurring before IDS consultation. RESULTS: Seventy-two percent of patients received bedside, 18% telephone, and 10% no IDS consultation. Patients with bedside consultation were less often treated in an intensive care unit during the first 3 days compared to those with telephone consultation (odds ratio [OR], 0.53; 95% confidence interval [CI], .29-.97; P = .037; 21% vs 34%), with no other initial differences between these groups. Patients with bedside consultation more often had deep infection foci localized as compared to patients with telephone consultation (OR, 3.11; 95% CI, 1.74-5.57; P < .0001; 78% vs 53%). Patients with bedside consultation had lower mortality than patients with telephone consultation at 7 days (OR, 0.09; 95% CI, .02-.49; P = .001; 1% vs 8%), at 28 days (OR, 0.27; 95% CI, .11-.65; P = .002; 5% vs 16%) and at 90 days (OR, 0.25; 95% CI, .13-.51; P < .0001; 9% vs 29%). Considering all prognostic markers, 90-day mortality for telephone-consultation patients was higher (OR, 2.31; CI, 95% 1.22-4.38; P = .01) as compared to bedside consultation. CONCLUSIONS: Telephone IDS consultation is inferior to bedside IDS consultation.

Predisposing factors, disease progression and outcome in 430 prospectively followed patients of healthcare- and community-associated Staphylococcus aureus bacteraemia.

Staphylococcus aureus bacteraemia (SAB) episodes identified in a prospective multicentre study during 1999-2002 (not including MRSA) were followed up by an infectious disease specialist. The aim of this study was to compare predisposing factors, disease progression and outcome of healthcare (HA)- and community (CA)-associated SAB. Of 430 SAB episodes, 232 (54%) were HA. The HA-SAB patients were significantly older and more chronically ill compared to CA-SAB. Deep infection foci prevalence within three days of onset of SAB for HA versus CA were deep-seated abscesses (26% vs 37%, P < 0.05), pneumonia [25% vs 31%, non-significant (NS)], osteomyelitis (24% vs 36%, P<0.01), permanent foreign body (24% vs 9%, P<0.001), endocarditis (11% vs 15%, NS), septic arthritis (9% vs 13%, NS) and no infection focus (3% vs 6%, NS). The case fatality rates for HA-SAB versus CA-SAB at 28 days were 14% vs 11% (NS). Independent risk factors according to multivariate analysis for a fatal outcome were age, chronic alcoholism, immunosuppressive treatment, ultimately or rapidly fatal underlying diseases, severe sepsis on the onset of SAB, S. aureus pneumonia and endocarditis. As a result of a prospective study design, meticulous infection foci search and infectious disease specialist follow-up of each SAB episode, the case fatality remained low and 97% of the HA-SAB episodes presented infection foci within three days of onset of bacteraemia.

Identification of antigenic components of Toxoplasma gondii by an immunoblotting technique.

Proteins of Toxoplasma gondii were separated by SDS-polyacrylamide gel electrophoresis with subsequent transfer to a nitrocellulose sheet by electrophoretic blotting. Immunologically reactive polypeptides were detected by human sera with previously known toxoplasma antibody levels. Heavy chain-specific, peroxidase-conjugated anti-human immunoglobulins were used as the indicator antibodies for the separate identification of IgG and IgM reactive polypeptides. IgG toxoplasma antibodies reacted with several antigens of Mr approximately 27 000-67 000, while toxoplasma-specific IgM seemed to detect only a few polypeptides. The Mr of 35 000 for the dominating IgM reactive polypeptide was observed.