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.

The association between bacterial infections and the risk of coronary heart disease in type 1 diabetes.

BACKGROUND: Diabetes increases the risk of infections and coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. OBJECTIVES: To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. METHODS: Individuals with type 1 diabetes (n = 3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or nonfatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1 January 1995 to 31 December 2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. RESULTS: Individuals with an incident CHD event (n = 370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82], P < 0.001), as well as higher levels of LPS activity (0.64 [0.60-0.67], versus 0.58 EU mL-1 [0.57-0.59], P < 0.001). In multivariable-adjusted Cox proportional hazards models, the mean number of antibiotic purchases per follow-up year was an independent risk factor for incident CHD (HR 1.21, 95% CI: 1.14-1.29, P < 0.0001). High LPS activity was a risk factor for incident CHD (HR 1.93 [1.34-2.78], P < 0.001) after adjusting for static confounders. CONCLUSION: Bacterial infections are associated with an increased risk of incident CHD in individuals with type 1 diabetes.

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.

Bloodstream infections following different types of surgery in a Finnish tertiary care hospital, 2009-2014.

The risk and outcome of bloodstream infections (BSIs) were evaluated following surgery. BSIs were identified in Helsinki University Hospital during 2009-2014 as part of the national surveillance. Of 711 BSIs identified, 51% were secondary and 49% primary. The rate was highest after cardiovascular surgery (8.7 per 1000 procedures) and lowest after gynaecologic (1.0 per 1000). Surgical site infection was the most frequent source of secondary BSIs (34%) and 45% of primary BSIs were central-line-associated. The 28-day case fatality ranged from zero in gynaecology/obstetrics to 21% in cardiovascular surgery. Besides BSIs related to surgical site infections, half of BSIs were primary, providing additional foci for prevention.

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.

Treatment of complicated skin and skin structure infections in areas with low incidence of antibiotic resistance-a retrospective population based study from Finland and Sweden.

Complicated skin and skin-structure infections (cSSSI) are a common reason for hospitalization and practically all new antimicrobial agents against Gram-positive bacteria are studied in cSSSI. The aim of this population-based observational study was to assess the treatment of patients with cSSSI in areas with a low incidence of antibiotic resistance. The study population consisted of adult residents who were treated because of cSSSI during 2008-2011 from two Nordic cities, Helsinki and Gothenburg. In the final analysis population (460 patients; mean age 60.8 years; 60.9% male) 13.3% of patients had bacteraemia, 15.9% were admitted to an Intensive Care Unit and 51.5% underwent at least one surgical intervention. Treatment failure occurred in 28.2%, initial antibiotic treatment modification to another intravenous drug in 38.5% and streamlining in 5.0% of the cases. Gram-positive bacteria were predominantly isolated, with staphylococci (24.5%) and streptococci (16.0%) being the most common aetiologies. Median overall durations of hospital stay and antimicrobial treatment were 13 and 17 days, respectively, and on average 3.5 (SD 2.1) different antibiotics were used per patient. Oral antimicrobial treatment was continued in 64.3% of patients after discharge. The overall mortality rates in 30 days and in 12 months were 4.1% and 11.8%, respectively, and 16.4% of patients had a recurrence of SSSI within 12 months. In conclusion, in this population-based study antimicrobial treatment modifications were frequent and the treatment time was longer than recommended. However, bacteraemia, clinical failure and recurrences were more common than in previous non-population-based studies.

Clinical findings in relation to mortality in non-tuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria.

We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p < 0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33-0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31-0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25-0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9-20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4-5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05-5.01, p < 0.001) and age (HR 1.07, 95 % CI 1.04-1.09, p < 0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24-0.59, p < 0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course.

2-hydroxyisocaproic acid is fungicidal for Candida and Aspergillus species.

The amino acid derivative 2-hydroxyisocaproic acid (HICA) is a nutritional additive used to increase muscle mass. Low levels can be detected in human plasma as a result of leucine metabolism. It has broad antibacterial activity but its efficacy against pathogenic fungi is not known. The aim was to test the efficacy of HICA against Candida and Aspergillus species. Efficacy of HICA against 19 clinical and reference isolates representing five Candida and three Aspergillus species with variable azole antifungal sensitivity profiles was tested using a microdilution method. The concentrations were 18, 36 and 72 mg ml(-1) . Growth was determined spectrophotometrically for Candida isolates and by visual inspection for Aspergillus isolates, viability was tested by culture and impact on morphology by microscopy. HICA of 72 mg ml(-1) was fungicidal against all Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA. HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus isolates and affected cell wall integrity. In conclusion, HICA has broad antifungal activity against Candida and Aspergillus at concentrations relevant for topical therapy. As a fungicidal agent with broad-spectrum bactericidal activity, it may be useful in the topical treatment of multispecies superficial infections.

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.

Two cases of food-borne botulism in Finland caused by conserved olives, October 2011.

In October 2011 in Finland, two persons fell ill with symptoms compatible with botulism after having eaten conserved olives stuffed with almonds. One of these two died. Clostridium botulinum type B and its neurotoxin were detected in the implicated olives by PCR and mouse bioassay, respectively. The olives were traced back to an Italian manufacturer and withdrawn from the market. The public and other European countries were informed through media and Europe-wide notifications.

Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia.

The soluble form of urokinase-type plasminogen activator receptor (suPAR) is a new inflammatory marker. High suPAR levels have been shown to associate with mortality in cancer and in chronic infections like HIV and tuberculosis, but reports on the role of suPAR in acute bacteremic infections are scarce. To elucidate the role of suPAR in a common bacteremic infection, the serum suPAR levels in 59 patients with Staphylococcus aureus bacteremia (SAB) were measured using the suPARnostic ELISA assay and associations to 1-month mortality and with deep infection focus were analyzed. On day three, after the first positive blood culture for S. aureus, suPAR levels were higher in 19 fatalities (median 12.3; range 5.7-64.6 ng/mL) than in 40 survivors (median 8.4; range 3.7-17.6 ng/mL, p = 0.002). This difference persisted for 10 days. The presence of deep infection focus was not associated with elevated suPAR levels as compared to patients with no deep infection focus. suPAR was found to be prognostic for mortality in receiver operator characteristic (ROC) curve analysis, which was not observed for serum C-reactive protein (CRP); the area under the curve (AUC) for suPAR was 0.754 (95% confidence interval [CI], 0.615-0.894, p = 0.003) and for CRP, it was 0.596 (95% CI, 0.442-0.750, p = 0.253). The optimal suPAR cut-off value in predicting 1-month mortality was 9.25 ng/mL. In conclusion, our study demonstrates that the new promising biomarker, serum suPAR concentration, was able to predict mortality in SAB.

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.

Pulmonary blood volume in mitral regurgitation in Cavalier King Charles spaniels.

BACKGROUND: Pulmonary edema and venous congestion are well-recognized signs of congestive heart failure (CHF) in advanced canine chronic mitral regurgitation (MR). However, little is known about pulmonary blood volume (PBV), blood pulmonary transit time (PTT), and the regulation of these. OBJECTIVES: To measure and evaluate the relationships of PBV, forward stroke volume (FSV), and heart rate normalized blood pulmonary transit time (nPTT) in healthy dogs and dogs with MR. ANIMALS: Thirty-three Cavalier King Charles Spaniels; 11 healthy, 4 in modified New York Heart Association (NYHA) class I, 11 in class II, and 7 in CHF. METHODS: Heart rate normalized PTTs were measured by radionuclide angiocardiography. Left ventricular end diastolic and systolic diameter, left atrial/aortic root ratio, and FSV were measured by echocardiography. PBV and pulmonary blood volume index (PBVI) were calculated by established formulas. RESULTS: PBVI was 308±56 (mean±SD) mL/m2 for healthy dogs, 287±51 mL/m2 in NYHA class I, 360±66 mL/m2 in Class II, and 623±232 mL/m2 in CHF (P=.0008). Heart rate normalized PTT, not FSV, was a predictor of PBV (r=0.92 and 0.02, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased PBV, not decreased FSV, is the main cause of increased nPTT in MR. Increased nPTT can be used as an indicator of abnormal cardiopulmonary function in dogs with MR.

Genetic polymorphism of the C-reactive protein (CRP) gene and a deep infection focus determine maximal serum CRP level in Staphylococcus aureus bacteremia.

C-reactive protein (CRP) is widely used in early detection of sepsis or organ dysfunction. Several single nucleotide polymorphisms (SNPs) in the CRP gene are shown to be associated with variability of basal CRP. To clarify the effect of these SNPs to CRP response in systemic infections, we compared genetic and clinical data on patients with Staphylococcus aureus bacteremia (SAB). Six SNPs in the CRP gene region (rs2794521, rs30912449, rs1800947, rs1130864, rs1205 and rs3093075) were genotyped in 145 patients and analyzed for associations with CRP and various clinical outcomes. We found that the rare minor A-allele of triallelic SNP rs30912449 (C > T > A) and presence of a deep infection focus were strongly associated to the higher maximal CRP during the first week of SAB. Median of the maximal CRP in patients who had the A-minor allele was 282 mg/L (interquartile range [IQR, defined as the difference between the third quartile and the first quartile], 169 mg/L) but only 179 mg/L (IQR, 148 mg/L) in patients without this allele (P = 0.004), and CRP in patients who had deep infection focus was higher 208 mg/L (IQR, 147 mg/L) than in other patients 114 mg/L (IQR, 121 mg/l) (P < 0.0001). Mortality, degree of leucocytosis, time to defervescence or number of deep infections were not affected by CRP gene SNPs. The maximal CRP during the first week in SAB was partly determined by variation in the CRP gene and partly by presence of deep infection focus. This finding suggests cautiousness in interpreting exceptionally high CRPs from SAB patients and comparison between patients.