Ulla Hohenthal

Infective endocarditis in a Finnish teaching hospital: a study on 326 episodes treated during 1980–2004

Objectives: To evaluate potential changes of infective endocarditis (IE) in patients treated in a Finnish teaching hospital during the past 25 years. Patients: 326 episodes of IE in 303 patients treated during 1980–2004 were evaluated for clinical characteristics and their changes over time. Results: The mean age of the patients increased with time (from 47.2 to 54.5 years, p  =  0.003). Twenty-five (7.7%) episodes were associated with intravenous drug use (IVDU), with a significant increase of these episodes after 1996 (from 0 to 19 (20%), p < 0.001). Viridans streptococci were the most common causative agents of IE during 1980–1994, but after that Staphylococcus aureus was the most common pathogen (p  =  0.015). The proportion of IE of the aortic valve decreased during the study (from 30 (49%) to 26 (27%), whereas the proportions of mitral (11 (18%) to 33 (35%) and tricuspid valve IE (0 to 13 (14%) increased correspondingly (p  =  0.001). This was mainly due to more patients with IVDU. Chronic dialysis for renal failure as an underlying condition increased over time (from 0 to 7 (7.4%), p  =  0.015) but no other predisposing conditions changed. Complications such as neurological manifestations and heart failure did not change in frequency, but the incidence of lung emboli increased (from 0% to 10.5%, p < 0.001); 83% of these emboli occurred in patients with IVDU. The proportion of patients requiring surgical treatment and mortality due to IE did not change. Conclusions: During these 25 years, the causative agents, affected valves and complications of IE changed to some degree. These changes were mainly attributed to the increase of IVDU-associated IE. Except for the increase in age, the clinical presentation and outcome in non-addicts remained substantially unchanged.

Utility of C-reactive protein in assessing the disease severity and complications of community-acquired pneumonia

Previous studies on the usefulness of C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) have yielded somewhat inconsistent results. Our aim was to assess the value of CRP in estimating the severity and complications of CAP. CRP levels during the first 5 days of hospitalization were measured in 384 adult patients with CAP, and the data were evaluated using comprehensive statistical analyses. Significantly higher CRP levels on admission were detected in Pneumonia Severity Index (PSI) classes III-V than in classes I and II (p <0.001). An increment of 50 mg/L CRP on admission was associated with a 1.22-fold odds for a patient to be in PSI classes III-V as compared with classes I and II (OR 1.22, 95% CI 1.11-1.34; p <0.001). CRP levels were significantly higher in bacteraemic pneumonia than in non-bacteraemic pneumonia (p <0.001). An increment of 50 mg/L CRP was associated with a 1.67-fold odds for a patient to be bacteraemic (OR 1.67, 95% CI 1.46-1.92; p <0.001). CRP levels >100 mg/L on day 4 after the admission were significantly associated with complications (p <0.01). There was a trend for an association between the level of CRP on admission and the time to reach clinical stability (p <0.01). In conclusion, CRP may be valuable for revealing the development of complications in CAP. It may also be useful to assess the disease severity, thus being complementary to the assessment of the PSI. In our patients, high CRP levels were associated with a failure to reach clinical stability.

Aetiological diagnosis of community acquired pneumonia: Utility of rapid microbiological methods with respect to disease severity

The present study investigated the utility of rapid microbiological methods in the aetiological diagnosis of community acquired pneumonia (CAP) according to the severity of CAP. Between 1999 and 2004, 384 adult patients with CAP were studied prospectively. In addition to standard microbiological methods, PCR and antigen detection techniques were used to identify pathogens. A total of 230 microbial agents in 209 patients were identified, with 134 (58.2%) identified by antigen detection or PCR tests. Of these 134 microbial agents, 95 (70.9%) were identified only by these rapid methods. Streptococcus pneumoniae urinary antigen detection was positive in 24.3% (81/333) of the patients with a diagnostic yield of 38.7% in those with severe pneumonia. Respiratory viral antigen detection was positive in 11.1% (35/314) of the patients with the highest diagnostic yield (20.3%) in patients with severe pneumonia. Mycoplasma pneumoniae PCR was positive in 7.5% (13/174) of the patients, all of whom were low-risk patients. Only 1 case of Chlamydia pneumoniae was identified by PCR. In conclusion, besides yielding the aetiological diagnosis rapidly, new methods add to the total diagnostic yield in CAP. The diagnostic yield of rapid methods differs according to the severity of the pneumonia.

Simultaneous quantitative analysis of FcγRI (CD64) and CR1 (CD35) on neutrophils in distinguishing between bacterial infections, viral infections, and inflammatory diseases

A flow cytometric quantitative analysis of receptors on neutrophils can be exploited in distinguishing between inflammatory and infectious diseases. In this prospective comparative study, simultaneous quantitative analysis of CD64 and CD35 on peripheral blood neutrophils was performed in febrile patients in order to differentiate between bacterial infections (n=89), viral infections (n=46), and inflammatory diseases (n=21). The patient data was compared to 60 healthy controls. We could divide patients into three groups depending on how they express CD35 and CD64 on neutrophils: (1) patients with a high probability of viral infection (low CD35/low CD64 and low CD35/high CD64), (2) patients with a high probability of inflammatory disease (high CD35/low CD64), and (3) patients with a high probability of bacterial infection (high CD35/high CD64). In summary, simultaneous quantitative analysis of CD64 and CD35 on neutrophils could potentially assist physicians to distinguish between inflammatory and infectious diseases.

18 F-FDG positron emission tomography/computed tomography in infective endocarditis

BackgroundThe diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in IE.MethodsSixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18F-FDG-PET/CT. 18F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference.ResultsThere was strong, focal 18F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUVmax of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE.Conclusions18F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

Measurement of complement receptor 1 on neutrophils in bacterial and viral pneumonia.

BackgroundA reliable prediction of the causative agent of community-acquired pneumonia (CAP) is not possible based on clinical features. Our aim was to test, whether the measurement of the expression of complement receptors or Fcγ receptors on neutrophils and monocytes would be a useful preliminary test to differentiate between bacterial and viral pneumonia.MethodsSixty-eight patients with CAP were studied prospectively. Thirteen patients had pneumococcal pneumonia; 13 patients, influenza A pneumonia; 5 patients, atypical pneumonia, and 37 patients, aetiologically undefined pneumonia. Leukocyte receptor expression was measured within 2 days of hospital admission.ResultsThe mean expression of complement receptor 1 (CR1) on neutrophils was significantly higher in the patients with pneumococcal pneumonia than in those with influenza A pneumonia. The mean expression of CR1 was also significantly higher in aetiologically undefined pneumonia than in influenza A pneumonia, but there was no difference between pneumococcal and undefined pneumonia.ConclusionOur results suggest that the expression of CR1 is higher in classical bacterial pneumonia than in viral pneumonia. Determination of the expression of CR1 may be of value as an additional rapid tool in the aetiological diagnosis, bacterial or viral infection, of CAP. These results are preliminary and more research is needed to assess the utility of this new method in the diagnostics of pneumonia.

Use of complement regulators, CD35, CD46, CD55, and CD59, on leukocytes as markers for diagnosis of viral and bacterial infections.

Several complement regulatory proteins exist on self-cells to prevent damage by the serum complement system. In the present study, we aimed to perform quantitative analysis of membrane-bound complement regulators, CR1 (CD35), MCP (CD46), DAF (CD55), and MIRL (CD59), on peripheral blood neutrophils, monocytes, and lymphocytes from healthy controls (n=36) and febrile patients diagnosed with either bacterial (n=21) or viral (n=26) infections. Our results show that: (a) increased CD35 and CD55 levels on neutrophils and monocytes present potent markers of bacterial infection, (b) increased expression of CD46 on monocytes is an indicator of viral infection, and (c) increased CD59 expression on neutrophils and monocytes is a general infection marker. Additionally, CD19-positive B-lymphocytes represent practically the only lymphocyte population capable of expressing CD35. We further developed two novel clinical flow cytometric markers (indices), specifically, clinical mononucleosis (CM)-INDEX (incorporating CD35, CD55, and CD59 expression on lymphocytes) and clinical bacterial infection (CBI)-INDEX (incorporating CD35 and CD55 expression on neutrophils and lymphocytes), for the effective detection of viral mononucleosis and bacterial infection, respectively. In summary, bacterial and viral infections induce different expression patterns of membrane-bound complement regulators in human leukocytes, which may be effectively exploited in clinical differential diagnosis.

CRP/CD11b ratio: a novel parameter for detecting gram-positive sepsis.

To commence proper antibiotic treatment in sepsis, timely knowledge of whether the cause of systemic infection is gram-negative (gram(-)) or gram-positive (gram(+)) bacteria in origin would be beneficial for clinicians. In this clinical prospective study, our objective was to develop a method for distinguishing between gram(+) and gram(-) bacterial infection. In gram(-) bacterial infection (n = 21), the average amount of CD11b on neutrophils was significantly higher than in gram(+) bacterial infection (n = 22). On the contrary, serum C-reactive protein (CRP) level was significantly higher in gram(+) than in gram(-) bacterial infection. By dividing the serum CRP value by the amount of CD11b on neutrophils, we derived a novel marker of gram(+) sepsis, CRP/CD11b ratio, which displayed 76% sensitivity and 80% specificity for the detection of gram(+) sepsis (n = 17) among febrile patients with microbiologically confirmed or clinically diagnosed bacterial infection. The detection of gram(+) sepsis is possible after the combination of neutrophil CD11b data and serum CRP level. In conclusion, our findings indicate that the proposed CRP/CD11b ratio test could potentially assist physicians in determining an appropriate antibiotic treatment in patients with severe bacterial infection.

A novel method for distinguishing between dsDNA and ssRNA virus infections.

BACKGROUND To commence proper antiviral treatment, timely knowledge of whether the infection is caused by DNA or RNA virus would be beneficial for the clinician. OBJECTIVES Our objective was to develop a method for distinguishing between DNA and RNA virus infections. STUDY DESIGN In this prospective study, total and differential count of leukocytes, serum C-reactive protein level, erythrocyte sedimentation rate, and quantitative flow cytometric analysis of FcgammaRI (CD64) on neutrophils and monocytes were obtained from 289 hospitalized febrile patients. After microbiological confirmation, 89 patients (31%) were found to have either bacterial (n=46) or viral (n=43) infection. The patient data was compared to 60 healthy controls. RESULTS For the first time ever, it was noticed that in dsDNA virus infections (n=21) the average amount of CD64 on neutrophils was over five-fold compared to ssRNA virus infections (n=22). CONCLUSIONS DNA virus score (DNAVS) point, which incorporates quantitative analysis of CD64 on neutrophils and total and differential count of leukocytes, varied between 0 and 8, and displayed 95% sensitivity and 100% specificity in distinguishing between dsDNA and ssRNA virus infections [average (S.D.); DNAVS points: 5.4 (2.5) vs. 0.3 (0.4); p<0.001].

Diagnostic Value of Bronchoalveolar Lavage in Community-acquired Pneumonia in a Routine Setting: A Study on Patients Treated in a Finnish University Hospital

Only a few previous studies have focused on the use of bronchoalveolar lavage (BAL) in patients with community-acquired pneumonia (CAP). Our aim was to evaluate the diagnostic value of BAL in CAP in a routine clinical setting. 71 disease episodes were retrospectively analysed. The patients had undergone BAL for serious or slowly responding pneumonia. All procedures were performed during antimicrobial treatment of the patient. BAL fluid was cultivated for bacteria, fungi, and viruses. In 68 episodes, 1 or several specific polymerase chain reaction tests were performed. Only 1 (1.3%) quantitative bacterial culture was considered diagnostic for CAP, and indicated a change of antimicrobial treatment. The diagnostic yield increased to 9.8% when other methods were used. A respiratory virus was the only aetiology in 3 (6.0%) patients. In slowly responding pneumonia, also hospital-acquired pathogens and malignancies were identified, resulting in a total diagnostic yield of 20.0%. Thus, even when a large array of diagnostic assays was applied, the value of BAL in pretreated patients with CAP was very small, and its therapeutic implications minimal. In a subgroup of slowly responding pneumonia, the procedure was of some usefulness even after commencement of antimicrobial treatment.