Anke H. W. Bruns

Usefulness of consecutive C-reactive protein measurements in follow-up of severe community-acquired pneumonia

Despite the introduction of new inflammatory markers, C-reactive protein (CRP) remains commonly used in patients hospitalised with severe infections. However, evidence on the usefulness of consecutive CRP measurements is still unclear. The clinical relevance of consecutive CRP measurements was studied in follow-up of antibiotic treatment in patients with severe community-acquired pneumonia (CAP). In a prospective multicentre trial, CRP levels were measured on admission, and on days 3 and 7. Patients were followed clinically for 28 days. Aetiology could be determined in 137 (47.4%) out of the 289 patients included. In 122 (38.8%) patients, initial antibiotic therapy was appropriate. A decline of <60% in CRP levels in 3 days and a decline of <90% in CRP levels in 7 days were both associated with an increased risk of having recieved inapproriate empiric antibiotic treatment (day 0–3, odds ratio (OR) 6.98, 95% confidence interval (CI) 1.56–31.33 and day 0–7, OR 3.74, 95% CI 1.12–13.77). In conclusion, consecutive C-reactive protein measurements are useful in the first week in follow-up of antibiotic treatment for severe community-acquired pneumonia when taking the causative microorganism and use of steroids into account. A delayed normalisation of C-reactive protein levels is associated with a higher risk of having received inappropriate antibiotic treatment.

Cause‐specific long‐term mortality rates in patients recovered from community‐acquired pneumonia as compared with the general Dutch population

Insights into long-term mortality, especially into the cause of death after initial recovery from an episode of community-acquired pneumonia (CAP), may help in determining optimal preventive measures in such patients. Prospective observational cohort studies were conducted to compare cause-specific long-term mortality rates for 356 patients who had recovered from CAP with those of the general Dutch population (16.3 million) between 2003 and 2007. The Dutch Municipal Public Records Database and death certificates were used to determine cause-specific mortality rates up to 7 years after discharge. In patients who had recovered from CAP, cumulative 1-year, 5-year and 7-year mortality rates were 17%, 43% and 53%, respectively, as compared with 4%, 19% and 24% for an age-matched and sex-matched population reference cohort. Overall, patients who had recovered from CAP had significantly higher long-term mortality than matched population controls (rate ratio (RR) 3.6; p <0.001). In the years after an episode of CAP, malignancy (27%), chronic obstructive pulmonary disease (COPD) (19%) and cardiovascular disease (16%) were the most frequent causes of death. Only 6% died of pneumonia, as compared with 3.2% in the general population. After initial recovery from an episode of CAP, long-term mortality rates are more than three times as high as in the general population. The causes of long-term mortality were mostly comorbidity-related, and significantly different from those in the general population. After an episode of CAP, optimization of treatment of comorbidities, such as treatment for COPD, might improve long-term survival rates.

Patterns of Resolution of Chest Radiograph Abnormalities in Adults Hospitalized with Severe Community-Acquired Pneumonia

BACKGROUND Timing of follow-up chest radiographs for patients with severe community-acquired pneumonia (CAP) is difficult, because little is known about the time to resolution of chest radiograph abnormalities and its correlation with clinical findings. To provide recommendations for short-term, in-hospital chest radiograph follow-up, we studied the rate of resolution of chest radiograph abnormalities in relation to clinical cure, evaluated predictors for delayed resolution, and determined the influence of deterioration of radiographic findings during follow-up on prognosis. METHODS A total of 288 patients who were hospitalized because of severe CAP were followed up for 28 days in a prospective multicenter study. Clinical data and scores for clinical improvement at day 7 and clinical cure at day 28 were obtained. Chest radiographs were obtained at hospital admission and at days 7 and 28. Resolution and deterioration of chest radiograph findings were determined. RESULTS At day 7, 57 (25%) of the patients had resolution of chest radiograph abnormalities, whereas 127 (56%) had clinical improvement (mean difference, 31%; 95% confidence interval, 25%-37%). At day 28, 103 (53%) of the patients had resolution of chest radiograph abnormalities, and 152 (78%) had clinical cure (mean difference, 25%; 95% confidence interval, 19%-31%). Delayed resolution of radiograph abnormalities was independently associated with multilobar disease (odds ratio, 2.87; P < or = .01); dullness to percussion at physical examination (odds ratio, 6.94; P < or = .01); high C-reactive protein level, defined as >200 mg/L (odds ratio, 4.24; P < or = .001); and high respiratory rate at admission, defined as >25 breaths/min (odds ratio, 2.42; P < or = .03). There were no significant differences in outcome at day 28 between patients with and patients without deterioration of chest radiograph findings during the follow-up period (P > .09). CONCLUSIONS Routine short-term follow-up chest radiographs (obtained <28 days after hospital admission) of hospitalized patients with severe CAP seem to provide no additional clinical value.

Comparative in vitro stimulation with lipopolysaccharide to study TNFα gene expression in fresh whole blood, fresh and frozen peripheral blood mononuclear cells

In vitro stimulation with fresh and frozen peripheral blood mononuclear cells (PBMCs) or fresh whole blood has been widely used in animal studies and clinical trials to study the immunological features of a number of human diseases. The objective of this study was to determine the difference in response to stimulation of fresh PBMCs, frozen PBMCs, and fresh whole blood by change of TNFalpha gene expression levels after 4-hour in vitro lipopolysaccharide (LPS) stimulation. Our results demonstrate that TNFalpha gene expression significantly increases in both fresh PBMCs and fresh whole blood when 1 microg/ml or 10 microg/ml LPS was used but only after stimulation with 10 microg/ml LPS in frozen PBMCs. Mean fold change of TNFalpha gene expression levels after 1 microg/ml LPS stimulation was significantly higher using fresh whole blood (51.01+/-7.91) as compared to fresh PBMCs (8.92+/-2.16) or frozen PBMCs (3.04+/-0.55) (p<or=0.007). The same trend was also observed with 10 microg/ml LPS stimulation (p<or=0.001). Decreased PBMC cell viability due to cryopreservation, cytokine depletion and removal of some minor cells during cell isolation could attribute to the low TNFalpha expression in the frozen PBMCs. Our results strongly suggest that fresh whole blood is the best choice for in vitro stimulation studies.

Impact of different empirical antibiotic treatment regimens for community-acquired pneumonia on the emergence of Clostridium difficile

BACKGROUND Treatment of community-acquired pneumonia (CAP) with newer fluoroquinolones may contribute to selection for Clostridium difficile. We studied the prevalence of C. difficile carriage and C. difficile infection (CDI) on admission, and nosocomial acquisition rates in patients hospitalized for CAP and compared different empirical treatment strategies. METHODS In a prospective study among patients admitted for antibiotic treatment of CAP, consecutive stool and skin samples were collected and cultured for C. difficile. Cultured isolates were typed by PCR ribotyping and characterized for toxinogenicity. RESULTS In total, 20 of 107 (18.7%) patients included carried C. difficile. Various ribotypes were found and 14 (70%) isolates were toxinogenic. On admission, prevalence of C. difficile carriage was 9.4% (n=9), of which 22% also carried C. difficile on the skin and one patient had mild CDI with persistent positive cultures. The overall nosocomial acquisition rate of C. difficile carriage was 11.2%. No nosocomially acquired CDI occurred. Acquisition rates of C. difficile were 11.9% (5/45) in moxifloxacin-, 11.1% (5/47) in β-lactam- and 9.0% (1/14) in β-lactam plus macrolide- or fluoroquinolone-treated patients (P=0.84). Risk factors for C. difficile carriage were intravenous antibiotic treatment >7 days [odds ratio (OR) 3.89; 95% confidence interval (CI) 1.30 to 11.79] and hospitalization during the past 3 months (OR 4.08; 95% CI 1.40 to 11.90). CONCLUSIONS In a non-outbreak setting with a low endemic rate, the prevalence of C. difficile carriage in patients admitted because of CAP is high and nosocomial acquisition rates for C. difficile colonization are 11%. Fluoroquinolones were not associated with increased acquisition rates for C. difficile as compared with other empirical regimens for CAP.

Genetic risk of acute pulmonary infections and sepsis

The focus of this review is the genetic influence on pneumonia and sepsis. A large number of polymorphisms in a diverse collection of genes have been identified as potential candidates to explain the genetic variability in susceptibility to acute pulmonary infection and its adverse outcomes. Unfortunately, apart from polymorphisms in mannose-binding lectin, CD14 and the IgG2 receptor, there is little consensus on which polymorphisms are truly important. As well as discussing some of the major published findings, this review will focus on the reasons for failure to make more progress. We will also address the issues for future research, particularly the need to address the limitations of past studies, including the grouping of patients with different pathogens, as the relationship between genotype and phenotype may be highly pathogen dependent. Finally, our approach to reporting genetic studies needs to change to minimize the number of publications of spurious findings.