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ABSTRACT: The influence of adjunctive corticosteroids on the cytokine response in community-acquired pneumonia (CAP) is largely unknown. In this study, we analyzed the effect of dexamethasone on the cytokine response in patients with CAP and evaluated whether this effect is dependent on the causative microorganism. We hypothesized that dexamethasone has a larger effect on the cytokine response in patients with pneumococcal pneumonia than in patients with pneumonia caused by an atypical bacterium. A total of 304 hospitalized, nonimmunocompromised patients with CAP were randomized to an adjunctive 4-day course of 5 mg dexamethasone once a day (n = 151) or a placebo (n = 153). Serum concentrations of interleukin-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, IL-17, tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), macrophage inflammatory protein-1 alpha (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) were measured on days 0, 1, 2, and 4 and at a control visit. Overall, the concentrations of IL-6 (P < 0.01), IL-8 (P < 0.01), MCP-1 (P < 0.01), and TNF-α (P < 0.01) were significantly lower on day 2 in the dexamethasone group than in the placebo group. In patients with pneumococcal pneumonia (n = 72), both treatment groups showed a rapid decrease of cytokine concentrations; only the concentration of TNF-α (P = 0.05) was significantly lower in the dexamethasone group on day 2. In patients with CAP caused by an atypical pathogen (Legionella pneumophila, Chlamydophila species, Coxiella burnetii, or Mycoplasma pneumoniae; n = 58), IL-1Ra (P < 0.01), IL-6 (P < 0.01), and MCP-1 (P = 0.03) decreased more rapidly in the dexamethasone group than in the placebo group. In conclusion, dexamethasone downregulates the cytokine response during CAP. This effect seems to be dependent on the causative microorganism. This study provides insight into which patients with CAP might benefit most from adjunctive dexamethasone.
Clinical and vaccine immunology: CVI 08/2012; 19(9):1532-8. · 2.37 Impact Factor
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Sabine C A Meijvis,
Hans Hardeman,
Hilde H F Remmelts,
Rik Heijligenberg,
Ger T Rijkers,
Heleen van Velzen-Blad, G Paul Voorn,
Ewoudt M W van de Garde,
Henrik Endeman,
Jan C Grutters,
Willem Jan W Bos,
Douwe H Biesma
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ABSTRACT: Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear. We aimed to assess effect of addition of dexamethasone on length of stay in this group, which might result in earlier resolution of pneumonia through dampening of systemic inflammation.
In our double-blind, placebo-controlled trial, we randomly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherlands to receive intravenous dexamethasone (5 mg once a day) or placebo for 4 days from admission. Patients were ineligible if they were immunocompromised, needed immediate transfer to an intensive-care unit, or were already receiving corticosteroids or immunosuppressive drugs. We randomly allocated patients on a one-to-one basis to treatment groups with a computerised randomisation allocation sequence in blocks of 20. The primary outcome was length of hospital stay in all enrolled patients. This study is registered with ClinicalTrials.gov, number NCT00471640.
Between November, 2007, and September, 2010, we enrolled 304 patients and randomly allocated 153 to the placebo group and 151 to the dexamethasone group. 143 (47%) of 304 enrolled patients had pneumonia of pneumonia severity index class 4-5 (79 [52%] patients in the dexamethasone group and 64 [42%] controls). Median length of stay was 6·5 days (IQR 5·0-9·0) in the dexamethasone group compared with 7·5 days (5·3-11·5) in the placebo group (95% CI of difference in medians 0-2 days; p=0·0480). In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups, although 67 (44%) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 (23%) of 153 controls (p<0·0001).
Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia.
None.
The Lancet 06/2011; 377(9782):2023-30. · 38.28 Impact Factor
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ABSTRACT: Recent initiation of proton-pump inhibitor (PPI) treatment may increase the risk of community-acquired pneumonia (CAP), hypothetically by allowing colonisation of the oropharynx by gastrointestinal bacteria. The aim of this study was to assess the causal pathway by considering microbial aetiology of pneumonia and indications for initiation of PPI treatment. This was a population-based, case-control study with 430 cases with pneumonia and 1,720 matched controls. An elaborate diagnostic protocol was used to identify the causative microorganism of pneumonia. For patients recently starting PPI treatment, indications for treatment were assessed. Recent initiation of PPI treatment (<30 days) was associated with an increased risk of CAP (adjusted OR 3.1, 95% CI 1.4-7.1). Oropharyngeal bacteria were evenly distributed among current users, past users and nonusers of PPIs (p=0.41). Gastrointestinal bacteria were identified in only five (1.2%) patients with pneumonia (two current users and three nonusers). Excluding patients who were possibly prescribed PPI treatment for early symptoms of pneumonia (protopathic bias) did not alter the study findings. This study reaffirmed that use of PPIs is associated with an increased risk of CAP, especially when treatment has recently been started. Neither protopathic bias nor shifts in microbial aetiology seem to explain the association.
European Respiratory Journal 04/2011; 38(5):1165-72. · 5.89 Impact Factor
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ABSTRACT: Community-acquired pneumonia (CAP) is most frequently caused by Streptococcus pneumoniae, Haemophilus influenzae, atypical pathogens, and respiratory viruses. Susceptibility to CAP can be increased by single-nucleotide polymorphisms (SNPs) within the mannose-binding lectin (MBL) gene. We questioned whether MBL polymorphisms are associated with the susceptibility to and outcome of CAP and its most common pathogens.
All adult patients presenting with CAP in a 23-month period were included in this study. Frequencies of SNPs were determined for the promoter X/Y and the three coding SNPs in exon 1 (A/0). Six genotypes were constructed representing patients with sufficient and deficient serum levels of MBL. The results of the patients with CAP were compared with control subjects.
In 199 patients and 223 control subjects, MBL genotypes were determined. There were no differences in MBL genotype frequencies between patients with CAP in general, pneumonia caused by S pneumoniae or H influenzae, and control subjects. The frequency of sufficient MBL genotypes was nonsignificantly higher in patients with pneumonia with Legionella sp and Mycoplasma pneumoniae. In Legionella spp, the sufficient YA/YA genotype was significantly more frequent than in control subjects (odds ratio [OR], 5.43; confidence interval [CI], 1.32 to 22.41; p = 0.02). The frequency of the MBL-deficient genotype was significantly higher in patients with viral (co)infections (OR, 2.36; CI, 1.06 to 5.26; p = 0.03) and nonsignificantly higher in patients with pneumococcal pneumonia and viral (co)infections. MBL genotypes had no effect on outcome.
MBL genotypes play a limited role in pneumococcal pneumonia. Sufficient MBL genotypes were more frequently found in a small group of patients with atypical pneumonia, and MBL-deficient genotypes were more frequently found in patients with viral (co)infections.
Chest 12/2008; 134(6):1135-40. · 5.25 Impact Factor
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ABSTRACT: Community acquired pneumonia (CAP) is caused by a variety of microorganisms. By identifying patients at risk for failure of pathogen identification, it is possible to make an early decision on the extent of diagnostic procedures to be performed. This is especially important in patients with severe CAP. The aim of this study was to identify these patients by using clinical and laboratory features. In 201 patients hospitalized for CAP, clinical and laboratory variables were collected. Pathogen identification was performed by culture of sputum and blood, urine antigen tests, polymerase chain reaction of sputum, serological testing and viral culture of the pharynx. In 128 patients a respiratory microorganism was identified. In both univariate and multivariate analysis, failure of pathogen identification was predicted by pre-hospital antibiotic therapy, a medical history of hypertension and a low C-reactive protein. We conclude that patients with pre-hospital antibiotic therapy, a medical history of hypertension and a relatively low C-reactive protein are at risk for failure of pathogen identification. These predictors should be confirmed in a larger population. Invasive testing in high-risk patients with CAP in the presence of these predictors should be considered at an early phase of hospitalization.
Scandinavian Journal of Infectious Diseases 05/2008; · 1.72 Impact Factor
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ABSTRACT: The causative micro-organism in community-acquired pneumonia (CAP) is often difficult to predict. Different studies have examined chronic morbidity and clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of our study was to assess whether prior outpatient antimicrobial treatment is predictive for determining the microbial aetiology of CAP.
This was a hospital-based prospective observational study including all patients admitted with CAP between 1 October 2004 and 1 August 2006. Microbial investigations included sputum, blood culture, sputum PCR, antigen testing and serology. Exposure to antimicrobial drugs prior to hospital admission was ascertained through community pharmacy dispensing records. Multivariate logistic regression analysis was conducted to assess whether prior outpatient antimicrobial treatment is a predictor of microbial aetiology. Patient demographics, co-morbidities and pneumonia severity were considered to be other potential predictors.
Overall, 201 patients were included in the study. The microbial aetiology was determined in 64% of the patients. The five most prevalent pathogens were Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had received initial antimicrobial treatment as outpatients. Multivariate analyses revealed that initial outpatient beta-lactam treatment was associated with a threefold increased chance of finding atypical pathogens and a threefold decreased probability of pneumococcal infection; the corresponding odds ratios were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients who received macrolides prior to hospitalisation had an increased probability of viral pneumonia.
Prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning corresponding antimicrobial treatment in patients hospitalised for pneumonia.
European Journal of Clinical Pharmacology 05/2008; 64(4):405-10. · 2.85 Impact Factor
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ABSTRACT: Community acquired pneumonia (CAP) is caused by a variety of microorganisms. By identifying patients at risk for failure of pathogen identification, it is possible to make an early decision on the extent of diagnostic procedures to be performed. This is especially important in patients with severe CAP. The aim of this study was to identify these patients by using clinical and laboratory features. In 201 patients hospitalized for CAP, clinical and laboratory variables were collected. Pathogen identification was performed by culture of sputum and blood, urine antigen tests, polymerase chain reaction of sputum, serological testing and viral culture of the pharynx. In 128 patients a respiratory microorganism was identified. In both univariate and multivariate analysis, failure of pathogen identification was predicted by pre-hospital antibiotic therapy, a medical history of hypertension and a low C-reactive protein. We conclude that patients with pre-hospital antibiotic therapy, a medical history of hypertension and a relatively low C-reactive protein are at risk for failure of pathogen identification. These predictors should be confirmed in a larger population. Invasive testing in high-risk patients with CAP in the presence of these predictors should be considered at an early phase of hospitalization.
Scandinavian Journal of Infectious Diseases 02/2008; 40(9):715-20. · 1.72 Impact Factor
