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Biomedical subjects

M Leinonen

Publications and source records attributed to M Leinonen.

At least 19 recordsLinked to original sources

The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease.

The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%). Only 19 (14%) patients discontinued because of AEs. Most dopaminergic AEs occurred shortly after initiation of entacapone, and these could be managed by levodopa down-adjustment. The mean duration of benefit of a single dose of levodopa increased significantly from 2.1 to 2.8 h (P < 0.01) at 3 months and remained prolonged for the whole study. At the end of the study, the mean daily dose of levodopa was significantly decreased from baseline (from 737 to 696 mg; P < 0.05). The patients' global assessment indicated that 69% of patients improved when given entacapone and this proportion was maintained until the end of the study (64%). There was a significant worsening of disability upon withdrawal of entacapone. In conclusion, entacapone given in combination with levodopa, has a good long-term safety profile and a sustained beneficial effect in patients with PD with motor fluctuations.

Aged↗

Detection of Streptococcus pneumoniae DNA by using polymerase chain reaction and microwell hybridization with Europium-labelled probes.

The present paper describes a novel modification of polymerase chain reaction (PCR) for the detection of Streptococcus pneumoniae DNA in clinical specimens. PCR was based on the detection of a 209-base pair segment of the S. pneumoniae pneumolysin gene. For the demonstration of the amplification product, microwell hybridization with a Europium-labelled oligonucleotide probe complementary to a biotinylated strand of the PCR product was performed, and the presence of the PCR product was monitored by time-resolved fluorescence (TRF) of the Europium chelate. The sensitivity of the assay for purified S. pneumoniae DNA was 50 fg DNA corresponding to 20 genome equivalents of S. pneumoniae DNA. The efficiency of the hybridization step was monitored by using known amounts of synthetic target oligonucleotides as standards. Sensitivity of 3 x 10(8) molecules per individual reaction well was achieved with a 30-min attachment time and a 3-h hybridization time. Detection of PCR-amplified products by the microwell hybridization technique and TRF was compared to agarose gel electrophoresis in 50 middle ear fluid samples obtained from children with acute otitis media. The agarose gel and TRF detection methods identified all culture-positive samples, but both were also positive for 55% of the culture-negative samples. The results suggest that the detection of amplified PCR products by microwell hybridization using Europium-labelled oligonucleotides is a reliable method for the demonstration of the pneumolysin gene fragment. Furthermore, the method is suitable for automation and, thus, for testing high numbers of samples. The clinical significance of the PCR findings remains to be studied.

Bacteriological Techniques↗

Evaluation of gene-technological and conventional methods in the identification of Streptococcus pneumoniae.

To find reliable methods able to identify the "difficult" Streptococcus pneumoniae isolates, an in-house polymerase chain reaction (PCR) for pneumolysin gene (Ply-PCR) and a commercial RNA hybridisation test (AccuProbe) were evaluated. Selected isolates of suspected pneumococci, sent for confirmation of identification and for serotyping, were classified into four groups based on their optochin sensitivity and capsule reaction. All isolates in Group 1, which consisted of 24 typical, optochin-sensitive, encapsulated pneumococcal strains, were positive in the Ply-PCR and AccuProbe tests. In Group 2, which consisted of 25 optochin-sensitive, but unencapsulated pneumococcal strains, all the isolates were positive in the Ply-PCR test, and 23 were positive in the AccuProbe test. In Group 3, which consisted of 15 atypical, optochin-resistant but encapsulated pneumococci, 12 of the isolates were positive in the Ply-PCR and 12 in the AccuProbe test, and 11 of these 12 strains were positive in both tests. In Group 4, which consisted of 36 equivocal optochin-resistant, unencapsulated isolates, 15 strains were positive in the Ply-PCR test and 8 strains in the AccuProbe test. As a conclusion, the Ply-PCR and AccuProbe tests identified similarly typical optochin-sensitive pneumococci, but gave partly controversial results about atypical pneumococci. Thus, they did not reliably help in the identification of suspected pneumococcal isolates lacking the conventional characteristics of pneumococcus.

Bacterial Capsules↗

Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study).

OBJECTIVES: To determine the efficacy and safety of the catechol-O-methyltransferase (COMT) inhibitor entacapone, used as an adjunct to levodopa, in Parkinson's disease (PD) patients. PATIENTS AND METHODS: In this parallel group, randomized, double-blind study, 301 PD patients, the majority with motor fluctuations, received entacapone (200 mg) or placebo with each daily dose of standard or controlled-release (CR) levodopa. The 24-week treatment period was followed by 2 weeks of entacapone withdrawal. Efficacy was determined by home diaries ('on' and 'off' times), Unified Parkinson's Disease Rating Scale (UPDRS) and changes in levodopa dosage, and safety by adverse-event inquiry, vital signs, electro cardiography (ECG) and laboratory tests. RESULTS: In the total population, the UPDRS activities of daily living and motor scores were significantly improved (P < 0.05) by entacapone vs placebo. In fluctuating patients, 'on' time increased (1.7 h) and 'off' time decreased (1.5 h) significantly more with entacapone than with placebo (0.5 and 0.6 h, respectively; P < 0.05), and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo (P < 0.05). Entacapone benefit was lost on withdrawal. Entacapone efficacy was comparable between patients using CR and standard levodopa preparations. Increased dyskinesias (entacapone 34%, placebo 26%) and nausea (10 and 5%, respectively), mostly occurring shortly after treatment initiation, were generally managed by reducing the levodopa dose. Diarrhoea (entacapone 8%, placebo 4%) was seldom severe. There were no differences in vital signs, ECG or laboratory results. CONCLUSION: Entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit.

Aged↗

Enterovirus, mycoplasma and other infections as predictors for myocardial infarction.

OBJECTIVES: To study antibodies against five infectious agents for their prediction of major coronary events in men with and without evidence of coronary heart disease at baseline. DESIGN: A case-control study nested within a prospective population study. SUBJECTS: The study cases included 441 men 45-64 years old with nonfatal myocardial infarction or coronary death within a mean follow-up time of 10 years. A total of 165 men had already signs of heart disease at baseline, whilst 276 were apparently healthy at the beginning of the study. Two controls for each case were matched for age, heart disease status and place of residence. Antibodies against enterovirus, Mycoplasma pneumoniae, Chlamydia pneumoniae, cytomegalovirus and adenovirus were determined. RESULTS: Men without reported baseline heart disease, but not those with heart disease, showing the highest quartile of antibodies to enterovirus and mycoplasma or increased levels of immune complex-bound antibodies to chlamydia had a significantly higher risk of coronary events than men with lower level of antibodies. The increased risk demonstrated in men with high levels of antibodies to enterovirus and mycoplasma remained significant after adjustment for other antibodies, acute-phase reactant and conventional risk factors. Serological evidence of infection by multiple agents was also significantly associated with coronary events. CONCLUSIONS: Serological evidence for several infectious agents is associated with the risk of coronary heart disease, but only in men without baseline history of heart disease.

Acute-Phase Reaction↗

Chlamydia pneumoniae inhibits apoptosis in human epithelial and monocyte cell lines.

Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to cause persistent infections that has been associated with many chronic conditions such as asthma and coronary artery disease. However, its immunopathogenic mechanisms are poorly understood. When aiming to study the impact of C. pneumoniae infection on host cell apoptosis, we found that epithelial infected (HL) cells and macrophages (U937-line) were resistant to staurosporine and tumour necrosis factor (TNF)-alpha-induced physiological apoptosis 48, 72 or 120 h post-infection, as determined by flow cytometry, DNA fragmentation assay and fluorescence microscopy. The antiapoptotic influence was observed even at a late stage of the chlamydial life cycle and was dependent on the chlamydial protein synthesis. The mechanisms involved blockage of mitochondrial cytochrome c release and caspase 3 activation. We also found that during a persistent C. pneumoniae infection induced in vitro by penicillin treatment of cell cultures, the inhibition of apoptosis was extended for up to 120 h of follow-up post-infection and was restricted to the cells carrying chlamydial inclusions. Our findings suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by which C. pneumoniae infection can mediate the development of chronic diseases.

Apoptosis↗

Effect of acute Chlamydia pneumoniae infection on lipoprotein metabolism in NIH/S mice.

Chlamydia pneumoniae is a well-known cause of respiratory infections, globally. Chronic C. pneumoniae infection has been associated with atherosclerosis. The aim of the present study was to investigate the effects of acute C. pneumoniae infection on serum lipid levels and some regulatory proteins/enzymes in NIH/S mice. Female mice (n=30) were intranasally infected with 5.3*10(5) inclusion forming units (IFU) of C. pneumoniae and control mice (n = 30) were inoculated with buffer. Six uninoculated mice at day 0 and then six mice from each group 3, 6, 9, 14 and 20 days post-inoculation were killed and serum samples were collected for analysis. Successful infection was confirmed by IgG response to C. pneumoniae and positive Chlamydia cultivation from the lungs. Serum triglycerides and total cholesterol, as well as the activities of hepatic lipase (HL), lecithin-cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) and the concentration of lipopolysaccharide-binding protein (LBP) were analyzed. In C. pneumoniae infected mice, a minor change in triglyceride (corrected p-value 0.020) levels was observed 9 days post-infection (p.i.). LCAT activity declined remarkably, and the lowest activities were measured on day 9 p.i. (67% from the baseline value). HL and PLTP activities did not differ from those in the control group during the whole experimental period. There was a 2.5-fold increase in the serum LBP concentration owing to the C. pneumoniae infection 9 days p.i. The data indicate that acute C. pneumoniae infection, although clinically almost asymptomatic, causes small, transient changes in serum total lipids and some key proteins involved in lipoprotein metabolism in mice.

Acute Disease↗

Microbial etiology of community-acquired pneumonia in the adult population of 4 municipalities in eastern Finland.

To determine the etiology of community-acquired pneumonia in the adult population of a defined area, specific antibody responses in paired serum samples, levels of circulating pneumococcal immune complexes in serum samples, and pneumococcal antigen in urine were measured. Samples (304 paired serum samples and 300 acute urine samples) were obtained from 345 patients > or =15 years old with community-acquired, radiologically confirmed pneumonia, which comprised all cases in the population of 4 municipalities in eastern Finland during 1 year. Specific infecting organisms were identified in 183 patients (including 49 with mixed infection), as follows: Streptococcus pneumoniae, 125 patients; Haemophilus influenzae, 12; Moraxella catarrhalis, 8; chlamydiae, 37 (of which, Chlamydia pneumoniae, 30); Mycoplasma pneumoniae, 30; and virus species, 27. The proportion of patients with pneumococcal infections increased and of those with Mycoplasma infections decreased with age, but for each age group, the etiologic profile was similar among inpatients and among outpatients. S. pneumoniae was the most important etiologic agent. The annual incidence of pneumococcal pneumonia per 1000 inhabitants aged > or =60 years was 8.0.

Adolescent↗

Infectious etiologies in acute exacerbation of COPD.

Acute exacerbation (AE) is a frequent episode during the prolonged chronic course of chronic obstructive pulmonary disease (COPD), which entails significant morbidity and mortality. The purpose of this study was to determine the frequency distribution of infectious etiologies in these episodes. Two hundred forty hospitalizations for AECOPD were included in a prospective, purely serologically based study. Paired sera were obtained for each of the hospitalizations and were tested using immunofluorescence or EIA methods to identify 13 different pathogens. Only significant changes in antibody titers were considered diagnostic. The mean age ( +/- SD) of the patients was 66.8 +/- 9.0 years and 179 (84%) were males. In 175 (72.9%) hospitalizations at least one infectious etiology was identified. In 117 (48.8%) hospitalizations at least one of 7 viral etiologies was identified. In 72 (30.0%) hospitalizations at least one of the following atypical bacteria was identified: Legionella spp. in 40 (16.7%), Mycoplasma pneumoniae in 34 (14.2%), and Coxiella burnetii in a single hospitalization. In 58 (24.2%) hospitalizations at least one classic bacterial etiology was found: Streptococcus pneumoniae in 48 (20.0%), Hemophilus influenzae in 10 (4.2%) and Moraxella catarrhalis in 9 (3.8%). More than one etiology was found in 72 (30.0%) hospitalizations. There were no significant differences in the etiologic distribution when the patients were classified by severity of airway obstruction or the clinical type of the exacerbation. We conclude that in most cases of hospitalization due to AECOPD the infectious etiology is viral or atypical bacteria and is classic bacteria in only a minority of cases. More than one etiologic cause can be identified in a third of the cases. The frequency distribution of the etiologies is not associated with the severity of airway obstruction or the clinical type of the exacerbation. The results of our study suggest that atypical bacteria should be covered in antibiotic regimens recommended for AECOPD. This issue should be addressed in future studies.

Adult↗

Twelve-month safety of entacapone in patients with Parkinson's disease.

The safety of entacapone combined with levodopa and a dopadecarboxylase (DDC) inhibitor was tested in a 12-month double-blind study of 326 patients with idiopathic Parkinson's disease (PD). The study population represented 'typical' PD outpatients, including patients with varying disease severity and with various concomitant medications. Two-thirds of the patients were randomized to receive 200 mg of entacapone with each of 2--10 daily levodopa doses, and one-third to receive placebo. All entacapone patients were included in the safety evaluation of adverse events (AEs), vital signs, ECG, and laboratory parameters. Entacapone was well tolerated with a discontinuation rate due to AEs of 14% compared with 11% with placebo (NS). As expected, due to dopaminergic enhancement, dyskinesia was more frequent as an AE with entacapone than with placebo. Dryness of mouth, urine discoloration and diarrhoea were more frequent non-dopaminergic AEs with entacapone than with placebo. Entacapone had no adverse effects on hepatic enzyme activity, ECG or haemodynamic parameters, and there was no evidence of any toxicity. As an indication of levodopa enhancement with entacapone, patients taking 5--10 doses of levodopa, most likely representing predominantly fluctuating patients, showed a significant decrease in their mean daily levodopa dose of 94 mg in the entacapone group compared with a decrease of 39 mg in the placebo group (P < 0.01). The interval between the first two morning doses of levodopa increased by 17% with entacapone, whereas with placebo no extension was observed (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was maintained. As further evidence of efficacy, Parkinsonian symptoms markedly worsened in all patients after withdrawal of entacapone. We conclude that entacapone is safe in optimizing levodopa in long-term treatment of idiopathic Parkinson's disease. Monitoring of liver or other safety parameters during entacapone treatment is not required.

Aged↗

Use of doxycycline to decrease the growth rate of abdominal aortic aneurysms: a randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: Eradication of Chlamydia pneumoniae infection and inhibition of elastolytic matrix metalloproteinases with doxycycline have been suggested to reduce the growth rates of small abdominal aortic aneurysms (AAA). We designed a study to investigate the efficacy of doxycycline in reducing the expansion of small AAAs. SUBJECTS AND METHODS: This was a prospective, double-blind, randomized, placebo-controlled study that was set in a university referral hospital. The study group consisted of 32 of 34 initially eligible patients who had an AAA diameter perpendicular to the aortic axis of 30 mm or more in size or a ratio of infrarenal to suprarenal aortic diameter of 1.2 or more and a diameter less than 55 mm. Patients were randomly assigned to receive either doxycycline (150 mg daily) or placebo during a 3-month period and underwent ultrasound surveillance during an 18-month period. Outcome measures included aneurysm expansion rates, the number of patients who had AAA rupture or repair, C pneumoniae antibody titers, and serum concentrations of C-reactive protein. RESULTS: The aneurysm expansion rate in the doxycycline group was significantly lower than that in the placebo group during the 6- to 12-month (P = .01) and the 12- to 18-month periods (P =.01). Five patients (41%) in the placebo group and 1 patient (7%) in the doxycycline group had an overall expansion of the aneurysm of 5 mm or more during the 18-month follow-up. Among the placebo group patients, a higher expansion rate was observed in those with enhanced C pneumoniae immunoglobulin G antibody titers (> 128) than in those with lower titers (P = .03). Doxycycline treatment had no clear effect on antibody titers. However, at 6-month follow-up, C-reactive protein levels in the doxycycline group were significantly lower than the baseline levels (P = .01). CONCLUSIONS: The results of this small pilot study suggest that doxycycline may favorably alter the outcome of patients with small AAA. However, because of the small size of this randomized study and of the potentially confounding effect of pretreatment risk factors, doxycycline-based treatment cannot be justified only on the ground of the current results. Because of the high prevalence of this disorder and its clinical, social, and economic relevance, a multicenter study should be performed to further investigate whether there is any place for medical treatment of small AAAs.

Aged↗

A multi-laboratory evaluation of an enzyme-linked immunoassay quantitating human antibodies to Streptococcus pneumoniae polysaccharides.

An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates human antibodies to serotype specific S. pneumoniae polysaccharide (PnPs) in human sera. Based on the observations previously described by Koskela (1), native PnPs are used as coating antigens and sera are absorbed with a soluble pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure measurement of serotype specific anti-PnPs antibodies. The robustness of this method was evaluated by ten laboratories using the same reagents, protocol, and five human serum samples. Reproducible antibody values were obtained for IgM, IgG, and IgA antibodies to five different PnPs serotypes, 3, 6B, 14, 19F, and 23F. The overall mean percent coefficients of variation in this interlaboratory study for all five selotype specific anti-PnPs determinations with the five coded sera were 30% for IgG, 3/% for IgM, and 36% for IgA. This assay can be standardized for quantitation of serotype specific anti-PnPs antibodies, allowing comparison of antibody values in vaccine trials evaluating pneumococcal vaccines.

Enzyme-Linked Immunosorbent Assay↗

Seroetiology of acute lower respiratory infections among hospitalized children in Beijing.

BACKGROUND: Little is known of the etiology of childhood acute lower respiratory infections in China, where the use of antimicrobials is indiscriminate. Trials to change such a policy require etiologic data, especially on the bacteria most relevant to these common diseases. METHODS: One hundred consecutive infants and children from 3 months to 14 years of age with symptoms and signs compatible with acute lower respiratory infections were studied prospectively in the largest pediatric hospital in Beijing from February to May, 1997. Blood culture, thorax radiography and paired sera for 20 microbiologic assays were taken, and the course of illness was monitored uniformly. Disease severity was graded. RESULTS: In 24 cases there was evidence only of bacterial etiology, and in 5 solely viral agents were found; 3 children probably had a mixed bacterial-viral infection. Surprisingly no pneumococcal infection was detected, Mycoplasma pneumoniae (n = 21), Haemophilus influenzae type b (n = 8) and Chlamydia pneumoniae (n = 7) being the dominant bacteria. All children recovered. CONCLUSIONS: Routine use of antimicrobials for these patients seems unjustified. Serologic evidence for the H. influenzae type b etiology is encouraging in terms of vaccination, but confirmatory studies are needed.

Adolescent↗

Pneumococcal carriage in children during their first two years: important role of family exposure.

BACKGROUND: Close family and day-care contacts have been identified as risk factors for pneumococcal (Pnc) carriage. This study addresses the risk of Pnc carriage by infants 2 to 24 months of age in terms of simultaneous carriage of pneumococcus by family members. METHODS: Nasopharyngeal swabs were collected from 100 Finnish infants and their family members on 10 scheduled visits (when infant was 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 months of age). The 7 most common pneumococcal serogroups (4, 6, 9, 14, 18, 19, 23), also represented in the new heptavalent Pnc conjugate vaccine, were analyzed. Marginal logistic regression analyses were performed to assess the relative importance of different predictors for carriage. RESULTS: The carriage of the studied Pnc serogroups increased with age, being highest at the age of 18 months (28%). Among children older than 6 months of age, the strongest predictor of carriage was simultaneous carriage of the same serogroup by another family member (odds ratio, 3.8; 95% confidence interval, 2.1 to 6.9). At the age of 6 months or younger, carriage was rare and was not significantly associated with a family carriage. CONCLUSIONS: Young infants (< or =6 months old) were largely protected from pneumococcal carriage. After this age family transmission seemed very important despite the small family size. Contrary to some earlier studies communal day care was not associated with an increased risk of Pnc carriage. This could be partly because of the long parental leave in Finland and thus the late age of starting organized day care.

Age Factors↗

Clinical profile of serologically diagnosed pneumococcal pneumonia.

OBJECTIVE: To describe the characteristics of serologically diagnosed pneumococcal pneumonia and compare them with those of respiratory syncytial virus (RSV) pneumonia and bacteremic pneumococcal pneumonia. METHODS: IgG antibodies to pneumococcal pneumolysin and C-polysaccharide as well as immune complexes containing IgG antibodies to pneumolysin and C-polysaccharide were measured from acute and convalescent sera of 254 children with community-acquired pneumonia. Evidence of pneumococcal infection was found in 93 children. Clinical and laboratory data were retrospectively collected from the records of 38 children with sole (all tests for 16 other microbes negative) pneumococcal pneumonia and compared with 26 sole RSV-induced pneumonia from the present series and with the data of our 85 bacteremic pneumococcal pneumonia cases reported earlier. RESULTS: Serologically diagnosed sole pneumococcal pneumonia clinically overlapped with RSV pneumonia, but RSV pneumonia was more often associated with tachypnea (45% vs. 17%, P < 0.05) and low white blood cell counts (means, 12.0 x 109/l vs. 20.8 x 109/l; P < 0.001) as well as low serum C-reactive protein levels (means, 28 mg/l vs. 137 mg/l; P < 0.001). Alveolar infiltrates were found in 15% of chest radiographs of children with RSV pneumonia compared with 76% of those in children with sole pneumococcal pneumonia (P < 0.001). Patients with bacteremic pneumonia more often appeared ill (79% vs. 50%, P < 0.001) and more often had typical pneumococcal pneumonia with high fever, leukocytosis and lobar infiltrates in their chest radiographs (70% vs. 34%, P < 0.05) than those with serologically diagnosed pneumococcal pneumonia. CONCLUSIONS: Serologically detected pneumococcal pneumonia differs significantly from RSV pneumonia in laboratory and chest radiography findings, but the clinical signs and symptoms overlap considerably. Bacteremic pneumococcal pneumonia is a more severe illness than the serologically diagnosed one.

Adolescent↗

Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community.

BACKGROUND: Acute lower respiratory tract illness in previously well adults is usually labelled as acute bronchitis and treated with antibiotics without establishing the aetiology. Viral infection is thought to be the cause in most cases. We have investigated the incidence, aetiology, and outcome of this condition. METHODS: Previously well adults from a stable suburban population consulting over one year with a lower respiratory tract illness were studied. For the first six months detailed investigations identified predetermined direct and indirect markers of infection. Evidence of infection was assessed in relation to presenting clinical features, indirect markers of infection, antibiotic use, and outcome. RESULTS: Consultations were very common, particularly in younger women (70/1000 per year in previously well women aged 16-39 years), mainly in the winter months; 638 patients consulted, of whom 316 were investigated. Pathogens were identified in 173 (55%) cases: bacteria in 82 (Streptococcus pneumoniae 54, Haemophilus influenzae 31, Moraxella catarrhalis 7), atypical organisms in 75 (Chlamydia pneumoniae 55, Mycoplasma pneumoniae 23), and viruses in 61 (influenza 23). Seventy nine (24%) had indirect evidence of infection. Bacterial and atypical infection correlated with changes in the chest radiograph and high levels of C reactive protein but not with (a) the GP's clinical assessment of whether infection was present, (b) clinical features other than focal chest signs, and (c) outcome, whether or not appropriate antibiotics were prescribed. CONCLUSIONS: Over 50% of patients have direct and/or indirect evidence of infection, most commonly bacterial and atypical pathogens, but the outcome is unrelated to the identified pathogens. Many patients improve without antibiotics and investigations do not help in the management of these patients. GPs can reassure patients of the causes and usual outcome of this self-limiting condition.

Acute Disease↗

Study of community acquired pneumonia aetiology (SCAPA) in adults admitted to hospital: implications for management guidelines.

BACKGROUND: Since the last British study of the microbial aetiology of community acquired pneumonia (CAP) about 20 years ago, new organisms have been identified (for example, Chlamydia pneumoniae), new antibiotics introduced, and fresh advances made in microbiological techniques. Pathogens implicated in CAP in adults admitted to hospital in the UK using modern and traditional microbiological investigations are described. METHODS: Adults aged 16 years and over admitted to a teaching hospital with CAP over a 12 month period from 4 October 1998 were prospectively studied. Samples of blood, sputum, and urine were collected for microbiological testing by standard culture techniques and new serological and urine antigen detection methods. RESULTS: Of 309 patients admitted with CAP, 267 fulfilled the study criteria; 135 (50.6%) were men and the mean (SD) age was 65.4 (19.6) years. Aetiological agents were identified from 199 (75%) patients (one pathogen in 124 (46%), two in 53 (20%), and three or more in 22 (8%)): Streptococcus pneumoniae 129 (48%), influenza A virus 50 (19%), Chlamydia pneumoniae 35 (13%), Haemophilus influenzae 20 (7%), Mycoplasma pneumoniae 9 (3%), Legionella pneumophilia 9 (3%), other Chlamydia spp 7 (2%), Moraxella catarrhalis 5 (2%), Coxiella burnetii 2 (0.7%), others 8 (3%). Atypical pathogens were less common in patients aged 75 years and over than in younger patients (16% v 27%; OR 0.5, 95% CI 0.3 to 0.9). The 30 day mortality was 14.9%. Mortality risk could be stratified by the presence of four "core" adverse features. Three of 60 patients (5%) infected with an atypical pathogen died. CONCLUSION: S pneumoniae remains the most important pathogen to cover by initial antibiotic therapy in adults of all ages admitted to hospital with CAP. Atypical pathogens are more common in younger patients. They should also be covered in all patients with severe pneumonia and younger patients with non-severe infection.

Adolescent↗