John Macfarlane

Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study

Background: In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. Methods: Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. Results: 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age ⩾65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate ⩾30/min, low systolic(<90 mm Hg) or diastolic (⩽60 mm Hg) Blood pressure), age ⩾65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. Conclusions: A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.

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 Chlamydiaspp 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% v27%; 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.

Influence of patients' expectations on antibiotic management of acute lower respiratory tract illness in general practice: questionnaire study.

Abstract Objective: To assess patients views and expectations when they consult their general practitioner with acute lower respiratory symptoms and the influence these have on management. Design: General practitioners studied consecutive, previously well adults and recorded clinical data, the certainty regarding their prescribing decision, and the influence of non-clinical factors on that decision. Patients completed a questionnaire at home after the consultation. Setting: 76 doctors from suburban, inner city, and rural practices. Subjects: 1014 eligible patients entered; 787 (78%) returned the questionnaire. Main outcome measures: The views of the patient, the views of and antibiotic prescription by the doctor. Results: Most patients thought that their symptoms were caused by an infection (662) and that antibiotics would help (656) and had both wanted (564) and expected (561) such a prescription. 146 requested an antibiotic, 587 received one. Of the 643 patients who thought they had an infection, 582 wanted an antibiotic and thought it would help. Severity of symptoms did not relate to wanting antibiotics. For those prescribed antibiotics, their doctor thought they were definitely indicated in only 116 cases and not indicated in 126. Patient pressure most commonly influenced the decision to prescribe even when the doctor thought antibiotics were not indicated. Doctors considered antibiotics definitely indicated in only 1% of the group in whom patient pressure influenced the prescribing decision. Patients who did not receive an antibiotic that they wanted were much more likely to express dissatisfaction. Dissatisfied patients reconsulted for the same symptoms twice as often as satisfied patients. Conclusion: Patients presenting with acute lower respiratory symptoms often believe that infection is the problem and antibiotics the answer. Patients expectations have a significant influence on prescribing, even when their doctor judges that antibiotics are not indicated. Key messages Three quarters of previously well adults consulting with the symptoms of an acute lower respiratory tract illness receive antibiotics even though their general practitioners assess that antibiotics are definitely indicated in only a fifth of such cases Most patients think their symptoms are caused by infection, think an antibiotic will help, and want antibiotics; a fifth ask for them Patients expectations and views and doctors concern that the patient may otherwise reconsult have a powerful effect on doctors decision to prescribe, even when they consider that an antibiotic is not indicated Patients who did not receive an antibiotic that they wanted were more likely to be dissatisfied. Dissatisfied patients reconsulted twice as frequently Terms such as chest infection and bronchitis, which imply infection needing antibiotics, are probably unhelpful. Patient education may be more effective in altering the cycle of antibiotic prescription and consultations

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 GPs 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.

Prospective case-control study of role of infection in patients who reconsult after initial antibiotic treatment for lower respiratory tract infection in primary care

Abstract Objective: To assess direct and indirect evidence of active infection which may benefit from further antibiotics in adults who reconsult within 4 weeks of initial antibiotic management of acute lower respiratory tract infection in primary care. Design: Observational study with a nested case-control group. Setting: Two suburban general practices in Arnold, Nottingham, over 7 winter months. Subjects: 367 adults aged 16 years and over fulfilling a definition of lower respiratory tract infection and treated with antibiotics. 74 (20%) patients who reconsulted within 4 weeks for the same symptoms and 82 “control” patients who did not were investigated in detail at follow up. Main outcome measures: Direct and indirect evidence of active infection at the time of the reconsultation or the follow up visit with the research nurse for the controls. Investigations performed included sputum culture, pneumococcal antigen detection, serial serology for viral and atypical pathogens and C reactive protein, throat swabs for detecting viral and atypical pathogens by culture and polymerase chain reaction, and chest radiographs. Results: Demographic and clinical features of the groups were similar. Two thirds of the 74 patients who reconsulted received another antibiotic because the general practitioner suspected continuing infection. Any evidence of infection warranting antibiotic treatment was uncommon at reconsultation. The findings for the two groups were similar for the occurrence of identified pathogens; chest x ray changes of infection (present in 13%); and C reactive protein concentrations, which had nearly all fallen towards normal. Only three patients in the reconsultation group had concentrations ≥40 mg/l. Pathogens identified at follow up in the 156 patients in both groups included ampicillin sensitive bacteria in six. Atypical infections diagnosed in 27 (Chlamydia pneumoniae in 22) and viral infections in 54 had probably been present at the initial presentation. Conclusion: Our study suggests that active infection, which may benefit from further antibiotics, is uncommon in patients who reconsult after a lower respiratory tract infection, and a repeat antibiotic prescription should be the exception rather than the rule. Other factors, such as patients perception of their illness, may be more important than disease and infection in their decision to reconsult. Key messages Lower respiratory tract infections are very common, but even if they have been given antibiotics, a fifth to a quarter of patients reconsult and many receive further antibiotics No demographic or clinical features at presentation identify those who may reconsult Direct and indirect evidence of infection warranting antibiotics is uncommon in those who reconsult and no different to those who do not Chlamydia pneumoniae is the commonest infection identified in this study population Antibiotics should be the exception rather than the rule for patients who reconsult

Pneumonia and pregnancy

Community acquired pneumonia (CAP) is recognised as a common problem that carries a substantial morbidity and mortality. The burden of disease falls mainly on people at the extremes of age and the occurrence of CAP in young adults is uncommon. Nevertheless, pneumonia in young adults can be severe and fatal.1 In the pregnant patient, pneumonia is the most frequent cause of fatal non-obstetric infection.2 nnConcern that pneumonia occurring in a pregnant patient may be more frequent, exhibit atypical features, run a more severe course, or be more difficult to treat than in a non-pregnant patient is not unusual. Underlying these concerns are the recognised physiological and immunological changes that occur during pregnancy which may compromise the mothers ability to respond to an infection. Added to this are concerns for the health of the fetus.nnAlterations in cellular immunity have been widely reported and are aimed primarily at protecting the fetus from the mother. These changes include decreased lymphocyte proliferative response, especially in the second and third trimesters, decreased natural killer cell activity, changes in T cell populations with a decrease in numbers of circulating helper T cells, reduced lymphocyte cytotoxic activity, and production by the trophoblast of substances that could block maternal recognition of fetal major histocompatibility antigens.3-7 nnIn addition, hormones prevalent during pregnancy—including progesterone, human chorionic gonadotropin, alpha-fetoprotein and cortisol—may inhibit cell mediated immune function.6These changes could theoretically increase the risk from infection, particularly by viral and fungal pathogens.nnAnatomically, the enlarging uterus causes elevation of the diaphragm by up to 4u2009cm and splaying of the thoracic cage. A 2.1u2009cm increase in the transverse diameter of the chest and a 5–7u2009cm increase in the circumference of the thoracic cage has been reported.8These changes may decrease the mothers ability to clear secretions. The …

Treatment of community-acquired lower respiratory tract infections during pregnancy.

The incidence of lower respiratory tract infection (LRTI) in women of child-bearing age is approximately 64 per 1000 population. The spectrum of illness ranges from acute bronchitis, which is very common, through influenza virus infection and exacerbations of underlying lung disease, to pneumonia, which, fortunately is uncommon (<1.5% LRTI), but can be severe.Acute bronchitis is generally mild, self-limiting and usually does not require antibacterial therapy. Influenza virus infection in pregnant women has been recently related to increased hospitalization for acute cardiorespiratory conditions. At present, the safety of the newer neuraminidase inhibitors for the treatment of influenza virus infection has not been established in pregnancy and they are not routinely recommended. In influenza virus infection complicated by pneumonia, antibacterial agents active against Staphylococcus aureus and Streptococcus pneumoniae superinfection should be used.There are few data on infective complications of asthma or COPD in pregnancy. The latter is rare, as patients with COPD are usually male and aged over 45 years. Management is the same as for nonpregnant patients.The incidence and mortality of pneumonia in pregnancy is similar to that in nonpregnant patients. Infants born to pregnant patients with pneumonia have been found to be born earlier and weigh less than controls. Risk factors for the development of pneumonia include anemia, asthma and use of antepartum corticosteroids and tocolytic agents. Based on the few available studies, the main pathogens causing pneumonia are S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and viruses. β-Lactam and macrolide antibiotics therefore remain the antibiotics of choice in terms of both pathogen coverage and safety in pregnancy. In HIV-infected pregnant patients, recurrent bacterial pneumonia, but not Pneumocystis carinii pneumonia (PCP), is more common than in nonpregnant patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) has not definitely been associated with adverse clinical outcomes despite theoretical risks. Currently it is still the treatment of choice in PCP, where mortality remains high.In conclusion, there are few data specifically related to pregnant women with different types of LRTI. Where data are available, no significant differences compared with nonpregnant patients have been identified. In considering the use of any therapeutic agent or investigation in pregnant patients with LRTI, safety aspects must be carefully weighed against potential benefit. Otherwise, management strategies should not differ from those for nonpregnant patients. Further research in this area is warranted.

PNEUMOCOCCAL AND INFLUENZA VACCINATION: CURRENT SITUATION AND FUTURE PROSPECTS

Background: The effectiveness of influenza and pneumococcal vaccination in the prevention of hospital admissions and death has not been assessed prospectively. We have therefore examined the effects of influenza and pneumococcal vaccination in individuals aged 65 years or older in a 3-year prospective study, between December 1 1998 and May 31 1999. Methods: All individuals in Stockholm County aged 65 years or older (259 627) were invited to take part in a vaccination campaign against influenza and pneumococcal infection. We recorded for all vaccine recipients (100 242) name and date of birth, and whether they had been given both or one of the vaccines. All individuals (>65 years) admitted to hospital in Stockholm County with influenza and pneumonia related diagnoses were identified between December 1 1998 and May 31 1999. Findings: The incidence (per 100 000 inhabitants per year) of hospital treatment was lower in the vaccinated than in the unvaccinated cohort for all diagnoses: 263 versus 484 (–46% (95% CI 34–56)) for influenza; 2199 versus 3097 (–29% (24–34)) for pneumonia; 64 versus 100 (–36% (3–58)) for pneumococcal pneumonia, and 20 versus 40 (–52% (1–77)) for invasive pneumococcal disease. The total mortality was 57% (55–60) lower in vaccinated than in unvaccinated individuals (15.1 vs 34.7 deaths per 1000 inhabitants). Interpretation: These findings show that general vaccination leads to substantial health benefits and to a reduction of mortality from all causes in this age group. (Lancet 2001;357:1008–11)

Disseminated Mycobacterium tuberculosis infection due to interferon γ deficiency. Response to replacement therapy

The case of a previously healthy HIV seronegative woman with disseminated Mycobacterium tuberculosis infection and markedly reduced interferon γ production is reported here. Complete healing of her disseminated lesions was seen only after addition of subcutaneous interferon γ to her tuberculosis treatment.

Severe pneumonia and a second antibiotic.

Streptococcus pneumoniae is the most common cause of community acquired pneumonia (CAP) and the pathogen causing most deaths. CAP management guidelines in North America and the UK recommended that patients with severe pneumonia be given initially a combination antibiotic therapy. According to a recent retrospective study adults with severe bacteremic pneumococcal pneumonia have significantly greater risk of death if they receive a single antibiotics rather than combination antibiotics on the first day of admission. Although some patients died shortly after admission half of the deaths occurred after 5 days and mortality rates continued to increase throughout the 15-day study suggesting that subsequent antibiotic therapy might be an important determinant of outcome. Hence the investigators recommended a double-blind trial of single versus combination therapy for patients with severe CAP and suspected bacteremic pneumococcal pneumonia. The need to cover this pathogen effectively in any empirical antibiotic regimen for CAP remains a priority.