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In addition to direct antibacterial actions, 14- and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis. A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions. A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects. Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.

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In the study presented here, data collected prospectively from 340 adult patients hospitalised in five countries with bacteremic pneumococcal CAP and treated with a ss-lactam +/- a macrolide were analysed retrospectively to evaluate the efficacy of this antimicrobial combination. Univariate and multivariate analyses revealed no significant effect on case fatality rate when a macrolide/ss-lactam regimen was used as initial therapy. Results were not affected by severity of illness, or by excluding patients who died within 2 days of admission. Identified predictors of death in a multivariate regression model were age >65 years (OR=2.6), two or more lung lobes affected (OR=2.2), and severity of disease as estimated using the acute physiology score (APS)>8.

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Patients with chronic renal failure (CRF) have a high incidence of tuberculosis (TB). Those from the Indian subcontinent are at particular risk. The frequency of side-effects associated with antituberculous treatment in a group of patients with CRF was studied. All cases of TB in patients with CRF occurring over a 13-yr period at the Manchester Royal Infirmary, from 1986-1999, were identified by diagnostic coding, microbiology records and a TB database. The case notes were then reviewed. Twenty-four cases were identified, eight predialysis and 16 requiring regular dialysis. TB occurring in the dialysis group was extrapulmonary in every case. Nineteen of 24 (79%) patients were of Indian subcontinent origin and 14 of 16 (87%) dialysis patients were non-Caucasian. Adverse effects of treatment occurred in two of eight (25%) in the predialysis group and nine of 16 (56%) of the dialysis group. These were most commonly neuropsychiatric (6), hepatic (4) and gastrointestinal (4). Neuropsychiatric symptoms occurred exclusively in dialysis patients. In conclusion, a high incidence of side-effects from antituberculous medication, especially neuropsychiatric, hepatic and gastrointestinal, was identified in patients with chronic renal failure. Careful monitoring for side-effects is essential in this group, and consideration should be given to administering antituberculous chemoprophylaxis to all high-risk groups.

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BACKGROUND: Patients with chronic renal failure have an increased risk of tuberculosis (TB). This occurs with much higher frequency within the first 12 months of initiating dialysis and is usually extrapulmonary in nature. Patients most at risk are those from susceptible ethnic groups, especially the Indian subcontinent. Peritoneal TB, otherwise relatively uncommon, has emerged as an important form of TB in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: All cases of peritoneal TB occurring at our institution in patients undergoing CAPD over a 13 year period were identified and analysed. RESULTS: Eight cases were identified, of which seven were non-Caucasian. These patients' characteristics and outcomes are presented. All were undergoing CAPD and most developed TB within 12 months of initiating dialysis. All presented with fever, but symptoms and signs were indistinguishable from bacterial peritonitis. Six were culture-positive, mainly from peritoneal dialysis fluid, but only two cases proved smear-positive. All were treated with standard anti-tuberculous chemotherapy. Three went on to permanent haemodialysis as a result of peritonitis and three have died, one of these as a result of TB. CONCLUSIONS: Peritoneal TB, whilst otherwise relatively uncommon, is an important manifestation of TB in CAPD patients and usually develops soon after commencing dialysis. The reasons for this are unknown and require further research.

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BACKGROUND: The aim of this study was to describe the frequency, causal pathogens, management, and outcome of a population of young adults who died from community acquired pneumonia (CAP). METHODS: Pneumonia deaths in England and Wales in adults aged 15-44 were identified between September 1995 and August 1996. Patients with underlying chronic illness including HIV infection were excluded. Clinical details for each case were collected from the hospital and general practitioner records. RESULTS: Death from CAP was identified in 27 previously well young adults (1.2 per million population per year). Twenty were known to have consulted a GP for this illness. Nine received antibiotics before hospital admission. A causative pathogen was identified in 17 cases (Streptococcus pneumoniae in eight). Bacteraemia was present in seven. All patients who reached a hospital ward received antibiotics (69% within two hours of admission). The British Thoracic Society antibiotic guidelines for severe CAP were followed in only 10 cases. Cardiac arrest at home or on arrival at hospital occurred in six cases, one of whom was successfully resuscitated. Of the remaining 21 patients, 71% had two or more markers of severe CAP. All 22 who were admitted reached an intensive care unit, but 11 of these required transfer to another hospital for some aspect of intensive care. One third of patients died within 24 hours of presenting to the hospital. CONCLUSIONS: Death from CAP in previously fit young adults still occurs. While some deaths might be preventable by better patient management, most are unlikely to be preventable by current management practices.

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A multicenter study was done during 1993-1995 to investigate prospectively the influence of several prognostic factors for predicting the risk of death among patients with pneumococcal bacteremia. Five centers located in Canada, the United Kingdom, Spain, Sweden, and the United States participated. Clinical parameters were correlated to antibiotic susceptibility and serotyping of the 354 invasive pneumococcal isolates collected and to molecular typing of 173 isolates belonging to the 5 most common serotypes (14, 9V, 23F, 3, and 7F). Serotype 14 was the most common among all isolates, but serotype 3 dominated in fatal cases and in isolates from Spain and the United States, the countries with the highest case-fatality rates. Fewer different patterns were found among the type 3 isolates, which suggests a closer clonal relationship than that among isolates belonging to other serotypes. Of type 3 isolates from fatal cases, 1 clone predominated. Other penicillin-susceptible invasive clones were also shown to spread in and between countries.

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To define the influence of prognostic factors in patients with community-acquired pneumococcal bacteremia, a 2-year prospective study was performed in 5 centers in Canada, the United States, the United Kingdom, Spain, and Sweden. By multivariate analysis, the independent predictors of death among the 460 patients were age >65 years (odds ratio [OR], 2.2), living in a nursing home (OR, 2.8), presence of chronic pulmonary disease (OR, 2.5), high acute physiology score (OR for scores 9-14, 7.6; for scores 15-17, 22; and for scores >17, 41), and need for mechanical ventilation (OR, 4.4). Of patients with meningitis, 26% died. Of patients with pneumonia without meningitis, 19% of those with >/=2 lobes and 7% of those with only 1 lobe involved (P=.0016) died. The case-fatality rate differed significantly among the centers: 20% in the United States and Spain, 13% in the United Kingdom, 8% in Sweden, and 6% in Canada. Differences of disease severity and of frequencies and impact of underlying chronic conditions were factors of probable importance for different outcomes.

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The purpose of this study was to identify risk factors for pneumonia diagnosed in the community by general practitioners, using a case control study in 29 general practices in Nottingham, U.K. Patients with radiographically confirmed pneumonia were compared with adults randomly selected from electoral registers corresponding to the catchment areas of the general practices taking part in the study. Sixty-six cases and 489 controls participated. Significant risk factors in univariate analysis included age, chronic obstructive pulmonary disease, congestive heart failure and lifetime consumption of cigarettes. Multiple logistic regression analysis of these four variables showed that age [adjusted odds ratio = 2.69 (for 30 year increment), 95%CI = 1.66-4.35] and chronic obstructive pulmonary disease (adjusted odds ratio= 1.99, 95%CI = 1.15-3.45) were independent risk factors. Only age and chronic obstructive pulmonary disease were independent risk factors for pneumonia in this study. Since cigarette smoking is the major cause of chronic obstructive pulmonary disease, these data suggest that cigarette smoking is the main avoidable risk factor for community-acquired pneumonia in adults.

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The objective of this report was to document the pattern of initial antibiotic prescribing in acute exacerbations of chronic obstructive pulmonary disease (COPD) in a hospital setting. All episodes of acute exacerbation of COPD, as diagnosed by the admitting doctor, in one hospital in the period January to May 1996, were identified. Case notes were reviewed retrospectively. Cases of radiographic pneumonia, bronchiectasis and incorrectly coded admissions were excluded. Symptoms, microbial cultures and initial antibiotic therapies were recorded. One hundred and fifty-nine patient episodes were identified; 40 were excluded yielding a sample of 119. Nineteen case notes were unavailable leaving a sample of 100 (84%) episodes. Eighty were treated with antibiotics on admission; amoxycillin was the most frequently prescribed, in 46 (58%) episodes. Of the antibiotic treated group, 42 (53%) patients were given dual therapy, most commonly a macrolide antibiotic with either amoxycillin or a cephalosporin. Intravenous treatment was used in 22 (28%) cases. The duration of intravenous treatment was >48 h in 12 (15%) cases. A total of 76 sputum samples were analysed from 55 patient episodes: 34 (45%) were culture positive. In 15 (27%) patient episodes, antibiotic therapy was changed or instituted on the basis of culture results. These data suggest that antibiotic treatment is not optimal, with overuse of antibiotics, especially intravenous and dual therapy.

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BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.

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Community-acquired pneumonia (CAP) is a common condition which has a significant mortality. The management of a patient with CAP is centred around assessment and correction of gas exchange and fluid balance together with administration of appropriate antibiotics. Up to 10 different pathogens regularly cause CAP, of which Streptococcus pneumoniae is the most important. These different pathogens cannot be distinguished by clinical features or simple laboratory tests. Microbiological tests are slow and insensitive, so empirical therapy is necessary, at least initially. Accurate assessment of illness severity is the most important factor determining initial management, since this assists the decision of whether to admit the patient to hospital in addition to guiding antibiotic choice and route of administration. Two different approaches to severity assessment are outlined. Our antibiotic recommendation for empirical therapy for the patient managed at home and the previously fit patient admitted to hospital is amoxicillin. Amoxicillin/clavulanate plus a macrolide is our choice for the severely ill previously fit patient and a third-generation cephalosporin plus a macrolide is recommended for the severely ill patient with comorbidity. Alternative pathogens and specific treatment regimens are also described. There may be several causes of treatment failure, and in patients who fail to respond to therapy, it is essential to review all the initial clinical and laboratory information, which if necessary must be repeated.

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Sputum isolation of Pseudomonas aeruginosa (PA) is associated with extensive disease in bronchiectasis. It is not known, however, whether infection with P. aeruginosa is the result or the cause of severe disease. We compared spirometry in patients with bronchiectasis before and after infection with P. aeruginosa, with that of patients infected by other organisms. All patients (n=12) with chronic colonization by P. aeruginosa (PA group) were studied. These were compared with other patients with bronchiectasis with no isolations of P. aeruginosa (n=37, non-PA group). In the PA group, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were lower than in the non-PA group. The PA group, however, also had lower values at the time of initial colonization with P. aeruginosa than the current values for the non-PA group. Change in FEV1 and FVC over time was faster in the PA group than in the non-PA group. Reduction of FEV1 and FVC over time in the PA group prior to P. aeruginosa colonization was intermediate, not being statistically different from either value above. Our results confirm the association of chronic P. aeruginosa colonization with poor lung function, but conclude that patients with bronchiectasis who become colonized by P. aeruginosa have poorer lung function when first colonized than those colonized by other organisms. Decline in lung function is faster in those chronically colonized by P. aeruginosa than in those colonized by other organisms. It is not clear whether chronic P. aeruginosa colonization causes an accelerated decline in lung function or whether it is simply a marker of those whose lung function is already declining rapidly.

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OBJECTIVE: To ascertain the effects of locally injected immunostimulant and tripeptide-copper complex (TCC) on improving healing of pad wounds. DESIGN: Wounds in pads of large dogs were injected with either medication or physiologic saline solution (controls). Healing was evaluated. ANIMALS: 12 mature English Pointers. PROCEDURE: Full-thickness 6 x 8-mm wounds in metatarsal and third and fourth digital pads were injected with immunostimulant or TCC at 0, 3, and 6 days after wounding. Wounds on control dogs were injected with physiologic saline solution. Using planimetric measurements at 0, 3, 6, 14, and 21 days, rates of healing were evaluated. Biopsy of the digital pad wounds at 3, 6, and 14 days was used to evaluate collagen content by hydroxyproline analysis. Biopsy specimens were also evaluated for type-I and type-III collagen, using Sirius red differential staining. RESULTS: Effect on healing rate and hydroxyproline content was best during the first week for immunostimulant. Immunostimulant- and TCC-injected wounds had more type-I collagen than did controls at 6 days; TCC-injected wounds had the most type-I collagen. At 14 days, the amount of type-I collagen in TCC-injected wounds was significantly greater than that in other wounds. CONCLUSIONS: Tested medications had positive effects on healing of pad wounds. CLINICAL RELEVANCE: Intralesional injection of medications helps ensure their presence for enhancement of wound healing. The benefit could be lost with topical use in a bandage if the bandage is lost or becomes wet.

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Despite concern over possible adverse cardiac effects of high-dose beta-agonists there have been no controlled studies of the effects of such a therapy in patients with severe chronic airflow obstruction (CAO). We therefore studied 22 CAO patients (FEV < 1 litre) with continuous ambulatory cardiac monitoring. Patients received either nebulised salbutamol (5 mg) or saline each given 4 times daily for 24 h on 2 consecutive days, single blind, in random order. Supraventricular arrhythmias were common on both saline and salbutamol days (8 vs. 9 patients, p = NS), but none were clinically apparent. There were no episodes of ventricular tachycardia. Ventricular ectopic activity was highly variable but did not significantly differ between the two study days overall or between specific periods after nebulised salbutamol or saline. Serum potassium (mean) fell by 0.23 (SD 0.06) mmol/l in 10 patients after salbutamol. Baseline FEV1, PaO2, PCO2 were not predictive of arrhythmias or ectopic activity. While occasional adverse effects cannot be excluded, we conclude that high-dose salbutamol does not lead to any general increase in arrhythmogenic potential in severe CAO.

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Three cases who presented with life threatening haemoptysis are reported, all of whom required surgery to control the bleeding. In all three patients chronic lung abscess was responsible for the haemoptysis. Even in the absence of typical clinical or radiographic features of an abscess this diagnosis should be considered in any patient presenting with life threatening haemoptysis.

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The way in which microbiological investigations are used in routine clinical practice and the value of such tests in directing antibiotic prescribing, was studied in adults admitted to hospital with a diagnosis of community-acquired pneumonia. One-hundred and twenty-two consecutive patients admitted to one teaching and one district general hospital were studied between April 1988 and March 1989. Blood cultures were performed in 81% of cases, sputum was examined in 45% and complete serological tests were performed in 28%. No causative pathogen was found in 74% of cases and results of microbial tests directed a change in antibiotic therapy in only 8% of cases. Routine microbial investigation of all adults admitted to hospital with community-acquired pneumonia is unhelpful and probably unnecessary. We suggest a strategy for microbial investigation linked to initial illness severity to replace the current haphazard approach.

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