Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg.

This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness. Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days. Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively). In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.

Summary of Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Disease Society and the Canadian Thoracic Society.

Community-acquired pneumonia (CAP) is a serious illness with a significant impact on individual patients and society as a whole. Over the past several years, there have been significant advances in our knowledge and understanding of the etiology of the disease, and an appreciation of problems such as mixed infections and increasing antimicrobial resistance. The development of additional fluoroquinolone agents with enhanced activity against Streptococcus pneumoniae has been important as well. It was decided that the time had come to update and modify the previous CAP guidelines, which were published in 1993. The current guidelines represent a joint effort by the Canadian Infectious Disease Society and the Canadian Thoracic Society, and they address the etiology, diagnosis and initial management of CAP. The diagnostic section is based on the site of care, and the treatment section is organized according to whether one is dealing with outpatients, inpatients or nursing home patients.

Cost-effective therapy for acute exacerbations of chronic bronchitis.

Pharmacoeconomic analysis involves the measurement of a ratio determining the extra costs required to achieve an additional unit of clinical benefit. Various techniques including modeling studies, retrospective analysis of databases, "piggy-back" economic analysis of prospective randomized clinical trials, and prospective randomized pharmacoeconomic trials have been developed to aid in economic and health decisions. In acute exacerbations of chronic obstructive pulmonary disease, it is possible to identify a group of patients that are at high risk of treatment failure from routine antimicrobial therapy, hospitalization, respiratory failure, and death. The cost of therapy for this relatively small group of patients is extraordinarily high. Data from a variety of approaches have suggested that aggressive antimicrobial therapy may lead to improved outcomes in these patients. The corollary is that aggressive therapy directed toward patients with either acute bronchitis (mainly a viral infection) or exacerbations of trivial chronic obstructive lung disease leads to emergence of resistance and increased costs.

The chronic obstructive pulmonary disease exacerbation.

Chronic obstructive pulmonary disease is the only leading cause of death with a rising prevalence. The medical and economic costs arising from acute exacerbations of COPD are therefore expected to increase over the coming years. Although exacerbations may be initiated by multiple factors, the most common identifiable associations are with bacterial and viral infections. These are associated with approximately 50% to 70% and 20% to 30% of COPD exacerbations, respectively. In addition to smoking cessation, annual influenza vaccination is the most important method for preventing exacerbations. Controlled O2 is the most important intervention for patients with acute hypoxic respiratory failure. Evidence from randomized, controlled trials justifies the use of corticosteroids, bronchodilators (but not theophylline), noninvasive positive-pressure ventilation (in selected patients), and antibiotics, particularly for severe exacerbations. Antibiotics should be chosen according to the patient's risk for treatment failure and the potential for antibiotic resistance. In the acute setting, combined treatment with beta-agonist and anticholinergic bronchodilators is reasonable but not supported by randomized controlled studies. Physicians should identify and, when possible, correct malnutrition. Chest physiotherapy has no proven role in the management of acute exacerbations.

Use of guidelines and risk stratification in acute exacerbations of chronic obstructive pulmonary disease.

Guidelines have been developed to simplify the antimicrobial treatment decision for patients with acute exacerbations of chronic obstructive lung disease. Approximately half of these patients will have a demonstrable bacterial infection and antibiotics have been demonstrated to shorten the clinical illness and prevent significant deterioration. Patients can be stratified by the risk of treatment failure with usual first-line antimicrobial agents. Patients presenting with worsening dyspnea, increased sputum volume and purulence should be offered antimicrobial therapy. In the presence of significant impairment of lung function (FEVI 50% predicted), frequent exacerbations, significant comorbidity, malnutrition, chronic corticosteroid administration and long duration of disease, should be treated with more aggressive therapy such as with a fluoroquinolone, amoxicillin-clavulanate, or a second or third generation cephalosporin or second generation macrolide. In the absence of these risk factors, first-line agents such as amoxicillin appear adequate. Patients with chronic suppurative airway disease (mainly bronchiectasis) should be treated with an antipseudomonal fluoroquinolone if P. aeruginosa is identified in pulmonary secretions. More prospective randomized trial are warranted to validate this approach.

Summary of Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Disease Society and the Canadian Thoracic Society.

Community-acquired pneumonia (CAP) is a serious illness with a significant impact on individual patients and society as a whole. Over the past several years, there have been significant advances in the knowledge and understanding of the etiology of the disease, and an appreciation of problems such as mixed infections and increasing antimicrobial resistance. The development of additional fluoroquinolone agents with enhanced activity against Streptococcus pneumoniae has been important as well.It was decided that the time had come to update and modify the previous CAP guidelines, which were published in 1993. The current guidelines represent a joint effort by the Canadian Infectious Diseases Society and the Canadian Thoracic Society, and they address the etiology, diagnosis and initial management of CAP. The diagnostic section is based on the site of care, and the treatment section is organized according to whether one is dealing with outpatients, inpatients or nursing home patients.

Treatment of community-acquired pneumonia in the elderly: the role of cefepime, a fourth-generation cephalosporin.

In a prospective, multicentre double-blind trial, 151 patients over the age of 65 years were randomly assigned to receive either cefepime 2 g every 12 h for a minimum of 3 days and up to 14 days or ceftriaxone 1 g every 12 h for a minimum of 3 days and up to 14 days. Antibiotics were maintained until 48 h after fever had resolved; no other antibiotics were permitted. The average age in each group exceeded 77 years and significant co-morbidity was found in the majority of patients. The mean total duration of therapy was 5.8+/-2.4 days for the cefepime group and 6.7+/-2.7 days for the ceftriaxone group (P = 0.06). The clinical success rate at the end of therapy was 79.1% with cefepime and 75.4% with ceftriaxone (P = 0.62). At the end of follow-up, 91.7% of the cefepime-treated patients and 86.5% of the ceftriaxone patients had a satisfactory clinical response (P = 0.38). In 35 bacteriological evaluable patients, potential pathogens were eradicated in all but one patient receiving cefepime. Seven patients in each group died during the study period but in each case the death was unrelated to study drug. The commonest side-effect was diarrhoea (cefepime, five patients; ceftriaxone, two patients). The clinical and microbiological efficacy of cefepime is similar to that of ceftriaxone in elderly patients with community-acquired pneumonia requiring hospitalization. Cefepime is an appropriate choice for the treatment of community-acquired respiratory tract infections in the elderly.

Management of acute exacerbation of chronic bronchitis.

In chronic bronchitis, a common respiratory illness marked by chronic productive cough and caused largely by cigarette smoking, bacterial exacerbations are thought to be a common cause of progressive airway damage. Common bacterial pathogens, found in 50% to 60% of episodes, include Haemophilus influenzae (the most common), as well as Haemophilus parainfluenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Bacterial resistance to antibiotics, especially beta-lactam drugs such as amoxicillin, is increasingly common in these pathogens. In this illness, clinical risk stratification based on age, history and comorbidity is an important strategy. Patients in the lowest risk group likely have viral infections and require no specific treatment. Patients in the higher risk groups require aggressive treatment to avoid treatment failure, which can lead to prolonged hospitalization and complications. Preventive therapies (smoking cessation and influenza vaccination) are worthwhile measures for these patients.

Airway infection.

Bronchitis in its acute and chronic forms with recurrent acute exacerbations is one of the most common reasons for physician visits, accounting for a significant cost to the health-care system, lost work days, and increased morbidity and mortality. Smoking and recurrent lower respiratory tract infections are major risk factors for chronic bronchitis. Therefore, smoking cessation and vaccination strategies are cornerstones of management in terms of halting disease progression and reducing the frequency of infectious exacerbations. Bacterial infection is the main culprit in acute flares of the disease. Routine antimicrobial therapy fails in a significant number of patients, and therapeutic failures lead to increased costs. Several stratification schemes have been proposed to improve initial antimicrobial selection. These schemes identify patient's age, severity of underlying pulmonary dysfunction, frequency of exacerbations, and the presence of comorbid illnesses as predictors for likely pathogens and to guide antimicrobial selection. This approach may reduce the risk for treatment failure, which would have significant medical and economic implications. Improved understanding of the roles of airway inflammation and infection in the pathogenesis of progressive airway disease, in addition to future studies examining the efficacy of newer classes of antimicrobials, should guide physicians to target early and effective treatment to high-risk patients.

What new antibiotics to offer in the outpatient setting.

The treatment of community-acquired pneumonia is empiric. Guidelines have been developed to assist the clinician in selecting antibiotics to cover the likely pathogens. Given the difficulty of predicting an etiologic agent from patient characteristics, radiologic findings, and laboratory studies, initial regimens recommend broad-spectrum coverage. In some circumstances, two antibiotics may be required. The prevalence of resistant organisms is increasing and must be considered when prescribing treatment. Patient compliance is essential for successful therapy but diminishes with inconvenient dosing schedules and with poorly tolerated medicines. A number of novel antimicrobials have either been just launched or are in the late stages of development. Most have been developed in an attempt to address the above concerns. This article focuses on the new oral cephalosporins, macrolides, and fluoroquinolones, and discusses the place of each in the therapy of community-acquired pneumonia.

The value of antibiotics and the outcomes of antibiotic therapy in exacerbations of COPD.

COPD is the fifth leading cause of death in the United States, and acute respiratory infections account for a significant proportion of all primary care visits. Approximately one half of all exacerbations of COPD can be attributed to bacterial infection, and antibiotic therapy has been demonstrated to improve clinical outcomes and hasten clinical and physiologic recovery. The major pathogen continues to be Haemophilus influenzae, and resistance to beta-lactam antibiotics such as ampicillin can be expected in 20 to 40% of isolated strains. Certain high-risk patients, in whom the cost of clinical treatment failure is high, can be identified by simple clinical criteria. Patients with significant cardiopulmonary comorbidity, frequent purulent exacerbations of COPD, advanced age, generalized debility, malnutrition, chronic corticosteroid administration, long duration of COPD, and severe underlying lung function tend to fail therapy with older drugs, such as ampicillin, and early relapse can be expected. Treatment directed toward resistant pathogens with potent bactericidal drugs may be expected to lead to improved clinical outcomes and overall lower costs, particularly if hospital admissions and respiratory failure can be prevented. Future studies examining the role of antibiotics should enroll these high-risk patients to determine if new therapies have significant clinical, quality-of-life, and economic advantages over older agents.

How do we achieve cost-effective options in lower respiratory tract infection therapy?

Acute bronchitis and acute exacerbations of chronic bronchitis, common illnesses encountered by general and family physicians, account for approximately 14 million physician visits per year. The pattern of antibiotic prescribing for these infections varies from country to country, but there is no clear rationale for these antimicrobial choices. A recent meta-analysis of all randomized, placebo-controlled trials of patients treated with antibiotics for acute exacerbations of chronic bronchitis concluded that a small but statistically significant improvement could be expected in antibiotic-treated patients. Haemophilus influenzae is the most commonly isolated organism from sputum in patients with acute exacerbations of chronic obstructive lung disease but other Haemophilus species, Streptococcus pneumoniae, and Moraxella catarrhalis may also be found. High-risk patients can be defined as being elderly, with significant impairment of lung function, having poor performance status with other comorbid conditions, having frequent exacerbations, and often requiring oral corticosteroid medication. Well-defined clinical trials measure efficacy of a drug but not the effectiveness in a real world situation. Future studies of new antimicrobials should examine their efficacy in patients with an increased risk of true bacterial infection.

Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid.

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.

Acute exacerbations of chronic bronchitis.

Not every patient with bronchitis needs to be treated with an antibiotic. When treatment is indicated, however, the regimen should be selected carefully. A simple four-part disease classification scheme serves as a practical aid for initial assessment of the patient and as a guideline for choosing therapy.

Critical care management of the obstetric patient.

PURPOSE: To review a series of critically ill obstetric patients admitted to a general intensive care unit in a Canadian centre, to assess the spectrum of diseases, interventions required and outcome. METHODS: A retrospective chart review was performed of obstetric patients admitted to the intensive care unit of an academic hospital with a high-risk obstetric service, during a five-year period. Data obtained included the admission diagnosis, ICU course and outcome. Daily APACHE II and TISS scores were recorded. RESULTS: Sixty-five obstetric patients, representing 0.26% of deliveries in this hospital, were admitted to the ICU during the study period. All had received prenatal care. Admission diagnoses included obstetric (71%) and non-obstetric (29%) complications. The mean APACHE II score was 6.8 +/- 4.2 and mean TISS score was 24 +/- 8.1. Twenty-seven patients (42%) required mechanical ventilation. No maternal mortality occurred and the perinatal mortality rate was 11%. CONCLUSIONS: A small proportion of obstetric patients develop complications requiring ICU admission. The outcome in this study was excellent, in contrast to that reported in other published studies with similar ICU admission rates. The universal availability of prenatal care may be an important factor in the outcome of this group of patients. The lack of a specific severity of illness scoring system for the pregnant patient makes comparison of case series difficult.