Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs.

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 µg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 µg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.

Cost-effectiveness of roflumilast as an add-on to triple inhaled therapy vs triple inhaled therapy in patients with severe and very severe COPD associated with chronic bronchitis in the UK.

Purpose: Patients with severe COPD are at high risk of experiencing disease exacerbations, which require additional treatment and are associated with elevated mortality and increased risk of future exacerbations. Some patients continue to experience exacerbations despite receiving triple inhaled therapy (ICS plus LAMA plus LABA). Roflumilast is recommended by the Global Initiative for Chronic Obstructive Lung Disease as add-on treatment to triple inhaled therapy for these patients. This cost-effectiveness analysis compared costs and quality-adjusted life-years for roflumilast plus triple inhaled therapy vs triple inhaled therapy alone, using data from the REACT and RE2SPOND trials. Patients and methods: Patients included in the analysis had severe to very severe COPD, FEV1 <50% predicted, symptoms of chronic bronchitis and ≥2 exacerbations per year. Our model was adapted from a previously published and validated model, and the analyses conducted from a UK National Health Service perspective. A scenario analysis considered a subset of patients who had experienced at least one COPD-related hospitalization within the previous year. Results: Roflumilast as add-on to triple inhaled therapy was associated with non-significant reductions in rates of both moderate and severe exacerbations compared with triple inhaled therapy alone. The incremental cost-effectiveness ratio (ICER) for roflumilast as add-on to triple inhaled therapy was £24,976. In patients who had experienced previous hospitalization, roflumilast was associated with a non-significant reduction in the rate of moderate exacerbations, and a statistically significant reduction in the rate of severe exacerbations. The ICER for roflumilast in this population was £7,087. Conclusions: Roflumilast is a cost-effective treatment option for patients with severe or very severe COPD, chronic bronchitis, and a history of exacerbations. The availability of roflumilast as add-on treatment addresses an important unmet need in this patient population.

Indacaterol para o tratamento de bronquite crônica simples / Indacaterol for the treatment of simple chronic bronchitis

CONTEXTO: A bronquite é uma inflamação dos brônquios. Existem dois tipos, a bronquite aguda, que geralmente é causada por vírus ou bactérias e que dura diversos dias e até semanas e a bronquite crônica com duração de anos, que faz parte da doença pulmonar obstrutiva crônica (DPOC). A DPOC é uma enfermidade respiratória prevenível e tratável, que se caracteriza pela presença de obstrução crônica do fluxo aéreo, que não é totalmente reversível. A obstrução do fluxo aéreo é geralmente progressiva e está associada a uma resposta inflamatória anormal dos pulmões à inalação de partículas ou gases tóxicos, causada primariamente pelo tabagismo. Embora a DPOC comprometa os pulmões, ela também produz consequências sistêmicas significativas. A heterogeneidade da DPOC permite identificar subgrupos de pacientes com diferentes características clínicas. Alguns autores têm proposto agrupar os fenótipos clínicos com desfechos relevantes, como a frequência e a gravidade das exacerbações, a progressão da doença, a resposta ao tratamento e a mortalidade. Os subgrupos clínicos mais estudados são: enfisema hiperinflação, bronquite crônica, exacerbador frequente e asma associada a DPOC. TECNOLOGIA: Indacaterol (Onbrize®). PERGUNTA: Eficácia e segurança do indacaterol para o tratamento da bronquite. EVIDENCIAS: Não foram encontrados estudos que avaliassem especificamente o subgrupo bronquite crônica no DPOC. Foi encontrada uma revisão sistemática que avaliou a eficácia e a segurança do indacaterol em comparação com o placebo ou agonista ß2 de longa duração para o tratamento de DPOC. Indacaterol apresentou melhora significativa e clinicamente relevante no VEF1, na média do escore do St George Respiratory Questionaire (SGRQ) e na proporção de participantes que experimentaram uma melhora na pontuação SGRQ quando comparado com placebo. No geral não há diferença estatisticamente significantes para eventos adversos graves e mortalidade entre indacaterol e placebo. Comparado com agonista ß2 duas vezes por dia, um pequeno, mas estatisticamente significativo aumento no VEF1 foi visto com indacaterol. Entretanto, este resultado não foi clinicamente relevante. Não foram encontradas diferenças estatisticamente significativas entre agonistas ß2 e indacaterol para qualidade de vida, eventos adversos graves e mortalidade. CONCLUSÕES: Não há diferenças clinicamente relevantes entre indacaterol e os agonistas ß2 disponibilizados pelo SUS. Logo, deve ser verificado o tratamento com menor custo no Brasil.

Glicopirrônio para o tratamento de bronquite crônica simples / Glycopyrronium for the treatment of simple chronic bronchitis

CONTEXTO: A bronquite é uma inflamação dos brônquios. Existem dois tipos, a bronquite aguda, que geralmente é causada por vírus ou bactérias e que dura diversos dias e até semanas e a bronquite crônica com duração de anos, que faz parte da doença pulmonar obstrutiva crônica (DPOC). A DPOC é uma enfermidade respiratória prevenível e tratável, que se caracteriza pela presença de obstrução crônica do fluxo aéreo, que não é totalmente reversível. A obstrução do fluxo aéreo é geralmente progressiva e está associada a uma resposta inflamatória anormal dos pulmões à inalação de partículas ou gases tóxicos, causada primariamente pelo tabagismo. Embora a DPOC comprometa os pulmões, ela também produz consequências sistêmicas significativas. A heterogeneidade da DPOC permite identificar subgrupos de pacientes com diferentes características clínicas. Alguns autores têm proposto agrupar os fenótipos clínicos com desfechos relevantes, como a frequência e a gravidade das exacerbações, a progressão da doença, a resposta ao tratamento e a mortalidade. Os subgrupos clínicos mais estudados são: enfisema hiperinflação, bronquite crônica, exacerbador frequente e asma associada a DPOC. TECNOLOGIA: Glicopirrônio (Seebri®). PERGUNTA: Eficácia e segurança do glicopirrônio para o tratamento da bronquite crônica simples. EVIDENCIAS: Foram selecionadas duas revisões que avaliaram o glicopirrônio para o tratamento de DPOC. Inaladores antimuscarínicos de longa ação (LAMA) e agonistas ß2 de longa ação (LABA) tiveram efeitos semelhantes para qualidade de vida e função pulmonar, sendo que quando LABA foi associado a corticosteroides essa intervenção apresentou melhores resultados. Tiotrópio e glicopirrônio têm eficácia similar na melhora da função pulmonar. Quando considerado as intervenções em combinação, foi verificado que tiotrópio/budesonida/formoterol e indacaterol/glicopirrônio foram mais eficazes para o desfecho exacerbações moderadas a grave. A ocorrência de pneumonia foi menor para glicopirrônio e indacaterol/glicopirrônio do que para fluticasona/salmeterol, fluticasona/vilanterol e fluticasona. CONCLUSÕES: Não há diferenças entre LABA e LAMA para a qualidade de vida e função pulmonar. No entanto, quando glicopirrônio é combinado com indacaterol ele é mais eficaz para as exacerbações moderadas a graves do que tiotrópio, fluticasona/salmeterol, indacaterol, glicopirrônio, salmeterol e formoterol. Já a combinação tiotrópio/budesonida/formoterol foi mais eficaz do que indacaterol/glicopirrônio.

Cost-effectiveness of pharmacotherapy for COPD in ambulatory care: a review.

RATIONALE, AIMS AND OBJECTIVES: This article conducts a literature review about the cost-effectiveness of pharmacotherapy for chronic obstructive pulmonary disease (COPD) in ambulatory care. METHODS: Relevant economic evaluations were identified by searching Medline (PubMed) and the National Health Service (NHS) Economic Evaluation Database. The search strategy focused on literature reviews and primary economic evaluations. Economic evaluations were included, which compared pharmacotherapy for COPD, chronic bronchitis or pulmonary emphysema with an alternative in terms of costs and health outcomes. RESULTS: The majority of economic evaluations show that pharmacotherapy for COPD in ambulatory care is cost-effective. Cost-effectiveness derives from an improvement in lung function and a reduction in the number of exacerbations, which translates into cost savings from fewer hospitalizations. Pharmacotherapy also tends to be more cost-effective in patients with more severe COPD. When applying these results to a specific country or setting, the cost-effectiveness of pharmacotherapy will depend on the distribution of COPD severity among patients, the alternative with which pharmacotherapy is compared, the impact of pharmacotherapy on exacerbations, costs and treatment patterns of exacerbations, and price of pharmacotherapy. Economic evaluations tended to suffer from short-time horizons, restricted scope of included costs and use of various health outcome measures. CONCLUSIONS: There is a case to be made in favour of economic evaluations from the societal perspective that are based on a decision-analytic model to allow for extrapolation beyond the duration of clinical trials and that use generic health outcome measures such as quality-adjusted life years.

Healthcare utilization and costs among chronic bronchitis patients treated with maintenance medications from a US managed care population.

OBJECTIVES: This study aimed to examine the real-world healthcare resource utilization (HCRU) and direct costs among chronic bronchitis (CB) patients treated with chronic obstructive pulmonary disease (COPD) maintenance medications. METHODS: This retrospective analysis utilized administrative claims data from 14 US commercial managed care plans. Eligible patients were ≥40 years old, had ≥2 years of continuous enrollment, ≥1 CB (ICD-9-CM code 491.xx) hospitalization or emergency department (ED) visit or ≥2 office visits between 1/1/2004 and 5/31/2011, and had ≥2 pharmacy fills for COPD medications during follow-up (first fill served as the index date). All-cause and COPD-related HCRU and costs were assessed during follow-up. Multivariate models were utilized to identify predictors of total costs. RESULTS: Treated CB patients (n = 17,382; 50.6% female; mean age 66.7 (SD = 11.4) years) had a mean of 7.6 (SD = 6.3) COPD maintenance medication fills during follow-up. Overall, 32.6% of patients had ≥1 COPD-related inpatient hospitalizations, 12.9% had ≥1 ED visit, and 81.8% had ≥1 office visit. Mean all-cause and COPD-related total costs were $25,747 (SD = $51,105) and $12,609 (SD = $36,801), respectively, during follow-up. Among the sub-group with ≥1 exacerbation during baseline year, 42.3% had ≥1 COPD-related inpatient hospitalization, 18.5% had ≥1 ED visit, and 88.2% had ≥1 office visit. Mean follow-up all-cause and COPD-related total costs were $29,861 (SD = $49,799) and $16,784 (SD = $34,170), respectively. The number of baseline exacerbations was a significant predictor of all-cause and COPD-related total costs during follow-up. LIMITATIONS: This study lacked standard measures of CB severity; however, severity proxies were utilized. CONCLUSION: HCRU and costs among CB patients were substantial during follow-up, despite treatment with COPD maintenance medications. Additional interventions aiming to prevent or reduce HCRU and costs among CB patients warrant exploration.

Chronic obstructive pulmonary disease and associated health-care resource use - North Carolina, 2007 and 2009.

Chronic obstructive pulmonary disease (COPD), including emphysema and chronic bronchitis, is a progressive condition in which airflow becomes limited, making it difficult to breathe. Chronic lower respiratory diseases, primarily COPD, are the third leading cause of death in the United States, and 5.1% of U.S. adults report a diagnosis of emphysema or chronic bronchitis. Smoking is the primary cause of COPD, and at least 75% of COPD deaths are attributable to smoking in the United States. Information on state-specific prevalence of COPD is sparse, as are data on the use of COPD-related health-care resources. To understand how COPD affects adults in North Carolina and what resources are used by persons with COPD, 2007 and 2009 data from the North Carolina COPD module of the Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. Among 26,227 respondents, 5.7% reported ever having been told by a health professional that they had COPD. Most adults with COPD reported ever having had a diagnostic breathing test (76.4% in 2007 and 82.4% in 2009). Among adults with COPD, 43.0% reported having gone to a physician and 14.9% visited an emergency department (ED) or were admitted to a hospital (2007) for COPD-related symptoms in the previous 12 months. Only 48.1% of persons reported daily use of medications for their COPD (2007). These results indicate that many adults with COPD might not have had adequate diagnostic spirometry, and many who might benefit from daily medications, such as long-acting bronchodilators and inhaled corticosteroids, are not taking them. Continued and expanded surveillance is needed to evaluate the effectiveness of prevention and intervention programs and support efforts to educate the public and physicians about COPD symptoms, diagnosis, and treatment.

Responsiveness of the cough and sputum assessment questionnaire in exacerbations of COPD and chronic bronchitis.

BACKGROUND: To assess the responsiveness of the Cough and Sputum Assessment Questionnaire (CASA-Q) in COPD and chronic bronchitis patients recovering from an acute exacerbation. The 20-item questionnaire with a 7-day recall assesses the frequency and severity of cough and sputum and their impact on everyday life in clinical (trial) settings. The four domains (cough/sputum symptom and impact) use scales from 0 to 100, with lower scores indicating higher symptom/impact levels. METHODS: Outpatients were enrolled within 48h of symptom onset of their exacerbation. Treatment was initiated at the discretion of the investigator, and patients observed for 6 weeks. During study visits, 59 eligible patients completed the CASA-Q at enrolment, week 1, 2 and 6. Responsiveness was assessed by calculating standardized effect sizes. RESULTS: Of the 19 male and 40 female patients with a mean (standard deviation, SD) age of 61.1 (10.5) years, all were classified by their physician to have improved or recovered after six weeks. The mean (SD) CASA-Q sores for the cough symptom, cough impact, sputum symptom and sputum impact domains increased from 32.6 (21.0), 40.7 (22.4), 37.4 (20.1), 47.1 (24.2) at enrolment to 54.0 (19.8), 63.7 (21.3), 55.1 (19.0), 65.5 (20.5) at week 6, respectively. Standardized effect sizes for patients improved or recovered from their exacerbation at week 6 were above 1.0 for the cough domains and at least 0.77 for the sputum domains. CONCLUSIONS: The CASA-Q was responsive to symptom changes in patients recovering from an exacerbation.

Gemifloxacin use in the treatment of acute bacterial exacerbation of chronic bronchitis.

The newest generation of fluoroquinolones have proven efficacy against bacterial organisms associated with acute exacerbation of chronic bronchitis (AECB). Gemifloxacin, as one of the quinolones in this class, exhibits many of the pharmacokinetic and pharmacodynamic characteristics of the class with a few notable differences. Against Streptococccus pneumoniae it has a lower minimal inhibitory concentration (MIC) than the other respiratory fluoroquinolones and it has activity against both bacterial DNA gyrase and topoisomerase IV. The increased activity of gemifloxacin against both enzymes may be associated with decreased rates of resistance. Clinically, gemifloxacin has been shown to have positive effects on length of hospitalization and increased success at long-term follow-up in AECB patients. These associations were observed in noninferiority comparison studies. Although an advantage with the use of gemifloxacin in AECB is suggested, there are no comparison data is available to conclude that gemifloxacin is superior to the other respiratory fluoroquinolones. Gemifloxacin is generally well tolerated, but is associated with a characteristic rash and gastrointestinal upset as its most common observed side effects.

A pharmacoeconomic review of the management of respiratory tract infections with moxifloxacin.

BACKGROUND: Moxifloxacin, a fluoroquinolone, has demonstrated its safety and effectiveness in the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute bacterial sinusitis. OBJECTIVE: The aim of this article was to provide a synthesis and critical appraisal of economic evaluations of the management of respiratory tract infections with moxifloxacin. METHODS: Studies were included if they assessed the costs and consequences of moxifloxacin as compared with an alternative antimicrobial in the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute bacterial sinusitis. RESULTS/CONCLUSIONS: Treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute bacterial sinusitis with moxifloxacin is equally or more effective and less expensive than treatment with other antimicrobials.

[Highlights 2007 in hospital-based internal medicine: the point of view from the chief residents]. / Nouveautés en médecine interne hospitatière 2007: perspective des chefs de clinique.

In 2007, several international studies brought useful information for the daily work of internists in hospital settings. This summary is of course subjective but reflects the interests and questions of the chief residents of the Department of internal medicine who wrote this article like an original trip in medical literature. This trip will allow you to review some aspects of important fields such as heart failure, diabetes, endocarditis, COPD, and quality of care. Besides the growing diversity of the fields covered by internal medicine, these various topics underline also the uncertainty internists have to face in a practice directed towards evidence.

Costs of treating lower respiratory tract infections.

OBJECTIVE: To determine the direct medical costs of treating lower respiratory tract infections (LRTIs) in a managed care organization (MCO). STUDY DESIGN: Retrospective analysis of a regional MCO identifying adults diagnosed with acute exacerbation of chronic bronchitis (AECB) or community- acquired pneumonia (CAP). METHODS: A claims database examination of International Classification of Diseases, Ninth Revision, Clinical Modification codes was conducted to identify adults receiving initial outpatient care for an LRTI during 2005-2006. Medical record review then was conducted to verify clinical diagnosis of AECB or CAP. Clinical and demographic data were collected. Outpatient office and clinic visits, hospitalization, and radiology, pathology, and pharmacy records were used to determine treatment costs. Treatment failure was determined by use of a second antibiotic course, follow-up emergency room presentation, or hospitalization for LRTI within 28 days of the index visit. The primary outcome was per-case treatment cost from the payer perspective. RESULTS: Clinical diagnosis was confirmed for 65 unique coded visits (60 patients; 39 with AECB, 22 with CAP; 1 in both cohorts). Initial visit, initial diagnostic testing, and subsequent hospitalization accounted for the majority (63%) of payer costs. Antibiotics were responsible for 15% of payer costs. Higher initial antibiotic expenditure in the AECB cohort yielded a cost-benefit ratio of 3:1. Mean per-case costs for success and failure were $277 & $372 for AECB, and $493 & $3019 for CAP, respectively. CONCLUSIONS: Initial visit and hospitalization costs contribute the majority of payer expenditure while antibiotic expenditure incurs a nominal burden. Higher expenditure on initial antibiotic therapy in the AECB population appears to be beneficial.

Acute exacerbations of chronic bronchitis in elderly patients: pathogenesis, diagnosis and management.

Chronic bronchitis (CB) is a disorder that is characterised by chronic mucus production. This disorder is called chronic obstructive pulmonary disease (COPD) when airflow obstruction is present. The majority of patients with COPD, which often goes undiagnosed or inadequately treated in the elderly, have symptoms consistent with CB. The clinical course of CB is usually punctuated by periodic acute exacerbations linked to infections caused by viral and typical or atypical bacterial pathogens. Acute exacerbations of chronic bronchitis (AECB) often lead to a decline in lung function and poor quality of life in association with increased risk of mortality and a significant economic impact on the healthcare system and society because of the direct costs of hospitalisations. In elderly individuals with COPD, co-morbidities play a vital role as determinants of health status and prognosis. Failure to eradicate infecting pathogens contributes to persistence of infection and inflammation that requires repeated courses of therapy and hospitalisation. Stratifying patients with AECB according to symptoms, degree of pulmonary function impairment and risk factors for poor outcome can help clinicians choose empirical antimicrobial chemotherapy regimens that are most likely to result in treatment success. Failure to cover likely pathogens associated with episodes of AECB can lead to lengthy hospital admissions and significant declines in functional status for elderly patients. Fluoroquinolones may provide the best therapeutic option for elderly patients with COPD who have complicated underlying CB but who are sufficiently stable to be treated in the outpatient setting. Optimised treatment for stable outpatients with CB may diminish the frequency of AECB, and effective antimicrobial therapy for AECB episodes can significantly diminish healthcare costs and maintain quality of life in the elderly patient.

Telithromycin: the perils of hasty adoption and persistence of off-label prescribing.

BACKGROUND: Telithromycin (Ketek) was approved in April 2004 for the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), bacterial sinusitis, and community-acquired pneumonia. The approval of telithromycin was controversial due to trial irregularities, noninferiority study designs, and use of foreign safety data. Safety concerns involving hepatotoxicity, myasthenia gravis exacerbation, and visual disturbances were increasingly documented in the literature after approval. On February 12, 2007, the U.S. Food and Drug Administration (FDA) removed the bacterial sinusitis and ABECB indications and strengthened safety warnings for telithromycin. OBJECTIVE: To (1) assess the prevalence and distribution of on-label telithromycin utilization before and after the revisions of the product label and (2) assess the association of pivotal events in the life cycle of telithromycin with its use as reflected in pharmacy and medical claims. METHODS: Using retrospective administrative medical and pharmacy claims from a large midwestern commercial insurer with an eligible membership of 1.8 million members, individuals with a telithromycin claim during January 1, 2007, through April 13, 2007, were identified. Their medical claims within 30 days prior to or on the initial telithromycin claim were analyzed for the presence of an on-label diagnosis code. Monthly telithromycin and clarithromycin claim totals per million members from January 2004 through March 2007 were calculated. Claim totals were plotted to identify utilization trends in relation to the FDA health advisory for telithromycin on January 20, 2006, and the telithromycin label changes on February 12, 2007. RESULTS: The medical diagnosis analysis consisted of 507 members with 1 or more medical claims with dates of service within 30 days of at least 1 pharmacy claim for telithromycin. Using the original approved telithromycin indications, 52.3% (256 of 507) of telithromycin use was on-label. The most common on-label diagnoses were sinusitis (33.9%) and bronchitis (14.4%). A diagnosis of pneumonia was present for 3.9% of telithromycin utilizers. After the February 12, 2007, label change limiting telithromycin to community-acquired pneumonia, on-label use was 6.7% (12 of 179) of utilizers. Telithromycin claims were first detected in August 2004 and overtook the clarithromycin rate of 729 claims per million members in January 2005, reaching a peak rate of 940 claims per million members in January 2006. Telithromycin monthly claims remained higher than clarithromycin until April 2006, 3 months after the liver toxicity health advisory. In comparison with January 2006, the January 2007 telithromycin claims were 186 claims per million members, a decrease of 80%. CONCLUSION: Despite revised FDA indications and safety warnings, fewer than 1 in 15 active telithromycin users have a medical claim consistent with the only currently approved indication (pneumonia). Pharmacy claims for telithromycin dropped substantially following reports of severe hepatotoxicity and strengthened safety warnings. The high prevalence of telithromycin off-label use despite hepatotoxicity and other safety risks is cause for continued concern.

Development of a COPD severity score.

OBJECTIVE: Treatment of chronic obstructive pulmonary disease (COPD) is based on symptom control. This suggests that COPD severity can be determined by analyzing treatment intensity. The objective of this analysis was to develop and validate a severity score for adult COPD based on treatments. RESEARCH DESIGN: Using principal components analysis, a COPD severity score was developed using data based on treatments extracted from an employer claims database (development group). Variables included were identified from literature review and clinical expert opinion. External validity was tested in a separate group of adult chronic bronchitis patients in whom principal components analysis was re-conducted and factor loadings were compared to the development group. Construct validity was tested by comparing the incidence of acute exacerbations of chronic bronchitis (AECB) in patients with high and lower severity scores. To illustrate the use of the COPD severity score, effectiveness of alternative AECB antibiotic treatments was compared in a separate patient sample categorized by severe versus mild/moderate COPD. RESULTS: In the development group (n = 2068), principal components analysis produced a single main factor for severity scoring. Of the 12 variables contributing to this factor, the 6 with the highest factor loadings were treatment related. The factor performed similarly in the external validity group (n = 9127) as it did in the development group. In construct validity testing, severe COPD patients were 4 times more likely to have AECB episodes than mild/moderate patients. Patients with severe COPD and an AECB were more likely to fail treatment with antibiotics than those with mild/moderate COPD. Based on the COPD severity score developed, we found that treatment of patients with severe COPD and an AECB with fluoroquinolones was more likely to result in treatment failure than treatment with macrolides (OR = 2.01; p = 0.03). CONCLUSIONS: The analysis was successful in developing and validating a method to score COPD severity based on treatments. This method may prove useful in providing insights about the benefits of COPD treatments.

Treating acute exacerbations of chronic bronchitis and community-acquired pneumonia: how effective are respiratory fluoroquinolones?

OBJECTIVE: To provide family physicians with a review of evidence supporting fluoroquinolone therapy for defined patient populations with acute exacerbations of chronic bronchitis (AECB) and community-acquired pneumonia (CAP). QUALITY OF EVIDENCE: A MEDLINE search found surveillance studies, randomized controlled trials, outcome studies, and expert consensus opinion. Descriptions of patient populations for which fluoroquinolone therapy is recommended are based on level I and level III evidence. MAIN MESSAGE: A growing body of evidence supports fluoroquinolones as first-choice agents for treatment of AECB or CAP patients with comorbidity or a recent history of antibiotic use. Judicious and targeted therapy using fluoroquinolones among patients at risk of infections of the lower respiratory tract should contribute to improved clinical outcomes and broader health care savings. CONCLUSION: Current data show clinical utility and cost-effectiveness of fluoroquinolones in lower respiratory tract infections. The most recently issued AECB and CAP guidelines now recommend these antimicrobial agents as first-choice agents for specific patient populations.

Appropriate outpatient treatment of acute bacterial exacerbations of chronic bronchitis.

Acute exacerbations of chronic bronchitis (AECB), which are characteristic of chronic obstructive pulmonary disease (COPD), contribute to morbidity and decreased quality of life for patients with COPD. A significant proportion of these exacerbations are due to bacterial infections. The Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria provide guidance for choosing the optimal drug at its optimal dose and duration for antimicrobial treatment of AECB due to bacterial infection. Evidence-based guidelines recommend stratifying patients according to risk factors to improve selection of targeted antimicrobial therapy. With increasing rates of resistance to some antimicrobials, resistance is also an important consideration for reducing treatment failures and decreasing the need for further pharmacologic treatment. Fluoroquinolones are recommended as first-line therapy for patients with chronic bronchitis who have risk factors; gatifloxacin, gemifloxacin, and levofloxacin are highly active against commonly encountered pathogens. Safety profiles are an important consideration because adverse events and poor tolerability can reduce patient adherence rates, which in turn can lead to poorer outcomes. Safety profiles also become an important consideration as shorter-course, higher-dose therapies become more prevalent. First-line therapy with a well-tolerated antibiotic that is active against the predominant pathogens, combined with low resistance rates and a convenient once-a-day dosing regimen, may reduce overall costs. Fluoroquinolones exhibit low resistance, good activity levels, and high respiratory penetration, and they are particularly well suited for shorter-course, higher-dose regimens in selected patients. Shorter-course, higher dose regimens, in turn, may be more effective, cost-efficient, and appropriate for controlling the rise of resistance than standard regimens.

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.