Top POEMs of 2016 Consistent with the Principles of the Choosing Wisely Campaign: Respiratory Disease

Top 20 POEMs of 2016 Consistent with the Principles of the Choosing Wisely Campaign

A Shorter Course of Antibiotics Based on Clinical Stability Is Safe and Effective for CAP

Clinical question
Are shorter courses of antibiotics based on clinical criteria effective in treating patients with community-acquired pneumonia?

Bottom line
As recommended by guidelines from the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS), a minimum of 5 days of antibiotic therapy with discontinuation of antibiotics based on clinical stability is an appropriate strategy for the treatment of community-acquired pneumonia (CAP). (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Uranga A, Espana PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia. JAMA Intern Med 2016 Jul 25. doi: 10.1001/jamainternmed.2016.3633. [Epub ahead of print].

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis
For patients with CAP, IDSA/ATS guidelines recommend a minimum of 5 days of antibiotic treatment with discontinuation of antibiotics if the patient is afebrile for at least 48 hours and otherwise has no signs of hemodynamic instability. To validate this, these investigators randomized patients hospitalized with CAP into either an intervention group that followed these guidelines or into a control group that allowed bedside physicians to determine antibiotic duration. The authors excluded patients who were immunosuppressed, admitted to the intensive care unit, or had complicated pneumonia. Baseline characteristics of both groups were similar: two thirds of patients were male, mean age was in the mid-60s, and approximately 40% had Pneumonia Severity Index scores of IV or V. The majority of patients were treated with quinolones. The primary outcomes were symptom severity at day 5 and day 10 (as assessed by an 18-item CAP symptom questionnaire) and clinical success rates at day 10 and day 30 (defined as resolution or improvement of signs and symptoms of CAP without further antibiotics). There were no significant differences detected in any of these outcomes by either intention-to-treat or per-protocol analyses. Success rates were approximately 50% to 60% in both groups at day 10 and 88% to 94% at day 30. Moreover, the control group had longer median duration of antibiotic use than the intervention group (10 days vs 5 days; P < .001), although the length of intravenous antibiotic use was similar. Overall, 70% of patients in the intervention group received only 5 days of antibiotics as compared with 3% of patients in the control group. Other secondary outcomes including mortality, in-hospital complications, recurrence of symptoms, and length of hospital stay were similar in the 2 groups. Of note, the control group had a higher 30-day readmission rate (6.6% vs 1.4%; P = .02).

Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL

No Benefit to Azithromycin for Acute Asthma Exacerbations

Clinical question
For patients with acute asthma exacerbations, does the addition of azithromycin improve the resolution of symptoms?

Bottom line
These data show no improved outcomes with the addition of azithromycin to standard treatment for patients with acute asthma exacerbations requiring systemic steroids. However, the recruitment for this study was difficult, as half the eligible patients were excluded because of current or recent use of antibiotics, which resulted in a very underpowered study that only reached half its recruitment target. For each person included, more than 10 were excluded. Beyond its impact on the study results, the recruitment difficulty suggests that antibiotic use for asthma exacerbation is widespread despite current treatment guidelines that recommend otherwise. (LOE = 1b-)(www.essentialevidenceplus.com)

Reference
Johnston SL, Szigeti M, Cross M, et al, for the AZALEA Trial Team. Azithromycin for acute exacerbations of asthma: the AZALEA randomized clinical trial. JAMA Intern Med 2016 Sep 19. doi: 10.1001/jamainternmed.2016.5664. [Epub ahead of print].

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (any)

Synopsis
Along with its antimicrobial activity, azithromycin may have anti-inflammatory and antiviral properties that could potentially help resolve an acute asthma exacerbation. To test this theory, investigators in the United Kingdom enrolled adult patients who presented with symptoms and signs of acute asthma exacerbation that required systemic steroids. This was done in order to exclude patients with mild exacerbations. Of the 4582 eligible patients, 4383 were excluded (!), mainly because they were currentlly taking antibiotics or had taken antibiotics within 28 days of enrollment. The remaining 199 patients were randomized to receive either azithromycin 500 mg daily or matching placebo for 3 days along with standard care. The 2 groups were balanced at baseline: mean age was 40 years, two thirds were women, and baseline asthma symptom scores were similar. Patients recorded their symptoms in a diary and were assessed at days 5 and 10 after the initiation of treatment. For the primary outcome of mean asthma symptom scores at day 10, no difference was detected between the 2 groups. Additionally, there were no differences in quality-of-life scores or on any measure of lung function during the entire study. Of note, patients in this study had a low likelihood of concurrent respiratory infections; sputum samples and nasal/throat swabs indicated only 10% had bacterial infections and 18% had viral infections.

Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL

Minimal Benefit to Tiotropium as Add-On Therapy for Adolescents with Moderate Asthma

Clinical question
Is tiotropium safe and effective as add-on therapy for adolescents with moderate asthma?

Bottom line
This study found minimal, if any, benefit to tiotropium (Spiriva) as add-on therapy for nonsmoking adolescents with persistent moderate asthma who are already using inhaled corticosteroids, long-acting beta2-agonists (LABAs), or leukotriene receptor antagonists (LTRAs). (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Hamelmann E, Bateman ED, Vogelberg C, et al. Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. J Allergy Clin Immunol 2016;138(2):441-450.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Synopsis
The safety and effectiveness of tiotropium as add-on therapy in nonsmoking adolescents with moderate asthma is uncertain. These investigators identified adolescents, 12 to 17 years of age, with a history of asthma (at least 3 months) who had a mean score of at least 1.5 on the 7-question Asthma Control Questionnaire at baseline. Eligible patients (N = 398) were all receiving maintenance therapy with inhaled corticosteroids with or without a LABA or a LTRA for 4 or more weeks before screening. Patients were required to stop using LABA therapy at least 72 hours before study entry but were permitted to continue their usual dose of LTRA throughout the study. Study patients randomly received (concealed allocation assignment) either 5 mcg or 2.5 mcg tiotropium or placebo as 2 puffs once daily in the evening via a Respimat Soft Mist inhaler. Open-label albuterol metered-dose inhalers served as rescue medication. Individuals masked to treatment group assignment assessed study outcomes. Complete follow-up occurred for 94.7% of participants at 48 weeks. Using intention-to-treat analysis, fewer children in the active treatment groups experienced episodes of severe asthma (defined as requiring treatment with systemic corticosteroids for 3 or more days) compared with children in the placebo group (1.5% and 4.0% in the 5 mcg and 2.5 mcg groups, respectively, vs 6.5%), but the differences were not significant. No significant group differences occurred for overall episodes of asthma worsening, weekly number of puffs of rescue medication, or the proportion of patients achieving clinically significant differences in quality of life using standardized asthma control scoring tools. Adverse events occurred in similar numbers among the 3 groups.

David Slawson, MD
Director of Information Sciences
University of Virginia Health System
Charlottesville, VA

POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com).

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