Clinical Health Updates

Pneumococcal conjugate vaccine prevents meningitis

Clinical Question:
What is the effect of pneumococcal conjugate vaccine on pneumococcal meningitis?

Bottom Line:
Although the pneumococcal conjugate vaccine (PCV7) has reduced the overall likelihood of pneumococcal meningitis, particularly in infants and older adults, there are worrisome recent trends regarding non-PCV7 serotype disease and antibiotic resistance that bear close watching. (LOE = 2c)

Reference:
Hsu HE, Shutt KA, Moore MR, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 2009;360(3):244-256.

Study Design:
Time series

Funding:
Government

Setting:
Population-based

Summary:
Invasive pneumococcal disease declined among children and adults after the introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, but its effect on pneumococcal meningitis is unclear. They examined trends in pneumococcal meningitis from 1998 through 2005 using active, population-based surveillance data from eight sites in the United States. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others). Changes in the incidence of pneumococcal meningitis were assessed against baseline values from 1998-1999. The researcher identified 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998-1999 and 2004-2005 (a 30.1% decline, P<0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P<0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P<0.001) among patients of all ages. Although rates of PCV7-related-serotype disease decreased by 32.1% (P=0.08), rates of non-PCV7-serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P<0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P=0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P=0.03).

Antibiotics and nasal steroids of little/no benefit for acute sinusitis

Clinical Question:
Are antibiotics or nasal steroids truly beneficial in the treatment of acute maxillary sinusitis?

Bottom Line:
Neither an antibiotic nor a topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting.

Reference:
Williamson IG, Rumsby K, Benge S, et al. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis. A randomized controlled trial. JAMA 2007;298(21):2487-2496.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Acute sinusitis is a common clinical problem that usually results in a prescription for antibiotics but the role of antibiotics is debated. Anti-inflammatory drugs such as topical steroids may be beneficial but are underresearched. The authors determine the effectiveness of amoxicillin and topical budesonide in acute maxillary sinusitis. They did a double-blind, randomized, placebo-controlled factorial trial of 240 adults (aged > or =16 years) with acute nonrecurrent sinusitis (had > or =2 diagnostic criteria: purulent rhinorrhea with unilateral predominance, local pain with unilateral predominance, purulent rhinorrhea bilateral, presence of pus in the nasal cavity) at 58 family practices (74 family physicians) between November 2001 and November 2005. Patients were randomized to 1 of 4 treatment groups: antibiotic and nasal steroid; placebo antibiotic and nasal steroid; antibiotic and placebo nasal steroid; placebo antibiotic and placebo nasal steroid. A dose of 500 mg of amoxicillin 3 times per day for 7 days and 200 mug of budesonide in each nostril once per day for 10 days. Proportion clinically cured at day 10 using patient symptom diaries and the duration and severity of symptoms. The proportions of patients with symptoms lasting 10 or more days were 29 of 100 (29%) for amoxicillin vs 36 of 107 (33.6%) for no amoxicillin (adjusted odds ratio, 0.99; 95% confidence interval, 0.57-1.73). The proportions of patients with symptoms lasting 10 or more days were 32 of 102 (31.4%) for topical budesonide vs 33 of 105 (31.4%) for no budesonide (adjusted odds ratio, 0.93; 95% confidence interval, 0.54-1.62). Secondary analysis suggested that nasal steroids were significantly more effective in patients with less severe symptoms at baseline.

Guideline for Medications in Cystic Fibrosis

Clinical Question:
What medications are effective in managing patients with cystic fibrosis?

Bottom Line:
In this evidence-based guideline, patients with cystic fibrosis should be treated with inhaled tobramycin, hypertonic saline, and dornase alfa. Patients with an FEV1 of more than 60% of predicted may benefit from ibuprofen, and those with persistent Pseudomonas aeruginosa may benefit from azithromycin. The guideline identified many areas in which the existing research is not helpful.

Reference:
Flume PA, O’Sullivan BP, Robinson KA, et al, and the Cystic Fibrosis Foundation, Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007;176(10):957-969.

Study Design:
Practice guideline

Synopsis:
The Cystic Fibrosis Foundation commissioned a committee to develop evidence-based guidelines for drug therapy in managing patients with cystic fibrosis. Only 4 of the 15 members had potential conflicts of interest. The committee developed a set of questions that were addressed in 1 of 3 ways: a commissioned systematic review, a modified systematic review, or a summary of existing Cochrane reviews. From these questions, the committee made a set of recommendations using the US Preventive Service Task Force rating scheme to grade them. Here is a summary of their main recommendations, all applied to patients aged 6 years or older.

A recommendations
For patients with moderate to severe disease:
Chronic use of inhaled tobramycin reduces exacerbations and improves lung function
Chronic use of dornase alfa reduces exacerbations and improves lung function

B recommendations
For patients with mild disease or who are asymptomatic:
Chronic use of inhaled tobramycin reduces exacerbations and improves lung function
Chronic use of dornase alfa reduces exacerbations and improves lung function
Chronic use of inhaled hypertonic saline reduces exacerbations and improves lung function
Chronic oral ibuprofen slows the loss of lung function in patients whose FEV1 is more than 60% predicted
Chronic azithromycin reduces exacerbations and improves lung function in patients with persistent Pseudomonas aeruginosa

D recommendations
Inhaled corticosteroids provide no benefit in patients with cystic fibrosis and should not be used
Prophylactic oral antistaphylococcal antibiotics should not be used

Antibiotics for URIs reduce complications (but not enough to matter)

Clinical Question:
Does antibiotic treatment of common respiratory infections decrease the risk of serious complications?

Bottom Line:
Antibiotics are not justified to reduce the risk of serious complications for upper respiratory tract infection, sore throat, or otitis media. Antibiotics substantially reduce the risk of pneumonia after chest infection, particularly in elderly people in whom the risk is highest.

Reference:
Petersen I, Johnson AM, Islam A, Duckworth G, Livermore DM, Hayward AC. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. BMJ 2007;335(76-27):982-987.

Study Design:
Cohort (prospective)

Synopsis:
The authors determined the extent to which antibiotics reduce the risk of serious complications after common respiratory tract infections. They did a Retrospective cohort study. They used UK primary care practices contributing to the general practice research database 3.36 million episodes of respiratory tract infection. The investigators study the risk of serious complications in treated and untreated patients in the month after diagnosis: mastoiditis after otitis media, quinsy after sore throat, and pneumonia after upper respiratory tract infection and chest infection. Number of patients needed to treat to prevent one complication. Serious complications were rare after upper respiratory tract infections, sore throat, and otitis media, and the number needed to treat was over 4000. The risk of pneumonia after chest infection was high, particularly in elderly people, and was substantially reduced by antibiotic use, with a number needed to treat of 39 for those aged > or =65 and 96-119 in younger age groups.

Pneumonia in patients aged 16 years to 64 years decreased from 6.73 to 5.4 per 10,000 URIs with the use of antibiotics. Though statistically significant, 4407 patients (of all ages) have to be treated with an antibiotic to prevent 1 episode of pneumonia (number needed to treat (NNT) = 4407 for all ages; NNTs were not provided for individual age groups). Results were similar for peritonsillar abscess following sore throat and mastoiditis associated with ear infection: antibiotics decreased complications but had NNTs greater than 4000. The only exception was the incidence of pneumonia after bronchitis: The NNTs varied by age from 119 in patients aged 16 years to 64 years to 39 for patients older than 65 years.

Pneumonia can be treated with 3 to 5 days of antibiotics

Clinical Question:
Can community-acquired pneumonia be treated with 3 days to 5 days of antibiotic therapy?

Bottom Line:
Ten to 14 days of antibiotics are no more effective in patients with community-acquired pneumonia than 3 to 5 days of treatment. Clinical failures and mortality were similar regardless of treatment length. The equivalent effectiveness was demonstrated with 3 to 5 days of oral or parenteral azithromycin, levofloxacin for 5 days, cefuroxime for 7 days, and intravenous ceftriaxone for 5 days.

Reference:
Li JZ, Winston LG, Moore DH, Bent S. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am J Med 2007;120(9):783-790.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
There is little consensus on the most appropriate duration of antibiotic treatment for community-acquired pneumonia. The authors systematically reviewed randomized controlled trials comparing short-course and extended-course antibiotic regimens for community-acquired pneumonia. They searched MEDLINE, Embase, and CENTRAL, and reviewed reference lists from 1980 through June 2006. Studies were included if they were randomized controlled trials that compared short-course (7 days or less) versus extended-course (>7 days) antibiotic monotherapy for community-acquired pneumonia in adults. The primary outcome measure was failure to achieve clinical improvement. They found 15 randomized controlled trials matching our inclusion and exclusion criteria comprising 2796 total subjects. Short-course regimens primarily studied the use of azithromycin (n=10), but trials examining beta-lactams (n=2), fluoroquinolones (n=2), and ketolides (n=1) were found as well. Of the extended-course regimens, 3 studies utilized the same antibiotic, whereas 9 involved an antibiotic of the same class. Overall, there was no difference in the risk of clinical failure between the short-course and extended-course regimens (0.89, 95% confidence interval [CI], 0.78-1.02). In addition, there were no differences in the risk of mortality (0.81, 95% CI, 0.46-1.43) or bacteriologic eradication (1.11, 95% CI, 0.76-1.62). In subgroup analyses, there was a trend toward favorable clinical efficacy for the short-course regimens in all antibiotic classes (range of relative risk, 0.88-0.94).

Only 1 in every 3 children with eczema will develop asthma

Clinical Question:
What is the risk that children with atopic eczema during the first 4 years of life will develop asthma later?

Bottom Line:
Approximately 1 in 3 young children with atopic eczema in the first 4 years of life will develop asthma at age 6 years or older.

Reference:
van der Hulst AE, Klip H, Brand PL. Risk of developing asthma in young children with atopic eczema: A systematic review. J Allergy Clin Immunol 2007;120(3):565-569.

Study Design:
Cohort (prospective)

Synopsis:
It is commonly believed that the majority of infants and young children with early atopic eczema will develop asthma in later childhood. This belief is mainly based on cross-sectional population studies. Recent evidence suggests a more complex relationship between early eczema and asthma. This systematic review was conducted to assess the risk of developing asthma in children with atopic eczema during the first 4 years of life. A sensitive search was performed to identify all prospective cohort studies on the topic. By pooling the eligible reports, we calculated the risk of developing asthma at 6 years of age or older in children with atopic eczema in the first 4 years of life. Thirteen prospective cohort studies were included, with 4 representing birth cohort studies and 9 representing eczema cohort studies. The pooled odds ratio for the risk of asthma after eczema, compared with children without eczema, in birth cohort studies was 2.14 (95% CI, 1.67-2.75). The prevalence of asthma at the age of 6 years in eczema cohort studies was 35.8% (95% CI, 32.2% to 39.9%) for inpatients and 29.5% (95% CI, 28.2% to 32.7%) for a combined group of inpatients and outpatients. CONCLUSION: Although there is an increased risk of developing asthma after eczema in early childhood, only 1 in every 3 children with eczema develops asthma during later childhood. This is lower than previously assumed.

Allergic rhinitis associated with increased risk of bronchial hyperreactivity (ECRHS)

Clinical Question:
Are patients with allergic rhinitis at increased risk of developing bronchial hyperreactivity (a euphemism for asthma)?

Bottom Line
This study shows that 9.7% of patients with allergic rhinitis will develop bronchial hyperreactivity within 9 years. Although this is the first study to prospectively assess this association, the low rate of follow up is concerning.

Reference:
Shaaban R, Zureik M, Soussan D, et al. Allergic rhinitis and onset of bronchial hyperresponsiveness: a population-based study. Am J Respir Crit Care Med 2007;176(7):659-666.

Study Design:
Cohort (prospective)

Synopsis:
Patients with allergic rhinitis have more frequent bronchial hyperresponsiveness (BHR) in cross-sectional studies. The authors estimated the changes in BHR in nonasthmatic subjects with and without allergic rhinitis during a 9-year period. BHR onset was studied in 3,719 subjects without BHR at baseline, who participated in the follow-up of the European Community Respiratory Health Survey. BHR was defined as a >or=20% decrease in FEV(1) for a maximum dose of 1 mg of methacholine. Allergic rhinitis was defined as having a history of nasal allergy and positive specific IgE (>or=0.35 IU/ml) to pollen, cat, mites, or Cladosporium. The cumulative incidence of BHR was 9.7% in subjects with allergic rhinitis and 7.0% in subjects with atopy but no rhinitis, compared with 5.5% in subjects without allergic rhinitis and atopy (respective odds ratios [OR] and their 95% confidence intervals [95% CI] for BHR onset, 2.44 [1.73-3.45]; and 1.35 [0.86-2.11], after adjustment for potential confounders including sex, smoking, body mass index and FEV(1)). Subjects with rhinitis sensitized exclusively to cat or to mites were particularly at increased risk of developing BHR (ORs [95% CI], 7.90 [3.48-17.93] and 2.84 [1.36-5.93], respectively). Conversely, in subjects with BHR at baseline (n = 372), 35.3% of those with allergic rhinitis, compared with 51.8% of those without rhinitis had no more BHR at follow-up (OR [95% CI], 0.51 [0.33-0.78]). BHR “remission” was more frequent in patients with rhinitis treated by nasal steroids than in those not treated (OR [95% CI], 0.33 [0.14-0.75]).

Dexamethasone not effective for bronchiolitis

Clinical Question:
Is dexamethasone effective for the treatment of bronchiolitis?

Bottom Line:
Oral dexamethasone is not an effective treatment for moderate to severe bronchiolitis.

Reference:
Corneli HM, Zorc JJ, Majahan P, et al, for the Bronchiolitis Study Group of the Pediatric Emergency Care Applied Research Network (PECARN). A multicenter randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007; 357:331-339.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Bronchiolitis, the most common infection of the lower respiratory tract in infants, is a leading cause of hospitalization in childhood. Corticosteroids are commonly used to treat bronchiolitis, but evidence of their effectiveness is limit. The authors conducted a double-blind, randomized trial comparing a single dose of oral dexamethasone (1 mg per kilogram of body weight) with placebo in 600 children (age range, 2 to 12 months) with a first episode of wheezing diagnosed in the emergency department as moderate-to-severe bronchiolitis (defined by a Respiratory Distress Assessment Instrument score > or =6). They enrolled patients at 20 emergency departments during the months of November through April over a 3-year period. The primary outcome was hospital admission after 4 hours of emergency department observation. The secondary outcome was the Respiratory Assessment Change Score (RACS). They also evaluated later outcomes: length of hospital stay, later medical visits or admissions, and adverse events. Baseline characteristics were similar in the two groups. The admission rate was 39.7% for children assigned to dexamethasone, as compared with 41.0% for those assigned to placebo (absolute difference, -1.3%; 95% confidence interval [CI], -9.2 to 6.5). Both groups had respiratory improvement during observation; the mean 4-hour RACS was -5.3 for dexamethasone, as compared with -4.8 for placebo (absolute difference, -0.5; 95% CI, -1.3 to 0.3). Multivariate adjustment did not significantly alter the results, nor were differences detected in later outcomes.

Inhaled steroids for COPD associated with increased risk of pneumonia

Clinical Question:
Are inhaled corticosteroids for patients with chronic obstructive pulmonary disease associated with an increased risk of hospitalization for pneumonia?

Bottom Line:
In this well-conducted case-control study, the use of inhaled corticosteroids is associated with an excess risk of pneumonia hospitalization and of pneumonia hospitalization followed by death within 30 days, among elderly patients with COPD.

Reference:
Ernst P, Gonzalez AV, Brassard P, Suissa S. Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. Am J Respir Crit Care Med 2007;176:162-166.

Study Design:
Case-control

Synopsis:
Inhaled corticosteroids are commonly prescribed to patients with chronic obstructive pulmonary disease (COPD). The authors examined whether these medications might be associated with an excess risk of pneumonia. They conducted a nested case-control study within a cohort of patients with COPD from Quebec, Canada, over the period 1988-2003, identified on the basis of administrative databases linking hospitalization and drug-dispensing information. Each subject hospitalized for pneumonia during follow-up (case subjects) was age and time matched to four control subjects. The effect of the use of inhaled corticosteroids was assessed by conditional logistic regression, after adjusting for comorbidity and COPD severity. The cohort included 175,906 patients with COPD of whom 23,942 were hospitalized for pneumonia during follow-up, for a rate of 1.9 per 100 per year, and matched to 95,768 control subjects. The adjusted rate ratio of hospitalization for pneumonia associated with current use of inhaled corticosteroids was 1.70 (95% confidence interval [CI], 1.63-1.77) and 1.53 (95% CI, 1.30-1.80) for pneumonia hospitalization followed by death within 30 days. The rate ratio of hospitalization for pneumonia was greatest with the highest doses of inhaled corticosteroids, equivalent to fluticasone at 1,000 microg/day or more (rate ratio, 2.25; 95% CI, 2.07-2.44). All-cause mortality was similar for patients hospitalized for pneumonia, whether or not they had received inhaled corticosteroids in the recent past (7.4 and 8.2%, respectively).

Antibiotics in first year of life associated with later asthma

Clinical Question:
Does the early use of antibiotics increase a child’s risk of developing asthma later in life?

Bottom Line:
Antibiotic use in early life was associated with the development of childhood asthma, a risk that may be reduced by avoiding the use of BS cephalosporins.

Reference:
Kozyrskyj AL, Ernst P, Becker AB. Increased risk of childhood asthma from antibiotic use in early life. Chest 2007;131:1753-1759.

Study Design:
Cohort (retrospective)

Synopsis:
To address the major methodological issues of reverse causation and selection bias in epidemiologic studies of antibiotic use in early life and the development of asthma, The authors undertook a cohort study of this association in a complete population of children. Using the health-care and prescription databases of Manitoba, Canada, this longitudinal study assessed the association between antibiotic prescription use during the first year of life and asthma at age 7 years in a 1995 birth cohort of 13,116 children. Independent of well-known asthma risk factors, asthma was significantly more likely to develop in children who had received antibiotics in the first year of life at age 7 years. The association with asthma was observed for antibiotic use in non-respiratory tract infections (adjusted odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02 to 3.37). The risk of asthma was highest in children receiving more than four courses of antibiotics (adjusted OR, 1.46; 95% CI, 1.14 to 1.88), especially among rural children, and in the absence of maternal asthma or a dog in the birth year. Broad-spectrum (BS) cephalosporin use was more common in these subpopulations of children.