Do negative "rapid strep" test results need to be confirmed by culture?
Although rheumatic heart disease due to group A streptococcal infection has all but disappeared in wealthy countries (Lancet 2012;379:953-964), some countries still go to great lengths to test for Streptococcal throat infections -- I'm talking to you, United States. As a result, we spend more than $8 million per each additional case of rheumatic heart disease prevented (Prev Med 2002;35(3):250 -257).This meta-analysis found that the rapid antigen tests widely in use are very effective in both identifying and excluding strep. Overall, the sensitivity of these tests is 86% and specificity is 96%, both overall and in children. The authors of this analysis argue that this sensitivity is high enough -- and the likelihood of rheumatic heart disease is low enough -- to drop the long-held practice of confirming negative antigen test results with culture. Maybe one day we'll retire strep testing; until then, maybe we can get rid of cultures. Show this paper to your local micro lab director. (LOE = 1a)(www.essentialevidenceplus.com)
Lean WL, Arnup S, Canchin M, Steer AC. Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis. Pediatrics 2014;134(4);771-781.
Study design: Meta-analysis (other)
Funding source: Self-funded or unfunded
Setting: Various (meta-analysis)
The investigators searched MEDLINE and EMBASE to identify 48 studies that compared rapid antigen tests for group A streptococcus with throat culture, the gold standard. They limited their search to English-language studies, but searched bibliographies of identified studies and previous reviews. Two investigators assessed all studies for quality. Studies were performed throughout the world and used 6 different testing methods (latex agglutination, ELISA, and so forth). Overall, the sensitivity of all rapid antigen tests was 86% (95% CI 83% - 88%) and specificity was 96% (94% - 97%). Results were similar when limited to studies performed in children. Molecular techniques (DNA probes, polymerase chain reaction methods) were slightly better, though these tests have a turnaround time of 1 hour to 3 hours.
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Are there subgroups of patients with acute lower respiratory tract infection (who do not have clinically suspected pneumonia) who may benefit from antibiotics?
Patients with acute lower respiratory tract infection (LRTI) and green sputum or cardiopulmonary comorbidities experience a slightly greater benefit with amoxicillin treatment. That outcome must be balanced against the harms of antibiotics on the individual and population level. (LOE = 1b-)(www.essentialevidenceplus.com)
Moore M, Stuart B, Coenen S, et al, for the GRACE consortium. Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis of potential high-risk groups. Br J Gen Pract 2014;64(619):e75-80.
Study design: Randomized controlled trial (double-blinded)
Funding source: Government
Setting: Outpatient (primary care)
This is a secondary analysis of data from a large European randomized trial of the treatment of acute LRTI. These researchers recruited 2061 adults with acute LRTI but no suspected pneumonia. The patients were randomized to receive 1 g amoxicillin 3 times daily for 7 days or matching placebo. Although US physicians may criticize the choice of antibiotic, the prevalence of mycoplasma was extremely low in this cohort (0.2%) and there is good susceptibility of common respiratory pathogens to amoxicillin in Europe and the United Kingdom where this study took place. The current study identified subgroups of patients traditionally felt to be at increased risk of bacterial infection, namely those with lung disease, abnormal lung findings, a longer duration of illness, smokers, and those with fever or green sputum. For each subgroup, the authors looked at the effect of amoxicillin on symptom duration, severity, and new or worsening symptoms. The overall results of the trial found a number needed to treat to prevent new or worsening symptoms of approximately 30, similar to the number needed to treat to harm for adverse events related to antibiotic use. Overall, the authors found minimal differences in outcomes for the identified "high-risk" subgroups. There was a somewhat greater reduction in duration of symptoms for patients with green sputum (approximately 2 days), and a greater reduction in symptom severity between days 2 and 4 for those with significant cardiopulmonary morbidities (approximately 3 more patients out of 10 who rated symptoms as mild rather than moderate). None of the subgroups saw a greater benefit in preventing a worsening of illness.
Mark H. Ebell, MD, MS
University of Georgia
How frequently do harms of amoxicillin (with or without clavulanic acid) occur?
The risk of diarrhea is significantly higher with amoxicillin/clavulanic acid (amoxiclav) than placebo with a number needed to treat to harm [NNTH] of 8, which is not dissimilar from the number needed to treat for conditions like otitis media. Cure one, make one sicker. Contrary to popular belief, the risks of nausea, vomiting, and rash are not increased, but the risk of candidiasis is (NNTH = 23). (LOE = 1a)(www.essentialevidenceplus.com)
Gillies M, Ranakusuma A, Hoffmann T, et al. Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication. CMAJ 2015;187(1): E21-E31.
Study design: Meta-analysis (randomized controlled trials)
Meta-analyses and systematic reviews are increasingly common in the literature, but most focus on benefit and give little attention to harm. This study is a good example of looking carefully at the harms instead. In this case, the authors searched for randomized, placebo-controlled trials of amoxicillin or amoxiclav for any indication.They did a careful search, had 2 authors review each article and abstract data, and evaluated study quality. Overall, the risk of bias was low, which is good. They found 45 studies of adults or children, but only 25 studies provided data regarding harms that were usable for the quantitative data synthesis. The most common conditions being treated with amoxicillin were a respiratory infection or an ear, nose, and throat infection. Studies reported between 0 and 10 harms, most commonly gastrointestinal and skin adverse effects. There was no increase in the likelihood of diarrhea overall (10 studies with 4284 patients), but it was increased with amoxiclav (odds ratio [OR] = 3.3; 95% CI 2.2 - 4.9). The pooled prevalence of diarrhea was 17.5% with amoxiclav and 5.6% with placebo (NNTH = 8). Only 3 studies (2 of amoxicillin, 1 of amoxiclav) with 456 patients reported rates of candidiasis, and the likelihood was significantly increased (OR = 7.8; 95% CI 2.2 - 27). The pooled rates were 4.4% in the amoxicillin groups and 0% in the placebo groups (NNTH = 23). Rates of nausea, vomiting, and rash were similar between the amoxicillin/amoxiclav groups and the placebo groups.
What is the epidemiology of community-acquired pneumonia in adults who require hospitalization?
The 3 key messages from this study: (1) Most patients did not have a pathogen identified, so choosing an appropriate initial empiric antibiotic is important; (2) human rhinovirus, influenza, and metapneumovirus are among the most commonly identified viral causes of pneumonia; and (3) the incidence of community-acquired pneumonia (CAP) increases substantially with increasing age. (LOE = 2b)(www.essentialevidenceplus.com)
Jain S, Self WH, Wunderink RG, et al, for the CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among US adults. N Engl J Med 2015;373(5):1415-1427.
Study design: Cohort (prospective)
Setting: Inpatient (any location)
This Centers for Disease Control study attempted to determine the etiology of CAP in 3 Chicago hospitals and 2 Nashville hospitals. CAP was defined as acute respiratory symptoms, accompanied by fever, altered mental status, chills, or leukocytosis or leukopenia; and an infiltrate consistent with pneumonia on a chest radiograph. The authors excluded patients who had been hospitalized in the previous 4 weeks, lived in a nursing home, had a clear alternative diagnosis, or who were immunosuppressed. Of the 3634 eligible patients admitted during the study period (January 1, 2010, to June 30, 2012), 2488 could be enrolled, of whom 2320 (93%) had radiographic evidence of pneumonia and 2259 had complete evaluation for bacterial and viral causes of pneumonia. The last group had bacterial cultures and PCR assays of sputum for a range of bacterial causes, and nasopharyngeal swabs for a variety of viral causes of respiratory infection. The median age of the population was 57 years, and the median length of stay was 3 days. Approximately 1 in 5 patients were admitted to the intensive care unit (ICU), about 1 in 16 required mechanical ventilation, and 1 in 50 died during the hospitalization. Overall, at least 1 pathogen was detected in only 38%: 1 or more viruses in 23%, one or more bacteria in 11%, at least 1 virus and bacteria in 3%, and fungi or mycobacteria in 1%. Thus, 62% had no pathogen detected despite a careful search. The most common pathogens were human rhinovirus (9%), influenza A or B (6%), strep pneumoniae (5%), human metapneumovirus (4%), respiratory syncytial virus (3%), coronavirus (3%), mycoplasma pneumoniae (2%), staph aureus (2%), adenovirus (1.5%), legionella pneumophila (1.5%), enterobacteriaceae (1.5%), and other (3.5%). The majority of patients had a single pathogen. Strep pneumoniae, staph aureus, and enterobacteriaceae were all more common among the presumably sicker patients in the ICU than in non-ICU patients. The incidence of hospitalization for CAP increased with age, from 6.7/10,000/year in those aged 18 to 49 years, to 26.3/10,000/year for those 50 to 64 years old, 63.0/10,000/year for those 65 to 79 years old, and 164/10,000/year for those 80 years and older.
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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Respiratory Tract Infection