Antibiotics for acute rhinosinusitis in adults.

BACKGROUND: Acute rhinosinusitis is an acute infection of the nasal passages and paranasal sinuses that lasts less than four weeks. Diagnosis of acute rhinosinusitis is generally based on clinical signs and symptoms in ambulatory care settings. Technical investigations are not routinely performed, nor are they recommended in most countries. Some trials show a trend in favour of antibiotics, but the balance of benefit versus harm is unclear.We merged two Cochrane Reviews for this update, which comprised different approaches with overlapping populations, resulting in different conclusions. For this review update, we maintained the distinction between populations diagnosed by clinical signs and symptoms, or imaging. OBJECTIVES: To assess the effects of antibiotics versus placebo or no treatment in adults with acute rhinosinusitis in ambulatory care settings. SEARCH METHODS: We searched CENTRAL (2017, Issue 12), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1950 to January 2018), Embase (January 1974 to January 2018), and two trials registers (January 2018). We also checked references from identified trials, systematic reviews, and relevant guidelines. SELECTION CRITERIA: Randomised controlled trials of antibiotics versus placebo or no treatment in people with rhinosinusitis-like signs or symptoms or sinusitis confirmed by imaging. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data about cure and side effects and assessed the risk of bias. We contacted trial authors for additional information as required. MAIN RESULTS: We included 15 trials involving 3057 participants. Of the 15 included trials, 10 appeared in our 2012 review, and five (631 participants) are legacy trials from merging two reviews. No new studies were included from searches for this update. Overall, risk of bias was low. Without antibiotics, 46% of participants with rhinosinusitis, whether or not confirmed by radiography, were cured after 1 week and 64% after 14 days. Antibiotics can shorten time to cure, but only 5 to 11 more people per 100 will be cured faster if they receive antibiotics instead of placebo or no treatment: clinical diagnosis (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.02 to 1.54; number needed to treat for an additional beneficial outcome (NNTB) 19, 95% CI 10 to 205; I² = 0%; 8 trials; high-quality evidence) and diagnosis confirmed by radiography (OR 1.57, 95% CI 1.03 to 2.39; NNTB 10, 95% CI 5 to 136; I² = 0%; 3 trials; moderate-quality evidence). Cure rates with antibiotics were higher when a fluid level or total opacification in any sinus was found on computed tomography (OR 4.89, 95% CI 1.75 to 13.72; NNTB 4, 95% CI 2 to 15; 1 trial; moderate-quality evidence). Purulent secretion resolved faster with antibiotics (OR 1.58, 95% CI 1.13 to 2.22; NNTB 10, 95% CI 6 to 35; I² = 0%; 3 trials; high-quality evidence). However, 13 more people experienced side effects with antibiotics compared to placebo or no treatment (OR 2.21, 95% CI 1.74 to 2.82; number needed to treat for an additional harmful outcome (NNTH) 8, 95% CI 6 to 12; I² = 16%; 10 trials; high-quality evidence). Five fewer people per 100 will experience clinical failure if they receive antibiotics instead of placebo or no treatment (Peto OR 0.48, 95% CI 0.36 to 0.63; NNTH 19, 95% CI 15 to 27; I² = 21%; 12 trials; high-quality evidence). A disease-related complication (brain abscess) occurred in one participant (of 3057) one week after receiving open antibiotic therapy (clinical failure, control group). AUTHORS' CONCLUSIONS: The potential benefit of antibiotics to treat acute rhinosinusitis diagnosed either clinically (low risk of bias, high-quality evidence) or confirmed by imaging (low to unclear risk of bias, moderate-quality evidence) is marginal and needs to be seen in the context of the risk of adverse effects. Considering antibiotic resistance, and the very low incidence of serious complications, we conclude there is no place for antibiotics for people with uncomplicated acute rhinosinusitis. We could not draw conclusions about children, people with suppressed immune systems, and those with severe sinusitis, because these populations were not included in the available trials.

Point-of-care CRP matters: normal CRP levels reduce immediate antibiotic prescribing for acutely ill children in primary care: a cluster randomized controlled trial.

OBJECTIVE: Antibiotics are prescribed too often in acutely ill children in primary care. We examined whether a Point-of-Care (POC) C-reactive Protein (CRP) test influences the family physicians' (FP) prescribing rate and adherence to the Evidence Based Medicine (EBM) practice guidelines. DESIGN: Cluster randomized controlled trial. SETTING: Primary care, Flanders, Belgium. INTERVENTION: Half of the children with non-severe acute infections (random allocation of practices to perform POC CRP or not) and all children at risk for serious infection were tested with POC CRP. SUBJECTS: Acutely ill children consulting their FP. MAIN OUTCOME MEASURE: Immediate antibiotic prescribing. RESULTS: 2844 infectious episodes recruited by 133 FPs between 15 February 2013 and 28 February 2014 were analyzed. A mixed logistic regression analysis was performed. Compared to episodes in which CRP was not tested, the mere performing of POC CRP reduced prescribing in case EBM practice guidelines advise to prescribe antibiotics (adjusted odds ratio (aOR) 0.54 (95% Confidence Interval (CI) 0.33-0.90). Normal CRP levels reduced antibiotic prescribing, regardless of whether the advice was to prescribe (aOR 0.24 (95%CI 0.11-0.50) or to withhold (aOR 0.31 (95%CI 0.17-0.57)). Elevated CRP levels did not increase antibiotic prescribing. CONCLUSION: Normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing. Key points What is previously known or believed on this topic •Antibiotics are prescribed too often for non-severe conditions. Point-of-care (POC) C-reactive Protein (CRP) testing without guidance does not reduce immediate antibiotic prescribing in acutely ill children in primary care. What this research adds •FPs clearly consider CRP once available: normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. •Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing.

Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial.

BACKGROUND: Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment. METHODS: Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12-30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L. RESULTS: Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8-82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP < 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP < 5 mg/L. CONCLUSIONS: CRP testing should be restricted to children at higher risk after clinical assessment. A CRP < 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282 (registered on 14th September 2012).

Diagnosing serious infections in acutely ill children in ambulatory care (ERNIE 2 study protocol, part A): diagnostic accuracy of a clinical decision tree and added value of a point-of-care C-reactive protein test and oxygen saturation.

BACKGROUND: Acute illness is the most common presentation of children to ambulatory care. In contrast, serious infections are rare and often present at an early stage. To avoid complications or death, early recognition and adequate referral are essential. In a recent large study children were included prospectively to construct a symptom-based decision tree with a sensitivity and negative predictive value of nearly 100%. To reduce the number of false positives, point-of-care tests might be useful, providing an immediate result at bedside. The most probable candidate is C-reactive protein, as well as a pulse oximetry. METHODS: This is a diagnostic accuracy study of signs, symptoms and point-of-care tests for serious infections. Acutely ill children presenting to a family physician or paediatrician will be included consecutively in Flanders, Belgium. Children testing positive on the decision tree will get a point-of-care C-reactive protein test. Children testing negative will randomly either receive a point-of-care C-reactive protein test or usual care. The outcome of interest is hospital admission more than 24 hours with a serious infection within 10 days. Aiming to include over 6500 children, we will report the diagnostic accuracy of the decision tree (+/- the point-of-care C-reactive protein test or pulse oximetry) in sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values. New diagnostic algorithms will be constructed through classification and regression tree and multiple logistic regression analysis. DISCUSSION: We aim to improve detection of serious infections, and present a practical tool for diagnostic triage of acutely ill children in primary care. We also aim to reduce the number of investigations and admissions in children with non-serious infections. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282.

Optimizing antibiotic prescribing for acutely ill children in primary care (ERNIE2 study protocol, part B): a cluster randomized, factorial controlled trial evaluating the effect of a point-of-care C-reactive protein test and a brief intervention combined with written safety net advice.

BACKGROUND: Despite huge public campaigns, there is still overconsumption of antibiotics in children with self-limiting diseases. Possible explanations may be the physicians' and parents' uncertainty about the gravity of the disease and inadequate communication between physicians and parents leading to lack of reassurance for the parents. In this paper we describe the design and methods of a trial aiming to rationalize antibiotic prescribing by decreasing this uncertainty and parental anxiety. METHODS/DESIGN: Acutely ill children without suspected serious disease consulting their family physician will be consecutively included in a four-armed cluster randomized factorial controlled trial. The intervention will consist a Point-of-Care C-reactive protein test and/or a brief intervention with safety net advice. The control group will receive usual care. We intend to include 2560 patients in 88 family practices. Patients will be followed up until cure. The primary outcome measure is the immediate antibiotic prescribing rate. Secondary outcomes are: comparison between groups of speed of clinical recovery, parental concern, parental perception of the quality of the communication, parental satisfaction, use of medication, use of diagnostic tests and medical services during the illness episode, and cost-effectiveness of the interventions. Besides this, we will observationally analyse data of the children included in the large ERNIE2-trial, but excluded in the cluster randomized trial, namely children suspected of serious disease presenting in primary care and children who initially present at the out-patient paediatric clinic or emergency department. We will search for predictors of antibiotic prescribing, speed of clinical recovery, parental concern, parental perception of communication, parental satisfaction, use of medication, diagnostic tests and medical services. DISCUSSION: This is a unique multifaceted intervention, in that it targets both physicians and parents by aiming specifically at their uncertainty and concerns during the consultation. Both interventions are easy to implement without special training. When proven effective, they could offer a feasible way to decrease inappropriate antibiotic prescribing for children in family practice and thus avoid emergence of bacterial resistance, side effects and unnecessary healthcare costs. Moreover, the observational part of the study will increase our insight in the course, management and parent's concern of acute illness in children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282.

Antibiotics for clinically diagnosed acute rhinosinusitis in adults.

BACKGROUND: In primary care settings, the diagnosis of rhinosinusitis is generally based on clinical signs and symptoms. Technical investigations are not routinely performed, nor recommended. Individual trials show a trend in favour of antibiotics, but the balance of benefit versus harm is unclear. OBJECTIVES: To assess the effect of antibiotics in adults with clinically diagnosed rhinosinusitis in primary care settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2012), MEDLINE (January 1950 to February week 4, 2012) and EMBASE (January 1974 to February 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) of antibiotics versus placebo in participants with rhinosinusitis-like signs or symptoms. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias. We contacted trial authors for additional information. We collected information on adverse effects from the trials. MAIN RESULTS: We included 10 trials involving 2450 participants. Overall, the risk of bias in these studies was low. Irrespective of the treatment group, 47% of participants were cured after one week and 71% after 14 days. Antibiotics can shorten the time to cure, but only five more participants per 100 will cure faster at any time point between 7 and 14 days if they receive antibiotics instead of placebo (number needed to treat to benefit (NNTB)) 18 (95% confidence interval (CI) 10 to 115, I(2) statistic 0%, eight trials). Purulent secretion resolves faster with antibiotics (odds ratio (OR) 1.58 (95% CI 1.13 to 2.22)), (NNTB 11, 95% CI 6 to 51, I(2) statistic 0%, three trials). However, 27% of the participants who received antibiotics and 15% of those who received placebo experienced adverse events (OR 2.10, 95% CI 1.60 to 2.77) (number needed to treat to harm (NNTH)) 8 (95% CI 6 to 13, I(2) statistic 13%, seven trials). More participants in the placebo group needed to start antibiotic therapy because of an abnormal course of rhinosinusitis (OR 0.49, 95% CI 0.36 to 0.66), NNTH 20 (95% CI 14 to 35, I(2) statistic 0%, eight trials). Only one disease-related complication (brain abscess) occurred in a patient treated with antibiotics. AUTHORS' CONCLUSIONS: The potential benefit of antibiotics in the treatment of clinically diagnosed acute rhinosinusitis needs to be seen in the context of a high prevalence of adverse events. Taking into account antibiotic resistance and the very low incidence of serious complications, we conclude that there is no place for antibiotics for the patient with clinically diagnosed, uncomplicated acute rhinosinusitis. This review cannot make recommendations for children, patients with a suppressed immune system and patients with severe disease, as these populations were not included in the available trials.

Encounters for common illnesses in general practice increased in obese patients.

BACKGROUND: Obese patients are known to have more chronic medical conditions. OBJECTIVE: To compare the frequency of encounter for episodes of the 10 most common illnesses in general practice between obese and non-overweight patients. METHODS: Data were derived from the Continuous Morbidity Registration, containing data from four general practices in and around Nijmegen (The Netherlands). In this research and registration network, a matched cohort study was performed. Each obese patient (body mass index > or = 30 kg/m(2)), aged 20-75 years, was matched for age, gender, socio-economic status and general practice, to approximately two patients without the diagnosis 'overweight' or 'obesity'. Over a period of 5 years (January 1, 2000 to December 31, 2004), the frequency of encounter for episodes of the 10 most common illnesses was compared, taking chronic medical conditions into account. RESULTS: At the start, 550 patients with obesity could be identified and were matched to 954 controls. Obese patients presented more common illnesses than non-overweight patients (incidence rate ratio 1.28, 95% confidence interval 1.12-1.47), in particular common cold (without fever), myalgia of the upper girdle, dermatophytosis and bruise (contusion, haematoma). CONCLUSION: Obese patients present more common illnesses to their GP, such as common cold (without fever), myalgia of the upper girdle, dermatophytosis and bruise (contusion, haematoma). This is in addition to their higher co-morbidity of chronic medical conditions.

Reducing inappropriate antibiotic prescribing for children in primary care: a cluster randomised controlled trial of two interventions.

BACKGROUND: Antibiotics are overprescribed for non-severe acute infections in children in primary care. AIM: To explore two different interventions that may reduce inappropriate antibiotic prescribing for non-severe acute infections. DESIGN AND SETTING: A cluster randomised, factorial controlled trial in primary care, in Flanders, Belgium. METHOD: Family physicians (FPs) enrolled children with non-severe acute infections into this study. The participants were allocated to one of four intervention groups according to whether the FPs performed: (1) a point-of-care C-reactive protein test (POC CRP); (2) a brief intervention to elicit parental concern combined with safety net advice (BISNA); (3) both POC CRP and BISNA; or (4) usual care (UC). Guidance on the interpretation of CRP was not provided. The main outcome was the immediate antibiotic prescribing rate. A mixed logistic regression was performed to analyse the data. RESULTS: In this study 2227 non-severe acute infections in children were registered by 131 FPs. In comparison with UC, POC CRP did not influence antibiotic prescribing, (adjusted odds ratio [AOR] 1.01, 95% confidence interval [CI] = 0.57 to 1.79). BISNA increased antibiotic prescribing (AOR 2.04, 95% CI = 1.19 to 3.50). In combination with POC CRP, this increase disappeared. CONCLUSION: Systematic POC CRP testing without guidance is not an effective strategy to reduce antibiotic prescribing for non-severe acute infections in children in primary care. Eliciting parental concern and providing a safety net without POC CRP testing conversely increased antibiotic prescribing. FPs possibly need more training in handling parental concern without inappropriately prescribing antibiotics.

Point-of-care C reactive protein to identify serious infection in acutely ill children presenting to hospital: prospective cohort study.

OBJECTIVE: Acute infection is the most common presentation of children to hospital. A minority of these infections are serious, but early recognition and adequate management are essential. We aimed to develop improved tools to assess children attending ambulatory hospital care, integrating clinical features with point-of-care C reactive protein (CRP). DESIGN: Prospective observational diagnostic study. SETTING AND PATIENTS: 5517 acutely ill children (1 month-16 years) presenting to 106 paediatricians at six outpatient clinics and six emergency departments in Belgium. INDEX TEST: Point-of-care CRP alongside vital signs and objective symptoms measurements. MAIN OUTCOME: Hospital admission for >24 hours with a serious infection <5 days after presentation. RESULTS: An algorithm was developed consisting of clinical features and CRP. This achieved 97.1% (95% CI 94.3% to 98.7%) sensitivity and 99.6% (95% CI 99.2% to 99.8%) negative predictive value, excluding serious infections in 36.4% of children. It stratifies patients into three groups based on CRP level: high-risk group with CRP >75 mg/L (26.8% risk of infection), intermediate-risk group with CRP 20-75 mg/L and at least one of seven clinical features (8.1%), and lower risk group with CRP <20 mg/L with at least one of the 11 features (3.8%). Children in intermediate-risk or low-risk groups with normal clinical assessment have 0.6% and 0.4% risk of serious infections, respectively. CONCLUSIONS: Conducting a CRP test may first enable children to be stratified into three risk groups, guiding assessment of clinical features that could be performed by junior doctors or nurses. In one-third of acutely ill children, the algorithm could exclude serious infection. Prospective validation of the algorithm is needed. CLINICAL TRIAL REGISTRATION: NCT02024282 (post-results).

Validating a decision tree for serious infection: diagnostic accuracy in acutely ill children in ambulatory care.

OBJECTIVE: Acute infection is the most common presentation of children in primary care with only few having a serious infection (eg, sepsis, meningitis, pneumonia). To avoid complications or death, early recognition and adequate referral are essential. Clinical prediction rules have the potential to improve diagnostic decision-making for rare but serious conditions. In this study, we aimed to validate a recently developed decision tree in a new but similar population. DESIGN: Diagnostic accuracy study validating a clinical prediction rule. SETTING AND PARTICIPANTS: Acutely ill children presenting to ambulatory care in Flanders, Belgium, consisting of general practice and paediatric assessment in outpatient clinics or the emergency department. INTERVENTION: Physicians were asked to score the decision tree in every child. PRIMARY OUTCOME MEASURES: The outcome of interest was hospital admission for at least 24 h with a serious infection within 5 days after initial presentation. We report the diagnostic accuracy of the decision tree in sensitivity, specificity, likelihood ratios and predictive values. RESULTS: In total, 8962 acute illness episodes were included, of which 283 lead to admission to hospital with a serious infection. Sensitivity of the decision tree was 100% (95% CI 71.5% to 100%) at a specificity of 83.6% (95% CI 82.3% to 84.9%) in the general practitioner setting with 17% of children testing positive. In the paediatric outpatient and emergency department setting, sensitivities were below 92%, with specificities below 44.8%. CONCLUSIONS: In an independent validation cohort, this clinical prediction rule has shown to be extremely sensitive to identify children at risk of hospital admission for a serious infection in general practice, making it suitable for ruling out. TRIAL REGISTRATION NUMBER: NCT02024282.