Are antibiotics beneficial for patients with sinusitis complaints? A randomized double-blind clinical trial. Primary-care-based randomised placebo-controlled trial of antibiotic treatment in acute maxillary sinusitis. Treatment of acute rhinosinusitis diagnosed by clinical criteria or ultrasound in primary care. A placebo-controlled randomised trial. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. The end of antibiotic treatment in adults with acute sinusitis-like complaints in general practice? A placebo-controlled double-blind randomized doxycycline trial. A randomized controlled trial of point-of-care evidence to improve the antibiotic prescribing practices for otitis media in children. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis: a randomized controlled trial. Communication training and antibiotic use in acute respiratory tract infections. A cluster randomised controlled trial in general practice. Antibiotic treatment of patients with mucosal thickening in the paranasal sinuses, and validation of cut-off points in sinus CT. A multicenter, randomized, investigator-blinded study of 5- and 10-day gatifloxacin versus 10-day amoxicillin/clavulanate in patients with acute bacterial sinusitis. A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children. Short therapy with amoxicillin-clavulanate and corticosteroids in acute sinusitis: results of a multicentre study in adults. Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age. Randomised, double blind, placebo controlled trial of penicillin V and amoxycillin in treatment of acute sinus infections in adults. Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16. Acute bacterial sinusitis. Minocycline vs amoxicillin. Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial. Penicillin in acute otitis media: a double-blind placebo-controlled trial. Management for the children with otitis media with effusion in the tertiary hospital. Comparison of cefuroxime with or without intranasal fluticasone for the treatment of rhinosinusitis. The CAFFS Trial: a randomized controlled trial. Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children. Antibiotic treatment of acute otorrhea through tympanostomy tube: randomized double-blind placebo-controlled study with daily follow-up. Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults. Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial. Reducing antibiotic use in children: a randomized trial in 12 practices. Relative importance of antibiotic and improved clearance in topical treatment of chronic mucopurulent rhinosinusitis. A controlled study. A randomised controlled trial of delayed antibiotic prescribing as a strategy for managing uncomplicated respiratory tract infection in primary care. Five vs. ten days of antibiotic therapy for acute otitis media in young children. Two versus seven days penicillin treatment for acute otitis media. A placebo controlled trial in children. A single topical agent is clinically equivalent to the combination of topical and oral antibiotic treatment for otitis externa. Efficacy of topical antibiotic therapy in acute conjunctivitis in children. Efficacy of daily hypertonic saline nasal irrigation among patients with sinusitis: a randomized controlled trial. The efficacy of a single dose antibiotic regimen in adults undergoing tonsillectomy. Short-course, low-dose oral betamethasone as an adjunct in the treatment of acute infective sinusitis : a comparative study with placebo. Clinical efficacy of three common treatments in acute otitis externa in primary care: randomised controlled trial. Pilot study for appropriate anti-infective community therapy. Effect of a guideline-based strategy to optimize use of antibiotics. Efficacy of isotonic nasal wash (seawater) in the treatment and prevention of rhinitis in children. Prospective randomized clinical trial assessing the efficacy of a short course of intravenously administered amoxicillin plus clavulanic acid followed by oral antibiotic in patients with uncomplicated acute diverticulitis. Treatment of acute maxillary sinusitis--comparing cefpodoxime proxetil with amoxicillin. Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. Effect of corticosteroids on wound healing after endoscopic sinus surgery. Acute red ear in children: controlled trial of non-antibiotic treatment in general practice. Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. Intranasal beclomethasone as an adjunct to treatment of chronic middle ear effusion. Amoxicillin for acute rhinosinusitis: a randomized controlled trial. Functional endoscopic sinus surgery: 5 year follow up and results of a prospective, randomised, stratified, double-blind, placebo controlled study of postoperative fluticasone propionate aqueous nasal spray. Efficacy and safety of a novel, single-dose azithromycin microsphere formulation versus 10 days of levofloxacin for the treatment of acute bacterial sinusitis in adults. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Improving appropriateness of antibiotic therapy: randomized trial of an intervention to foster reassessment of prescription after 3 days. Comparative effectiveness and safety of cefdinir and amoxicillin-clavulanate in treatment of acute community-acquired bacterial sinusitis. Cefdinir Sinusitis Study Group. Cefaclor vs amoxicillin in the treatment of acute, recurrent, and chronic sinusitis.
Sinusitis is the fifth most common reason for patients to visit primary care physicians, yet clinical outcomes relevant to patients are seldom studied.
                To determine whether patients with purulent rhinitis, "sinusitis-type symptoms," improved with antibiotics. Second, to examine a clinical prediction rule to provide preliminary validation data.
                Prospective clinical trial, with double-blinded placebo controlled randomization. The setting was a suburb of Washington, DC, from Oct 1, 2001, to March 31, 2003. All participants were 18 years or older, presenting to a family practice clinic with a complaint of sinusitis and with pus in the nasal cavity, facial pressure, or nasal discharge lasting longer than 7 days. The main outcome measures were resolution of symptoms within a 14-day follow-up period and the time to improvement (days).
                After exclusion criteria, 135 patients were randomized to either placebo (n=68) or amoxicillin (n=67) for 10 days. Intention-to-treat analyses showed that 32 (48%) of the amoxicillin group vs 25 (37%) of the placebo group (P=.26) showed complete improvement by the end of the 2-week follow-up period (relative risk=1.3; 95% confidence interval [CI], 0.87-1.94]). Although the rates of improvement were not statistically significantly different at the end of 2 weeks, the amoxicillin group improved significantly earlier, in the course of treatment, a median of 8 vs 12 days, than did the placebo group (P=.039).
                For most patients with sinusitis-type complaints, no improvement was seen with anti-biotics over placebo. For those who did improve, data suggested there is a subgroup of patients who may benefit from antibiotics. The value of antibiotics in acute rhinosinusitis is uncertain. Although maxillary sinusitis is commonly diagnosed and treated in general practice, no effectiveness studies have been done on unselected primary-care patients. We used a randomised, placebo-controlled design to test the hypothesis that there would be an improvement associated with amoxycillin treatment for acute maxillary sinusitis patients presenting to general practice.
                Adult patients with suspected acute maxillary sinusitis were referred by general practitioners for radiographs of the maxillary sinus. Those with radiographic abnormalities (n = 214) were randomly assigned treatment with amoxycillin (750 mg three times daily for 7 days; n = 108) or placebo (n = 106). Clinical course was assessed after 1 week and 2 weeks, and reported relapses and complications were recorded during the following year.
                After 2 weeks, symptoms had improved substantially or disappeared in 83% of patients in the study group and 77% of patients taking placebo. Amoxycillin did not influence the clinical course of maxillary sinusitis nor the frequency of relapses during the 1-year follow-up. Radiographs had no prognostic value, nor were they an effect modifier. Side-effects were recorded in 28% of patients given amoxycillin and in 9% of those taking placebo (p < 0.01). The occurrence of relapses was similar in both groups (21 vs 17%) during the follow-up year.
                Antibiotic treatment did not improve the clinical course of acute maxillary sinusitis presenting to general practice. For these patients, an initial radiographic examination is not necessary and initial management can be limited to symptomatic treatment. Whether antibiotics are necessary in more severe cases warrants further study. To compare antibiotics and placebo in patients with clinically diagnosed acute maxillary sinusitis (AMS). To study whether sinus ultrasound examination would help to detect those patients who benefit from antibiotic therapy.
                A double-blind, randomised, placebo-controlled multicentre trial.
                Nine primary care sites in Finland.
                150 adult patients (mean age 39.7 years) with a clinical diagnosis of sinusitis.
                Antibiotics (amoxicillin 750 mg x 2, doxycycline 100 mg x 2 or penicillin V 1500 mg x 2) or placebo twice daily for 7 days; all patients were examined with sinus ultrasound after randomisation.
                Clinical success (patients' report of recovery) in telephone interview at 2 weeks.
                A total of 146 patients completed the 2-week follow-up. Patients receiving antibiotics achieved a slightly higher rate of clinical success than patients receiving placebo (80% vs 66%; p = 0.068).
                Antibiotics hasten symptom relief in AMS. Yet many patients recover in 2 weeks without antimicrobial treatment. Only half of patients with a clinical diagnosis of AMS have sinusitis in ultrasound examination. To compare immediate with delayed prescribing of antibiotics for acute otitis media.
                Open randomised controlled trial. Setting: General practices in south west England.
                315 children aged between 6 months and 10 years presenting with acute otitis media.
                Two treatment strategies, supported by standardised advice sheets-immediate antibiotics or delayed antibiotics (antibiotic prescription to be collected at parents' discretion after 72 hours if child still not improving).
                Symptom resolution, absence from school or nursery, paracetamol consumption.
                On average, symptoms resolved after 3 days. Children prescribed antibiotics immediately had shorter illness (-1.1 days (95% confidence interval -0.54 to -1.48)), fewer nights disturbed (-0.72 (-0.30 to -1.13)), and slightly less paracetamol consumption (-0.52 spoons/day (-0.26 to -0.79)). There was no difference in school absence or pain or distress scores since benefits of antibiotics occurred mainly after the first 24 hours-when distress was less severe. Parents of 36/150 of the children given delayed prescriptions used antibiotics, and 77% were very satisfied. Fewer children in the delayed group had diarrhoea (14/150 (9%) v 25/135 (19%), chi(2)=5.2, P=0.02). Fewer parents in the delayed group believed in the effectiveness of antibiotics and in the need to see the doctor with future episodes.
                Immediate antibiotic prescription provided symptomatic benefit mainly after first 24 hours, when symptoms were already resolving. For children who are not very unwell systemically, a wait and see approach seems feasible and acceptable to parents and should substantially reduce the use of antibiotics for acute otitis media. Acute sinusitis-like complaints are very common and are usually treated with antibiotics in spite of the lack of evidence for the effectiveness of antibiotic therapy and the increasing number of resistant strains.
                To assess the effectiveness of doxycycline in adults with acute sinusitis-like complaints in general practice.
                The effects of doxycycline in a placebo-controlled, double-blind, randomized trial were assessed in adults consulting their general practitioner (GP) with complaints after a common cold or influenza, pain in the head when bending forward, purulent nasal discharge, predominantly unilateral maxillary pain, toothache, or pain when chewing. Primary outcome events were the resolution of facial pain and the resumption of daily activities. Treatment differences were assessed by means of Kaplan-Meier curves and hazard ratios. The follow-up period was 42 days.
                No significant difference was found in time to recover between the doxycycline-treated group and the placebo-treated group. However, the adjusted hazard ratio for the group receiving doxycycline was 1.17 (95% CI = 0.87-1.57) for the resolution of pain and 1.31 (95% CI = 0.96-1.78) for the resumption of daily activities. After 10 days, 85% of all patients reported improvement and 60% were completely cured. Side effects were reported by 17% of the doxycycline-treated group, with two patients withdrawing because of side effects.
                Data from this study indicate that doxycycline does not add to the effectiveness of decongestive nose drops and steam inhalation in treating acute sinusitis-like complaints in general practice adults. Prescribing practices for otitis media are not consistent with current evidence-based recommendations.
                To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written.
                Randomized, controlled trial.
                Primary care pediatric clinic affiliated with university training program. Intervention. A point-of-care evidence-based message system presenting real time evidence to providers based on their prescribing practice for otitis media.
                Proportion of prescriptions for otitis media that were for <10 days and frequency with which antibiotics were prescribed.
                Intervention providers had a 34% greater reduction in the proportion of time they prescribed antibiotics for <10 days. Intervention providers were less likely to prescribe antibiotics than were control providers.
                A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition. 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.
                To determine the effectiveness of amoxicillin and topical budesonide in acute maxillary sinusitis.
                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.
                Neither an antibiotic nor a topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting.
                isrctn.org Identifier: ISRCTN60825437. A cluster-randomised controlled trial in general practice
                Physician-patient communication plays a key role in treatment decisions in primary care. We aimed to reduce the antibiotic prescription rate for acute respiratory tract infections using a short training programme in patient-centred communication.
                We conducted a cluster-randomised controlled trial in 45 general practices in Switzerland. Thirty physicians received evidence-based guidelines for the management of acute respiratory tract infections; 15 physicians randomised to the full intervention additionally received training in patient-centred communication. A further 15 physicians, not randomised, served as a control to blind the physicians in the other two groups to the true comparison. The primary outcome was the antibiotic prescription rate reported by pharmacists. Secondary outcomes were patient satisfaction and enablement, re-consultation rates, days with restrictions, and days off work. 1108 adults with acute respiratory infections were screened between January and May 2004. Outcomes were measured in 837 consultations; 624 patients had follow-up interviews at 7 and 14 days.
                The antibiotic prescription rate reported by pharmacists was low in both full and limited intervention groups (13.5% and 15.7% respectively) but only half of the antibiotics were prescribed according to guidelines (53.8% and 53.1%). No significant differences were seen between the two randomised groups in primary and secondary outcomes. In both groups patient satisfaction was high (median score for both 68 out of 70).
                In this trial, patient-centred communication training did not reduce the rate of antibiotic prescriptions below an already unusually low level. Even with this low prescription rate, patient satisfaction with received care was high. We compared the efficacy of penicillin V and amoxycillin treatment with placebo in 70 adult patients from Norwegian family practice with a clinical diagnosis of acute sinusitis and mucosal thickening on CT, but without fluid level or total opacification. The study was randomized and double-blind. Three different outcomes were evaluated; subjective status after 10 days of treatment, difference in clinical score between day 0 and day 10, and duration of the illness episode. Amoxycillin and penicillin V gave no better response to treatment than placebo, evaluated by all three outcome measures. The median duration of the sinusitis episode was 10 days in the amoxycillin- and placebo groups and 13 days in the penicillin-V group. In patients with a clinical diagnosis of acute sinusitis, fluid level and total opacification on CT are good criteria to differentiate between groups of patients that need or do not need antibiotic treatment. Treatment guidelines for acute bacterial sinusitis recommend 10 to 14 days of therapy with amoxicillin/clavulanate, high-dose amoxicillin, cefpodoxime, cefuroxime, or a newer fluoroquinolone. Objective: This study compared the clinical efficacy of short-course (5-day) gatifloxacin with standard 10-day regimens of amoxicillin/clavulanate or gatifloxacin in patients with a diagnosis of acute, uncomplicated maxillary sinusitis.
                This was a multicenter, investigator-blinded study in adult patients (age >18 years) with physical findings, signs and symptoms (for at least 7 days), and radiographic findings indicating acute, uncomplicated maxillary sinusitis. Patients were randomized to receive gatifloxacin 400 mg once daily for 5 days, gatifloxacin 400 mg once daily for 10 days, or amoxicillin/clavulanate 875 mg twice daily for 10 days. Clinical response was assessed once between days 3 and 5 of treatment, once I to 3 days after the completion of study treatment, once 7 to 14 days posttreatment (test-of-cure visit), and once 21 to 28 days posttreatment. Safety was assessed throughout the study.
                The study enrolled 445 patients. The treatment groups were similar in terms of history of sinusitis, presenting signs and symptoms, and radiographic findings. The most common presenting symptoms were nasal congestion, sinus tenderness, and purulent nasal discharge (>90% of patients); 99% of patients had abnormal radiographic findings. At the test-of-cure visit, clinical cure rates for clinically evaluable patients in the 3 treatment groups were 74% (102/137) for 5-day gatifloxacin, 80% (101/127) for 10-day gatifloxacin, and 72% (101/ 141) for 10-day amoxicillin/clavulanate (95% CI for the difference in cure rates: 5-day gatifloxacin vs amoxicillin/clavulanate, -7.6 to 13.2; 5- vs 10-day gatifloxacin, -15.2 to 5.1; 10-day gatifloxacin vs amoxicillin/clavulanate, -2.3 to 18.1). The distribution and incidence of drug-related adverse events (AEs) were comparable between treatment groups, and the majority (>95%) were mild or moderate in severity. The most common drug-related AEs included vaginitis, diarrhea, and nausea.
                In this population of patients with acute, uncomplicated sinusitis of presumed bacterial origin, a short course (5 days) of gatifloxacin therapy was associated with comparable clinical cure rates and tolerability to those of standard 10-day therapy with gatifloxacin or amoxicillin/clavulanate. All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure.
                In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period.
                Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008).
                When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM. Evolution of bacterial resistance shortens antibiotic treatment in ENT infections. The efficacy and tolerance of amoxicillin-clavulanate (ACA), with and without associated short steroid therapy, was evaluated in acute sinusitis of adults at a dosage of 1.5 g/d for 5 d vs. 10 d. This multicentre, randomized, double-blind, placebo-controlled study included 433 patients, 417 of whom were suitable for intent-to-treat (ITT) analysis. The therapeutic success rate in the ITT population, assessed according to strict clinical and radiological criteria, was respectively, 80% and 85% in the 5-d and 10-d treatment groups. Due to the statistical risks that were evidenced, the 2 durations of treatment could not be considered equivalent. The analysis of medical history shows that some risk factors (recurrence of sinusitis, previous surgical sinus drainage) seem to promote therapeutic failure and that 5-d treatment is inappropriate in these patients. The persistence of therapeutic success on day 30 was not influenced by the initial duration of treatment. The efficacy and good tolerance of ACA in acute sinusitis in adults were confirmed. Further studies will be needed to define the indications of short treatments better, which seem to be indicated in the absence of specific risk factors. The widespread use of antibiotics for treatment of acute otitis media (AOM) has resulted in the emergence of multidrug-resistant pathogens that are difficult to treat. However, it has been shown that most children with nonsevere AOM recover without ABX. The objective of this study was to evaluate the safety, efficacy, acceptability, and costs of a non-ABX intervention for children with nonsevere AOM.
                Children 6 months to 12 years old with AOM were screened by using a novel AOM-severity screening index. Parents of children with nonsevere AOM received an educational intervention, and their children were randomized to receive either immediate antibiotics (ABX; amoxicillin plus symptom medication) or watchful waiting (WW; symptom medication only). The investigators, but not the parents, were blinded to enrollment status. Primary outcomes included parent satisfaction with AOM care, resolution of symptoms, AOM failure/recurrence, and nasopharyngeal carriage of Streptococcus pneumoniae strains resistant to ABX. Secondary outcomes included medication-related adverse events, serious adverse events, unanticipated AOM-related office and emergency department visits and telephone calls, the child's absence from day care or school resulting from AOM, the parent's absence from school or work because of their child's AOM, and costs of treatment. Subjects were defined as failing (days 0-12) or recurring (days 13-30) if they experienced a higher AOM-severity score on reexamination.
                A total of 223 subjects were recruited: 73% were nonwhite, 57% were <2 years old, 47% attended day care, 82% had experienced prior AOM, and 83% had not been fully immunized with heptavalent pneumococcal vaccine. One hundred twelve were randomized to ABX, and 111 were randomized to WW. Ninety-four percent of the subjects were followed to the 30-day end point. Parent satisfaction with AOM care was not different between the 2 treatment groups at either day 12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved faster in subjects treated with immediate ABX. At day 12, among the immediate-ABX group, 69% of tympanic membranes and 25% of tympanograms were normal, compared with 51% of normal tympanic membranes and 10% of normal tympanograms in the WW group. Parents of children in the ABX group gave their children fewer doses of pain medication than did parents of children in the WW group. Subjects in the ABX group experienced 16% fewer failures than subjects in the WW group. Of the children in the WW group, 66% completed the study without needing ABX. Immediate ABX resulted in eradication of S pneumoniae carriage in the majority of children, but S pneumoniae strains cultured from children in the ABX group at day 12 were more likely to be multidrug-resistant than strains from children in the WW group. More ABX-related adverse events were noted in the ABX group, compared with the WW group. No serious AOM-related adverse events were observed in either group. Office and emergency department visits, phone calls, and days of work/school missed were not different between groups. Prescriptions for ABX were reduced by 73% in the WW group compared with the ABX group. Costs of ABX averaged $47.41 per subject in the ABX group and $11.43 in the WW group.
                Sixty-six percent of subjects in the WW group completed the study without ABX. Parent satisfaction was the same between groups regardless of treatment. Compared with WW, immediate ABX treatment was associated with decreased numbers of treatment failures and improved symptom control but increased ABX-related adverse events and a higher percent carriage of multidrug-resistant S pneumoniae strains in the nasopharynx at the day-12 visit. Key factors in implementing a WW strategy were (a) a method to classify AOM severity; (b) parent education; (c) management of AOM symptoms; (d) access to follow-up care; and (e) use of an effective ABX regimen, when needed. When these caveats are observed, WW may be an acceptable alternative to immediate ABX for some children with nonsevere AOM. Debate continues with respect to a "watch and wait" approach versus immediate antibiotic treatment for the initial treatment of acute otitis media. In this double-blind noninferiority trial, we compared clinical improvement rates at 14 days for children (6 months to 5 years of age) with acute otitis media who were randomly assigned to receive amoxicillin or placebo.
                We enrolled healthy children who presented to clinics or the emergency department with a new episode of acute otitis media during the fall and winter months in Ottawa (from December 1999 to the end of March 2002). The children were randomly assigned to receive amoxicillin (60 mg/kg daily) or placebo for 10 days. Telephone follow-up was performed on each of days 1, 2 and 3 and once between day 10 and day 14. The primary outcome was clinical resolution of symptoms, defined as absence of receipt of an antimicrobial (other than the amoxicillin in the treatment group) at any time during the 14-day period. Secondary outcomes were the presence of pain and fever and the activity level in the first 3 days, recurrence rates, and the presence of middle ear effusion at 1 and 3 months.
                According to clinical scoring, 415 of the 512 children who could be evaluated had moderate disease. At 14 days 84.2% of the children receiving placebo and 92.8% of those receiving amoxicillin had clinical resolution of symptoms (absolute difference -8.6%, 95% confidence interval -14.4% to -3.0%). Children who received placebo had more pain and fever in the first 2 days. There were no statistical differences in adverse events between the 2 groups, nor were there any significant differences in recurrence rates or middle ear effusion at 1 and 3 months.
                Our results did not support the hypothesis that placebo was noninferior to amoxicillin (i.e., that the 14-day cure rates among children with clinically diagnosed acute otitis media would not be substantially worse in the placebo group than the treatment group). Nevertheless, delaying treatment was associated with resolution of clinical signs and symptoms in most of the children. To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis.
                Randomised, double blind, placebo controlled trial.
                Norwegian general practice.
                130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography.
                Subjective status after three and 10 days of treatment, difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner, difference in score from computed tomography on day 0 and day 10, and duration of sinusitis.
                Amoxycillin and penicillin V led to significantly faster and better recovery than placebo. By day 10, 71 patients receiving antibiotic treatment- (86%) considered themselves to be recovered or much better compared with 25 (57%) receiving placebo. The mean (95% confidence interval) reductions in clinical severity scores by day 10 were 5.4 (5.0 to 5.8) for penicillin V, 5.5 (4.9 to 6.0 for amoxycillin, and 3.4 (2.8 to 4.0) for placebo. For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography (scale 0-16)-that is, score 5-16 on day 10-was 31/83 (37%) compared with 10/44 (23%) receiving placebo. The median duration of the sinusitis was nine days in the amoxycillin group, 11 days in the penicillin V group, and 17 days in the placebo group.
                Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis. To study the clinical recovery from acute otitis media (AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin (PcV).
                An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM (without perforation) with symptom duration of less than four days, were included. The children were randomized to PcV for five days or to no primary antibiotic treatment. A health score and compliance were registered on a daily basis for seven days.
                A total of 32 health centres and 72 GPs in south-east Sweden. Subjects. Children aged 2-16 presenting with earache.
                Recovery time, symptom duration, frequency of complications (up to three months) and consumption of healthcare services independent of treatment with or without antibiotics.
                A total of 179 patients carried out the trial; 92 were randomized to PcV, 87 to no primary antibiotic treatment. The median recovery time was four days in both groups. Patients who received PcV had less pain (p <0.001) and used fewer analgesics. There were no significant differences in the number of middle-ear effusions or perforations at the final control after three months. Children randomized to PcV treatment consulted less (p <0.001) during the first seven days.
                Our investigation supports that PcV treatment of AOM does not affect the recovery time or complication rates. PcV provided some symptomatic benefit in the treatment of AOM in otherwise healthy children, aged 2-16 years. The efficacy and safety of minocycline were compared with that of amoxicillin in the treatment of 58 patients with acute bacterial sinusitis. The most frequently isolated pathogens were streptococci, staphylococci, and Haemophilus influenzae. After therapy for a mean time of 11 days, clinical cure or improvement and bacterial eradication were evident in 100% of the patients treated with minocycline and in 95% of the patients treated with amoxicillin. Roentgenographic results indicated clearing or improvement in 91% of the minocycline recipients and in 70% of those who received amoxicillin. These differences between treatments were not statistically significant. A low incidence of generally mild adverse clinical experiences occurred in both treatment groups. Thus, minocycline and amoxicillin were equally safe and effective in the treatment of these patients with acute bacterial sinusitis. Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions.
                To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection.
                A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics).
                Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics).
                Symptom duration and severity.
                A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least "a slight problem" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were "very satisfied" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02).
                No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics. The effect of peroral penicillin-V (55 mg/kg/day in 7 days) on acute otitis media was studied in 149 children between the ages of 1 and 10 years in a double-blind, placebo-controlled investigation. The parameters of the disease employed were symptom scores for earache, fever and common cold, the use of analgetics, otoscopy, as well as tympanometry. The children were followed-up for 3 months. Penicillin had no effect on fever and common cold, but earache was significantly reduced on the 2nd day of treatment. The acute course of the disease was satisfactory in 69% of the children in the placebo group and in 86% in the penicillin group. In patients with pneumococci or haemolytic streptococci in the nasopharynx, the pain disappeared after 1-2 doses of penicillin, whereas the treatment had no effect in children with Haemophilus influenzae. There was no difference between the penicillin and the placebo groups with regard to the results of otoscopy and tympanometry after 1 week, 1 month and 3 months. No serious complications were observed. It is concluded that an attitude of "masterly inactivity" with regard to the treatment of acute otitis media is justifiable, provided sufficient analgesic treatment is given and also that the patient can be closely followed. As there are still many unanswered questions more controlled investigations are warranted. Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.
                Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.
                Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).
                In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals. It is not known whether intranasal corticosteroids are beneficial to treat acute rhinosinusitis in patients with a history of chronic or recurrent sinus symptoms.
                To assess whether the addition of an intranasal corticosteroid to antibiotic therapy affects the speed and rate of recovery of such patients with acute rhinosinusitis.
                A double-blind, randomized, placebo-controlled multicenter trial of 95 patients (median age, 39 years) with a history of recurrent sinusitis or chronic rhinitis and evidence of acute infection by sinus radiograph or nasal endoscopy, which was conducted from October 1998 through April 2000 at 22 sites (12 primary care and 10 otolaryngology).
                Two puffs (total dose, 200 microgram) of fluticasone propionate (n = 47) or placebo nasal spray (n = 48) in each nostril once daily for 21 days; all received 2 puffs of xylometazoline hydrochloride in each nostril twice daily for 3 days and 250 mg of cefuroxime axetil twice daily for 10 days.
                Time to clinical success (patient reported cured or much improved) during telephone follow-up at 10, 21, and 56 days.
                A total of 88 patients (93%) completed follow-up. Patients recorded their symptoms, work assessment, and compliance during the 3-week treatment phase. Patients receiving fluticasone achieved a significantly higher rate of clinical success than patients receiving placebo (93.5% vs 73.9%; P =.009). Patients treated with fluticasone improved significantly more rapidly (median of 6.0 days to clinical success) vs patients in the placebo group (median of 9.5 days; P =.01).
                The addition of fluticasone to xylometazoline and antimicrobial therapy with cefuroxime improves clinical success rates and accelerates recovery of patients with a history of chronic rhinitis or recurrent sinusitis who present for treatment of acute rhinosinusitis. The role of topical corticosteroids in the treatment of acute sinusitis has not been established in children.
                An attempt was made to determine the impact of topical corticosteroids as an adjunct to antibiotic treatment in the management of childhood sinusitis.
                In a double-blind, placebo-controlled study, 151 children with sinusitis were recruited from a general pediatric outpatient clinic and 89 completed a 3-week trial. Treatment consisted of amoxicillin-clavulanate potassium, 40 mg/kg/d tid, combined with bid nasal spray of either budesonide, 50 micrograms, to each nostril (n = 43) or placebo )n = 46_ for 3 weeks. Patients maintained daily symptom cards throughout the study and were examined by the same physician each week.
                Clinical symptoms and signs decreased significantly in both treatment groups in comparison to baseline (P < .01). We detected a significant improvement in the scores of the cough and nasal discharge at the end of second week in the budesonide group when compared with placebo (P < .05). Friedman nonparametric repeated measures ANOVA test revealed a significant decrease in the total weekly scores of cough during the second week of budesonide treatment (P < .001) in contrast to continuous decline during the second and third weeks in the placebo group (P < .001 and P < .05, respectively). While the nasal discharge score decreased significantly during the second week in the budesonide group (P < .01), no significant effect on the nasal discharge score was observed in the placebo group.
                These data suggest that topical corticosteroids may be a useful ancillary treatment to antibiotics in childhood sinusitis and effective in reducing the cough and nasal discharge earlier in the course of acute sinusitis. The role of routine antimicrobial treatment of acute middle-ear infections is under debate, because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven. Acute tube otorrhea is regarded as evidence of acute otitis media, and for methodologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment. The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea.
                Randomized, double-blind, placebo-controlled study in outpatient setting.
                Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube. Eligibility required having acute tube otorrhea of <48 hours' of duration and no prior treatment within the last 2 weeks. The mean age of the participants was 25 months; they had a history of 3 episodes of acute otitis media (median), and 99% had manifestations of a concomitant respiratory infection. Of 79 randomized patients, 7 were withdrawn because of adverse events; 66 patients completed the study.
                Amoxicillin-clavulanate (N = 34; 45 mg/kg/d) or matching placebo (N = 32) for 7 days and daily suction of middle-ear fluid through tympanostomy tube.
                Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid.
                The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group (3 vs 8 days). At the end of the 7-day medication period, tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo (treatment-control difference 41%; 95% confidence interval, 20%-63%; number needed to treat, 2.4). The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group (1 vs 8 days).
                Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid. The emergence and spread of antibiotic-resistant Streptococcus pneumoniae in US communities is due, in part, to the excessive use of antibiotics for acute respiratory tract infections.
                To decrease total antibiotic use for uncomplicated acute bronchitis in adults.
                Prospective, nonrandomized controlled trial, including baseline (November 1996-February 1997) and study (November 1997-February 1998) periods.
                Four selected primary care practices belonging to a group-model health maintenance organization in the Denver, Colo, metropolitan area.
                Consecutive adults diagnosed as having uncomplicated acute bronchitis. A total of 2462 adults were included at baseline and 2027 adults were included in the study. Clinicians included 56 physicians, 28 physician assistants or nurse practitioners, and 9 registered nurses.
                The full intervention site received household and office-based patient educational materials, as well as a clinician intervention consisting of education, practice-profiling, and academic detailing. A limited intervention site received only office-based educational materials, and control sites provided usual care.
                Antibiotic prescriptions for uncomplicated acute bronchitis during baseline and study periods.
                Antibiotic prescription rates for uncomplicated acute bronchitis were similar at all 4 sites during the baseline period. During the study period, there was a substantial decline in antibiotic prescription rates at the full intervention site (from 74% to 48% [P = .003]), but not at the control and limited intervention sites (78% to 76% [P = .81] and 82% to 77% [P = .68], respectively). Compared with control sites, changes in nonantibiotic prescriptions (inhaled bronchodilators, cough suppressants, and analgesics) were not significantly different for intervention sites. Return office visits (within 30 days of the incident visit) for bronchitis or pneumonia did not change significantly for any of the sites.
                Antibiotic treatment of adults diagnosed as having uncomplicated acute bronchitis can be safely reduced using a combination of patient and clinician interventions. To assess the effectiveness of a multiple intervention aimed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care.
                Randomised controlled trial.
                Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht, Netherlands.
                The intervention consisted of group education meetings, with a consensus procedure on indication for and type of antibiotics and with training in communication skills; monitoring and feedback on prescribing behaviour; group education for assistants of general practitioners and pharmacists; and education material for patients. The control group did not receive any of these elements.
                Antibiotic prescription rates for acute symptoms of the respiratory tract and patients' satisfaction.
                89 general practitioners completed the study (89%). At baseline, prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group (27% v 29%, respectively). After nine months, the prescription rates in the intervention group fell to 23%, whereas the control group's rose to 37% (mean difference in change -12%, 95% confidence interval -18.9% to -4.0%). Multilevel analysis confirmed the results of the unadjusted analysis (intervention effect -10.7%, -20.3% to -1.0%). Patients' satisfaction was high and did not differ in the two groups at baseline or after the intervention.
                A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients. Further research should focus on the sustainability and cost effectiveness of this intervention. To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old.
                Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years. The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate. Confirmatory analyses at the practice level were also performed.
                The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices. Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices. Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups. The direction and approximate magnitude of effect were confirmed in practice-level analyses.
                A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse. 50 patients with chronic mucopurulent rhinosinusitis were randomly allocated to treatment with nasal sprays of dexamethasone, tramazoline, and neomycin, dexamethasone and tramazoline with no antibiotic, or matched placebo (propellant alone) four times daily to both nostrils for 2 weeks. The patients were assessed in a double-blind manner for symptomatic response and improvement in nasal mucociliary clearance, nasal airway resistance, sinus radiographs, and intranasal bacteriology and appearance. Both active preparations (with antibiotic 14 of 20 patients responded; without antibiotic 12 of 20 patients responded) were more effective than the placebo (2 of 10 patients responded). There was no significant difference in response between the active preparations with and without antibiotic. Thus, in treatment of chronic mucopurulent rhinosinusitis, reduction of the inflammatory response and decongestion make topical antibiotic unnecessary, probably by allowing host clearance mechanisms to recover. Despite evidence that uncomplicated lower respiratory tract infection (cough) does not respond appreciably to antibiotics and that bacterial resistance is increasing, general practitioners (GPs) still prescribe frequently.
                To assess delayed antibiotic prescribing as a strategy for reducing the unnecessary use of antibiotics for cough in primary care.
                Open randomised controlled trial of delayed versus immediate prescribing of antibiotics.
                One hundred and ninety-one adult patients with uncomplicated cough in 22 Scottish practices who would have received antibiotics under the GP's usual practice were randomised to receive either an immediate prescription (92 patients) or a delayed prescription (99 patients).
                Delayed subjects were asked to wait a week before deciding whether to collect their prescription. Outcome measures included symptom duration, prescription uptake, patient satisfaction, patient enablement, and subsequent consultation rates. The 48 GPs who recruited patients were surveyed six months after the trial to see whether they used delayed prescribing as a part of their normal practice.
                Study and control groups were similar at baseline. Of the subjects in the delayed arm, 55% did not pick up their prescription. Although most patients were satisfied, more patients in the immediate arm were very satisfied with the treatment (P = 0.001) and the consultation (P = 0.03). The patients in the immediate arm were also more enabled (3.3 versus 2.4; P = 0.04), although more of them intended to consult for similar complaints in the future (85% versus 69%, P = 0.02). We were unable to detect any difference in actual consulting behaviour in the follow-up period (mean = 15 months [SD = 5 months]). Subsequently, 68% of GPs used delayed prescribing at least monthly; all gave the prescription to the patient.
                Delayed prescribing is effective at reducing the use of antibiotics for self-limiting cough; however, patients are less satisfied and enabled as a result. Patients may be deterred from consulting rather than becoming enabled. Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years.
                In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period.
                Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68).
                The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol. 103 children between 1 and 10 years of age participated in a double-blind placebo-controlled trial testing the effect of penicillin-V, 55 mg/kg/day, for two days versus seven days in acute otitis media. No significant differences could be demonstrated with regard to earache, healing of the tympanic membrane, tympanometry, fever or common cold symptoms. 76% in the group treated for seven days had a satisfactory course of the disease, compared to 71% in the group treated for two days (p greater than 0.1). In spite of the relatively small number of patients, it is concluded that the effect of penicillin for additional five days in acute otitis media after the initial treatment for two days, can at most be marginal. The advantages of a shortened treatment period are several; the authors have outlined a new treatment modality, consisting of masterful inactivity for 8-12 hours, penicillin-V for two days, and myringotomy in refractory cases, after a new evaluation by the otologist. We believe hereby to be able to reduce penicillin consumption in children with acute otitis media to about 15% of the previous level, without increasing the risk of serious complications. To demonstrate clinical equivalence (statistical noninferiority) of topical ciprofloxacin and hydrocortisone (CHC, Cipro HC) and topical neomycin/polymyxin b/hydrocortisone (NPH, Cortisporin) with systemic amoxicillin (AMX, Amoxil), for treatment of acute otitis externa (AOE).
                Randomized, active-control, observer-blind, multicenter trial.
                Altogether, 206 patients were enrolled (CHC, 106; NPH + AMX, 100). Patients were > or =1 year of age, had AOE >2 days with at least mild symptoms, and gave informed consent. All were evaluable for safety, and 151 were evaluable for efficacy.
                Ciprofloxacin and hydrocortisone 3 drops twice daily for 7 days (adults and children) or NPH 4 drops (adults) or 2 drops (children) with AMX 250 mg (adults and children) 3 times daily for 10 days, as directed in approved product labeling.
                The primary efficacy variable was response to therapy 7 days after treatment ended (test of cure). Secondary variables included time to end of pain, symptom scores (otalgia and tenderness) and microbiological eradication. Noninferiority was declared if the lower confidence limit around the measurement difference was above -10 (nearer zero).
                Response to therapy was higher for CHC (95.71% vs 89.83%) but was statistically noninferior (lower confidence limit, -4.98) to NPH + AMX. Median time to end of pain was 6 days for both groups. Noninferiority was declared for symptom scores at all measurement periods and for microbiological eradication. No serious adverse events related to treatment were reported.
                Ciprofloxacin and hydrocortisone is clinically equivalent to NPH + AMX for the treatment of AOE in adults and children. However, low systemic exposure, absence of ototoxicity, and less frequent dosing clearly favor Cipro HC. We studied 102 children aged 1 month to 18 years in a randomized, double-blind trial designed to determine both the natural history of bacterial conjunctivitis and whether topical antibiotic therapy is beneficial. Affected eyes were treated four times a day for 7 days with drug (polymyxin-bacitracin ophthalmic ointment) or placebo. Eighty-four patients had proved bacterial conjunctivitis (Haemophilus influenzae 61, Streptococcus pneumoniae 22, both one); 66 of these received only topical therapy. By 3 to 5 days, 21 of 34 (62%) patients receiving topical antibiotic were clinically cured, whereas only nine of 32 (28%) patients given placebo were cured (P less than 0.02). By 8 to 10 days, 31 (91%) of the patients given antibiotic and 23 (72%) of the placebo group were cured (P = NS). The bacterial pathogen was eradicated by day 3 to 5 in 71% and by day 8 to 10 in 79% of patients given antibiotic, compared to 19% and 31% of the placebo group (P less than 0.001). Acute bacterial conjunctivitis is a self-limited disease, but topical antibiotic therapy with polymyxin-bacitracin shortens the duration of clinical disease and enhances eradication of the causative organism from the conjunctiva. To test whether daily hypertonic saline nasal irrigation improves sinus symptoms and quality of life and decreases medication use in adult subjects with a history of sinusitis.
                Randomized controlled trial. Experimental subjects used nasal irrigation daily for 6 months.
                Seventy-six subjects from primary care (n=70) and otolaryngology (n=6) clinics with histories of frequent sinusitis were randomized to experimental (n=52) and control (n=24) groups.
                Primary outcome measures included the Medical Outcomes Survey Short Form (SF-12), the Rhinosinusitis Disability Index (RSDI), and a Single-Item Sinus-Symptom Severity Assessment (SIA); all 3 were completed at baseline, 1.5, 3, and 6 months. Secondary outcomes included daily assessment of compliance and biweekly assessment of symptoms and medication use. At 6 months, subjects reported on side effects, satisfaction with nasal irrigation, and the percentage of change in their sinus-related quality of life.
                No significant baseline differences existed between the 2 groups. Sixty-nine subjects (90.8%) completed the study. Compliance averaged 87%. Experimental group RSDI scores improved from 58.4 -/+ 2.0 to 72.8 -/+ 2.2 (P < or =.05) compared with those of the control group (from 59.6 -/+ 3.0 to 60.4 -/+ 1.1); experimental group SIA scores improved from 3.9 -/+ 0.1 to 2.4 -/+ 0.1 (P < or =.05) compared with those of the control group (from 4.08 -/+ 0.15 to 4.07 -/+ 0.27). The number needed to treat to achieve 10% improvement on RSDI at 6 months was 2.0. Experimental subjects reported fewer 2-week periods with sinus-related symptoms (P <.05), used less antibiotics (P <.05), and used less nasal spray (P =.06). On the exit questionnaire 93% of experimental subjects reported overall improvement of sinus-related quality of life, and none reported worsening (P <.001); on average, experimental subjects reported 57 -/+ 4.5% improvement. Side effects were minor and infrequent. Satisfaction was high. We found no statistically significant improvement on the SF-12.
                Daily hypertonic saline nasal irrigation improves sinus-related quality of life, decreases symptoms, and decreases medication use in patients with frequent sinusitis. Primary care physicians can feel comfortable recommending this therapy. Several studies have indicated that antibiotics given for 5-7 days post-tonsillectomy are beneficial. A prospective double blind randomized study was undertaken to evaluate the efficacy of a long-acting antibiotic (Cefonicid) given prophylactically at the time of tonsillectomy. Dependent variables were percent weight loss, number of doses of pain medications required postoperatively, the number of days required to resume a normal diet, and return to work. The results of all independent tests indicated that there were no statistically significant differences between the Cefonicid group and the placebo group. The results of this study indicate that single dose prophylactic application of Cefonicid is not effective in adults undergoing tonsillectomy. To assess the effect of a short course of low-dose oral corticosteroid used as an adjunct to antimicrobials in patients with acute infective sinusitis.
                Double-blind, randomised, placebo-controlled study including 42 patients with a clinical diagnosis of acute infective sinusitis. The study was performed at three primary healthcare sites in South Africa during the period January-November 2003.
                Two equal groups received either betamethasone 1mg orally (n = 21; the treatment group) or placebo tablets (n = 21; the placebo group) once a day in the morning for five consecutive days. All patients received amoxicillin-clavulanic acid 625mg orally, three times daily for 5 days.
                Patients rated symptoms on a daily symptom score card for 5 days and were examined by the investigator at diagnosis (day 0) and on the second visit (day 6).
                Headache, facial pain, nasal congestion and dizziness improved significantly from baseline in the treatment group compared with the placebo group over 5 days of treatment (p = 0.028, p </= 0.047, p </= 0.04 and p </= 0.051, respectively). Percussion tenderness improved significantly (p = 0.049) and clearance of purulent secretions almost reached significance (p = 0.058) in the treatment group compared with the placebo group.
                This study suggests a benefit of oral corticosteroid added to antimicrobial treatment of acute sinusitis and documents the first successful use of a short course of low-dose oral corticosteroid in patients with acute infective sinusitis. To compare the clinical efficacy of ear drops containing acetic acid, corticosteroid and acetic acid, and steroid and antibiotic in acute otitis externa in primary care.
                Randomised controlled trial.
                79 general practices, Netherlands.
                213 adults with acute otitis externa.
                Primary outcome: duration of symptoms (days) according to patient diaries. Secondary outcome: cure rate according to general practitioner completed questionnaires and recurrence of symptoms between days 21 and 42.
                Symptoms lasted for a median of 8.0 days (95% confidence interval 7.0 to 9.0) in the acetic acid group, 7.0 days (5.8 to 8.3) in the steroid and acetic acid group, and 6.0 days (5.1 to 6.9) in the steroid and antibiotic group. The overall cure rates at seven, 14, and 21 days were 38%, 68%, and 75%, respectively. Compared with the acetic acid group, significantly more patients were cured in the steroid and acetic acid group and steroid and antibiotic group at day 14 (odds ratio 2.4, 1.1 to 5.3, and 3.5, 1.6 to 7.7, respectively) and day 21 (5.3, 2.0 to 13.7, and 3.9, 1.7 to 9.1, respectively). Recurrence of symptoms between days 21 and 42 occurred in 29% (50/172) of patients and was seen significantly less in the steroid and acetic acid group (0.3, 0.1 to 0.7) and steroid and antibiotic group (0.4, 0.2 to 1.0) than in the acetic acid group.
                Ear drops containing corticosteroids are more effective than acetic acid ear drops in the treatment of acute otitis externa in primary care. Steroid and acetic acid or steroid and antibiotic ear drops are equally effective. To determine whether a community-wide, multi-intervention educational strategy (CoMPLI model) could enhance adoption of clinical guidelines and improve the use of antibiotics.
                Before-after trial using baseline and study periods with a control group.
                A small community in central Ontario.
                Health professionals, the general public, and the pharmaceutical industry.
                The educational strategy (CoMPLI), carried out during 6 winter months, consisted of continuing medical education sessions for health professionals and pharmaceutical representatives and a parallel public education campaign that included town hall meetings and pamphlets distributed by local pharmacists. The two main messages were: do not use antibiotics for viral respiratory infections, and use drugs recommended in the publication, Anti-infective Guidelines for Community-Acquired Infections.
                Total number of antibiotic claims and adjusted odds ratios (OR) were used to measure the likelihood of physicians prescribing first- or second-line agents compared with the previous year and compared with control physicians.
                Claims in the study community decreased by nearly 10% during the 6-month study period compared with the baseline period from the previous year. Study physicians were 29% less likely (OR-1 = 0.71, range 0.67 to 0.76) to prescribe second-line antibiotics during the study period than physicians in the rest of the province.
                Physicians participating in the pilot study were more likely to follow drug recommendations outlined in published guidelines. To evaluate the potential of nasal isotonic saline application to prevent reappearance of cold and flu in children during the winter.
                Prospective, multicenter, parallel-group, open, and randomized comparison.
                Eight pediatric outpatient clinics.
                A total of 401 children (aged 6-10 years) with uncomplicated cold or flu.
                We randomly assigned patients to 2 treatment groups, one with just standard medication, the other with nasal wash with a modified seawater solution (Physiomer) plus standard medication, and observed them for 12 weeks.
                The primary efficacy end points were nasal symptoms resolution during acute illness (visits 1 and 2). We also looked for reappearance of cold or flu, consumption of medication, complications, days off school, and reported days of illness during the following weeks when preventive potential was evaluated (visits 3 and 4).
                At visit 2, patients in the saline group achieved primary end points (measured on a 4-point numeric scale on which 1 indicated no symptoms and 4, severe symptoms) in the parameters nasal secretion and obstruction (mean scores vs nonsaline group, 1.79 vs 2.10 and 1.25 vs 1.58, respectively) (P < .05 for both). During the prevention phase (at visit 3, 8 weeks after study entry) patients in the saline group showed significantly lower scores in sore throat, cough, nasal obstruction, and secretion (P < .05 for all). By visit 3, significantly fewer children in the saline group were using antipyretics (9% vs 33%), nasal decongestants (5% vs 47%), mucolytics (10% vs 37%), and systemic antiinfectives (6% vs 21%) (P < .05 for all). During the same period children in the saline group also reported significantly fewer illness days (31% vs 75%), school absences (17% vs 35%), and complications (8% vs 32%) (P < .05 for all). Similar results were found at the final visit.
                Children in the saline group showed faster resolution of some nasal symptoms during acute illness and less frequent reappearance of rhinitis subsequently. Medical treatment of uncomplicated acute diverticulitis is not standardized, and there is an enormous diversity in clinical practice. Our aim was to demonstrate that uncomplicated diverticulitis can be managed with orally administered amoxicillin plus clavulanic acid and a short hospital admission.
                A prospective randomized trial was established to compare patients with uncomplicated diverticulitis who received oral antibiotic after a short course of intravenous antibiotic with those who received intravenous antibiotic for a longer period. The antibiotic treatment consisted of amoxicillin plus clavulanic acid 1 g every 8 h. We included 50 patients, 25 in each group. Patients in group 1 began oral antibiotic as soon as they improved and were discharged the day after. Patients in group 2 received intravenous antibiotic for 7 days. Both groups received oral antibiotic at discharge. The endpoint of the study was "failure of treatment," which was defined as the impossibility of discharging on the expected day, emergency admission, or hospital readmission.
                Both groups were comparable in patient demographics and clinical characteristics. Most patients clearly improved between 24 and 48 h after admission. There were no significant differences between the groups when comparing failure of treatment. Treatment of patients in group 1 represented a savings in hospitalization costs of 1,244<euro> per patient.
                Most patients with uncomplicated diverticulitis can be managed safely with oral antibiotic; thus, a very short hospital stay is a safe option. In order to evaluate the clinical efficacy and tolerance of cefpodoxime proxetil, compared with that of amoxicillin in the treatment of acute bacterial maxillary sinusitis, a randomized, double-blind, parallel group comparative study was performed. A total of 286 adults patients were included at 12 centres, each treatment group consisting of 143 patients. Each patient was treated for 10 days and observed before and after treatment. The observations included clinical, roentgenological, bacteriological and laboratory examinations. At inclusion, the most common pathogens were Haemophilus influenzae (24%) and Streptococcus pneumoniae (17%). In the per protocol analysis, 117 patients in the cefpodoxime group and 113 in the amoxicillin group were evaluable for clinical efficacy. The clinical response rates were 96% and 91%, respectively. The corresponding figures in the intent-to-treat analysis were 130 and 128 patients, with clinical response rates of 93% and 88%, respectively. Cefpodoxime proxetil proved clinically as effective as amoxicillin in the treatment of acute bacterial maxillary sinusitis. It was more effective in eradicating H. influenzae and was more efficient in improving the radiological score. Adverse events were reported in 20% of cefpodoxime cases and in 16% of amoxicillin cases. There was no statistically significant difference between the groups. In recent years there has been considerable interest in reducing the duration of antibiotic treatment regimens in patients with common bacterial infections. We conducted two independent, investigator-blinded, multicenter, randomized clinical trials, one of which included microbiologic evaluation of middle ear fluid obtained by tympanocentesis, comparing the efficacy and safety of 5 or 10 days of treatment with cefuroxime axetil suspension (CAE) with that of 10 days of treatment with amoxicillin/clavulanate suspension (AMX/CL) in children with acute otitis media.
                A total of 719 pediatric patients from the ages of 3 months to 12 years were enrolled in the 2 studies. Patients received CAE for either 5 or 10 days at 30 mg/kg/day in 2 divided doses (n = 242 and 235, respectively) or AMX/CL for 10 days at 40 mg/kg/day in 3 divided doses (n = 242). Patients in the CAE (5 days) group received placebo on Days 6 through 10. In the study that included tympanocentesis, bacteriologic assessments were based on middle ear fluid cultures obtained pretreatment and, when possible, after treatment in patients with an unsatisfactory clinical outcome.
                Organisms were isolated from the pretreatment middle ear fluid specimens of 177 of 244 (73%) patients undergoing tympanocentesis, with the primary pathogens being Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (37, 35 and 12% of isolates, respectively). Pathogens were eradicated or presumed to be eradicated in 92% (24 of 26), 84% (32 of 38) and 95% (36 of 38) of bacteriologically evaluable patients treated with CAE for 5 or 10 days or with AMX/CL, respectively. A satisfactory clinical outcome (cure or improvement) occurred in 69% (101 of 147), 70% (121 of 173) and 74% (131 of 177) of clinically evaluable patients treated with CAE (5 days), CAE (10 days) or AMX/CL, respectively. Treatment with AMX/CL was associated with a significantly higher incidence of drug-related adverse events than was treatment with CAE for either 5 or 10 days (P < 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (34% vs. 17 and 12%, respectively; P < 0.001), particularly diarrhea.
                Treatment with CAE given twice daily for 5 days is equivalent to treatment for 10 days either with the same regimen of CAE or with AMX/CL given three times daily in pediatric patients with acute otitis media. To determine the effect of antibiotic treatment for acute otitis media in children between 6 months and 2 years of age.
                Practice based, double blind, randomised, placebo controlled trial.
                53 general practices in the Netherlands.
                240 children aged 6 months to 2 years with the diagnosis of acute otitis media.
                Amoxicillin 40 mg/kg/day in three doses.
                Persistent symptoms at day four and duration of fever and pain or crying, or both. Otoscopy at days four and 11, tympanometry at six weeks, and use of analgesic.
                Persistent symptoms at day four were less common in the amoxicillin group (risk difference 13%; 95% confidence interval 1% to 25%). The median duration of fever was two days in the amoxicillin group versus three in the placebo group (P=0.004). No significant difference was observed in duration of pain or crying, but analgesic consumption was higher in the placebo group during the first 10 days (4.1 v 2.3 doses, P=0.004). In addition, no otoscopic differences were observed at days four and 11, and tympanometric findings at six weeks were similar in both groups.
                Seven to eight children aged 6 to 24 months with acute otitis media needed to be treated with antibiotics to improve symptomatic outcome at day four in one child. This modest effect does not justify prescription of antibiotics at the first visit, provided close surveillance can be guaranteed. Approximately 20% patients with chronic rhinosinusitis undergoing Functional Endoscopic Sinus Surgery (FESS) experience impaired wound healing, leading to recurrences of sinusitis and polyps.
                We investigated the efficacy of oral+ local steroids in wound healing, following FESS in subjects with a chronic rhinosinusitis with/without nasal polyps. Ninety-nine subjects were randomised to receive 6 months' treatment with mometasone furoate nasal spray (MFNS) 200 microg bid or placebo in double-blind manner approximately 2 weeks after FESS. Postoperative mean total score for several endoscopic parameters scores assessed at 6 months was calculated as the primary efficacy end-point. An endoscopic combination score (for inflammation, oedema, and polyps), a total symptoms score, and percent subjects requiring rescue medication, were assessed as secondary end-points.
                MFNS led to greater, although not significant, reductions in total endoscopic scores in all subjects, compared with placebo. The combination scores, however, indicated significantly improved healing with MFNS than with placebo for all subjects (median scores: 0.0 vs 2.0, p = 0.02), and particularly for subjects with nasal polyps (median scores: 2.0 vs 4.0, p = 0.03). The total symptom scores and percent subjects requiring rescue medication were similar in the two groups. MFNS was well tolerated.
                These results suggest that treatment with MFNS following sinus surgery may improve wound healing, particularly in subjects with nasal polyps. To examine the efficacy and safety of conservative management of mild otitis media ("the acute red ear") in children.
                Double blind placebo controlled trial.
                17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth.
                232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo).
                Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml.
                Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year.
                Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7). Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132). Differences in recorded pain were not significant. The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year. No characteristics could be identified which predicted an adverse outcome.
                Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy. Chronic suppurative otitis media in young children is a major problem in Africa, with socio-economic consequences at a later age. Common treatment regimens with antibiotics are expensive and often not practically feasible. Therefore, a project was started to develop a low-cost and effective treatment in a rural area of Malawi by studying the clinical efficacy of an inexpensive application regimen of ofloxacin (0.075%) in hydroxypropyl methylcellulose (1.5%) ear drops. In earlier studies with this treatment regimen, it was possible to cure approximately 70% of ears. The aim of this study was to find out whether the bacteriological spectrum cultured from wet ears before and after treatment, and patterns of resistance to antibiotics, played a role in the percentage of cures. Patients with long-standing chronic suppurative otitis media were clinically assessed and treated with suction cleaning and instillation of ear drops on days 1, 3, 7 and 10. Bacterial swabs were taken for culture and sensitivity tests for ofloxacin were on days 1 and 10 from the ears that were still discharging. After 21 weeks, the ears were assessed again clinically. Clinical cure was considered to be complete cessation of otorrhea. Ninety of 104 tested patients (124 ears) completed the study. About 73% of the ears had become dry by day 10. This dropped to 42% after 21 weeks. Before treatment, most ears (91%) harbored fecal bacteria, Proteus mirabilis (74%) and enterococci (60%) being the most frequently isolated microbes. The second group of frequently cultured bacteria were water bacteria e.g. Pseudomonas species and other non-fermenters (69%), whereas the classical otitis media pathogens were detected only in 15% of ears. Before treatment, 9.7% of strains were resistant to ofloxacin, most (30/35) of which were cultured from ears that were eventually cured. After treatment, fecal and water bacteria were still the most frequently found, with 36% new strains and an overall sensitivity to ofloxacin of 58%. Bacterial resistance did not appear to play an important role in the outcome of treatment. These data rather suggest a very high risk of infection due to poor hygiene conditions. Medical treatment can only have a longer-lasting effect if accompanied by community-based programs that focus on improvement of hygiene. A public health approach is necessary alongside a medical approach for the management of CSOM. In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs).
                To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes.
                A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008.
                Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based.
                Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics.
                The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%).
                In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects.
                isrctn.org Identifier: ISRCTN95122877. Following otitis media, 10% to 50% of children develop residual middle ear effusion with concurrent hearing loss and potential cognitive, behavioral, and language impairment. Prophylactic antibiotics and tympanostomy tubes are currently recommended treatments for chronic middle ear effusion.
                In a double-blind, placebo-controlled, randomized study of chronic middle ear effusion, we assessed the effectiveness of topical intranasal beclomethasone as an adjunct to prophylactic antibiotic therapy.
                Sixty-one children, aged 3 to 11 years with persistent middle ear effusion greater than 3 months, were randomized into three treatment groups: (1) prophylactic antibiotics; (2) prophylactic antibiotics plus intranasal beclomethasone (336 micrograms/day); and (3) prophylactic antibiotics plus intranasal placebo. Patients were evaluated with aeroallergen skin tests at entry; and tympanogram, otoscopic examination, and symptom questionnaire at 0, 4, 8, and 12 weeks.
                While middle ear pressures, otoscopic examinations, and symptom scores were improved for each treatment group over 12 weeks of therapy, the beclomethasone plus antibiotics group improved all three measures more rapidly than the antibiotics-alone and placebo nasal spray plus antibiotics groups over the first 8 weeks. Only the beclomethasone group significantly improved left (P = .004) and right (P = .01) middle ear pressures over 12 weeks. Resolution of chronic middle ear effusions was more frequent in the beclomethasone group (P < or = .05 at 4 and 8 weeks). No difference in response to nasal steroids was observed between atopic and nonatopic subjects.
                We conclude that intranasal beclomethasone may be a useful adjunct to prophylactic antibiotic treatment of chronic middle ear effusion. Evidence to support antibiotic treatment for acute rhinosinusitis is limited, yet antibiotics are commonly used.
                To determine the incremental effect of amoxicillin treatment over symptomatic treatments for adults with clinically diagnosed acute rhinosinusitis.
                A randomized, placebo-controlled trial of adults with uncomplicated, acute rhinosinusitis were recruited from 10 community practices in Missouri between November 1, 2006, and May 1, 2009.
                Ten-day course of either amoxicillin (1500 mg/d) or placebo administered in 3 doses per day. All patients received a 5- to 7-day supply of symptomatic treatments for pain, fever, cough, and nasal congestion to use as needed.
                The primary outcome was improvement in disease-specific quality of life after 3 to 4 days of treatment assessed with the Sinonasal Outcome Test-16 (minimally important difference of 0.5 units on a 0-3 scale). Secondary outcomes included the patient's retrospective assessment of change in sinus symptoms and functional status, recurrence or relapse, and satisfaction with and adverse effects of treatment. Outcomes were assessed by telephone interview at days 3, 7, 10, and 28.
                A total of 166 adults (36% male; 78% with white race) were randomized to amoxicillin (n = 85) or placebo (n = 81); 92% concurrently used 1 or more symptomatic treatments (94% for amoxicillin group vs 90% for control group; P = .34). The mean change in Sinonasal Outcome Test-16 scores was not significantly different between groups on day 3 (decrease of 0.59 in the amoxicillin group and 0.54 in the control group; mean difference between groups of 0.03 [95% CI, -0.12 to 0.19]) and on day 10 (mean difference between groups of 0.01 [95% CI, -0.13 to 0.15]), but differed at day 7 favoring amoxicillin (mean difference between groups of 0.19 [95% CI, 0.024 to 0.35]). There was no statistically significant difference in reported symptom improvement at day 3 (37% for amoxicillin group vs 34% for control group; P = .67) or at day 10 (78% vs 80%, respectively; P = .71), whereas at day 7 more participants treated with amoxicillin reported symptom improvement (74% vs 56%, respectively; P = .02). No between-group differences were found for any other secondary outcomes. No serious adverse events occurred.
                Among patients with acute rhinosinusitis, a 10-day course of amoxicillin compared with placebo did not reduce symptoms at day 3 of treatment.
                clinicaltrials.gov Identifier: NCT00377403. One hundred nine patients with chronic rhinosinusitis underwent functional endoscopic sinus surgery. Seventy seven patients had polyposis. The population was studied prospectively for 5 years postoperatively. Seventy two patients attended the 5 year follow-up visit. At 1, 2, 3, 4 and 5 years of follow-up all outcome measures except olfactory detection thresholds (visual analogue scores, endoscopic findings, nasal mucociliary clearance times, total nasal volumes) were significantly improved compared to preoperative baseline values. Olfactory detection thresholds were significantly improved at 1 and 2 years postoperation. Patient symptom scores were improved in a greater percentage of patients than more objective outcome measures. Thirty eight patients required a total of 88 postoperative rescue medication courses with prednisolone and antibiotic. Twelve patients failed the study as they required at least 1 rescue medication course a month for 2 consecutive months. We demonstrated an 89% 5 year "survival" rate with regards to the risk of failure. The patients were also entered into a randomised, stratified, prospective, double-blind, placebo controlled study of fluticasone propionate aqueous nasal spray 200 mcg twice daily, commencing 6 weeks after FESS, with a 5 year follow-up. The change in overall visual analogue score was significantly better in the FPANS group at 5 years. The changes in endoscopic oedema and polyp scores and in total nasal volumes were significantly better in the FPANS group at 4 years but not 5 years. Last value carried forward analysis demonstrated that changes in endoscopic polyp score and in total nasal volume was significantly better in the FPANS group at 5 years. Significantly more prednisolone rescue medication courses were prescribed in the placebo group. Of the 12 patients who failed the study, 10 were in the placebo group. This difference nearly achieved significance. To compare the efficacy and safety of a single 2.0-g dose of a novel azithromycin microsphere formulation with that of 10 days of levofloxacin, 500 mg/d, when used to treat adults with uncomplicated acute bacterial maxillary sinusitis (ABS).
                An international, multicenter, randomized, double-blind, double-dummy trial. Eligible outpatients > or =18 years of age with clinical and radiographic evidence of ABS underwent maxillary sinus aspiration before randomization. Primary endpoint was clinical efficacy at the test-of-cure visit (day 17-24).
                Clinical success rates were 94.5% (242/256) in azithromycin-microspheres-treated patients and 92.8% (233/251) in the levofloxacin group. In patients with documented Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, clinical cure rates were 97.3% (36/37), 96.3% (26/27), and 100% (8/8), respectively, for the azithromycin group and 92.3% (36/39), 100% (30/30), and 90.9% (10/11), respectively, for the levofloxacin group.
                Single-dose azithromycin microspheres provided clinical and bacteriologic efficacy and safety comparable to 10 days of levofloxacin.
                A novel microsphere formulation of azithromycin given as a single dose was safe and effective for the treatment of ABS. Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL(-1). Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73-0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%. Reassessment of ongoing antibiotic therapy is an important step towards appropriate use of antibiotics. This study was conducted to evaluate the impact of a short questionnaire designed to encourage reassessment of intravenous antibiotic therapy after 3 days.
                Patients hospitalized on the surgical and medical wards of a university hospital and treated with an intravenous antibiotic for 3-4 days were randomly allocated to either an intervention or control group. The intervention consisted of mailing to the physician in charge of the patient a three-item questionnaire referring to possible adaptation of the antibiotic therapy. The primary outcome was the time elapsed from randomization until a first modification of the initial intravenous antibiotic therapy. It was compared within both groups using Cox proportional-hazard modelling.
                One hundred and twenty-six eligible patients were randomized in the intervention group and 125 in the control group. Time to modification of intravenous antibiotic therapy was 14% shorter in the intervention group (adjusted hazard ratio for modification 1.28, 95% CI 0.99-1.67, P = 0.06). It was significantly shorter in the intervention group compared with a similar group of 151 patients observed during a 2 month period preceding the study (adjusted hazard ratio 1.17, 95% CI 1.03-1.32, P = 0.02).
                The results suggest that a short questionnaire, easily adaptable to automatization, has the potential to foster reassessment of antibiotic therapy. Cefdinir is an extended-spectrum oral cephalosporin that is active against pathogens commonly seen in acute community-acquired bacterial sinusitis (ACABS), including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Two randomized, investigator-blind, multicenter trials (one in the United States and one in Europe) compared two dosage regimens of cefdinir (600 mg once a day for 10 days and 300 mg twice a day for 10 days) to amoxicillin-clavulanate (A-C) (500 mg three times a day for 10 days) for adult and adolescent patients with ACABS. Twelve hundred twenty-nine patients entered the U.S. study, 698 with antral puncture; 569 patients entered the European study, all with antral puncture. Clinical response (cure or improvement) was determined 7 to 14 days and 3 to 5 weeks posttherapy. Microbiologic eradication rates were determined 10 to 30 days posttherapy in a subset of patients who underwent pre- and posttherapy sinus aspirate culture. Rates of adverse events and treatment discontinuations due to adverse events were examined. Cefdinir, given once or twice daily, was as effective clinically (approximately 90% cure rate) as amoxicillin-clavulanate given three times daily in the treatment of ACABS. Microbiologic eradication rates were also similar in the three groups. The major side effect was mild diarrhea, occurring in approximately 20% of each group. Cefdinir caused fewer adverse events requiring treatment discontinuation. The treatment of acute, recurrent, and chronic sinusitis remains controversial because of the presence of a wide variety of aerobic and anaerobic bacteria in the sinuses.
                This double-blind, randomized trial compared cefaclor with amoxicillin in the treatment of acute, recurrent, and chronic maxillary sinusitis using clinical evaluation, roentgenography, and microbiologic evaluation of antral aspirates.
                Outpatient office of five otorhinolaryngologists in Salt Lake City, Utah.
                One hundred eight adult patients with acute, recurrent, or chronic maxillary sinusitis.
                Oral treatment with cefaclor (500 mg) twice daily or amoxicillin (500 mg) three times daily for 10 days.
                Clinical response to treatment with cefaclor vs amoxicillin.
                Fifty-six patients with acute sinusitis, 25 with recurrent sinusitis, and 15 with chronic sinusitis were evaluable. Although multiple organisms were common in each group, patients with acute sinusitis were more likely to have Haemophilus influenzae or Streptococcus pneumoniae, and patients with recurrent or chronic sinusitis were more likely to have anaerobes in sinus aspirate. Whether treated with cefaclor or amoxicillin, clinical improvement occurred in 86% of patients with acute sinusitis and 56% of patients with recurrent sinusitis. Patients with chronic sinusitis were too few to allow statistical analysis of the differences in outcome between them and patients with recurrent or acute sinusitis. Resistance of the cultured organisms to the study drug used was unrelated to treatment outcome.
                The rate of clinical improvement was high in patients with acute sinusitis but was less favorable in those with recurrent and chronic disease regardless of the study drug used. The susceptibility of organisms isolated to the study drugs was unrelated to outcome.
There is moderate evidence that antibiotics provide a small benefit for clinical outcomes in immunocompetent primary care patients with uncomplicated acute sinusitis. However, 80% of participants treated without antibiotics improved within two weeks. Clinicians need to weigh the small benefits of antibiotic treatment against the potential for adverse effects at both the individual and general population level.