Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo. Effect of amoxicillin-clavulanate in clinically diagnosed acute rhinosinusitis: a placebo-controlled, double-blind, randomized trial in general practice. Amoxicillin for acute rhinosinusitis: a randomized controlled trial. Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis. Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults. 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. Broncho-Vaxom in children with rhinosinusitis: a double-blind clinical trial. Cefdinir versus levofloxacin in patients with acute rhinosinusitis of presumed bacterial etiology: a multicenter, randomized, double-blind study. Relative importance of antibiotic and improved clearance in topical treatment of chronic mucopurulent rhinosinusitis. A controlled study.
Intranasal corticosteroids used with antibiotics are known to improve rhinosinusitis symptoms compared with antibiotic therapy alone. However, the efficacy of intranasal corticosteroid monotherapy for acute, uncomplicated rhinosinusitis is not established.
                To evaluate efficacy and safety of mometasone furoate nasal spray (MFNS) versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis.
                In this double-blind, double-dummy trial, subjects (> or =12 years; N = 981) were randomized to MFNS 200 microg once daily or twice daily for 15 days, amoxicillin 500 mg 3 times daily for 10 days, or respective placebo. Follow-up was 14 days. The primary efficacy endpoint was mean am/pm major symptom score over the treatment phase. Secondary efficacy endpoints included total symptom score. Safety assessments included disease recurrence during follow-up and adverse event monitoring.
                Mometasone furoate nasal spray 200 microg twice daily was significantly superior to placebo (P < .001) and amoxicillin (P = .002) at improving major symptom score. Starting on day 2, MFNS 200 microg twice daily improved total symptom score throughout treatment versus amoxicillin (P = .012) and placebo (P < .001). Global response to treatment was significantly greater with MFNS 200 microg twice daily versus amoxicillin (P = .013) and placebo (P = .001). Although significantly superior to placebo, MFNS 200 microg once daily was not superior to amoxicillin for the primary or secondary efficacy endpoints. All treatments were well tolerated with a similar incidence of adverse events.
                In patients with acute, uncomplicated rhinosinusitis, MFNS 200 microg twice daily produced significant symptom improvements versus amoxicillin and placebo, without predisposing the patient to disease recurrence or bacterial infection. Acute rhinosinusitis is one of the most common reasons for prescribing antibiotics in primary care. However, it is not clear whether antibiotics improve the outcome for patients with clinically diagnosed acute rhinosinusitis. We evaluated the effect of a combination product of amoxicillin-potassium clavulanate on adults with acute rhinosinusitis that was clinically diagnosed in a general practice setting.
                We conducted a randomized, placebo-controlled, double-blind trial with 252 adults recruited at 24 general practices and 2 outpatient clinics. Each patient had a history of purulent nasal discharge and maxillary or frontal pain for at least 48 hours. Patients were given amoxicillin, 875 mg, and clavulanic acid, 125 mg, or placebo twice daily for 6 days. Main outcome measures were time to cure (primary outcome), number of days during which rhinosinusitis restricted activities at home or work, and frequency of adverse effects (secondary outcomes).
                The adjusted hazard ratio for the effect of amoxicillin-clavulanate was 0.99 (95% confidence interval [CI], 0.68-1.45) on time to cure and 1.28 (95% CI, 0.80-2.05) in the prespecified subgroup of patients with a positive rhinoscopy result. At 7 days the mean difference between amoxicillin-clavulanate and placebo was -0.29 (95% CI, -0.93 to 0.34) in the number of days with restrictions due to rhinosinusitis and -0.60 (95% CI, -1.41 to 0.21) in patients with a positive rhinoscopy result. At 7 days patients who took amoxicillin-clavulanate were more likely to have diarrhea (odds ratio, 3.89; 95% CI, 2.09-7.25).
                Adult patients in general practice with clinically diagnosed acute rhinosinusitis experience no advantage with antibiotic treatment with amoxicillin-clavulanate and are more likely to experience adverse effects. 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. Mometasone furoate nasal spray (MFNS) 400 microg, twice daily, as adjunctive treatment with oral antibiotic significantly improved symptoms of recurrent rhinosinusitis.
                To evaluate the effectiveness and safety of MFNS 200 microg, twice daily, and 400 microg, twice daily, compared with placebo as adjunctive treatment with oral antibiotic for acute rhinosinusitis.
                In this multicenter, double-blind, placebo-controlled study, 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin/clavulanate potassium (Augmentin, GlaxoSmithKline, Research Triangle Park, NC) 875 mg, twice daily, for 21 days with adjunctive twice daily MFNS 200 microg, MFNS 400 microg, or placebo nasal spray. Patients recorded scores of six rhinosinusitis symptoms and any adverse events twice daily. Pre- and postcosyntropin-stimulation plasma cortisol levels were measured in a subset of patients at selected study sites.
                Treatment with MFNS 200 microg or 400 microg, twice daily, produced significantly greater improvements in total symptoms score (primary efficacy variable) day 1 to day 15 average (50% and 51%, respectively) than placebo (44%, P < or = 0.017). Both doses of MFNS produced significant total symptoms score improvement over placebo by day 4, and maintained efficacy over the entire 21-day study. Relief of individual symptoms showed a similar pattern. Both doses of MFNS were well tolerated, and adverse events were similar to that of placebo. Cosyntropin stimulation showed no evidence of hypothalamic-pituitary-adrenal axis suppression.
                As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 microg or 400 microg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone. 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. 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. Fifty-one children aged 4-12 years, presenting with an acute epidose of chronic rhinosinusitis, were treated for 6 months with either Broncho-Vaxom (BV; marketed in Yugoslavia under the trade mark of Broncho-Munal) or placebo under double-blind randomized conditions. The efficacy of BV was assessed on the basis of clinical symptoms (cough, nasal discharge, congestion of nasal mucosa), number and duration of concomitant treatments (antibiotics, secretolytics, antitussives), number and duration of acute episodes during the trial and serum IgA levels. In BV treated patients the incidence and duration of infectious episodes and the number and duration of concomitant treatments decreased significantly in comparison with the placebo group, and the clinical response correlated positively with an increase in the serum levels of IgA. The results of treatment of acute episodes of chronic rhinosinusitis in children demonstrated the curative and prophylactic efficacy of BV. Treatment guidelines for acute bacterial rhinosinusitis (ABRS) recommend 10 to 14 days of therapy with high-dose amoxicillin, amoxicillin/clavulanate, cefdinir, cefpodoxime, cefuroxime, a macrolide, or a newer fluoroquinolone, among other agents.
                This study compared the clinical efficacy and tolerability of cefdinir and levofloxacin in patients with a diagnosis of acute rhinosinusitis of presumed bacterial origin.
                In this multicenter, double-blind, noninferiority study, ambulatory adult patients who had signs and symptoms for >7 to 21 days before the screening visit and radiographic findings consistent with acute rhinosinusitis were randomized to receive cefdinir 600 mg or levofloxacin 500 mg, each once daily for 10 days. Clinical and radiologic response rates were determined at the test-of-cure (TOC) visit, which took place 9 to 14 days after the completion of treatment.
                Two hundred seventy-one patients (138 cefdinir, 133 levofloxacin) were enrolled and randomized to treatment at 27 study centers in the United States and Poland between November 2003 and March 2004. Of these, 241 (123 cefdinir, 118 levofloxacin) were clinically evaluable. The cefdinir group consisted of 75 women and 48 men, of whom 117 were white and 6 black; their mean (SD) age was 42.5 (14.3) years. The levofloxacin group consisted of 71 women and 47 men, of whom 111 were white and 7 black; their mean age was 40.4 (13.6) years. The 2 groups were similar in terms of presenting signs and symptoms and baseline radiographic findings. The most common presenting symptoms were sinus pain, sinus pressure, and purulent nasal discharge, each of which was reported by > or =89% of patients. Clinical cure rates at the TOC visit in the cefdinir and levofloxacin groups were 83% (102/123) and 86% (101/118), respectively (95% Cl for the difference in cure rates, -12.3 to 7.0). Cefdinir and levofloxacin were comparable in the treatment of infections classified as moderate to severe. The incidence of drug-related adverse events was generally comparable in the 2 treatment groups, although there were significant differences between cefdinir and levofloxacin in the incidence of vaginal moniliasis in women (11% vs 0%, respectively; P = 0.003), drug-related diarrhea (8% vs 1%; P = 0.005), and insomnia (0% vs 4%; P = 0.027). Only 2% of patients discontinued therapy prematurely as a result of a drug-related adverse event.
                In this population of patients with ABRS, the extended-spectrum cephalosporin cefdinir was as efficacious as the fluoroquinolone levofloxacin, suggesting that cefdinir may be a suitable alternative to the currently recommended fluoroquinolones. 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.
The potential benefit of antibiotics in the treatment of clinically diagnosed acute rhinosinusitis needs to be seen in the context of a high prevalence of adverse events. Taking into account antibiotic resistance and the very low incidence of serious complications, we conclude that there is no place for antibiotics for the patient with clinically diagnosed, uncomplicated acute rhinosinusitis. This review cannot make recommendations for children, patients with a suppressed immune system and patients with severe disease, as these populations were not included in the available trials.