Acute bacterial sinusitis is an important clinical entity and one of the most common causes of medical attention especially in winter months. The pathogens most frequently isolated include Streptococcus pneumonia, Hemophilus influenza, and anaerobic bacteria.1,2 Several pathogens implicated in sinusitis have developed a notable incidence of antibiotic resistance usually through the production of a beta-lactamase.3
Sultamicillin is a combination of the familiar penicillin, ampicillin, and the beta-lactamase inhibitor sulbactam.4,5 The addition of sulbactam theoretically broadens the spectrum of ampicillin to include activity against beta-lactamase-producing organisms that would otherwise have been unaffected by penicillin alone.6,7 This study is a randomized clinical trial to compare the effectiveness of amoxicillin-clavulanic acid, which is the standard therapeutic regimen, and low-dose sultamicillin in the treatment of acute bacterial sinusitis.
MATERIALS AND METHODS
A randomized clinical trial was performed on 44 consecutive patients with a diagnosis of acute bacterial sinusitis made in Amir-Alam hospital between March 2004 and August 2004. Inclusion criteria were age more than 12 years, presence of clinical symptoms (frontal pain, facial pressure, nasal obstruction, rhinorrhea, low-grade fever, and cough) and signs (sinus tenderness and mucoid or purulent secretion in nasopharynx on examination) of acute bacterial sinusitis, duration of symptoms more than 7 days, and typical radiographic findings (air-fluid level, sinus opacity, or thickness). Exclusion criteria were presence of allergic rhinitis, chronic sinusitis, or hypersensitivity to drugs.
Patients were randomly allocated in either of 2 groups: patients in group A (n = 21) received the traditional protocol, namely, 625 mg amoxicillin-clavulanic acid 3 times daily for 10 days, and group B (n = 23) received the new protocol, namely, 375 mg oral sultamicillin 2 times daily for the same duration. Both groups received routine decongestant medications for symptom relief as well. All patients were visited at least 3 times for evaluating clinical improvement and treatment complications: on day 3 after initiating the treatment, on the last day (day 10) of treatment, and on day 7 after the end of treatment.
The clinical response of each patient was classified as either cure (defervescence and remission of all presenting signs and symptoms on the day of last visit) or treatment failure (persistence of at least one of signs or symptoms on the day of last visit). The intention-to-treat (for all patients included in the study) and per-protocol (for patients completing the protocol) cure rates were calculated and compared between the 2 groups. SPSS 11.5 was used for statistical analysis, and a P value smaller than 0.05 was considered significant. All patients had given written informed consent, and the study protocol was approved by the ethics committee of Tehran University of Medical Sciences.
The mean age of patients was 27.3 years (range, 16-45) in group A and 23.8 years (range, 13-41) in group B. In groups A and B, there were 12 (57.1%) and 11 (47.8%) men, respectively. The 2 groups were not statistically different regarding age and sex. All patients in group A completed the treatment course, and no side effects were reported. In this group, 18 patients were cured; thus, both intention-to-treat and per-protocol cure rates were 85.7%. In group B, 1 patient (4.3%) discontinued the therapy due to developing severe diarrhea, and 2 patients (8.7%) reported loose stools but continued the protocol and were cured in the end. In this group, 19 patients were cured. The intention-to-treat and per-protocol cure rates in group B were therefore 82.6% and 86.4%, respectively. Neither the intention-to-treat nor the per-protocol cure rates were statistically different between the 2 groups. Side effects in group B were not significantly more common than in group A.
This study was probably one of the first large randomized clinical trials to compare the effectiveness of amoxicillin-clavulanic acid, which is the standard therapeutic regimen, and low-dose sultamicillin in the treatment of acute bacterial sinusitis. The efficacy of sultamicillin was similar to amoxicillin-clavulanic acid in our study. Although complications were slightly more common with sultamicillin than with amoxicillin-clavulanic acid, the difference was not statistically significant.
In a previous study on 108 patients (ranging in age from 16 to 56 years, with a mean age of 32.8 years) who had clinically and radiographically proven acute sinusitis, the efficacy of sultamicillin with the same dosage as in our study was compared with that of amoxicillin. All patients completed the treatment course, and the cure rates were 74.2% and 66.6% in the sultamicillin and amoxicillin groups, respectively. All side effects were gastrointestinal, occurring in 3.0% and 11.9% of the sultamicillin and amoxicillin groups, respectively. The cure and complication rates were not significantly different between the 2 groups.8
Sultamicillin was shown to be an effective compound for the treatment of bacterial infections of the upper respiratory tract of children in 1 study. Patients either had acute otitis media or acute epiglottitis.9 In another study on 13 adult patients receiving sultamicillin for 10 days, the intention-to-treat and per-protocol cure rates were 76.9% and 83.3%, respectively. All patients had a clinical diagnosis of acute maxillary sinusitis (rhinorrhea, nasal obstruction, and facial pressure) substantiated radiographically by the finding of an air-fluid level or opacity of one or both sinuses. One patient (7.7%) discontinued the therapy due to developing severe diarrhea. Loose stools were experienced in 8 (61.5%) patients. No side effects other than diarrhea or loose stools occurred in that study.3
The cure rate by sultamicillin obtained in our study was slightly higher than those reported previously.3,8 Comparing the results of our study with previous ones, it can be concluded that prescribing low-dose sultamicillin for 10 days is expected to lead to cure rates comparable with those achieved by amoxicillin-clavulanic acid. The most common side effect of sultamicillin is diarrhea, which is usually self-limited. The frequency of this side effect has been reported to be 0% to 50% in previous studies.10 On the other hand, potentially severe liver toxicity especially in elderly patients has been described to rarely accompany amoxicillin-clavulanic acid.11,12
The sample size of our study was large in comparison with most previous studies on the subject. However, the power is still low, and further clinical trials with larger sample sizes are needed to support the common negative result obtained so far, that is, the statistically similar frequency of complications with sultamicillin and amoxicillin-clavulanic acid. With current evidence, low-dose sultamicillin (375 mg 2 times daily for 10 days) can be considered as an effective and safe therapeutic regimen for acute bacterial sinusitis.
The authors thank Dr Akbar Bayat in Kowsar Pharmaceutical Co for providing sultamicillin.
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