Pharmacokinetically enhanced amoxicillin/clavulanate (2,000/125 mg) in acute bacterial rhinosinusitis caused by Streptococcus pneumoniae, including penicillin-resistant strains.

We evaluated the efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2,000/125 mg) twice daily for the treatment of acute bacterial rhinosinusitis (ABRS) caused by Streptococcus pneumoniae, particularly penicillin-resistant S pneumoniae (PRSP; penicillin minimum inhibitory concentrations [MICs]: > or = 2 microg/ml. A total of 2,482 patients received study medication (safety population). Of these, 2,324 were clinically evaluable (efficacy population), and 1,156 of them had at least one pathogen isolated at screening (bacteriology population). S pneumoniae was isolated from 371 patients in the bacteriology population, including 37 with PRSP. Follow-up in the bacteriology population on days 17 through 28 revealed that amoxicillin/clavulanate therapy was successful in 345 of 371 patients with S pneumoniae infection (93.0%) and in 36 of 37patients with PRSP infection (97.3%), including 7 of 8 patients (87.5%) whose amoxicillin/clavulanic acid MICs were 4/2 microg/ml or higher. Pharmacokinetically enhanced amoxicillin/clavulanate was generally well tolerated, as only 2.2% of patients withdrew because of adverse events. This agent represents a valuable new therapeutic option for the empiric treatment of ABRS, particularly in areas where antimicrobial-resistant pathogens (including beta-lactamase-positive organisms) are prevalent, and for the treatment of patients who are at increased risk of infection with PRSP.

Treatment of rhinosinusitis in the outpatient setting.

Rhinosinusitis is one of the most common respiratory tract conditions seen by primary care physicians. Each year approximately 20 million cases of acute bacterial rhinosinusitis (ABRS) occur in the United States. Since diagnosis of ABRS relies on clinical evaluation, treatments are usually empirical and include an antibiotic treatment that covers the common bacteria associated with ABRS infection, Streptococcus pneumoniae and Haemophilus influenzae. The Council for Appropriate and Rational Antibiotic Therapy (CARAT) recommends that antimicrobial therapy for rhinosinusitis should combine high susceptibility, clinical effectiveness, safety, and tolerability. The most efficacious antibiotics for ABRS include the respiratory fluoroquinolones gatifloxacin, levofloxacin, and moxifloxacin, as well as ceftriaxone and amoxicillin-clavulanate. The use of fluoroquinolones or high-dose amoxicillin-clavulanate is recommended for patients with mild disease who have had recent antimicrobial therapy or for patients with moderate disease. These drugs are generally well tolerated with mild adverse effects. Resistance to fluoroquinolones in S pneumoniae and H influenzae has remained low in spite of their increased use. Recent studies indicate that short-course, high-dose treatment regimens may reduce total drug use, improve tolerability and adherence, prevent increases in resistance, and increase efficacy. The use of fluoroquinolones or amoxicillin-clavulanate in a short-course, high-dose regimen may represent an exciting new protocol in the treatment of rhinosinusitis.

Comparison of performance by otolaryngologists, pediatricians, and general practioners on an otoendoscopic diagnostic video examination.

OBJECTIVE: To compare the performance of United States, South African, and Greek otolaryngologists, pediatricians, and general practitioners in recognizing the otoscopic examination findings of acute otitis media (AOM) and otitis media with effusion (OME) as presented in an otoendoscopic video evaluation test. DESIGN/SUBJECTS: Otolaryngologists, pediatricians, and general practitioners from the United States (n = 273, 2190, and 360 respectively), South Africa (n = 36, 36, and 206), and Greece (n = 58, 115, and 126) viewed nine different video-recorded otoscopic examinations, including pneumatic otoscopy of tympanic membranes. The ability to differentiate AOM, OME, and normal was ascertained. RESULTS: Overall, the average +/- standard deviation correct diagnosis on the otoscopic video exam by otolaryngologists was superior to pediatricians and general practitioners in all three countries: from the United States, it was 74 +/- 16% for otolaryngologists versus 51 +/- 11% for pediatricians (p < 0.000l) and 46+/-21% for general practitioners (p < 0.0001); from South Africa, it was 72 +/- 16% versus 53 +/- 21% (p = 0.16) and 47 +/- 19% (p = 0.002); and from Greece, it was 61 +/- 15% versus 36 +/- 12% (p < 0.003) and 39 +/- 10% (p = 0.009). CONCLUSIONS: A video-based otoscopy examination test may be a useful tool for evaluation of otoscopy-based diagnostic skills. Otolaryngologists performed significantly better than pediatricians in differentiating AOM, OME, and normal in such a test described here. However, all specialists who examine patients with AOM or OME may benefit from viewing video otoscopies to improve diagnostic accuracy.

Second branchial cleft anomaly presenting as a rudimentary pinna in the nasopharynx of a newborn.

We describe the case of a 4-day-old girl who presented with an epiglottic cyst that was later identified as a rudimentary pinna attached to the soft palate.

Acute bacterial rhinosinusitis: clinical impact of resistance and susceptibility.

Sinusitis is a common disorder associated with notable direct and indirect economic costs. Acute bacterial rhinosinusitis (ABRS) is a relatively poorly defined clinical syndrome characterized by a high spontaneous resolution rate, wide variations in presenting symptoms, and an incomplete understanding of the pathogenesis and clinical course of the disease. Streptococcus pneumoniae and Haemophilus influenzae are the most common causative pathogens in adult ABRS. A relative lack of bacteriological eradication data compared with other respiratory illnesses, uncertainty on the part of many clinicians as to when to treat, and increasing rates of antimicrobial resistance hamper logical treatment strategies. Because it is impossible to know which cases of ABRS will spontaneously resolve and which will not, antimicrobials are recommended. In general, antimicrobial treatment for ABRS should cover both S. pneumoniae and H. influenzae while considering the risk of infection with resistant organisms. Treatment guidelines for ABRS were developed by the Sinus and Allergy Health Partnership in 2000 and were updated in 2004. This article discusses a Sinusitis Therapeutic Outcome Model, a data-driven model used in the development of the treatment guidelines, with respect to different scenarios involving ABRS to illustrate the implications of antimicrobial selection on therapeutic outcome.

A mathematical therapeutic outcomes model for sinusitis.

The therapeutic outcomes model (TOM) provides a logical and consistent manner in which bacteriologic and clinical efficacy can be predicted and calculated. It not only allows antibiotics to be ranked in efficacy, it gives precise estimates of the magnitude of differences in efficacy, which is typically lacking in older antimicrobial guidelines. The TOM identifies the major variables that need to be considered in accurately estimating outcome and places those variables into the appropriate relationships and formulas so that outcomes will be automatically calculated. In the case of rhinosinusitis, the major variables are (1) likelihood of spontaneously resolving nonbacterial cause, (2) likelihood of nonresolving nonbacterial cause, (3) prevalence of subcauses (eg, different species of bacteria), (4) the spontaneous resolution rates of each subcause, (5) the antibacterial efficacy of the treatment (eg, antibiotic) against each of the subcauses, and (6) the compliance rate of the treatment recommended. Minor variables, such as prior antibiotic use, patient age, or bacterial vaccination status, affect the efficacy of a given agent by modifying the value of one or more of the major variables. The TOM is a superior mechanism for ranking and evaluating relative antibiotic efficacy than previous methodologies.

Management of anomalies of the third and fourth branchial pouches.

Third and fourth branchial pouch anomalies are rare and usually present as lateral neck masses, abscesses or with acute suppurative thyroiditis. An opening in the piriform sinus can be identified in most cases. We present four cases of fourth branchial pouch sinuses, one of a third branchial cyst and discuss our management. Cannulation of the sinus tract at laryngoscopy, followed by complete surgical excision, via a modified oblique thyrotomy above the cricothyroid joint after detaching the inferior constrictor was used to treat the fourth branchial pouch anomalies. This surgical approach adequately exposes the piriform sinus apex and also affords protection to the recurrent laryngeal nerve. The third pouch cyst and tract were excised at the level of the thyrohyoid membrane. There were no complications or recurrences.

Community-acquired methicillin-resistant Staphylococcus aureus in children and adolescents: changing trends.

OBJECTIVE: To identify current trends in antibiotic sensitivity patterns of community-acquired methicillin-resistant Staphylococcus aureus (CA MRSA) infections of the head and neck in children and adolescents and evaluate outcomes after therapy. DESIGN: Retrospective review of cases consisting of a medical record review with telephone follow-up. SETTING: Two tertiary university medical referral centers. PATIENTS: Pediatric patients (age <18 years). MAIN OUTCOME MEASURES: Number of cases, sensitivities of cultured organisms, treatments used, and outcome of treatments. RESULTS: Seven patients were identified with CA MRSA in a 4-month period. Superficial abscesses (3 patients [43%]) and suppurative lymphadenitis (3 patients [43%]) were the most common causes. An erythromycin-resistant, clindamycin-sensitive pattern was observed in 6 (86%) of the 7 isolates. All infections resolved with prescribed treatments; there were no complications. CONCLUSIONS: A high prevalence of erythromycin-resistant, clindamycin-sensitive CA MRSA was noted. This new resistance pattern is indicative of inducible macrolide-lincomycin-streptogramin-B resistance. Basic science data suggest that these strains of bacteria could develop resistance to clindamycin during therapy despite appearing susceptible on initial laboratory testing. In our small series, clindamycin was used alone and effectively in 2 such cases. This appears to support its continued use as initial, empiric therapy in suspected cases of CA MRSA.

Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate.

The efficacy of a new pharmacokinetically enhanced formulation of amoxycillin/clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of amoxycillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP) with amoxycillin (+/-clavulanic acid) MICs of /=4 mg/l. In the pooled comparator group, the success rate at follow-up was 86.5% (45/52). For PRSP (AMX/CA MICs of 0.5-8 mg/l), the overall success rate was 98.2% (55/56) at follow-up for AMX/CA 2000/125 mg and 50.0% (2/4) for comparators. AMX/CA 2000/125 mg shows efficacy comparable to that of the comparators evaluated against S. pneumoniae infections. Due to its favorable pharmacokinetic/pharmacodynamic profile and promising clinical success, the new AMX/CA 2000/125 mg formulation should be considered for the empirical treatment of respiratory tract infections in regions with a high prevalence of antimicrobial-resistant S. pneumoniae and in patients at high risk of antimicrobial-resistant S. pneumoniae infection as this formulation covers many PRSP that are non-susceptible to amoxycillin (+/-clavulanic acid) (MICs of >/=4 mg/l) as well as common beta-lactamase-producing respiratory pathogens.

Matrix metalloproteinases and their inhibitors in bone remodelling following distraction osteogenesis of the sheep mandible.

AIM: Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), are responsible for the controlled degradation of collagen and other matrix substrates in bone and other tissues. This study evaluated the expression of MMPs and TIMPs in bony remodelling in a bilateral sheep mandible model up to 12 months following lengthening by distraction osteogenesis. METHODOLOGY: Sheep mandibles were harvested 3, 6, 9 or 12 months following lengthening by bilateral mandibular distraction (1 mm/day for 20 days). Undistracted sheep mandibles were used as controls. The tissues underwent routine histology and immunohistochemical staining with monoclonal antibodies specific to MMPs 1-3 and TIMP-1, 2. Matrix and cell staining was assessed using a semi-quantitative analysis. RESULTS: Matrix metalloproteinases and their tissue inhibitors (TIMPs) expression levels were marked at 3 months and decreased thereafter becoming similar to undistracted controls by 12 months. The histologic development of mature lamellar cortical bone was similar to undistracted controls by 9 months following distraction. CONCLUSIONS: A temporal expression of MMPs and TIMPs was found in distraction osteogenesis. MMPs and TIMPS may, in part, reflect the state of bony remodelling following mandibular lengthening by distraction osteogenesis. Matrix metalloproteinases and TIMP expression were comparable to undistracted controls by 12 months, suggesting that equilibrium had been achieved and that bony relapse is unlikely.

Community-based treatment of acute uncomplicated bacterial rhinosinusitis with gatifloxacin.

OBJECTIVE: We sought to evaluate gatifloxacin in adults with acute uncomplicated bacterial rhinosinusitis. STUDY DESIGN: TeqCES was an open-label, multicenter, noncomparative study of the safety and efficacy of gatifloxacin. More than 11,000 adult patients with acute uncomplicated rhinosinusitis received gatifloxacin 400 mg once daily for 10 days. RESULTS: Moraxella catarrhalis (91% beta-lactamase producers), Haemophilus influenzae (28% beta-lactamase producers), Streptococcus pneumoniae (18% intermediately resistant and 14% fully resistant to penicillin), and Staphylococcus aureus were the predominant pathogens isolated from purulent nasal discharge. More than 99% of rhinosinusitis pathogens isolated from the nasopharynx of patients meeting the clinical criteria for rhinosinusitis were susceptible to gatifloxacin. Among 10,353 patients whose clinical response could be determined, 91.6% were cured. Clinical cure rates exceeded 90% for the major pathogens. Gatifloxacin was well tolerated; drug-related adverse events that occurred in 1% or more of patients were nausea (4.4%), dizziness (1.8%), diarrhea (1.4%), and headache (1.0%). CONCLUSION: Gatifloxacin is effective for patients with acute bacterial rhinosinusitis in the community.

Short treatment durations for acute bacterial rhinosinusitis: Five days of gemifloxacin versus 7 days of gemifloxacin.

OBJECTIVE: The primary objective of this study was to demonstrate the clinical and radiologic efficacy of 5 days compared with 7 days of gemifloxacin therapy in the treatment of acute bacterial rhinosinusitis (ABRS). STUDY DESIGN: In this prospective, double-blind, multicenter, parallel-group study, adult patients presenting with ABRS were randomized to receive gemifloxacin 320 mg once daily for either 5 days (n = 218) or 7 days (n = 203). RESULTS: For the primary efficacy end point, clinical response to therapy at follow-up, 5 days of therapy with gemifloxacin was as effective as 7 days of therapy (per-protocol population; treatment difference 0.44%; 95% confidence interval [CI], -6.54 to 7.41). Five and 7 days of treatment with gemifloxacin were well tolerated. CONCLUSION AND SIGNIFICANCE: The clinical efficacy of gemifloxacin 320 mg daily for 5 days is at least as good as the efficacy of gemifloxacin 320 mg daily for 7 days in the treatment of ABRS.

Antimicrobial guidelines for the treatment of acute bacterial rhinosinusitis in immunocompetent children.

Acute rhinosinusitis represents a condition for which educational efforts could help minimize the inappropriate use of antibiotics, particularly for children. The majority of acute rhinosinusitis cases are of viral etiology and thus, are self limiting. Although bacterial infection complicates a small number of cases, the lack of accessibility to the sinus, the limitations of diagnostic modalities and the lack of specificity among signs and symptoms often make it difficult to determine when bacterial infection occurs. Furthermore, antimicrobial resistance among the pathogens that frequently cause bacterial infection complicates the election of empiric therapy. The Sinus and Allergy Health Partnership recently developed and published antimicrobial guidelines to provide practitioners in the US with recommendations for the diagnosis and treatment of acute bacterial rhinosinusitis. The purpose of this paper is to review the rationale behind the development of these guidelines and how they apply to the management of acute bacterial rhinosinusitis in children.