Biomedical subjects
Publications and source records attributed to Jack B Anon.
This study assessed daily aspirate samples from an indwelling sinus catheter during high-dose, short-course levofloxacin (750 mg daily x 5 days) treatment of acute maxillary sinusitis. Pathogens were isolated from 4 of 18 recruited patients. Bacteriologic eradication occurred within 24 h for 3 patients and 72 h for the 4th.
OBJECTIVE: To define carriage of bacterial respiratory pathogens in children undergoing pressure equalization tube placement. STUDY DESIGN: Nasopharyngeal cultures were performed during tube placement. Antibiotic susceptibilities and serotypes of pneumococci were determined. RESULTS: Sixty-nine Streptococcus pneumoniae, 72 Haemophilus influenzae (41% beta-lactamase positive), and 39 Moraxella catarrhalis (all beta-lactamase positive) were isolated from 201 children. Overall, 42% of pneumococci were nonsusceptible to penicillin, and 34.8% were resistant to macrolides. In relation to the pneumococcal conjugate vaccine, 17.4% were vaccine, 31.9% vaccine-related, and 50.7% nonvaccine serotypes. CONCLUSION: Twenty-five percent of children colonized with pneumococci carried antibiotic resistant nonvaccine serotypes rarely detected before the introduction of pneumococcal conjugate vaccine, including serotype 19A isolates (7%) resistant to all oral agents tested and type 35B isolates (12%) nonsusceptible to penicillin and cefuroxime. SIGNIFICANCE: Pneumococcal colonization suggests replacement of vaccine serotypes with vaccine related and nonvaccine serotypes, many of which are resistant to common oral antimicrobials.
A 10-kg 9-month-old infant with recurrent, unresponsive otitis media presented with bilateral acute otitis media caused by Streptococcus pneumoniae type 19A, resistant to all oral agents and intermediately susceptible to ceftriaxone. Treatment with myringotomies and intramuscular ceftriaxone, 50 mg/kg/d for 5 days, was unsuccessful. The patient responded to pressure equalization tubes and local ciprofloxacin with dexamethasone drops.
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.
Episodes of acute rhinosinusitis are common among adults and are associated with a significant amount of morbidity. The symptoms of rhinosinusitis are nasal drainage, congestion, and sinus pressure. A bacterial sinus infection is more likely if these symptoms worsen after 5-7 days or do not improve after 10-14 days. The majority of bacterial episodes have been associated with Streptococcus pneumoniae and Haemophilus influenzae. In the current era of increasing resistance to beta -lactams and macrolides, treatment guidelines have been formulated worldwide to assist clinicians in the selection of antibacterials. According to one model, the following antibacterials are most likely to provide desired outcomes (90%-92% predicted clinical efficacy) for adults: respiratory fluoroquinolones (i.e., moxifloxacin, gatifloxacin, and levofloxacin), ceftriaxone, and high-dose amoxicillin-clavulanate (4 g of amoxicillin/day and 250 mg of clavulanate/day). Although the role of the fluoroquinolones in the treatment of this condition is evolving, fluoroquinolones are often recommended as second-line therapy or as first-line therapy for selected patients (e.g., those who received antibacterials in the previous 4-6 weeks or adults with moderate-to-severe disease).
Acute bacterial rhinosinusitis (ABRS) is a secondary bacterial infection of the nose and paranasal sinuses, usually preceded by a viral upper respiratory infection or allergy, with symptoms that have not improved after 10 days or that have worsened after 5 to 7 days. Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of ABRS in adults. Increasing rates of antimicrobial resistance among S. pneumoniae and beta-lactamase production among H. influenzae are formidable challenges to the successful treatment of infections caused by these organisms. To this end, various formulations of amoxicillin-clavulanate have been developed, the most recent of which is pharmacokinetically enhanced and provides a total daily dose of 4,000 mg of amoxicillin and 250 mg of clavulanate. This formulation has been shown to be safe and effective in the treatment of infections caused by penicillin-resistant S. pneumoniae (minimum inhibitory concentration 2 microg/mL); the clavulanate component provides adequate coverage of beta-lactamase-producing pathogens.
The relationship between drug exposure and the time course of antimicrobial effect at the primary infection site for acute maxillary sinusitis has not previously been explored. This single-center, open-label study quantified the time course of sinus sterilization, described gatifloxacin exposure at the infection site, and posed the hypothesis that the use of continuous and quantitative time-related end points may allow for better characterization of drug effect with fewer patients than traditional clinical trial approaches. Of the 12 enrolled patients, 10 were clinically evaluable, from whom 7 pathogens were isolated: 4 Streptococcus pneumoniae, 2 staphylococci, and 1 Enterobacter aerogenes. The median predicted 24-h area under the curve (AUC) in sinus aspirates and plasma samples was 54.7 mg x h/L and 30.1 mg x h/L, respectively. The median 24-h AUC ratio for sinus aspirates and plasma samples was 1.51 (range, 0.88-2.23). For patients infected with pneumococci, the median time to sinus sterilization was 50 h. The use of quantitative time-related end points may be useful in evaluating the efficacy of antimicrobial agents with fewer patients.
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OBJECTIVE: To determine the efficacy and safety of topical ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution in the treatment of acute otitis media with otorrhea through tympanostomy tubes (AOMT) in pediatric patients. METHODS: This multicenter, prospective, randomized, observer-masked, parallel-group study was conducted at 39 sites in 599 children aged >or=6 months to 12 years with an AOMT episode of <or=3 weeks' duration. The mean age of patients was 2.5 years (standard deviation: 2.37 years). Patients received either ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension 4 drops twice daily for 7 days or ofloxacin 0.3% otic solution 5 drops twice daily for 10 days. Clinical signs and symptoms of AOMT were evaluated at clinic visits on days 1 (baseline), 3 (on therapy), 11 (end of therapy), and 18 (test of cure). A patient diary was used to measure time to cessation of otorrhea. Principal pretherapy pathogens included Streptococcus pneumoniae (16.8%), Staphylococcus aureus (13.0%), Pseudomonas aeruginosa (12.7%), Haemophilus influenzae (12.4%), S epidermidis (10.2%), and Moraxella catarrhalis (4.1%). RESULTS: Ciprofloxacin/dexamethasone is superior to ofloxacin for clinical cure (90% vs 78%) and microbiologic success (92% vs 81.8%) at the test-of-cure visit, produces fewer treatment failures (4.4% vs 14.1%), and results in a shorter median time to cessation of otorrhea (4 days vs 6 days). Ciprofloxacin/dexamethasone treatment is also superior to improvement in clinical response by visit, absence of otorrhea by visit, and reduction of otorrhea volume by visit. Both topical otic preparations are safe and well tolerated in pediatric patients. No change in speech recognition threshold or decrease in hearing from baseline, based on audiometric testing, was noted with either regimen. CONCLUSION: Topical ciprofloxacin/dexamethasone treatment is superior to topical ofloxacin in the treatment of AOMT.
OBJECTIVE: To determine whether topical administration of a corticosteroid improves resolution of acute tympanostomy tube otorrhea when combined with topical antibiotic drops. STUDY DESIGN: Randomized, patient-masked, parallel-group, multicenter trial of topical otic ciprofloxacin/dexamethasone versus topical ciprofloxacin alone in 201 children aged 6 months to 12 years with acute otitis media with tympanostomy tubes (AOMT) of less than or equal to 3 weeks' duration and visible otorrhea. METHODS: Eligible patients were randomized to receive three drops of either ciprofloxacin 0.3%/dexamethasone 0.1% or ciprofloxacin 0.3% into the affected ear or ears twice daily for 7 days. Clinical signs and symptoms of AOMT were evaluated on days 1 (baseline), 3, 8 (end-of-therapy), and 14 (test-of-cure), and twice-daily assessments of otorrhea were recorded in patient diaries. RESULTS: The mean time to cessation of otorrhea in the microbiologically culture-positive patient population (n = 167) was significantly shorter with topical ciprofloxacin/dexamethasone than with ciprofloxacin alone (4.22 vs. 5.31 days; P =.004). This resulted in significantly better clinical responses on days 3 and 8 (P <.0001 and P =.0499, respectively). However, there were no significant differences between the two treatment groups in either the clinical response or the microbial eradication rate by day 14. CONCLUSIONS: Topical otic treatment with ciprofloxacin/dexamethasone is superior to treatment with ciprofloxacin alone and results in a faster clinical resolution in children with AOMT. The contribution of the corticosteroid in achieving a 20% reduction (1.1 day) in time to cessation of otorrhea is clinically meaningful and represents an important advance over single-agent antibiotic therapy.
In children, acute bacterial rhinosinusitis is a common infection and although rare, carries a potential for serious, life threatening complications. Bacterial rhinosinusitis usually follows a viral infection or allergic rhinitis. Early, effective antibacterial therapy is essential to shorten the duration of infection and illness, to diminish mucosal damage, and to prevent contiguous infectious involvement of the orbit or central nervous system. Because the signs and symptoms of acute bacterial rhinosinusitis are similar to those of viral upper respiratory tract infection, establishing an accurate diagnosis in children poses a clinical challenge. Infection with Streptococcus pneumoniae accounts for 30-66% of episodes of acute bacterial rhinosinusitis in children. Other important pathogens include Haemophilus influenzae (20-30%) and Moraxella catarrhalis (12-28%). In selecting initial antimicrobial therapy, priority should be given to drugs with activity against S. pneumoniae. The oral agents that currently offer the greatest activity against this pathogen include amoxicillin, amoxicillin-clavulanate, cefdinir, cefpodoxime proxetil, and cefuroxime axetil; all are considered appropriate for the initial treatment of acute bacterial rhinosinusitis in children. Amoxicillin is customarily used as first-line therapy for uncomplicated acute bacterial rhinosinusitis. For patients who are allergic to amoxicillin, second- or third-generation oral cephalosporins may be used as first-line therapy. Clarithromycin has been suggested as an alternative to amoxicillin or cephalosporins in beta-lactam allergic patients. Clindamycin may also be indicated as first-line treatment in patients who have culture-proven penicillin-resistant S. pneumoniae. If no clinical response occurs within 72 hours, the choice of a second-line antibiotic is governed by the drug's known antimicrobial efficacy, resistance patterns, dosing schedules, the potential for compliance, and knowledge of the patient's drug allergies. High-dose amoxicillin-clavulanate (90 mg/kg/d of the amoxicillin component) has been recommended for high-risk children (e.g. those in day care, and those who have recently received antibiotics) who show no improvement after treatment with the usual dose of amoxicillin (45 mg/kg/d). Broad-spectrum, third-generation oral cephalosporins, such as cefdinir, should be considered as second-line agents when standard therapy has failed or when patients show hypersensitivity to penicillin. Intramuscular ceftriaxone may be appropriate for patients who fail on a second course of antibiotic treatment.
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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.
PURPOSE: Acute bacterial rhinosinusitis (ABRS) is a common and uncomfortable condition, frequently caused by Streptococcus pneumoniae or Haemophilus influenzae. Antibacterial resistance among these and other common respiratory pathogens is now widespread and of concern. Pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg was developed to be effective against the common respiratory pathogens, including many resistant strains. MATERIALS AND METHODS: This open-label, noncomparative study assessed the bacteriologic and clinical efficacy of amoxicillin/clavulanate 2000/125 mg in adult patients with ABRS. Requirements for study entry included a clinical diagnosis of ABRS supported by radiologic findings. In addition, sinus puncture for bacteriologic assessment was required at study entry. RESULTS: Overall, bacteriologic success (eradication or clinical evidence of eradication) at the follow-up visit (days 17-28) was achieved in 87.8% (722/822) of patients with 1 or more pathogen isolated at screening, in 93.2% (246/264) of patients with S pneumoniae, in 96.7% (29/30) of those with penicillin-resistant S pneumoniae (penicillin minimum inhibitory concentrations >or=2 microg/mL), and in 88.7% (110/124) of patients with beta-lactamase-positive pathogens. Bacteriologic success was achieved against 6 of 7 S pneumoniae isolates with amoxicillin/clavulanic acid minimum inhibitory concentrations of 4/2 microg/mL or higher. CONCLUSIONS: Amoxicillin/clavulanate 2000/125 mg was generally well tolerated. This new amoxicillin/clavulanate formulation provides a suitable option for empiric therapy for ABRS in adults.
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