Michael D. Poole

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, was evaluated in patients with respiratory infections caused by S. pneumoniae, including PRSP (penicillin MICs 2-16 mg/l). Data from nine clinical studies were combined (total intent-to-treat N=5531). Six randomized, double-blind studies used levofloxacin 500 mg od in acute bacterial sinusitis (ABS), levofloxacin 500 mg od in acute exacerbations of chronic bronchitis (AECB), clarithromycin 500 mg bid in AECB, AMX/CA 875/125 mg bid and tid in community-acquired pneumonia (CAP) and AMX/CA 1000/125 mg tid in CAP as comparators. The three remaining studies (two in ABS and one in CAP) were non-comparative. In the AMX/CA 2000/125 mg bid-treated patients evaluable at follow-up (Day 14-39), outcome was successful in 60/64 (93.7%) patients with S. pneumoniae infections in the comparative studies and 348/363 (95.9%) in the non-comparative studies, including 95.6% of all patients and 95.2% of patients whose isolates had AMX/CA 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.

A Trial of High-Dose, Short-Course Levofloxacin for the Treatment of Acute Bacterial Sinusitis

OBJECTIVES: Compare two dosage strengths of levofloxacin in the treatment of acute bacterial sinusitis. STUDY DESIGN AND SETTING: Multicenter clinical trial comparing levofloxacin 750 mg for 5 days vs levofloxacin 500 mg for 10 days. RESULTS: Sinus fluid samples were obtained by antral puncture (59.2%) or by sinus endoscopy (40.8%). Among microbiologically evaluable patients, 91.4% (139/152) of patients receiving levofloxacin 750 mg achieved clinical success vs 88.6% (132/149) of patients receiving levofloxacin 500 mg (95% CI −10.0, 4.2). Clinical success rates by pathogen were above 90% in both treatment groups for the 3 typical pathogens of acute sinusitis: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The safety profile of the 2 dosage strengths was similar. CONCLUSION: Levofloxacin 750 mg for 5 days is noninferior to levofloxacin 500 mg for 10 days. SIGNIFICANCE: Levofloxacin 750 mg for 5 days represents a safe and effective treatment regimen for acute bacterial sinusitis. EBM rating: A-1b

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 Plexiform Neurofibroma of the Larynx

We report the ninth case of plexiform neurofibroma of the larynx, which occurred in a 2-year-old with multiple café au lait spots and obstructive sleep apnea. In discussing this clinical problem, we have attempted to make the following points. 1) A patients having more than six café au lait spots of greater than 1.5-cm diameter is diagnostic of von Recklinghausens disease. 2) It is much more difficult to completely excise plexiform neurofibroma than nonplexiform neurofibroma. 3) The association of juvenile xanthogranuloma with von Recklinghausens disease may be a risk factor for the later development of leukemia.

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.

The impact of day care on ventilation tube insertion.

OBJECTIVE To study the effect of day care and tube type, as well as other risk factors related to ventilation tube insertion and reinsertion. DESIGN A case series of 456 consecutive cases with 162 controls from a well-baby examination group evaluated for age, sex, smoking history and day care attendance. SETTING Private practice in a mid-sized, southeastern university town. PATIENTS AND CONTROLS This was a referred sample of patients who were entered consecutively in a private-practice setting. All children were age five or less at entry into the study. INTERVENTIONS Children underwent ventilation tube insertion with or without adenoidectomy, using standing indications. MAIN OUTCOME MEASURES The primary outcome measures were whether or not a child had the need for a second set of tubes, and also determining the status of the childs ears for at least 1 year after tubes had extruded. RESULTS Day care and younger age were both identified as risk factors associated with initial ventilation tube insertion. Only 11% (seven out of 63) of home care children, as compared with 31% (108 out of 346) day care children, had the insertion of ventilation tubes (P = 0.000). Day care children who had tubes inserted and adenoidectomy (with or without tonsillectomy) had a significantly lower rate of reintubation than children who had tube insertion alone (P = 0.00). Day care and young age are significant risk factors for any child, both with a first set of tubes and for ventilation tube reinsertion. Children in day care had a reintubation rate of 36% as compared to 11% for those in home care. Parents should be aware that day care can represent a two-fold hazard both in the observed connection between day care and tube insertion and the demonstrated increased probability of reinsertion. Any studies looking at ventilation tube outcomes need to make certain to monitor for day care attendance.

Characterization of cough associated with angiotensin-converting enzyme inhibitors.

Chronic cough is a side effect of the angiotensin-converting enzyme (ACE) inhibitor class of antihypertensives. The cough is thought to be a result of inhibition of the enzymes that break down some of the mediators of inflammation, such as the bradykinins and tachykinins. We report 20 patients with chronic cough caused by ACE inhibitors and some of the characteristics of the cough. The cough is typically dry, nonproductive, and worse at night. Interference with sleep is common and was severe in three patients. Women outnumbered men in this series: urinary stress incontinence developed in five, rectal and vaginal prolapse developed in one. Three patients felt they were incapacitated by the cough. Most had been on multiple medications; only oxycodone was reported to be effective in controlling the cough, and four patients thought they were addicted to that. All coughs resolved with withdrawal of the ACE inhibitor. Chronic cough is common among individuals taking ACE inhibitors. It may be severe and associated with complications. The incidence and potential severity is understated in drug information sources, and patients and physicians often fail to recognize cough as a drug side effect.

Errors by Pediatricians in Characterizing Treated Otitis Media Cases As Failures

Abstract Objectives: When clinicians mistakenly catagorize cases of AOM treated with appropriate antibiotics as treatment failures, they often recommend therapies that are inappropriate or less efficacious. We sought to understand and describe the reasons why primary clinicians characterize antibiotics prescribed for cases of acute otitis media (AOM) as being ineffective at a much higher rate than the actual bacteriologic failure rates for guideline-recommended antibiotics (eg, amoxicillin or amoxicillin-clavulanate). Methods: Prospective critical observation and video-otoscopy of cases of AOM recently deemed treatment failures by pediatricians, combined with interviews with the pediatricians. Results: We identified 4 major types of errors that were repetitively made. Two were due to inaccurate perceptions of data: (1) misunderstanding that new infection is much more common than relapse/failure in patients with AOM who recently finished a guideline antibiotic, and (2) inaccurate perceptions about the relative bacteriologic efficacy of various agents. There were 2 additonal types of errors related to wrong diagnoses and suboptimal otoscopic skill: (1) the correct initial diagnosis was either absence of effusion or OM with effusion (OME), not AOM, so that antibiotics had no appreciable effect, and (2) after completing therapy, OME was present (with or without residual TM inflammation) but the degree of improvement was appropriate and it was no longer AOM. Conclusions: These errors in management help explain why, even though clinicians may be generally knowledgable about antibiotic guidelines for AOM, they may recommend relatively inappropriate options such as less efficacious antibiotics or premature surgical consultation. Educational efforts directed at these errors should improve OM management.

3-d computerized tomography reconstructions alter management decisions of facial fractures

Abstract Objectives: The recent availability of high speed, high resolution computerized tomography (CT) with 3-dimensional (3-D) reconstruction now offers striking clarity of external bony facial anatomy. We undertook a prospective study to determine the impact of the 3-D images on management decisions that were previously based on 2-dimensional (2D) views. Methods: We prospectively evaluated 20 nontrivial traumatic facial fractures. Isolated nasal or mandible fractures were excluded. The patients underwent CT scanning of the face and cranium, without contrast, with 1 mm cuts. Commercially available software generated 3-D reconstructions. Assessments and operative planning was made on the basis of 2D views, and compared with the 3-D views. Results: In this series of maxillofacial fractures, the precise anatomy demonstrated by the 3-D reconstructions resulted in altering or canceling the surgical procedures in over half of the cases. The largest impact of the 3-D scans on the decision-making was seen in naso-orbital-ethmoid (NOE) fractures, with significant but lesser alterations in decisions regarding fractures of the anterior table of the frontal sinus and in those involving zygoma fractures. Conclusion: Three-dimensional CT scanning of facial fractures appears to have a major impact on surgical planning of these complex injuries.

11:24 AM: Tympanosclerosis and Perforations Related to Tympanostomy Tubes

choanal stenosis, vocal fold nodules, and chronic sinusitis/ otitis/bronchitis were reviewed in an effort to quantify the role of GER in each of these disorders. Methods: The pH probe and bronchoalveolar lavage resuits for 51 children, ages 2 days to 12 years, were reviewed. Children who were treated empirically for GER were excluded from this review. Two children had incomplete pH probes and were excluded from the study. Two children had two diagnoses. Results: Positive pH probes were obtained in 19 of 20 patients (95%) with subglottic stenosis, three of three patients (100%) with recurrent croup, three of four patients (75%) with laryngomalacia, one of one patients (100%) with TVC nodules, five of five patients (100%) with apnea, and five of five patients (100%) with chronic cough. BAL results were suggestive but not positive for the two patients with recurrent choanal stenosis. Five of 11 patients with chronic sinusitis/otitis/bronchitis had pH probe studies, and five of the five patients (100%) were positive. Of six patients who underwent BAL, three (50%) were positive for microaspiration of gastric contents. The majority of children treated for GER required high doses of antireflux medication to suppress acidity, as documented by repeat pH probe or empiric titration of medication. Fifty percent of children in the sinusitis/otitis/bronchitis group improved with T&A or aggressive medical management of sinusitis. GER tended to be a more important factor in the younger children in this group. Conclusions: This review suggests that GER plays a causative role in subglottic stenosis, recurrent croup, apnea, and chronic cough. It is an important inflammatory cofactor in laryngomalacia and possibly in TVC nodules and problematic recurrent choanal stenosis. GER is also an important inflammatory cofactor in chronic sinusitis/otitis/bronchitis, but may be the result of chronic illness in the older patients. Prospective pH probe studies will further elucidate the role of GER in pediatric upper airway disorders.