The application of pharmacokinetic (PK) and pharmacodynamic (PD) data in conjunction with minimum inhibitory concentrations (MICs) of antibacterial agents has been shown to allow for improved selection and appropriate dosing of antimicrobial agents for specific infections, increasing the likelihood of bacteriologic cure and, through this, reducing the risk for the development of resistant organisms.
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The high-performance liquid chromatography (HPLC) coupled with on-line solid phase extraction (SPE) and ultraviolet (UV) detection was developed for determining cefdinir in beagle dog plasma. After simple pretreatment for plasma with 6% perchloric acid, a volume of 100 μL upper layer of the plasma sample was injected into the self-made on-line SPE column. The analytes were retained on the trap column (Lichrospher C(18), 4.6 mm × 37 mm, 25 μm), and the biological matrix was washed out with the solvent (20mM KH(2)PO(4) adjusted pH 3.0) at flow rate of 2 mL/min. By rotation of the switching valve, the target analytes could be eluted from trap column to analytical column in the back-flush mode by the mobile phase (methanol-acetonitrile-20mM KH(2)PO(4) adjusted pH 3.0, 11.25:6.75:82, v/v/v) at flow rate of 1.5 mL/min, and then separated on the analytical column (Ultimate XB-C(18), 4.6 mm × 50 mm, 5 μm). The complete cycle of the on-line SPE preconcentration, purification and HPLC separation of the analytes was 4 min. The UV detection was performed at 286 nm. The calibration curves showed excellent linear relationship (R(2)=0.9995) over the concentration range of 0.05-50 μg/mL. The optimized method showed good performance in terms of specificity, linearity, detection and quantification limits, precision and accuracy. This method was successfully applied to quantify cefdinir in beagle dog plasma to support the pre-clinical pharmacokinetic trial.
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The present report presents two cases of confluent and reticulate papillomatosis. Case 1 was a 24-year-old man who had suffered from skin eruptions for six months, and Case 2 was a 19-year-old woman who had had this disease for three days. In both patients, reticular dark brown papules, accompanied by mild keratosis and infiltration, spread from the trunk to the neck and upper arm. Direct light microscopy did not detect the presence of any fungi, and histopathological examinations confirmed hyperkeratosis, acanthosis, papillomatosis, and mild small-round-cell infiltration. Thus, these patients were diagnosed as confluent and reticulate papillomatosis. Neither one had diabetes or thyroid dysfunction. In Case 1, cefdinir was effective, and in Case 2, minocycline hydrochloride and ketoconazole were effective. To the best of our knowledge, this was the first documented case of confluent and reticulate papillomatosis responding to cefdinir.
Sinusitis generally develops as a complication of viral or allergic inflammation of the upper respiratory tract. The bacterial pathogens in acute sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, while anaerobic bacteria and Staphylococcus aureus are predominant in chronic sinusitis. Pseudomonas aeruginosa has emerged as a potential pathogen in immunocompromised patients and in those who have nasal tubes or catheters, or are intubated. Many of these organisms recovered from sinusitis became resistant to penicillins either through the production of beta-lactamase (H. influenzae, M. catarrhalis, S. aureus, Fusobacterium spp., and Prevotella spp) or through changes in the penicillin-binding protein (S. pneumoniae). The pathogenicity of beta-lactamase-producing bacteria is expressed directly through their ability to cause infections, and indirectly through the production of betalactamase. The indirect pathogenicity is conveyed not only by surviving penicillin therapy, but also by 'shielding' penicillin-susceptible pathogens from the drug. The direct and indirect virulent characteristics of these bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. The antimicrobials that are the most effective in management of acute sinusitis are amoxycillin-clavulanate (given in a high dose), the newer quinolones (gatifloxacin, moxifloxacin) and the second generation cephalosporins (cefuroxime, cefpodoxime, cefprozil or cefdinir). The antimicrobials that are the most effective in management of chronic sinusitis are amoxycillinclavulanate, clindamycin and the combination of metronidazole and a penicillin.
Multicenter, randomized, investigator-blinded trials.
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Few studies were found that examined the accuracy and precision of the diagnosis of AOM. Since PCV7's introduction, AOM microbiology has shifted significantly, with Streptococcus pneumoniae becoming less prevalent and Haemophilus influenzae (HF) increasing in importance. For uncomplicated AOM, pooled analysis indicates that nine children (95% CI: 6, 20) would need to be treated with ampicillin or amoxicillin rather than placebo to note a difference in the rate of clinical success. However, in four studies of delayed treatment approaches for uncomplicated AOM, two had higher rates of clinical success with immediate antibiotic therapy while two did not, and in three studies, a marked decrease in antibiotic utilization was noted. We are unable to draw definitive conclusions regarding the comparative effectiveness of different antibiotics for AOM in children with recurrent otitis media (ROM). For ROM, long-term antibiotic administration will decrease AOM episodes from 3 to 1.5 for every 12 months of treatment per otitis prone child during active treatment (95% CI: 1.2, 2.1); however, potential consequences of long-term treatment need to be considered. Data were insufficient to draw conclusions about comparative effectiveness of different treatment strategies in subgroups of children with uncomplicated AOM. Adverse events were generally more frequent for amoxicillin-clavulanate than for cefdinir, ceftriaxone, or azithromycin. Higher quality studies and improved reporting of study characteristics related to quality are needed to provide definitive conclusions for AOM and ROM treatment options.
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Of 367 parents/guardians who completed the questionnaire, better ease of use (p = 0.009) and taste (p < 0.0001) were associated with cefdinir versus amoxicillin/clavulanate treatment, and children were significantly more likely to experience vomiting with amoxicillin/clavulanate (16% vs 8%; p = 0.016). Parents also reported that their children were much more likely to take all of their medication if receiving cefdinir (68% vs 53% for amoxicillin/clavulanate; p = 0.005). There were no statistically significant differences between groups in work/daycare missed.
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We consider studies in which an enrolled subject tests positive on a fallible test. After an intervention, disease status is re-diagnosed with the same fallible instrument. Potential misclassification in the diagnostic test causes regression to the mean that biases inferences about the true intervention effect. The existing likelihood approach suffers in situations where either sensitivity or specificity is near 1. In such cases, common in many diagnostic tests, confidence interval coverage can often be below nominal for the likelihood approach. Another potential drawback of the maximum likelihood estimator (MLE) method is that it requires validation data to eliminate identification problems. We propose a Bayesian approach that offers improved performance in general, but substantially better performance than the MLE method in the realistic case of a highly accurate diagnostic test. We obtain this superior performance using no more information than that employed in the likelihood method. Our approach is also more flexible, doing without validation data if necessary, but accommodating multiple sources of information, if available, thereby systematically eliminating identification problems. We show via a simulation study that our Bayesian approach outperforms the MLE method, especially when the diagnostic test has high sensitivity, specificity, or both. We also consider a real data example for which the diagnostic test specificity is close to 1 (false positive probability close to 0).
The eradication of S pyogenes and the clinical cure of the signs and symptoms of pharyngitis, both determined 5 to 10 days after the completion of therapy.
A total of 125 of 177 enrolled children had 134 pathogens isolated by tympanocentesis: Streptococcus pneumoniae, 69 (51.5%); Haemophilus influenzae 44 (32.8%; beta-lactamase-positive in 18 of 44 strains); beta-lactamase-positive Moraxella catarrhalis, 15 (11.2%); and Streptococcus pyogenes, 6 (4.5%). The clinical cure rates by patient in the microbiologically and overall clinically evaluable groups, respectively, were 73% (84 of 115) and 77.4% (130 of 168) at the end of therapy visit and 57.4% (66 of 115) and 61.9% (104 of 168) at Visit 3. Presumptive eradication rates at end of therapy were 8 of 11 (72.7%) and 4 of 8 (50%) for patients with penicillin-intermediate and -resistant S. pneumoniae isolates, respectively. Adverse reactions occurred in 16% of patients, with diarrhea (11%) occurring most frequently.