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In this study, a selective and sensitive LC/MS/MS method for the determination of trace amounts of cefmetazole (CMZ) and cefpodoxime proxetil (CPDXPR) contaminants in manufacturing environments was developed. The necessary sensitivity of this method was estimated based on the detection limit for Penicillin G required by the FDA and the total surface area and volume of the manufacturing facility. The detection limits of this method were estimated to be 10 pg/ml for CMZ and 5 pg/ml for CPDXPR from the signal to noise ratio and as a result satisfactory sensitivity was achieved. The method was linear in a concentration range from 0.20 to 3.20 ng/ml. The accuracy and precision were verified by the determination of the amount of CMZ and CPDXPR added to the sampling materials, a glass plate and a silica fiber filter. The mean recoveries of nine replicated determinations from the glass plate were 99.1% with 5.58%R.S.D. for CMZ and 97.1% with 3.80%R.S.D. for CPDXPR, and those from the silica fiber filter were 100.7% with 4.50%R.S.D. for CMZ and 95.4% with 2.85%R.S.D. for CPDXPR. This method has been successfully applied to the determination of CMZ and CPDXPR contaminants in samples collected from an actual manufacturing environment.
Seventeen patients undergoing tonsillectomy received cefpodoxime proxetil orally in a dose equivalent to 100 mg cefpodoxime 4, 7 or 12 h before operation. Plasma and tonsillar tissue concentrations of cefpodoxime were assayed by a microbiological method. Tonsillar tissue concentrations after 4 and 7 h were 0.24 and 0.09 mg/kg respectively--being 23% of the plasma concentration. The tonsillar tissue concentration after 12 h was less than 0.06 mg/kg. As the MIC for Streptococcus pyogenes is less than 0.06 mg/l, cefpodoxime proxetil may be of value in acute tonsillitis.
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twenty patients were selected, based on clinical assessment, to be converted from intravenous ceftriaxone to oral cefpodoxime proxetil. Twenty other comparable patients who would have been appropriate for step-down therapy, did not receive pharmacy intervention and were used as a control group.
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The in vitro activity of the compound RU-51746, the sodium salt of cefpodoxime (which is administered orally as the ester cefpodoxime proxetil) was compared with that of other commonly used oral antibiotics against a selection of clinical isolates of common bacteria from patients with urinary tract, soft tissue and respiratory tract infections. RU-51746 was found to inhibit 90% of Enterobacteriaceae at less than 1 mg/l; pneumococci, pyogenic streptococci (Lancefield groups A, C and G) and Streptococcus agalactiae were almost all inhibited by concentrations of less than 0.06 mg/l; Haemophilus influenzae (including beta-lactamase producers) were inhibited by less than 1 mg/l; 90% of Branhamella catarrhalis were inhibited at less than 2 mg/l. Activity against Acinetobacter spp. and staphylococci was variable and enterococci were all resistant.
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Both groups were assessed and compared for length of ceftiaxone therapy, length of oral follow-up therapy (if any), length of hospitalization, results of culture and sensitivity testing, treatment success and readmissions, and cost of respective therapeutic regimens.
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Azithromycin, the prototypical azalide antibiotic, has a wide spectrum of activity that is characterized by resistance to beta-lactamase-producing microbes and efficacy against Gram-positive and Gram-negative pathogens, including Haemophilus influenzae. Tissue-directed pharmacokinetics include tissue concentrations up to 100-fold higher than those in plasma and a tissue half-life of up to 4 days. Pharmacokinetics of azithromycin permits a reduction in dosage frequency and duration while maintaining efficacy comparable to that of conventional 7- to 10-day three or four times daily regimens. Dosage interval, duration of treatment, side effects and palatability can affect compliance and thus clinical outcome. Compliance among children is important in light of the high incidence of community-acquired infections such as otitis media and streptococcal pharyngitis.
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The clinical efficacy was examined for the newly developed oral cephem antibiotic, cefpodoxime proxetil (CPDX-PR) dry syrup, in the treatment of various acute infections in the field of pediatrics. CPDX-PR dry syrup was administered at 10 mg/kg/day in 3-divided doses to 535 children at 21 institutions, including Tottori University Hospital and its related hospitals. The efficacy rate of this drug was determined to be 80.8%. Among isolates, Staphylococcus aureus and Streptococcus sp. were highly susceptible to the drug, whereas Haemophilus influenzae showed relatively poor susceptibility. Side effects were observed in 2.80% of all of the patients, and abnormal laboratory findings were detected in 1.87%. The low incident of side effects demonstrated its high safety, and this drug was considered to be very useful for such pediatric infections as acute tonsillitis, acute pharyngitis and acute bronchitis.
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U-76,252 is the prodrug of U-76,253. MICs of U-76,253 were 0.015 to 0.06 microgram/ml for greater than or equal to 90% of the strains of Streptococcus spp., Haemophilus influenzae, and Proteus mirabilis; 0.25 to 1 microgram/ml for Branhamella catarrhalis, Escherichia coli, Klebsiella spp., and Citrobacter diversus; 1 to 8 micrograms/ml for Staphylococcus spp.; and 2 to greater than 16 micrograms/ml for other members of the family Enterobacteriaceae and Aeromonas hydrophila; for 72% of the latter group, MICs were less than or equal to 4 micrograms/ml. MICs for Pseudomonas aeruginosa and Enterococcus faecalis were greater than 16 micrograms/ml.
This review analyzes the pharmacokinetics of new oral cephalosporins, including esters, non-esters, and the carbacephem loracarbef, in healthy volunteers, as described in the literature and evaluated in several studies of our own. Single-dose studies have demonstrated considerable pharmacokinetic differences among these compounds. Cefixime, cefpodoxime proxetil, and cefetamet pivoxil are characterized by a low peak concentration and a prolonged half-life, while the other new agents have higher peak levels and shorter half-lives. Except for cefixime, the new oral cephalosporins are eliminated mainly by the kidneys. Pharmacokinetic studies in the elderly and in children indicate that the bioavailability of these agents is not influenced by age. Food increases the bioavailability of the ester cephalosporins but does not affect the absorption kinetics of the other new drugs.
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From 2007 to 2008, 30 pediatricians enrolled 3141 patients 3 to 36 months old with AOM. Standardized history and physical examination findings were recorded. Factors related to AOM failures were identified by multivariate logistic regression.