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The comparative pharmacokinetics of the new oral cephalosporins (ester and nonester types), together with that of the first generation carbacephem, loracarbef, are considered in healthy volunteers. Also in this review, pharmacokinetic and microbiological data are combined in order to predict the possible clinical efficacy of this group of agents. Despite apparent similarities in the structure of these agents, single dose studies have revealed marked differences in the pharmacokinetics of the oral cephalosporins. Multiple dose studies showed no evidence of accumulation with these agents. In the elderly, only minor changes in the pharmacokinetics of the oral agents were observed, and were insufficient to warrant dosage adjustment. Unlike that of the nonester compounds, the bioavailability of the ester cephalosporins is increased when they are administered after food. Variable effects are observed when the ester agents are coadministered with antacids or H2-antagonists; while the absorption of cefetamet pivoxil was unaffected by coadministered antacids or H2-antagonists, the absorption of cefpodoxime proxetil was reduced.
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Multiple dose pharmacokinetics of a new third-generation cephalosporin, cefpodoxime, were evaluated in adults (15, 18-60 years) and elderly adults (10, greater than or equal to 70 years), all out-patients suffering from acute lower respiratory tract infection. A dose of 200 mg cefpodoxime proxetil (expressed in mg cefpodoxime) was administered 12-hourly for seven to ten days and timed blood samples were evaluated on days 0, 3, 5, 6/7 and on the last day of treatment. Results showed that the pharmacokinetics in adult and elderly patients were comparable with those of healthy volunteers and with each other, with the exception of one elderly patient with severe renal impairment. Dosage adjustment of cefpodoxime proxetil does not therefore appear to be necessary in the elderly unless there is evidence of severe renal insufficiency.
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Cefpodoxime proxetil was administered to 36 children undergoing tonsillectomy, adenoidectomy or both. It was very well tolerated. The detectable tissue concentrations of cefpodoxime were moderate but remained constant (approximately 0.05 mg/kg) 3, 6, and 12 h after the last dose of the drug, while the respective plasma concentrations were declining. This suggests the possibility of twice-daily administration. However, 30% of children did not have quantifiable concentrations in the tonsil and more than half the adenoids did not have quantifiable levels. Whether a higher dosage would lead to higher and more satisfactory tissue concentrations is a matter for further investigation.
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The rising rate of CA-MRSA as a cause for many pediatric infections is a major concern. It is very important to obtain cultures from patients with nonresponsive or persistent otorrhea with AOM to look for MRSA and determine the sensitivity of the pathogen to antibacterial therapy. Trimethoprim-sulfamethoxazole is a good choice for initial, empirical therapy when combined with a topical agent for AOM with otorrhea if CA-MRSA is suspected. Further studies are needed to determine whether there is a link between the overuse of topical fluoroquinolones in pediatric patients and the recent rising rate of CA-MRSA.
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A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for analysis of cefpodoxime proxetil both in bulk and in pharmaceutical formulation has been developed and validated.
The results of this study suggest that cefditoren may have a role in the treatment of CAP in ambulatory patients.
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The risk for a child to carry penicillin-resistant S. pneumoniae (MIC > or = 0.125 mg/l) did not increase after antibiotic treatment: 84 of 364 (23.1%) before, 70 of 364 (19.2%) after. There was a significant decrease of penicillin-susceptible S. pneumoniae carriage, 117 of 364 (32.1%) before treatment compared with 24 of 364 (6.6%) (P = 0.0001) after treatment. However, among the children carrying S. pneumoniae at the end of the treatment there was an increase in the percentage of penicillin-resistant pneumococci: 84 of 201 (41.8%) before treatment and 70 of 94 (74.5%) after treatment. Among the 94 children carrying S. pneumoniae at the end of the treatment, 22 did not harbor pneumococcus before, 16 carried another genotypically different serotype and 56 harbored the same serotype. Among these 56 children 2 patients harbored strains that had increased MICs for the tested beta-lactam antibiotics. The randomly amplified polymorphic DNA analysis showed that in one case, the strains were genetically different.
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The influence of age on the pharmacokinetics of cefpodoxime was evaluated in 12 elderly (ages 65-85 years) and 12 weight- and sex-matched young (ages 20-33 years) subjects, each of whom received two cefpodoxime proxetil 200-mg tablets every 12 hours for 14.5 days. Serial blood samples and urine were collected after the first dose on day 1, after the morning dose on day 8, and after the last (morning) dose on day 15. Plasma and urine samples were assayed for cefpodoxime concentrations using HPLC methods. Within each age group, mean pharmacokinetic parameters determined on day 1 were similar to corresponding values on days 8 and 15, indicating that cefpodoxime does not accumulate after twice-daily dosing of cefpodoxime proxetil. Based on this result, parameters were pooled across days in each age group. No significant differences were observed between healthy and elderly volunteers in area under the plasma concentration-time curve for the 12-hour dosing interval, peak plasma concentration, or time to peak concentration. Mean urinary excretion and renal clearance of cefpodoxime were significantly lower in elderly subjects. Differences in renal clearance were attributed to the corresponding age-related reduction that was noted in creatinine clearance values, whereas the lower urinary excretion of cefpodoxime probably reflected slightly reduced systemic drug absorption in the elderly. Differences in these parameters between groups were less than 30%, and were unlikely to be of clinical importance. The data indicate that dose adjustment of cefpodoxime in elderly subjects having normal (age-adjusted) creatinine clearance values is not required.
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In this study, a 5-day course of cefpodoxime-proxetil at 200 mg bid was as clinically effective as amoxicillin-clavulanic acid 1 g/125 mg bid for 8 days with a significantly better safety profile and compliance.
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Our results show that treatment with cefpodoxime proxetil may be effective in reducing symptoms of recurrent pharyngotonsillitis and preventing recurrences without causing side effects or developing bacterial resistance.