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We evaluated the resistance to 20 different antibacterial agents of 362 clinically isolated strains of Streptococcus pneumoniae accumulated from October 2000 to July 2001 (phase 1) and of 332 different strains accumulated from January to June 2004 (phase 2), from institutions throughout Japan that participated in the surveys carried out by the Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. In phase 1, the proportions of penicillin-sensitive S. pneumoniae (PSSP), penicillin-insensitive S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 35.4%, 34.8%, and 29.8%, respectively, and the proportions were almost the same in phase 2: 33.1%, 37.0%, and 29.8%, respectively. Comparison of the MIC(90) values of the antibacterial agents for PRSP in phase 1 and phase 2 revealed that these values for cefditoren, cefpodoxime, cefdinir, faropenem, ceftriaxone, cefotaxime, meropenem, and vancomycin increased by twofold to fourfold during the 3 years between phase 1 and phase 2. However the MIC(90) of rokitamycin increased more than fourfold. The proportion of S. pneumoniae that were PISP + PRSP remained almost constant over the 3 years between phase 1 and phase 2. The background factors of patient age, previous administration of antibacterial agents, and attendance at a day nursery were examined; we found that in phase 1, the proportion of PISP + PRSP was significantly higher than that of PSSP in patients under 4 years old who had previously received antibacterial agents, but no significant differences were found in any of these background factors in the phase 2 survey. No significant difference was found in the proportions of penicillin-resistant bacteria according to whether or not the child had attended a day nursery.
Acute otitis media (AOM) is not only the most common bacterial infection in children in the United States, it is also the most common indication for the prescription of antibiotics. Unfortunately, antibiotic resistance to pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) typically causative of AOM, continues to increase. More than 30% of the beta-lactamase producing H. influenzae are resistant to amoxicillin and virtually all strains of M. catarrhalis are beta-lactamase-positive. The emergence of multidrug-resistant strains, particularly S. pneumoniae, complicates the management of AOM and increases the risk for treatment failure. Because of growing resistance, the Centers for Disease Control and the American Academy of Pediatrics promote the judicious use of antibiotics in the treatment of AOM. Their recommendations emphasize the importance of distinguishing AOM from otitis media with effusion, minimizing the use of antibiotics, and discerning between first- and second-line antibiotics in the treatment of simple uncomplicated AOM versus non-responsive/recurrent AOM. Because spontaneous cure rates are lower in complicated AOM and AOM secondary to S. pneumoniae infection, antibiotic therapy remains an appropriate treatment option for most children with AOM. When amoxicillin, the treatment of choice in AOM, is not effective or not tolerated in children, the prescriber should consider an alternative that displays not only excellent antimicrobial activity against the suspected pathogens, but also characteristics, such as convenient dosing, tolerability, and palatability, that promote compliance and adherence in children. The cephalosporins offer an alternative to penicillins. Cephalosporins such as cefuroxime axetil (second-generation) and cefdinir and cefpodoxime proxetil (third-generation), offer a broad spectrum of activity and are approved for use in a convenient once- or twice-daily dosing schedule, thus increasing the likelihood of compliance with the full course of therapy. Cefdinir is a possible second-line alternative to amoxicillin for children with AOM, particularly among children who are likely to be noncompliant with a two- to three-times-daily dosing schedule, and those instances where there is a high likelihood for, or a known infection with an amoxicillin-resistant pathogen.
Acute bacterial rhinosinusitis is a common infection resulting in substantial morbidity. Cefdinir, an oral cephalosporin, has extended-spectrum, bactericidal activity against common acute bacterial rhinosinusitis pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Cefdinir shows rapid oral absorption and good respiratory tissue penetration, and may be administered once daily. In randomised clinical trials, cefdinir showed efficacy similar to that of other recommended regimens in the treatment of acute bacterial rhinosinusitis, namely amoxicillin/clavulanate and levofloxacin. Cefdinir is well tolerated and has shown a low propensity to suppress the normal commensal flora. Cefdinir oral suspension is rated highly by children in terms of its taste and smell. As the only once-daily beta-lactam currently recommended by acute bacterial rhinosinusitis guidelines (for first-line use in patients with mild acute bacterial rhinosinusitis and no recent antibacterial use), cefdinir offers a convenient and attractive treatment option.
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Clinical trials of cefdinir (CFDN) in pediatric infections were carried out. Results are summarized as follows. 1. Mean half-lives of CFDN in serum in children when administered on an empty stomach were 1.24 hours (3 mg/kg per os) and 1.85 hours (6 mg/kg per os). 2. Mean 8 hour urinary excretion rates of CFDN were 19.0% (3 mg/kg/per os) and 10.5% (6 mg/kg per os). 3. CFDN was administered to 28 children with various infections: 12 patients with tonsillitis, 8 with bronchitis, 2 with pneumonia, 4 with urinary tract infections, 1 staphylococcal scalded skin syndrome and 1 with impetigo. The overall efficacy rate was 89.3%. 4. Diarrhea was noted in 1 patient. Abnormal laboratory test values encountered were eosinophilia in 2 patients, thrombocytosis in 1.
The interactions of cefdinir, a new orally-active third-generation cephalosporin, with cell-free beta-lactamase preparations were studied in comparison with some other beta-lactams. Cefdinir was very resistant to narrow-spectrum Ambler's class A beta-lactamases, as it was for other oximino beta-lactams: cefotaxime, ceftazidime, cefixime and cefuroxime. Cefaclor showed a low but significant hydrolysis by these beta-lactamases. These class-A enzymes include the widespread plasmid mediated TEM-1, TEM-2, SHV-1 and also the enzymes of Gram-positive penicillinases, such as that produced by S. aureus. The hydrolysis of cefdinir was hardly detectable by the Ambler's class C beta-lactamases (cephalosporinases) produced by E. coli, E. cloacae and M. morganii. A similar conclusion is shown for cefotaxime, ceftazidime, cefixime and cefuroxime: for these beta-lactamases, the hydrolysis of cefaclor was high. The P. vulgaris cephalosporinase differs from the previous cephalosporinases in that it hydrolyses cefotaxime, cefuroxime and cefaclor efficiently. However, the hydrolysis of cefdinir remains too low to be detected. Cefdinir, as other third-generation cephalosporins, showed some hydrolysis by the novel extended-spectrum beta-lactamases (ESBL): SHV-2, TEM-3, TEM-5, MEN-1 and other ESBL.
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Medline, Embase, reference lists, and abstract searches were conducted to identify randomized, controlled trials of cephalosporin versus penicillin treatment of GABHS tonsillopharyngitis in children. Trials were included if they met the following criteria: patients <18 years old, bacteriologic confirmation of GABHS tonsillopharyngitis, random assignment to antibiotic therapy of an orally administered cephalosporin or penicillin for 10 days of treatment, and assessment of bacteriologic outcome using a throat culture after therapy. Primary outcomes of interest were bacteriologic and clinical cure rates. Sensitivity analyses were performed to assess the impact of careful clinical illness descriptions, compliance monitoring, GABHS serotyping, exclusion of GABHS carriers, and timing of the test-of-cure visit.
Cefdinir, a semi-synthetic third generation cephalosporin antibiotic being considered as an emerging pollutant, demands removal from aquatic ecosystems. A yeast strain isolated from pharmaceutical wastewater which was identified as Ustilago sp. SMN03 by molecular techniques and was found to be capable of utilizing cefdinir as a sole carbon source. The isolate was found to degrade 81 % of cefdinir within 6 days under optimized conditions viz. pH 6.0, temperature 30 °C, a shaking speed of 120 rpm, an inoculum dosage of 4 % (w/v) and an initial cefdinir concentration of 200 mg L(-1). Kinetic studies revealed that cefdinir degradation followed the pseudo-first order model, a rate constant of 0.222 per day and a half-life period of 3.26 days. Using LC-MS analysis, six novel intermediates formed during the cefdinir degradation were identified and characterized. FT-IR analysis showed that the functional groups ranging from 1,766 to 1,519 cm(-1), characteristic for lactam ring were completely removed during the cefdinir degradation. The opening of the β-lactam ring was one of the major steps in the cefdinir degradation process. Based on the results from the present study, a possible pathway of cefdinir degradation by Ustilago sp. SMN03 was proposed. To the best of our knowledge, this is the first report on microbial degradation of cefdinir by yeast.
The post-antibiotic effects (PAEs) of a new cephalosporin, cefdinir, were determined against a range of organisms using a viable counting technique. Cefdinir exerted considerable PAEs against Staphylococcus aureus and Streptococcus pyogenes, but no overall post-antibiotic inhibition of growth was detected against Escherichia coli or Klebsiella pneumoniae. Exposure to cefdinir made the gram-negative organisms susceptible to the washing procedure used for drug removal, but this was followed by rapid recovery of viability in drug-free broth.
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The Pharmacokinetics and clinical effectiveness of cefdinir (CFDN, FK482) were examined in pediatric patients. The results are summarized as follows. 1. Plasma concentrations and urinary excretions of CFDN after administration of 5% fine granules were investigated on 4 children at a dose level of 6 mg/kg. Average plasma concentrations peaked at 4 hours after administration at 0.99 micrograms/ml with a half-life of 2.12 hours. The first 24-hour urinary recovery rates of CFDN in 3 children averaged 22.0%. 2. CFDN was given to 24 children (11 with pharyngitis, 3 with tonsillitis, 8 with scarlet fever, 1 with urinary tract infection and 1 with enteritis due to Salmonella); 15 were treated with 5% fine granules and 9 with 10% fine granules at daily doses of about 10 mg/kg in 2 to 3 divided portions. Clinical effects were excellent in 16, good in 7 and not evaluable in 1, with an overall efficacy rate of 100%. 3. Identified causative organisms were 12 strains of Streptococcus pyogenes, 4 of Haemophilus influenzae, 5 of Haemophilus parainfluenzae, 1 of Escherichia coli, and 1 of Salmonella. Bacteriological effects were rated as "eradicated" for 19 strains, "unchanged" for 4 with an eradication rate of 82.6%. 4. No side effects were observed. As for abnormal laboratory test results, a transient decrease of white blood cells was observed in 1 patient. 5. The CFDN fine granule preparations were preferably accepted by the children. 6. The fine granular preparations of CFDN, a new oral antibiotic, were useful for the treatment of bacterial infections in pediatrics.
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The synthesis, antibacterial activity and oral absorption of the 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinylcephalosporins (Ia--e) are described. All of these compounds exhibited excellent activity against Staphylococcus aureus. Against Gram-negative bacteria FK482 exhibited more excellent activity than the other compounds (Ia--e). These compounds except Ie showed good oral absorption. The relationship between the oral absorption rates and the lipophilicity of these cephalosporins is discussed.