ISSN:0009-3157    

DOI:10.1159/000239089

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Differences in the pharmacokinetic parameters of cephalosporins between children and adults may be predictable on the basis of the level of maturation of the physiologic processes involved in drug disposition. It appears that the most important of these factors (gastrointestinal, renal and hepatic function) are reasonably mature by the age of 1 year. As a result, the primary difference between adults and children relates to size and body composition. Comparable bioavailability is expected in children and adults. However, absolute values for systemic clearance (Cls) and volume of distribution (Vss) will be lower in children. It has been suggested that Cls in children is reduced in proportion to body surface area. This may also be true for the Vss of the cephalosporins since they distribute primarily into the extracellular fluid space which has been shown to be similar in children and adults when adjusted for surface area. If both Cls and Vss are proportional to surface area, half-life will be similar in adults and children. Data with cefetamet generally support these principles. Clearance normalized for body surface area averaged 69.3 ml/min/m2 in children aged 3-7 years, 64.9 ml/min/m2 in children of 8-12 years and 68.9 ml/min/m2 in adults. The Vss remained somewhat smaller in children than adults even after correction for surface area. Bioavailability and elimination half-life in children were similar to values in adults. Data with other new cephalosporins are limited, but differences between children and adults in bioavailability and half-life appear to be insignificant. These observations suggest that the maintenance dose for new oral cephalosporins such as cefetamet in children should be the adult dose multiplied by the ratio of the surface area of the child to the average surface area of an adult. The dosing interval for these compounds should be the same in children and adults.

ISSN:0009-3157    

DOI:10.1159/000239090

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Phenotypic resistance to β-lactam antibiotics is mainly due to the prevalence of β-lactamases. The most common enzymes responsible for resistance to aminopenicillins and older (1st generation) cephalosporins are the TEM-1, TEM-2, OXA-1 and SHV-1 enzymes, all of which are plasmid-mediated. The recent development of oral cephalosporins sharing structural features and an antimicrobial spectrum comparable to that of 3rd-generation cephalosporins has provided highly active compounds for the management of outpatient infections. Two principal mechanisms, however, may cause resistance to these new compounds: the overproduction of chromosomally encoded β-lactamases with predominating cephalosporinase activity, and the recently observed extended-spectrum β-lactamases. The overproduction of chromosomally mediated β-lactamases has been observed only in some species (Enterobacter cloacae, Citrobacter freundii, Serratia spp.) which cause mainly nosocomial infections and are therefore of minor importance in outpatients. The extended-spectrum β-lactamases TEM-3 to TEM-12 and SHV-2 to SHV-7 have been observed in various countries, they derived from the original enzymes by point mutations and occurred in intensive-care units. These enzymes may cause resistance to 3rd-generation cephalosporins including the recently developed orally active compounds. Moderate resistance to cefetamet is observed only in strains producing either the TEM-3 or the TEM-4 enzyme, whereas the prevalence of the other enzymes is of no consequence for the activity of cefetamet. Consequently, cefetamet will not exhibit a marked selection pressure favoring the spread of extended-spectrum β-lactamase-producing s

ISSN:0009-3157    

DOI:10.1159/000239092

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In recent years, attempts have been made to make the regulatory requirements for clinical studies more uniform, and much has been discussed on the issue of good clinical practice. There is no doubt that clinical trials involving new drugs have to be conducted according to the highest standards. However, ideal design is not always feasible or ethical. The ideal design for efficacy studies demands randomization, double-blind comparisons, adequate group size, specification of the type of patients and isolated organisms. The present paper points out some difficulties regarding these points when studying cephalosporins in pediatric respiratory-tract infections, and proposes some solutions.

ISSN:0009-3157    

DOI:10.1159/000239093

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Cefetamet, an oral 3rd-generation cephalosporin, was investigated in 40 children with acute otitis media in a comparative randomized trial. The efficacy of 20 mg/kg cefetamet syrup in 20 patients was compared with that of 20 mg/kg cefaclor in another 20, both drugs being given orally twice daily for 7 days. Tympanocentesis was performed for every child before the initiation of antimicrobial treatment. After 7 days treatment with cefetamet pivoxil, clinical cure was obtained in 12 patients, 3 were failures and 5 could not be assessed. In the cefaclor group, 10 patients were cured, 1 improved and 9 were failures. No severe adverse events were observed with either drug.

ISSN:0009-3157    

DOI:10.1159/000239094

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

A total of 30 pediatric patients suffering from lower-respiratory-tract infections were admitted to a three-arm, open, randomized study comparing two different doses of cefetamet pivoxil (either 10 or 20 mg/kg b.i.d.; groups A and B, respectively) with the standard cefaclor treatment (10 mg/kg t.i.d.; group C) for 7-12 days. The 30 cases were randomly assigned to the three treatment arms which were comparable with regard to demographics as well as to diagnosis on admission and concomitant medication. The children ranged from 1.08 to 12 years in age, and comprised 18 males and 12 females, with a weight range of 11-42 kg. As is to be expected in these patients, bacteriology was mostly not assessable. The overall clinical outcome was cure in 9, 8 and 9 cases, respectively, and improvement in 1, 2 and 0 cases, respectively. In the cefaclor group 1 patient failed to respond. Signs and symptoms of disease improved significantly in the three treatment groups; there were no intergroup differences. Vital signs (morning and evening temperature and pulse rate) improved in parallel. Radiological results had improved by the end of treatment in 9/10 patients in group A, in 10/10 patients in group B, and in 9/10 evaluable patients in group C. Mild to moderate nausea or vomiting were each reported in 1 patient in group A. Platelet increase was reported as a mild adverse event in 2 patients in each of the cefetamet pivoxil groups and in 4 patients given cefaclor. Patient acceptance was considered good in 7 patients in group A, in 6 in group B and in 5 in the cefaclor group. Our data suggest that the standard dose of cefetamet pivoxil 10 mg/kg b.i.d. was at least as effective and well tolerated as cefaclor 10 mg/kg t.i.d. or cefetamet pivoxil 20 mg/kg b.i.d. in children with respiratory-tract infections.

ISSN:0009-3157    

DOI:10.1159/000239095

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The efficacy of cefetamet pivoxil (20 mg/kg and 10 mg/kg b.i.d.) was investigated in an open, prospective, randomized, comparative multicenter trial involving 148 children suffering from group A β-hemolytic streptococcal (GABHS) pharyngotonsillitis. Phenoxymethylpenicillin given for 10 days was used as the reference drug and resulted in 15% treatment failures. After treatment with cefetamet pivoxil 20 mg/kg b.i.d., 2 failures (5.8%) were observed in 34 patients treated for 7 days and 2 (6%) in 33 patients after 10 days treatment. In 8 children treated with cefetamet pivoxil 10 mg/kg b.i.d. for 10 days, 7 were cured and 1 relapsed in the late follow-up. Recruitment for this dosage group is being continued. No serious adverse events occurred. Cefetamet pivoxil, given b.i.d., can be considered an alternative to phenoxymethylpenicillin in the treatment of GABHS pharyngotonsillitis

ISSN:0009-3157    

DOI:10.1159/000239096

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0009-3157    

DOI:10.1159/000239097

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0009-3157    

DOI:10.1159/000239098

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The distribution of β-lactamases of indoor and outdoor origin was studied over a 9-month period. We consecutively selected 37 indoor and 48 outdoor strains of the following genera of the Enterobacteriaceae family: Escherichia (species coli), Enterobacter, Proteus, and Klebsiella. All isolates were resistant to amoxicillin and/or cephalothin and/or cefamandole. All strains showed β-lactamase activity. We characterized the enzymes by an isoelectric focusing method and by a disc diffusion test. For both indoor and outdoor isolates we found that plasmid-mediated β-lactamases were encountered mostly in the E. coli and Klebsiella species, whereas chromosomally mediated enzymes predominated in the Proteus and Enterobacter species. No significant difference in distribution of β-lactamases could be found comparing both groups, but it was noted that chromosomally mediated β-lactamases predominated in the Department of Urology, while plasmid-mediated β-lactamases prevailed in other departments (p <

ISSN:0009-3157    

DOI:10.1159/000238945

出版商:S. Karger AG    

年代:1992

数据来源: Karger