ABSTRACT
Objectives: Augmented renal clearance (ARC) of primarily renally eliminated antibacterial agents may result in subtherapeutic antibiotic concentrations and, as a consequence, worse clinical outcomes. Cefathiamidine is frequently used as empirical antimicrobial therapy in children with ARC, but pharmacokinetic studies in infants are lacking. This population pharmacokinetic study in infants with ARC was conducted to determine optimal dosing regimens of cefathiamidine. Methods: The population pharmacokinetics was conducted in 20 infants treated with cefathiamidine. Plasma samples of cefathiamidine were collected using opportunistic sampling, and the concentrations were detected by UPLC-MS/MS. Data analysis was performed to determine pharmacokinetic parameters and to characterize pharmacokinetic variability of cefathiamidine using nonlinear mixed effects modelling (NONMEM) software program. Results: The data (n = 36) from 20 infants (age range, 0.35-1.86 years) with ARC were fitted best with a 1-compartment model. Allometrically scaled weight and age as significant covariates influenced cefathiamidine pharmacokinetics. The median (range) values of estimated clearance and the volume of distribution were 0.22 (0.09-0.29) L/h/kg and 0.34 (0.24-0.41) L/kg, respectively. Monte Carlo simulations showed that the cefathiamidine doses of 100 mg/kg/day q12 h, 50 mg/kg/day q8 h and 75 mg/kg/day q6 h were chosen for bacteria with MIC 0.25, 0.5 and 2 mg/L, respectively. Conclusion: The population pharmacokinetic model of cefathiamidine for infants with ARC was developed. The PTA - based dosing regimens were recommended based on the final model.
ABSTRACT
PURPOSE: Cefathiamidine, a first-generation cephalosporin, has approval from the China Food and Drug Administration for the treatment of infections caused by susceptible bacteria in both adults and children. As pharmacokinetic data are limited in the pediatric population, we aimed to evaluate the population pharmacokinetics of cefathiamidine in children and to define the appropriate dose in order to optimize cefathiamidine treatment. METHODS: Blood samples were collected from children treated with cefathiamidine, and concentrations were quantified by high-performance liquid chromatography and tandem mass spectrometry. Population pharmacokinetic analysis was conducted using NONMEM software. RESULTS: Fifty-four children (age range: 2.0-11.8 years) were included. Sparse pharmacokinetic samples (n=120) were available for analysis. A two-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that bodyweight had a significant impact on cefathiamidine pharmacokinetics. Monte Carlo simulation demonstrated that the currently used dosing regimen of 100 mg/kg/day q12h was associated with a high risk of underdosing in pediatric patients. To reach the target 70% fT>MIC, a dose of 100 mg/kg/day cefathiamidine q6h is required for effective treatment against Haemophilus influenzae. CONCLUSION: A population pharmacokinetics model of cefathiamidine in children with hematologic disease was established. A dosing regimen of 100 mg/kg/day cefathiamidine q6h should be used in clinical practice against H. influenza infections.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Cephalosporins/administration & dosage , Cephalosporins/pharmacokinetics , Haemophilus Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Cephalosporins/pharmacology , Child , Child, Preschool , China , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Female , Haemophilus Infections/microbiology , Haemophilus influenzae/drug effects , Humans , Infusions, Intravenous , Male , Microbial Sensitivity Tests , Molecular Dynamics Simulation , Monte Carlo Method , Prospective Studies , Software , Structure-Activity Relationship , Tandem Mass SpectrometryABSTRACT
OBJECTIVE:To evaluate the pharmacoeconomics of cefathiamidine, ceftriaxone sodium, cefuroxime sodium, amoxicillin sodium/clavulanate potassium and cefoperazone sodium/sulbactam sodium in the treatment of pediatric bronchopneumo-nia,and to provide reference for rational drug use in the clinic. METHODS:By retrospective study,338 children with broncho-pneumonia were divided into groups A,B,C,D and E according to different therapy regimens. There were 75,65,76,66 and 56 cases in groups A,B,C,D and E,and they were given cefathiamidine,ceftriaxone sodium,cefuroxime sodium,amoxicillin sodium/clavulanate potassium and cefoperazone sodium/sulbactam sodium intravenously. The pharmacoeconomics of therapy regi-mens in group A,B,C,D and E were evaluated by cost-effectiveness analysis and decision tree analysis model. RESULTS:The effective rates of groups A,B,C,D and E were 93.33%,90.77%,96.05%,87.88% and 87.50%,respectively. The treatment cost of those groups were 1 929.09,2 173.73,1 611.91,1 661.42,1 801.32 yuan,respectively. The cost/effectiveness(C/E)ratio of those groups were 20.67,23.95,16.78,18.91,20.59,respectively. The treatment cost of group C was the smallest,so was the C/E. Results of cost-effectiveness analysis were supported by sensitivity analysis. CONCLUSIONS:Cefuroxime sodium is the best treatment for pediatric bronchopneumonia among 5 antibiotics in respect of cost-effectiveness.
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Objective To evaluate the efficacy and safety of domestic cefepime ,ceftazidime and cefathiami-dine on bacterial infection in gynecology .Methods 460 patients were randomly divided into Group A (155 patients) for 2.0g.bid of cefepime,Group B (155 patients) for 2.0g.bid of ceftazidime and Group C (150 patient) for 2.0g. bid of cefathiamidine ( intramuscular injection:once every 12 hours ) , and the periods of treatment were all 7 to 10 days.Control observation and study was carried out following Guiding Principle of Clinical Application of Antibacterial Agents.Results The clinical efficacies in Groups A ,B and C were 94.84%,82.58% and 67.33%respectively(χ2 =11.63,37.96,all Pthat of Group B>that of Group C;the adverse effectives were 9.68%,10.32% and 9.33% respectively (χ2 =0.09,P>0.05).Conclusion Cefepime may still be used as the first line drugs ,and drug resistance of various degrees has occurred to ceftazidime and cefathi -amidine,and especially cefathiamidine ,which should be used with caution .
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Aim: To study the in virto interaction of Cefathiamidine in combination with Ciprofloxacin against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis. Methods: The activity of each drug alone was determined against all the isolates. Chequerborad synergy testing was then performed against all the isolates. Results: The percentage of the FIC index less than 0.5, from 0.5 to 1, from 1 to 2, more than 2 was 53.3% - 93.3%, 6.7% - 46.7%, 0%, 0% respectively. Conclusion: Synergism and additivity of cefathiamidine combined with ciprofloxacin respectively against 90 strains of Gram positive cocci were the main inter actions, there were little autonomy and no antagonism.
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OBJECTIVE: To study the compatible stability of gatifloxacin for injection in combination with cefathiamidine for injection in 0.9% sodium chloride injection or in 5% glucose injection.METHODS: Changes in appearance and pH value of the mixture of gatifloxcation and cefathiamidine within 8 hours after mixing were respectively observed and determined under room temperature(20?1)℃,and the contents were determined by dual ultraviolet spectrophotometry.RESULTS: The appearance,pH value and contents as well as the ultraviolet absorption peak shape of the mixture showed no significant change within 8 hours after mixing in 0.9% sodium chloride injection or 5% glucose injection.CONCLUSION: Gatifloxacin for injection can be mixed with cefathiamidine for injection in 0.9% sodium chloride injection or 5% glucose injection to use.
ABSTRACT
Aim To study the in virto interaction o f Cefathiamidine in combination with Ciprofloxacin against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis. Methods The activity of each drug alone was determined against all the isolates. Chequerborad synergy testing was then performed against all the isolat es. Results The percentage of the FIC index less than 0.5, from 0.5 t o 1,from 1 to 2,more than 2 was 53.3%～93.3%,6.7%～46.7%,0%,0% respectiv ely. Conclusion Synergism and additivity of cefathiamidine comb ined with ciprofloxacin respectively against 90 strains of Gram positive cocci w ere the main inter actions, there were little autonomy and no antagonism.
