cefotaxime and Anemia--Sickle-Cell

Children with sickle cell disease are at increased risk for bacterial sepsis and, when febrile, are usually hospitalized for intravenous antibiotic therapy pending results of blood cultures. In this study, we prospectively identified a group of febrile patients with sickle cell disease who were at low risk for sepsis and treated them with outpatient therapy.. Children identified as low risk for sepsis were treated with an initial dose of intravenous ceftriaxone, followed by outpatient therapy with oral cefixime, and were monitored for 14 days after the initial visit. Compliance was assessed by phone calls to parents and by analysis of urine samples.. In 107 eligible febrile episodes (80 patients) over a 21-month period, no patient developed sepsis. One child developed bacteremia 3 days after completing the course of cefixime, and one had splenic sequestration on the fourth study day. Both patients did well. Side effects of cefixime were modest, and overall compliance was excellent (approximately 95%), although urine samples were returned by only 56% of parents.. We conclude that outpatient therapy is safe and effective in febrile patients with sickle cell disease who meet the criteria for a low risk of sepsis.

Topics: Administration, Oral; Adolescent; Anemia, Sickle Cell; Anti-Infective Agents; Bacteremia; Bacterial Infections; Cefixime; Cefotaxime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Humans; Infant; Male; Outpatients; Patient Compliance

The pharmacokinetic profile of most drugs is dependent on the patient's covariates and may be influenced by the disease. Cefotaxime is frequently prescribed in pediatric patients with sickle cell disease (SCD), characterized by vaso-occlusive complications, chronic hemolytic anemia, and a defective immunological function predisposing the individual to severe infection. Data on the impact of the disease on the disposition of cefotaxime are missing. In the present study, our aims were to determine cefotaxime pharmacokinetics when prescribed to children with SCD for suspected or proven bacterial infection, identify significant covariates, and perform Monte Carlo simulations to optimize the drug dosage. Cefotaxime serum concentrations were measured in 78 pediatric SCD patients receiving cefotaxime intravenously at a daily dose of 200 mg/kg of body weight in three or four divided doses over 30 min. A total of 107 concentrations were available for pharmacokinetic analysis. A population pharmacokinetic model was developed with NONMEM software and used for Monte Carlo simulations. Cefotaxime concentrations ranged from 0.05 to 103.7 mg/liter. Cefotaxime pharmacokinetics were best described by a one-compartment model: the median estimated weight-normalized volume of distribution and clearance were 0.42 liter/kg (range, 0.2 to 1.1 liter/kg) and 0.38 liter/h/kg (range, 0.1 to 1.2 liter/h/kg). Cefotaxime clearance increased by 22% in patients with acute chest syndrome. Dosing optimization, performed using EUCAST MIC susceptibility breakpoints, showed that a dose of 100 mg/kg/6 h should be used, depending on the patient's characteristics and clinical presentation, in order to reach a value of the percentage of time that the drug concentration exceeded the MIC under steady-state pharmacokinetic conditions of 80% in 80% of the patients when targeting sensitive Gram-positive cocci and Gram-negative bacilli with MICs of 1 mg/liter or below.

Topics: Adolescent; Anemia, Sickle Cell; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Female; Gram-Negative Bacteria; Humans; Infant; Male; Microbial Sensitivity Tests; Monte Carlo Method

Topics: Amoxicillin; Anemia, Sickle Cell; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Cefotaxime; Humans; Prospective Studies

Topics: Anemia, Sickle Cell; Bacteremia; Cefotaxime; Cephalosporin Resistance; Child; Drug Therapy, Combination; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; Vancomycin

Topics: Anemia, Sickle Cell; Cefotaxime; Cephalosporins; Drug Therapy, Combination; Female; Humans; Infant; Meningitis, Pneumococcal; Penicillin Resistance; Vancomycin

Topics: Anemia, Sickle Cell; Bacteremia; Cefotaxime; Cephalosporins; Child; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; Vancomycin

Topics: Amikacin; Anemia, Sickle Cell; Cefotaxime; Child; Diagnosis, Differential; Humans; Injections, Intravenous; Klebsiella pneumoniae; Male; Osteomyelitis