Pharmacokinetics of cefuroxime axetil suspension in infants and children

Powell, Dwight A.; James, N C; Ossi, Michael; Nahata, Milap C.; Donn, Karl H.

doi:10.1128/aac.35.10.2042

Cited by 37 publications

(17 citation statements)

References 16 publications

(25 reference statements)

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“…Nascimento et al [14] reported a volume of distribution (V D ) of 0.19, 0.25 and 0.22 L/kg (mean 0.22 L/kg), which matched the V D of 0.21 L/kg (range 0.081 – 0.423 L/kg) reported by Knoderer et al [12]. Powell et al reported a half-life (t 1/2 ) of 1.9, 1.4, and 1.9 h (mean 1.75 h) which was similar to the t 1/2 of 1.8 h reported by del Rio et al [15, 17]. Therefore, a one-compartment PK model with first-order elimination was utilized.…”

Section: Methodssupporting

confidence: 79%

Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

Huang

Sunstrom

Munar

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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OBJECTIVES Perioperative antibiotics have decreased, but not eradicated post-operative infections. In patients undergoing cardiac surgery with cardiopulmonary bypass, the dilutional effect of the priming and any additional volume given during the procedure may lead to subtherapeutic antibiotic levels. Our aim was to determine whether children undergoing cardiac surgery with cardiopulmonary bypass receive subtherapeutic perioperative antibiotics. METHODS Using published pharmacokinetic data on cefuroxime, we developed a computer simulation model to generate a nomogram predicting patients at risk for subtherapeutic cefuroxime levels based on time from initial dosing and additional volume given. RESULTS A computer-generated one-compartment pharmacokinetic model was created predicting cefuroxime plasma levels over time for patients of all weights and additional volumes given for both a 25- and 50 mg/kg intravenous dose. For example, following a 25 mg/kg dose, a subject receiving an additional volume of 275 mL/kg is predicted to be subtherapeutic (<16 mg/L = 4 x mininum inhibitory concentration) at 4 hours. Our nomogram predicts all subjects will be subtherapeutic at 8 hours consistent with general pediatrics dosing schemes. Following a 50 mg/kg dose, levels are predicted to be subtherapeutic after an additional volume of 315 ml/kg at 5.5 hours. CONCLUSION Our model predicts which patients undergoing cardiac surgery with cardiopulmonary will have subtherapeutic cefuroxime levels. This nomogram enables providers to determine when to re-dose antibiotics in patients receiving large additional volumes during cardiac surgeries. This rational approach to perioperative antibiotic dosing may result in a reduction in post-operative infection in this vulnerable patient population.

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Section: Methodssupporting

confidence: 79%

Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

Huang

Sunstrom

Munar

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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“…After oral ingestion, cefuroxime axetil is deesterified in the intestinal mucosa and appears as cefuroxime in the blood. Peak concentrations in serum increase in proportion to dose and are 3.3 and 5.1 ,ug/ml after oral doses of a cefuroxime axetil suspension of 10 and 15 mg/kg of body weight, respectively (12). These results are comparable to those achieved in adults following administration of a 250-mg cefuroxime axetil tablet (7).…”

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confidence: 74%

Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections

Jacobs

Brown

Chartrand

et al. 1992

Antimicrob Agents Chemother

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A randomized, single-blind, multicenter study was conducted to evaluate the safety and efficacy of cefuroxime axetil and cefadroxil suspensions for the treatment of skin or skin structure infections in 287 children. Each drug was given at a dosage of 30 mg/kg of body weight per day in two divided doses. Staphylococcus aureus and Streptococcus pyogenes, or a combination of the two, were the primary pathogens isolated from infected skin lesions. A satisfactory bacteriological response (cure or presumed cure) was obtained in 97.1 and 94.3% of children in the cefuroxime axetil and cefadroxil groups, respectively (P > 0.05). Satisfactory clinical responses (cure or improvement) were more likely to occur in cefuroxime axetil recipients than in cefadroxil recipients (97.8 versus 90.3%; P < 0.05). Both regimens were equally well tolerated, with adverse events occurring in 7.9 and 6.1% of cefuroxime axetil and cefadroxil recipients, respectively. There were more patients who refused to take cefuroxime axetil (7 of 189) than there were who refused to take cefadroxil (0 of 98), but the difference was not statistically significant (P = 0.1). In this study, cefuroxime axetil was at least as effective as cefadroxil in resolving skin and skin structure infections in children.Cefuroxime is an expanded-spectrum cephalosporin with improved P-lactamase stability and a broad spectrum of activity against clinically important gram-positive and gramnegative pathogens. The lowest concentrations that inhibited the growth of 90% of the Staphylococcus aureus and Streptococcus pyogenes strains tested are 1 to 2 and <0.125 ,ug/ml, respectively (2).Cefuroxime axetil, the acetyloxyethyl ester of cefuroxime, is a prodrug that is suitable for oral administration. After oral ingestion, cefuroxime axetil is deesterified in the intestinal mucosa and appears as cefuroxime in the blood. Peak concentrations in serum increase in proportion to dose and are 3.3 and 5

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“…The pharmacokinetics of cefuroxime in infants and children following 10-, 15-, and 20-mg/kg doses of cefuroxime axetil suspension have been studied (23). A mean maximum cefuroxime concentration of 3.3 ,ug/ml was achieved in serum 3.6 h following a single 10-mg/kg dose of cefuroxime axetil suspension.…”

Section: Resultsmentioning

confidence: 99%

Efficacy of cefuroxime axetil suspension compared with that of penicillin V suspension in children with group A streptococcal pharyngitis

Gooch

McLinn

Aronovitz

et al. 1993

Antimicrob Agents Chemother

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The bacteriological and clinical efficacies of cefuroxime axetil suspension (20 mg/kg of body weight per day in two divided doses) were compared with those of penicillin V suspension (50 mg/kg/day in three divided doses) in a multicenter, randomized, evaluator-blinded study. Children aged 2 to 13 years with clinical signs and symptoms of acute pharyngitis and a positive throat culture for group A beta-hemolytic streptococci (GABHS) were eligible. Patients were assessed and samples from the throat for culture were obtained at the time of diagnosis, 3 to 7 days after the initiation of treatment, and 4 to 8 days and 19 to 25 days after the completion of 10 days of therapy. Of the 385 evaluable patients, GABHS were eradicated from 244 of 259 (94.2%) cefuroxime-treated patients and 106 of 126 (84.1%) penicillin-treated patients (P = 0.001). Complete resolution of the signs and symptoms present at the time of diagnosis was achieved in 238 of 259 (91.9%o) cefuroximetreated patients and 102 of 126 (81.0%) penicillin-treated patients (P = 0.001). Potential drug-related adverse events were reported in 7.0 and 3.2% of the cefuroxime-and penicillin-treated patients, respectively (P = 0.078). In the present study, cefuroxime axetil suspension given twice daily resulted in significantly greater bacteriological and clinical efficacies than those of penicillin V suspension given three times daily to pediatric patients with acute pharyngitis and a positive throat culture for GABHS.

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Pharmacokinetics of cefuroxime axetil suspension in infants and children

Cited by 37 publications

References 16 publications

Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections

Efficacy of cefuroxime axetil suspension compared with that of penicillin V suspension in children with group A streptococcal pharyngitis

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