Population Pharmacokinetics of Cefoxitin Administered for Pediatric Cardiac Surgery Prophylaxis

Ricci, Zaccaria; Benegni, Simona; Cies, Jeffrey J.; Marinari, Eleonora; Haiberger, Roberta; Garisto, Cristiana; Rizza, Alessandra; Giorni, Chiara; Chiara, Luca Di; Berlier, Gloria; Muntoni, Elisabetta; Ferrari, Fiorenza; Milla, Paola

doi:10.1097/inf.0000000000002635

Cited by 3 publications

(1 citation statement)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The number of analyzed patients and collected samples derived from a previous pharmacokinetic study published by this group. 9 We enrolled patients who received vancomycin added to cefoxitin as prophylaxis, according to institutional protocol. In our hospital, due to an outbreak of MRSA mediastinitis, surgical patients have received vancomycin added to standard second generation cephalosporine, cefoxitin, as surgical prophylaxis.…”

Section: Study Design and Durationmentioning

confidence: 99%

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study

et al. 2021

Self Cite

View full text Add to dashboard Cite

Introduction: Few data are available regarding intraoperative plasma concentrations of vancomycin administered as prophylaxis in pediatric cardiac surgery. The aims of this study were to investigate during pediatric cardiac surgery with cardiopulmonary bypass(CPB) the attainment of the area-under-the-curve of the vancomycin serum concentrations versus time over surgery to minimum inhibitory concentration ratio(AUCintra/MIC) of 400 (mg × h)/l and/or a target concentration of 15–20 mg/l. Methods: In a prospective study, 40 patients divided into four subgroups (neonates, infants, children <10 years-old, ⩾10 years-old) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. A slow vancomycin bolus of 20 mg/kg, up to a maximum dose of 1000 mg was administered before skin incision and a further dose of 10 mg/kg (up to 500 mg) at CPB start. Vancomycin samples were collected intraoperatively at four time points. Results: The median (interquartile range) age was 241.5 days (47–3898) and the median weight was 7.1 kg (3.1–37). The median AUCintra/MIC was 254.73 (165.89–508.06). In 11 patients the AUCintra/MIC target was not reached. Neonates displayed the lowest AUCintra/MIC values, and these were significantly lower than those of children ⩾10 years old (p = 0.02). Vancomycin concentrations were above the maximal target of 20 mg/l in 82.5% and 80% of patients at surgery and CPB start, respectively. At CPB and surgery end, 42.5% of patients showed vancomycin concentrations above 20 mg/l and 42.5% below 15 mg/l. Patients⩾10 years old showed the highest peak values whereas neonates were those with the lowest troughs. AUCintra/MIC correlated with age(r:0.36, p = 0.02), weight(r:0.35, p = 0.03), intraoperative protein value(r:0.40, p = 0.01), CPB priming volume/kg(r:−0.33, p = 0.04), CPB duration(r:0.36, p = 0.02) and vancomycin troughs(r:0.35, p = 0.04). Conclusions: An AUCintra/MIC ⩾400 target was not reached in one-quarter of children undergoing heart surgery. Vancomycin peaked before the start of surgery and neonates were those with the lowest troughs. Vancomycin concentrations are affected by CPB hemodilution and by patients’ age and weight.

show abstract

Section: Study Design and Durationmentioning

confidence: 99%

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

Dose optimization of cefazolin in South African children undergoing cardiac surgery with cardiopulmonary bypass

Gebreyesus,

Dresner,

Wiesner

et al. 2024

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

Cefazolin is an antibiotic used to prevent surgical site infections. During cardiac surgery with cardiopulmonary bypass (CPB), its efficacy target could be underachieved. We aimed to develop a population pharmacokinetic model for cefazolin in children and optimize the prophylactic dosing regimen. Children under 25 kg undergoing cardiac surgery with CPB and receiving cefazolin at standard doses (50 mg/kg IV every 4–6 h) were included in this analysis. A population pharmacokinetic model and Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) for efficacy and toxicity with the standard regimen and an alternative regimen of continuous infusion, where loading and maintenance doses were calculated from model‐derived individual parameters. Twenty‐two patients were included, with median (range) age, body weight, and eGFR of 19.5 (1–94) months, 8.7 (2–21) kg, and 116 (48–159) mL/min, respectively. Six patients received an additional dose in the CPB circuit. A two‐compartment disposition model with an additional compartment for the CPB was developed, including weight‐based allometric scaling and eGFR. For a 10 kg patient with eGFR of 120 mL/min/1.73 m2, clearance was estimated as 0.856 L/h. Simulations indicated that the standard dosing regimen fell short of achieving the efficacy target >40% of the time within a dosing duration and in patients with good renal function, PTA ranged from <20% to 70% for the smallest to the largest patients, respectively, at high MICs. In contrast, the alternative regimen consistently maintained target concentrations throughout the procedure for all patients while using a lower overall dose.

show abstract

The influence of cardiopulmonary bypass on pediatric pharmacokinetics

Saet

Tibboel

2023

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

Population Pharmacokinetics of Cefoxitin Administered for Pediatric Cardiac Surgery Prophylaxis

Cited by 3 publications

References 22 publications

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study

Dose optimization of cefazolin in South African children undergoing cardiac surgery with cardiopulmonary bypass

The influence of cardiopulmonary bypass on pediatric pharmacokinetics

Contact Info

Product

Resources

About