Skeletal muscle and plasma concentrations of cefazolin during complex paediatric spinal surgery.
Surgical site infections (SSIs) can have devastating consequences for children who undergo spinal instrumentation. Prospective evaluations of prophylactic cefazolin in this population are limited. The purpose of this study was to describe the pharmacokinetics and skeletal muscle disposition of prophylactic cefazolin in a paediatric population undergoing complex spinal surgery.



This prospective pharmacokinetic study included 17 children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, with a median age of 13.8 [interquartile range (IQR) 13.4-15.4] yr and a median weight of 60.6 (IQR 50.8-66.0) kg. A dosing strategy consistent with published guidelines was used. Serial plasma and skeletal muscle microdialysis samples were obtained during the operative procedure and unbound cefazolin concentrations measured. Non-compartmental pharmacokinetic analyses were performed. The amount of time that the concentration of unbound cefazolin exceeded the minimal inhibitory concentration for bacterial growth for selected SSI pathogens was calculated.



Skeletal muscle concentrations peaked at a median of 37.6 (IQR 26.8-40.0) µg ml(-1) within 30-60 min after the first cefazolin 30 mg kg(-1) dose. For patients who received a second 30 mg kg(-1) dose, the peak concentrations reached a median of 40.5 (IQR 30.8-45.7) µg ml(-1) within 30-60 min. The target cefazolin concentrations for SSI prophylaxis for meticillin-sensitive Staphylococcus aureus (MSSA) and Gram-negative pathogens were exceeded in skeletal muscle 98.9 and 58.3% of the intraoperative time, respectively.



For children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, the cefazolin dosing strategy used in this study resulted in skeletal muscle concentrations that were likely not to be effective for intraoperative SSI prophylaxis against Gram-negative pathogens.
Department of Anesthesiology and Critical Care Medicine Center for Clinical Pharmacology himebaucha@email.chop.edu.
A S
AS
Himebauch
Department of Surgery, Division of Orthopedic Surgery.
W N
WN
Sankar
Department of Surgery, Division of Orthopedic Surgery.
J M
JM
Flynn
Department of Anesthesiology and Critical Care Medicine.
M T
MT
Sisko
Center for Clinical Pharmacology.
G S
GS
Moorthy
Department of Pediatrics, Division of Infectious Diseases.
J S
JS
Gerber
Department of Anesthesiology and Critical Care Medicine Center for Clinical Pharmacology.
A F
AF
Zuppa
Center for Clinical Pharmacology Department of Pediatrics, Division of Oncology, Perelman School of Medicine, University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
E
E
Fox
Division of Orthopedic Surgery, Texas Children's Hospital, Houston, TX 77030, USA.
J P
JP
Dormans
Department of Anesthesiology and Critical Care Medicine.
T J
TJ
Kilbaugh
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D002437:Cefazolin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010372:Pediatrics; D011446:Prospective Studies; D012600:Scoliosis / Q000601:surgery*; D013123:Spinal Fusion; D013530:Surgical Wound Infection / Q000517:prevention & control*
D000900:Anti-Bacterial Agents; D002437:Cefazolin
cefazolin; microdialysis; paediatric; scoliosis; surgery, spinal