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Continuous Cefuroxime Infusion Achieves Superior Tissue Exposure Over Bolus Dosing in Oral Cancer Surgery
Both bolus and continuous infusion regimens of 4500 mg daily cefuroxime met the minimum pharmacodynamic target of 50% time above MIC across all sampled tissue compartments, but continuous infusion achieved 100% time above MIC in every compartment at both MIC thresholds, compared to 79–98% with bolus dosing. Continuous infusion also produced statistically significantly higher target attainment in subcutaneous tissue at both MIC levels and in plasma at the higher MIC threshold.
What Was Studied
This study investigated whether the method of cefuroxime administration — bolus infusion versus continuous infusion — affects free antibiotic concentrations in surgically relevant tissue compartments during oral cavity cancer surgery involving facial artery musculomucosal (FAMM) flap reconstruction. Because regional flap procedures carry elevated surgical site infection risk, optimizing antibiotic exposure at the tissue level is a meaningful clinical and pharmacological question.
How It Was Studied
This was a prospective, randomized clinical microdialysis study enrolling 18 patients scheduled for tumour resection with FAMM flap reconstruction. Patients were randomly assigned to receive cefuroxime either as bolus infusion (1500 mg every 8 hours; Group BI) or as continuous infusion (4500 mg per day; Group CI), with the total daily dose equivalent across arms. Microdialysis catheters were surgically placed in three tissue sites — the FAMM flap itself, the buccal submucosa, and subcutaneous neck tissue — alongside plasma sampling, and free cefuroxime concentrations were tracked over an 8-hour monitoring window. The primary endpoints were the proportion of time that unbound drug concentrations exceeded the minimum inhibitory concentration (T > MIC) and attainment of the widely accepted beta-lactam pharmacodynamic target of ≥50% T > MIC, evaluated at MIC breakpoints of 2 mg/L and 4 mg/L.
What Was Observed
- Both regimens met the minimum treatment target: every patient in both groups achieved ≥50% T > MIC across all four sampled compartments at both MIC thresholds, confirming that 4500 mg/day cefuroxime provides at least adequate pharmacodynamic coverage regardless of administration mode.
- Continuous infusion reached perfect target attainment: the CI group achieved 100% T > MIC in all tissue compartments and plasma at both MIC 2 mg/L and MIC 4 mg/L, representing an absolute ceiling effect with no time spent below the inhibitory threshold.
- Bolus infusion showed meaningful gaps at higher MIC thresholds: mean T > MIC values in the BI group ranged from 89–98% at MIC 2 mg/L and fell to 79–90% at MIC 4 mg/L across compartments, indicating that for organisms at the upper end of susceptibility, bolus dosing leaves a non-trivial proportion of the dosing interval with potentially sub-inhibitory tissue concentrations.
- Statistically significant advantages for CI were tissue- and threshold-specific: continuous infusion produced significantly higher T > MIC than bolus infusion in subcutaneous tissue at both MIC levels, and in plasma at the MIC 4 mg/L threshold — findings that point to more consistent drug exposure rather than a universal superiority across all compartments.
Why This Matters
Pharmacokinetic-pharmacodynamic optimization of perioperative antibiotic prophylaxis is an underexplored area, particularly in complex oncological head and neck surgery where flap perfusion and tissue penetration may differ substantially from systemic compartments. This study provides direct microdialysis-derived evidence — measuring free, pharmacologically active drug concentrations at the surgical site — rather than relying on plasma surrogates. The demonstration that continuous infusion eliminates sub-inhibitory exposure windows, especially at higher MIC values, adds mechanistic support for considering infusion strategy as a lever for prophylaxis optimization in high-risk patients.
How to Read This Result
With only 18 patients across two groups, the study is adequately powered to describe pharmacokinetic profiles but too small to draw conclusions about clinical infection outcomes, and results may not generalize beyond the specific surgical context and patient population studied.
Limitations
The abstract does not explicitly report study limitations.