Discussion

We evaluated the impact of cefazolin administration method—continuous versus intermittent infusion—on 90-day incidence of SSIs within a cohort of adult cardiac and neurosurgical patients. Although SSIs were numerically less frequent with cefazolin prophylaxis by continuous infusion—particularly within the cardiac surgery subgroup—the differences failed to reach statistical significance.

Continuous infusions of cefazolin have been employed to optimize the pharmacokinetic-pharmacodynamic relationship while facilitating optimal tissue concentrations. However, data to support such practices are sparse. A pharmacokinetic study in patients undergoing cardiopulmonary bypass (CPB) reported serum target trough concentrations were maintained more effectively in patients receiving cefazolin by continuous infusion. ^{Reference Adembri, Ristori and Chelazzi7} In patients undergoing neurosurgical procedures, total drug exposure in plasma was similar in both intermittent and continuous cefazolin infusion groups. ^{Reference Yu, Dooley and Woods9}

Clinical data examining the impact of cefazolin infusion method on SSI incidence are also sparse. Several prior studies have observed lower SSI rates with continuous rather than intermittently dosed cefazolin—mostly among cardiac procedures—though nearly all are hindered by either risk of confounding or small sample sizes after careful propensity matching.

In the present study, the small number of matched subjects and nearly bimodal distribution in propensity scores indicates significant confounding within the overall (unmatched) cohort. While stringent propensity matching successfully minimized this confounding, we were left with much smaller case numbers for outcome assessment—limiting power.

To further explore potential differences within the treatment groups, infection-free survival was compared between exposure groups and was also not statistically significant. Exploratory subgroup analyses did suggest a potential difference in benefit between cardiac and neurosurgical procedures. Low observed infection rates and diverging infection-free survival curves suggest continuous infusion regimens may have greater benefit for cardiac surgeries—a finding that warrants further investigation, as larger numbers may be necessary to confirm benefit.

There are several limitations to our study. The retrospective cohort within a single health system may not be extrapolated to other institutions. Our assignment of infusion method was dependent on the presence of a cefazolin infusion rate; therefore, a missing value in that field may have been assigned to intermittent group in error. However, infusion method assignments followed closely with expected use (shift toward intermittent) due to the IV fluid shortage in late 2024. The primary endpoint (culture-confirmed infections) may have excluded those clinically diagnosed and meeting additional NHSN supportive criteria for infection. Given its retrospective nature, we were unable to determine compliance with cefazolin prophylaxis guidelines. However, the compliance in each group would likely closely mimic “real-world” performance. Finally, differences in infusion method may not be reflected solely in prophylactic efficacy. Expense, medication waste, drug compatibility with medications using the same IV line, equipment needs, missed or delayed redosing, and training needs for OR staff (if the process differs from other surgeries) should also be considered.

In summary, among a matched cohort of 1,342 cardiac and neurosurgical patients, we were unable to detect a difference in SSI through postoperative day 90. Subgroup analysis revealed potential differences between these patient groups that, while small, may combine with logistic advantages to the use of continuous infusions of cefazolin particularly for cardiac surgery.