# Cefazolin prophylaxis is associated with lower surgical site infection risk than vancomycin following elective spine surgery

**Authors:** Michael S. Kim, Melissa R. Romoff, Ryan Beyer, Emily Tse, Hao-Hua Wu, Don Y. Park, Yu-Po Lee, Nitin Bhatia, Sohaib Hashmi, Emily S. Mills

PMC · DOI: 10.1016/j.xnsj.2026.100857 · North American Spine Society Journal · 2026-02-08

## TL;DR

Using cefazolin instead of vancomycin before spine surgery reduces the risk of surgical site infections, according to a large study.

## Contribution

This study provides large-scale evidence that cefazolin is more effective than vancomycin in preventing surgical site infections after spine surgery.

## Key findings

- Cefazolin was associated with significantly lower SSI risk in TLIF/PLIF and microdiscectomy procedures.
- Cefazolin showed comparable or lower SSI risk than vancomycin across all spine surgery types.
- The study supports cefazolin as the preferred antibiotic for spine surgery when no allergy is present.

## Abstract

Surgical site infection (SSI) remains a major cause of morbidity following elective spine surgery, with incidence rates up to 3%. Current guidelines recommend cefazolin as the first-line prophylactic antibiotic due to its efficacy against methicillin-sensitive Staphylococcus aureus (MSSA) and coagulase-negative staphylococci (CoNS). However, reported B-lactam allergies are commonly cited in clinical practice as a reason for substitution with vancomycin, which provides inferior coverage for MSSA and limited gram-negative activity. Prior single center studies suggest higher SSI risk with vancomycin, but large-scale evidence remains limited.

A retrospective cohort analysis was conducted using the TriNetX US Collaborative Network (2015-2023). Adults undergoing elective spine surgery, including transforaminal or posterior interbody fusion (TLIF/PLIF), multilevel lumbar fusion, posterior cervical fusion, anterior cervical discectomy and fusions (ACDF), and microdiscectomy, were identified. Patients receiving perioperative cefazolin or vancomycin within 24 hours of surgery were included. 1:1 propensity score matching controlled for demographics, comorbidities, and infection risk factors. The primary outcome was 90-day SSI, assessed using ICD-10 diagnosis codes. Risk ratios (RR) were estimated using Cox proportional hazards models.

After matching, 12,996 patients were included across 5 procedure cohorts. Cefazolin prophylaxis was associated with lower or comparable SSI risk compared with vancomycin across all procedures. Statistically significant differences were observed for TLIF/PLIF (0.82% vs. 2.30%; RR 0.36, 95% CI 0.18–0.7; p = .0019) and microdiscectomy (0.34% vs. 0.69%; RR 0.50, 95% CI 0.27–0.93; p = .025). Nonsignificant trends favored cefazolin for posterior cervical fusion (0.88% vs. 1.41%), multilevel lumbar fusion (1.25% vs. 1.51%), and ACDF (0.30% vs. 0.54%).

Cefazolin prophylaxis is associated with significantly lower SSI risk in elective spine procedures. These findings support cefazolin as the preferred perioperative antibiotic and emphasize the need for accurate B-lactam allergy assessment to optimize infection prevention and antimicrobial stewardship in spine surgery.

## Linked entities

- **Chemicals:** cefazolin (PubChem CID 33255), vancomycin (PubChem CID 14969)

## Full-text entities

- **Diseases:** SSI (MESH:D013530), site (MESH:D009371), infection (MESH:D007239), allergies (MESH:D004342)
- **Chemicals:** vancomycin (MESH:D014640), B-lactam (-), methicillin (MESH:D008712), Cefazolin (MESH:D002437)
- **Species:** Staphylococcus aureus (species) [taxon 1280], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12995863/full.md

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Source: https://tomesphere.com/paper/PMC12995863