Importance: The association of the nasal microbiome with outcomes in surgical patients is poorly understood.

Objective: To characterize the composition of nasal microbiota in patients undergoing clean elective surgical procedures and to examine the association between characteristics of preoperative nasal microbiota and occurrence of postoperative infection.

Design, Setting, and Participants: Using a nested matched case-control design, 53 individuals who developed postoperative infection were matched (approximately 3:1 by age, sex, and surgical procedure) with 144 individuals who were not infected (ie, the control group). The 2 groups were selected from a prospective cohort of patients undergoing surgical procedures at 2 tertiary care university hospitals in Baltimore, Maryland, who were at high risk for postoperative infectious complications. Included individuals were aged 40 years or older; had no history of autoimmune disease, immunocompromised state, immune-modulating medication, or active infection; and were scheduled to undergo elective cardiac, vascular, spinal, or intracranial surgical procedure. Data were analyzed from October 2015 through September 2020. Exposures: Nasal microbiome cluster class served as the main exposure. An unsupervised clustering method (ie, grades of membership modeling) was used to classify nasal microbial samples into 2 groups based on features derived from 16S ribosomal RNA gene sequencing. The microbiome cluster groups were derived independently and agnostic of baseline clinical characteristics and infection status.

Main Outcomes and Measures: Composite of surgical site infection, bacteremia, and pneumonia occurring within 6 months after surgical procedure.

Results: Among 197 participants (mean [SD] age, 64.1 [10.6] years; 63 [37.7%] women), 553 bacterial taxa were identified from preoperative nasal swab samples. A 2-cluster model (with 167 patients in cluster 1 and 30 patients in cluster 2) accounted for the largest proportion of variance in microbial profiles using grades of membership modeling and was most parsimonious. After adjusting for potential confounders, the probability of assignment to cluster 2 was associated with 6-fold higher odds of infection after surgical procedure (odds ratio [OR], 6.18; 95% CI, 3.33-11.7; P <.001) independent of baseline clinical characteristics, including nasal carriage of Staphylococcus aureus. Intrasample (ie, α) diversity was inversely associated with infectious outcome in both clusters (OR, 0.57; 95% CI, 0.42-0.75; P <.001); however, probability of assignment to cluster 2 was associated with higher odds of infection independent of α diversity (OR, 4.61; 95% CI, 2.78-7.86; P <.001).

Conclusions and Relevance: These findings suggest that the nasal microbiome was an independent risk factor associated with infectious outcomes among individuals who underwent elective surgical procedures and may serve as a biomarker associated with infection susceptibility in this population.