Elevated risk of wound and systemic complications in MRSA-colonized patients undergoing lower extremity orthopedic trauma surgery

Abstract

Purpose

Preoperative colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a known risk factor for adverse outcomes in arthroplasty but remains under-investigated in orthopedic trauma. This study evaluates the impact of preoperative MRSA colonization on postoperative complication rates in patients undergoing lower extremity orthopedic trauma surgery.

Methods

We conducted a retrospective cohort study using the TriNetX Research Network, identifying adult patients who underwent lower extremity orthopedic trauma procedures over a 20-year period. Patients with a documented MRSA diagnosis within three months before surgery were matched 1:1 to MRSA-negative controls based on demographics and comorbidities. Postoperative outcomes were assessed within three months of surgery, including surgical site infections (SSIs), wound dehiscence, organ dysfunction, thromboembolic events, and healthcare utilization. Odds ratios (ORs) and p-values were calculated, with statistical significance set at p < 0.05.

Results

A total of 1,868 MRSA+ and 629,342 control patients were identified. After matching, MRSA+ patients remained at significantly increased risk for wound dehiscence (OR = 1.80, p = 0.005), pneumonia (OR = 2.33, p < 0.001), sepsis (OR = 3.71, p < 0.001), acute renal failure (OR = 1.45, p < 0.001), blood transfusion (OR = 1.74, p < 0.001), deep vein thrombosis (OR = 2.29, p < 0.001), and pulmonary embolism (OR = 2.80, p < 0.001). No significant differences in SSIs were observed after matching.

Conclusion

Preoperative MRSA colonization is associated with increased risks of wound dehiscence, pneumonia, sepsis, thromboembolic events, blood transfusions, and acute renal failure in orthopedic trauma patients. Preoperative MRSA screening may serve as a risk-stratification tool, enabling surgeons to anticipate systemic complications and optimize management. Where feasible, screening with targeted decolonization or prophylactic strategies may mitigate risk.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00068-026-03283-5.

Highlights

MRSA colonization in orthopedic trauma is linked to systemic complications after surgery and wound dehiscence.

No significant increase in surgical site infections after matching for comorbidities.

MRSA positivity may reflect patient frailty and overall vulnerability, not direct infection risk.

Screening for MRSA can aid risk stratification and optimize perioperative management.

Findings support investigating standardized screening and decolonization protocols in trauma care.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00068-026-03283-5.

Background

Lower extremity fractures are among the most common injuries managed in U.S. emergency departments, comprising approximately 18% of all lower extremity trauma presentations. These fractures are particularly prevalent in the toes (38%), upper legs (31%),and lower legs (29%), with the lower trunk (28%) and ankle (20%) also frequently involved [1]. Such injuries are associated with considerable morbidity, including surgical site infections, malunion, wound dehiscence, and vascular injury [2–4]. As the burden of lower extremity trauma continues to rise, identifying modifiable risk factors for postoperative complications is critical.

One such factor—preoperative colonization with methicillin-resistant Staphylococcus aureus (MRSA)—has emerged as a potential contributor to adverse outcomes, though its impact in the trauma population remains incompletely characterized [5]. In contrast, preoperative MRSA colonization has been extensively studied in total joint arthroplasty, where it has been associated with increased rates of periprosthetic joint infection (PJI), superficial and deep surgical site infections (SSI), and wound dehiscence [6, 7]. As a result, routine preoperative screening and decolonization protocols have been widely implemented in arthroplasty patients [8, 9]. Moreover, the absence of timely preoperative MRSA screening results may lead to inadequate utility of antibiotic prophylaxis, thereby increasing the risk of MRSA-associated SSIs [5].

Although some studies have reported relatively low MRSA colonization rates among orthopedic trauma patients, the elevated risk of infections and wound complications—observed both preliminarily and in arthroplasty populations—warrants further investigation [2, 5, 10, 11]. Robicsek et al. reported that 48.8% of patients remain colonized with MRSA one year after a positive culture, and 21.2% remain colonized at four years [12]. Building on this, our study leverages the largest known cohort of acute lower extremity orthopedic trauma patients with a documented history of MRSA colonization within three months before surgery to evaluate postoperative complication rates.

Methods

Database description

This retrospective cohort study utilized the TriNetX Research Network (https://trinetx.com, Cambridge, MA, USA). The data used in this study were collected on February 17, 2025, from the TriNetX Research Network, which provides access to electronic medical records, including diagnoses, procedures, medications, laboratory values, and genomic information from approximately 74 million patients across 82 U.S. healthcare organizations. TriNetX complies with the Health Insurance Portability and Accountability Act (HIPAA) and is ISO 27001:2013 certified, ensuring data protection and privacy.

Data acquisition

This study was deemed Institutional Review Board (IRB) exempt, as it involved secondary analysis of de-identified data with no direct patient contact or intervention, in accordance with Section 164.514(a) of the HIPAA Privacy Rule.

Patients who underwent lower extremity orthopedic trauma surgeries were identified using relevant Current Procedural Terminology (CPT) codes as outlined in Appendix A [see Appendix File] from the last 20 years. Patients with a documented diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) within three months prior to surgery were identified using ICD-10 code Z22.322 and classified as the MRSA+ cohort. Patients without a prior MRSA diagnosis formed the control group.

Preoperative variables collected included age, sex, race, ethnicity, marital status, smoking status, obesity, and comorbidities such as diabetes. Postoperative outcomes up to three months from index event were identified using ICD-10 codes and included: deep and superficial SSI, wound dehiscence, pneumonia, septicemia, acute renal failure, blood transfusion, cardiac arrest, anemia, myocardial infarction, stroke, shock, deep vein thrombosis (DVT), pulmonary embolism (PE), malunion, and emergency department (ED) visits.

Data analysis

The date of surgery was designated as the index event from which all postoperative outcomes were measured. Descriptive statistics were used to summarize the study population’s baseline demographic and clinical characteristics. Both unmatched and 1:1 propensity score-matched analyses were conducted to reduce confounding and improve group comparability. Matching was performed using the following baseline variables: age; sex (male and female); race and ethnicity, including American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, Hispanic or Latino, White, and Other Race; and clinical comorbidities including chronic kidney disease, chronic obstructive pulmonary disease (COPD), immune disorders, hypertension, malnutrition, diabetes mellitus (other type), type 2 diabetes mellitus, type 1 diabetes mellitus, and use of opioid analgesics.

Comparisons of continuous variables between groups were made using independent samples t-tests. Categorical variables were compared using chi-squared tests or Fisher’s exact tests when expected frequencies were small. A p-value of less than 0.05 was considered statistically significant. For each postoperative complication, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated. Where applicable, hazard ratios (HRs) and associated p-values were also reported for time-to-event outcomes.

Software employed for statistical analysis and data visualization

Data compilation and statistical analysis were performed entirely on the TriNetX Live platform. The platform was used to conduct cohort selection, matching, outcome comparisons, and generating summary statistics. Microsoft Excel was used to format and visualize data tables and figures for presentation and manuscript preparation.

Results

Among patients undergoing surgery for lower extremity orthopedic trauma fractures, 1,868 had documented preoperative MRSA colonization (MRSA+), while 629,342 patients comprised the unmatched MRSA-negative control group. Table 1 summarizes the baseline demographic characteristics of these two cohorts before matching. MRSA+ patients were slightly older on average than control patients (57.7 ± 19.7 vs. 55.5 ± 22.8 years, p < 0.001), with no significant differences in sex distribution (male: 46.7% vs. 45.4%, p = 0.268; female: 51.8% vs. 52.3%, p = 0.682). Significant racial differences were observed. MRSA+ patients were more likely to be White (84.8% vs. 76.7%, p < 0.001) and American Indian or Alaska Native (0.5% vs. 0.2%, p = 0.002), while control patients had higher proportions of Asian (2.2% vs. 0.5%, p < 0.001), Black or African American (9.7% vs. 6.6%, p < 0.001), Other Race (3.2% vs. 1.4%, p < 0.001), and Hispanic or Latino ethnicity (7.1% vs. 2.6%, p < 0.001).

Table 1.

Patient demographic and comorbidities of methicillin-resistant Staphylococcus aureus (+) and Control group before matching

Variable		Experimental (n = 1,868)	Control (n = 629,342)	Significance
Age		57.7 ± 19.7	55.5 ± 22.8	<0.001
Sex (Males)		872 (46.7%)	276,878 (45.4%)	0.268
Sex (Females)		968 (51.8%)	318,899 (52.3%)	0.682
Race
	American Indian or Alaska Native	10 (0.5%)	1,286 (0.2%)	0.002
	Asian	10 (0.5%)	13,646 (2.2%)	<0.001
	Black or African American	124 (6.6%)	58,875 (9.7%)	<0.001
	Native Hawaiian or Other Pacific Islander	10 (0.5%)	1,970 (0.3%)	0.107
	Other Race	27 (1.4%)	19,636 (3.2%)	<0.001
	Hispanic or Latino	49 (2.6%)	43,577 (7.1%)	<0.001
	White	1,584 (84.8%)	467,834 (76.7%)	<0.001
Chronic Kidney Disease		510 (27.3%)	65,969 (10.8%)	<0.001
Chronic Obstructive Pulmonary Disease		600 (32.1%)	66,206 (10.9%)	<0.001
Immune Disorders		101 (5.4%)	11,960 (2.0%)	<0.001
Hypertension		1,341 (71.8%)	272,339 (44.7%)	<0.001
Malnutrition		439 (23.5%)	30,401 (5.0%)	<0.001
Diabetes Mellitus (any)		795 (42.6%)	107,400 (17.6%)	<0.001
Type 2 Diabetes Mellitus		790 (42.3%)	111,988 (18.4%)	<0.001
Type 1 Diabetes Mellitus		208 (11.1%)	15,713 (2.6%)	<0.001
Use of opioid analgesics		1,665 (89.1%)	394,781 (64.7%)	<0.001

Table 1 also details the comorbidities of MRSA+ and control patients prior to matching. MRSA+ patients exhibited significantly higher rates of comorbid conditions, including chronic kidney disease (27.3% vs. 10.8%, p < 0.001), COPD (32.1% vs. 10.9%, p < 0.001), immune disorders (5.4% vs. 2.0%, p < 0.001), hypertension (71.8% vs. 44.7%, p < 0.001), and malnutrition (23.5% vs. 5.0%, p < 0.001). Diabetes was also more prevalent in the MRSA+ group, with significantly higher rates of both type 1 (11.1% vs. 2.6%, p < 0.001) and type 2 diabetes mellitus (42.3% vs. 18.4%, p < 0.001). Opioid analgesic use was nearly universal in the MRSA+ group (89.1% vs. 64.7%, p < 0.001).

Following 1:1 matching, Table 2 shows that demographic differences between MRSA+ and control patients were successfully balanced. There were no significant differences in age (57.7 ± 19.7 vs. 58.0 ± 19.5 years, p = 0.682), sex (male: 46.7% vs. 45.4%, p = 0.450; female: 51.8% vs. 53.1%, p = 0.451), or race/ethnicity. All racial groups were equally represented between matched cohorts (all p ≥ 0.30), confirming the success of the matching process in controlling for baseline demographic variation. In addition, After propensity score matching, no statistically significant differences in baseline comorbidities remained between MRSA+ and control cohorts, indicating adequate balance across measured covariates, as seen in Table 2.

Table 2.

Patient demographic and comorbidities of methicillin-resistant Staphylococcus aureus (+) and Control group after matching

Variable		Experimental (n = 1,868)	Control (n = 629,342)	Significance
Age		57.7 ± 19.7	58.0 ± 19.5	0.682
Sex (Males)		872 (46.7%)	849 (45.4%)	0.45
Sex (Females)		968 (51.8%)	991 (53.1%)	0.451
Race
	American Indian or Alaska Native	10 (0.5%)	10 (0.5%)	1
	Asian	10 (0.5%)	10 (0.5%)	1
	Black or African American	124 (6.6%)	140 (7.5%)	0.307
	Native Hawaiian or Other Pacific Islander	10 (0.5%)	10 (0.5%)	1
	Other Race	27 (1.4%)	22 (1.2%)	0.472
	Hispanic or Latino	49 (2.6%)	55 (2.9%)	0.551
	White	1,584 (84.8%)	1,596 (85.4%)	0.581
Chronic kidney disease		510 (27.3%)	517 (27.7%)	0.798
Chronic Obstructive Pulmonary Disease	600 (32.1%)	600 (32.1%)	606 (32.4%)	0.834
Disorders involving the immune mechanism	101 (5.4%)	101 (5.4%)	97 (5.2%)	0.77
Hypertensive diseases	1,341 (71.8%)	1,341 (71.8%)	1,353 (72.4%)	0.662
Malnutrition	439 (23.5%)	439 (23.5%)	434 (23.2%)	0.847
Diabetes mellitus (any type)	795 (42.6%)	795 (42.6%)	761 (40.7%)	0.259
Type 2 diabetes mellitus	790 (42.3%)	790 (42.3%)	798 (42.7%)	0.791
Type 1 diabetes mellitus	208 (11.1%)	208 (11.1%)	217 (11.6%)	0.643
Use of opioid analgesics	1	1,665 (89.1%)	1,667 (89.2%)	0.916

Postoperative outcomes prior to matching are reported in Table 3. MRSA+ patients demonstrated significantly higher odds of numerous postoperative complications compared to controls, including deep surgical site infections (0.5% vs. 0.2%, OR = 2.35 [95% CI: 1.26–4.38]), superficial surgical site infections (1.2% vs. 0.3%, OR = 3.58 [95% CI: 2.35–5.46]), wound dehiscence (3.3% vs. 1.2%, OR = 2.94 [95% CI: 2.28–3.78]), periprosthetic infections (2.8% vs. 0.4%, OR = 7.03 [95% CI: 5.34–9.26]), pneumonia (14.1% vs. 3.5%, OR = 4.54 [95% CI: 3.99–5.17]), septicemia (14.5% vs. 2.5%, OR = 6.55 [95% CI: 5.76–7.46]), acute renal failure (15.0% vs. 5.3%, OR = 3.13 [95% CI: 2.76–3.55]), blood loss anemia (2.6% vs. 1.3%, OR = 2.05 [95% CI: 1.54–2.72]), blood transfusion (27.8% vs. 11.7%, OR = 2.91 [95% CI: 2.63–3.22]), cardiac arrest (1.6% vs. 0.5%, OR = 3.51 [95% CI: 2.44–5.04]), myocardial infarction (6.2% vs. 2.8%, OR = 2.34 [95% CI: 1.94–2.82]), stroke (4.5% vs. 2.3%, OR = 1.97 [95% CI: 1.59–2.45]), shock unspecified (2.3% vs. 0.4%, OR = 5.32 [95% CI: 3.92–7.21]), cardiogenic shock (0.8% vs. 0.3%, OR = 2.65 [95% CI: 1.59–4.41]), deep vein thrombosis (6.3% vs. 2.3%, OR = 2.89 [95% CI: 2.40–3.48]), pulmonary embolism (6.2% vs. 1.6%, OR = 3.97 [95% CI: 3.29–4.79]), and emergency department visits (88.6% vs. 79.8%, OR = 1.96 [95% CI: 1.70–2.26]) (all p < 0.001 unless otherwise noted). Malunion showed no significant difference between groups.

Table 3.

Risk Analysis for post-operative outcomes prior to matching

Outcome	Experimental Outcome (n, %)	Outcome Risk for Experimental Group	Control Outcome (n, %)	Outcome Risk for Control	Odds Ratio (95% CI)	Significance
Deep Surgical Site Infections	10 (0.5%)	0.005	1,385 (0.2%)	0.002	2.345 (1.257–4.375)	0.006*
Wound Dehiscence	63 (3.3%)	0.033	7,107 (1.2%)	0.012	2.935 (2.280–3.777)	<0.001*
Periprosthetic Infection	53 (2.8%)	0.028	2,501 (0.4%)	0.004	7.030 (5.335–9.264)	<0.001*
Pneumonia	266 (14.1%)	0.141	21,304 (3.5%)	0.035	4.541 (3.986–5.173)	<0.001*
Septicemia	274 (14.5%)	0.145	15,433 (2.5%)	0.025	6.553 (5.760–7.456)	<0.001*
Superficial Surgical Site Infections	22 (1.2%)	0.012	2,007 (0.3%)	0.003	3.579 (2.346–5.462)	<0.001*
Acute Renal Failure	283 (15.0%)	0.15	32,596 (5.3%)	0.053	3.130 (2.757–3.553)	<0.001*
Blood Loss Anemia	49 (2.6%)	0.026	7,854 (1.3%)	0.013	2.047 (1.540–2.721)	<0.001*
Blood Transfusion	525 (27.8%)	0.278	71,489 (11.7%)	0.117	2.907 (2.628–3.216)	<0.001*
Cardiac Arrest	30 (1.6%)	0.016	2,802 (0.5%)	0.005	3.506 (2.440–5.039)	<0.001*
Myocardial Infarction	118 (6.2%)	0.062	16,918 (2.8%)	0.028	2.342 (1.943–2.824)	<0.001*
Stroke	85 (4.5%)	0.045	14,276 (2.3%)	0.023	1.971 (1.585–2.452)	<0.001*
Shock	43 (2.3%)	0.023	2,668 (0.4%)	0.004	5.317 (3.920–7.211)	<0.001*
Cardiogenic Shock	15 (0.8%)	0.008	1,845 (0.3%)	0.003	2.645 (1.588–4.406)	<0.001*
Deep Vein Thrombosis	120 (6.3%)	0.063	14,033 (2.3%)	0.023	2.889 (2.399–3.478)	<0.001*
Pulmonary Embolism	117 (6.2%)	0.062	10,015 (1.6%)	0.016	3.966 (3.286–4.787)	<0.001*
Malunion	47 (2.5%)	0.025	15,681 (2.6%)	0.026	0.970 (0.726–1.296)	0.835
Emergency Care Visits	1,675 (88.6%)	0.886	488,752 (79.8%)	0.798	1.960 (1.701–2.258)	<0.001*

Postoperative outcomes following matching are reported in Table 4. MRSA+ patients had significantly higher odds of wound dehiscence (3.32% vs. 1.87%, OR = 1.80 [95% CI: 1.18–2.74], p = 0.005), pneumonia (14.08% vs. 6.58%, OR = 2.33 [95% CI: 1.86–2.91]), sepsis (14.4% vs. 4.34%, OR = 3.71 [95% CI: 2.87–4.80]), acute renal failure (14.83% vs. 10.71%, OR = 1.45 [95% CI: 1.20–1.76]), blood transfusion (27.94% vs. 18.2%, OR = 1.74 [95% CI: 1.49–2.04]), shock (2.3% vs. 1.18%, OR = 1.98 [95% CI: 1.18–3.32], p = 0.009), deep vein thrombosis (6.37% vs. 2.89%, OR = 2.29 [95% CI: 1.65–3.17]), pulmonary embolism (6.32% vs. 2.36%, OR = 2.80 [95% CI: 1.97–3.98]) (all p < 0.001 unless otherwise noted). No significant differences were observed in deep and superficial SSIs, myocardial infarction, or emergency department visits.

Table 4.

Risk Analysis for post-operative outcomes after matching

Outcome	Experimental Outcome (n, %)	Outcome Risk for Experimental Group	Control Outcome (n, %)	Outcome Risk for Control	Odds Ratio (95% CI)	Significance
Deep Surgical Site Infections	10 (0.54%)	0.005	10 (0.54%)	0.005	1.000 (0.415 - 2.408)	1
Wound Dehiscence	62 (3.32%)	0.033	35 (1.87%)	0.019	1.798 (1.182 - 2.735)	0.005*
Pneumonia	263 (14.08%)	0.141	123 (6.58%)	0.066	2.325 (1.857 - 2.910)	<0.001*
Sepsis	269 (14.4%)	0.144	81 (4.34%)	0.043	3.711 (2.869 - 4.801)	<0.001*
Superficial Surgical Site Infections	20 (1.07%)	0.011	10 (0.54%)	0.005	2.011 (0.939 - 4.308)	0.067
Acute Renal Failure	277 (14.83%)	0.148	200 (10.71%)	0.107	1.452 (1.195 - 1.764)	<0.001*
Blood Loss Anemia	47 (2.52%)	0.025	41 (2.19%)	0.022	1.150 (0.753 - 1.757)	0.517
Blood Transfusion	522 (27.94%)	0.279	340 (18.2%)	0.182	1.743 (1.493 - 2.035)	<0.001*
Cardiac Arrest	30 (1.61%)	0.016	26 (1.39%)	0.014	1.156 (0.681 - 1.963)	0.59
Myocardial Infarction	24 (1.28%)	0.013	44 (2.36%)	0.024	0.540 (0.327 - 0.891)	0.014*
Stroke	84 (4.5%)	0.045	69 (3.69%)	0.037	1.228 (0.887 - 1.699)	0.216
Shock	43 (2.3%)	0.023	22 (1.18%)	0.012	1.977 (1.178 - 3.318)	0.009*
Cardiogenic Shock	15 (0.8%)	0.008	13 (0.7%)	0.007	1.155 (0.548 - 2.434)	0.704
Deep Vein Thrombosis	119 (6.37%)	0.064	54 (2.89%)	0.029	2.286 (1.646 - 3.174)	<0.001*
Pulmonary Embolism	118 (6.32%)	0.063	44 (2.36%)	0.024	2.795 (1.965 - 3.976)	<0.001*
Malunion	46 (2.46%)	0.025	54 (2.89%)	0.029	0.848 (0.569 - 1.263)	0.417
Emergency Care Visits	1,652 (88.44%)	0.884	1,653 (88.49%)	0.885	0.995 (0.814 - 1.216)	0.959

Discussion

Previous studies examining lower extremity orthopedic trauma cohorts have reported relatively low MRSA colonization rates [11]. However, our findings suggest that the clinical relevance of MRSA colonization in trauma patients extends beyond infection risk alone. After propensity score matching, preoperative MRSA colonization was not independently associated with increased surgical site infection rates but was associated with significantly higher risks of wound dehiscence, pneumonia, sepsis, acute renal failure, and thromboembolic events. This pattern indicates that MRSA colonization may function less as a direct driver of postoperative infection and more as an objective marker of underlying physiologic vulnerability and diminished reserve in orthopedic trauma patients. In the acute trauma setting—where formal frailty assessments are often unavailable—MRSA status represents a readily accessible signal that may help identify patients at heightened risk for multisystem complications.

Before matching, our study identified an increased risk of wound infections - including superficial and deep surgical site infections - as well as wound dehiscence among MRSA+ patients. After controlling for comorbidities, wound dehiscence emerged explicitly as the primary complication. Current literature aligns with our findings, consistently indicating that MRSA carriage significantly increases the risk of SSI among orthopedic patients, particularly following surgical fixation of fractures [10, 13]. However, identifying wound dehiscence specifically as a significant complication in MRSA+ cohorts represents a novel finding within orthopedic trauma. In studies involving total knee arthroplasty patients and patients undergoing major lower extremity amputations, a history of MRSA+ colonization has similarly been associated with higher overall rates of wound complications, including wound dehiscence [7, 14]. After controlling for comorbid burden, the loss of an independent association between MRSA colonization and surgical site infections suggests that postoperative infection risk in trauma patients may be driven more by underlying patient vulnerability than by MRSA status alone [15, 16]. Additionally, found before matching, increased emergency department visits—reflective of poorer overall health or limited healthcare access—can independently influence complication rates, further confounding the association [17, 18].

Consistent with the interpretation of MRSA colonization as a marker of systemic vulnerability rather than an isolated infectious exposure, another set of complications found to be significantly associated with MRSA+ status includes sepsis and pneumonia. Although not commonly reported among orthopedic trauma patients, these complications have been thoroughly studied and found to be associated with MRSA colonization, regardless of the procedure type. For example, Huang et al. reported that 29% of patients newly identified as harboring MRSA subsequently developed MRSA infections, with 28% of these infections involving bacteremia (a precursor to sepsis) and 56% involving pneumonia [19]. Moreover, current literature identifies critically ill MRSA+ patients as having an increased risk for sepsis and pneumonia. Bunnell et al. observed an 11.4% incidence of MRSA pneumonia among critically ill trauma and burn patients [20]. Additionally, the Surviving Sepsis Campaign guidelines, issued by the Society of Critical Care Medicine and the American College of Chest Physicians, emphasize that prior MRSA colonization significantly increases the risk of MRSA-related sepsis and pneumonia in critically ill patients [21]. The underlying mechanism may involve surgical trauma disrupting the skin and soft tissues, thereby compromising the body’s primary immune barrier and increasing susceptibility to infections such as pneumonia [22]. While MRSA colonization is typically asymptomatic, it can progress to active infection when weakened host defenses permit bacterial virulence to prevail [23].

Critically ill patients with sepsis and pneumonia are often at risk for septic shock. In our study, shock was a significantly associated complication in the MRSA+ cohort. This cohort was at an increased risk for developing MRSA bacteremia—a known precursor to septic shock [24]. Similarly, von Dossow et al. found that hospital-acquired pneumonia in surgical patients frequently progressed to septic shock [25]. In addition, critically ill patients with wound infections are more susceptible to significant blood loss, often necessitating transfusions in trauma and critical care settings [26]. Our findings support this, as MRSA+ patients demonstrated a higher risk of requiring blood transfusions. Johan et al. further corroborated this, showing that MRSA carriers undergoing orthopedic surgery had a significant association with surgical site infections and blood loss exceeding 500 mL, a well-established risk factor for transfusion [13].

Our study also identified acute renal failure as a significant postoperative complication, potentially linked to the lack of standardized prophylactic antibiotic protocols amongst orthopedic trauma cases. Courtney et al. found that adding vancomycin to cefazolin prophylaxis in orthopedic joint surgery significantly increased the incidence of acute kidney injury (AKI) compared to cefazolin alone [27]. Beyond antibiotic toxicity, MRSA colonization and subsequent infections can also directly contribute to renal pathology. For example, Liang et al. reported a case of severe renal impairment following a cutaneous MRSA infection that progressed to advanced IgA nephropathy and irreversible renal damage [28].

Our results indicate that PE and DVT are significantly associated with postoperative complications in the MRSA+ cohort. This finding aligns with current literature demonstrating that patients with MRSA colonization or MRSA-associated systemic illness are at increased risk of venous thromboembolism (VTE) [29]. This may be due to the hypercoagulable state induced by MRSA infections and surgical trauma [30]. MRSA can stimulate the release of tissue factor, activating the extrinsic coagulation pathway while also reducing levels of natural anticoagulants and impairing fibrinolysis [31]. Additionally, MRSA can directly damage and activate endothelial cells, leading to increased expression of adhesion molecules and recruitment of leukocytes and platelets [31]. Sepsis, which was also significantly associated with MRSA in our cohort, can trigger a systemic inflammatory response that contributes to disseminated intravascular coagulation and microthrombus formation, further increasing the risk of DVT and PE [29]. MI was also a significant postoperative complication in our MRSA+ cohort. This may result from the systemic inflammatory response triggered by MRSA and other wound infections, as well as surgical trauma [6, 30]. The release of pro-inflammatory cytokines such as IL-6 and TNF-α during this response can destabilize atherosclerotic plaques, leading to plaque rupture and subsequent MI [6, 32]. Additionally, the infection-induced hypercoagulable state and increased cardiac workload further contribute to the risk of MI [13, 31].

The clinical utility of MRSA colonization does not depend on a direct causal relationship with postoperative complications. Similar to other non-causal risk markers, such as hypoalbuminemia or frailty indices, MRSA positivity may serve as an early, objective indicator of diminished physiologic reserve. In orthopedic trauma patients, MRSA status may therefore be used to prompt heightened surveillance for systemic complications, earlier multidisciplinary involvement, and individualized perioperative planning. Importantly, these findings do not support indiscriminate escalation of antibiotic prophylaxis for all patients, but rather the use of MRSA status as a pragmatic risk-stratification tool in a high-acuity population.

We recommend preoperative MRSA screening as a risk-stratification tool to help surgeons anticipate systemic complications and optimize perioperative management. Validated measures such as the Risk Analysis Index (RAI) and the modified 5-factor frailty index (mFI-5) have demonstrated utility in predicting postoperative complications, and our findings suggest that preoperative MRSA screening could represent an additional marker of systemic vulnerability in this context [33, 34]. While MRSA colonization has been shown to play a causal role in the development of surgical site infections, its association with broader systemic complications likely reflects underlying patient vulnerability rather than direct pathogenic effects. Prior studies reinforce this approach to utilizing MRSA nasal swabs in order to predict subsequent infections and complication: Goyal et al. demonstrated that nasal colonization with MRSA is an important independent risk factor for surgical site infections following orthopedic surgery, and they recommend preoperative screening and treatment of MRSA-positive patients to reduce infection risk [35]. Similarly, Ahmann et al. found that MRSA carriage significantly increased the risk of SSI after operative fracture fixation, and many carriers had not undergone decolonization, highlighting the need for a standardized, simplified decolonization protocol [10]. Iqbal et al. further reported a higher risk of SSIs in MRSA-colonized trauma patients who did not receive appropriate antibiotic prophylaxis [5].

Limitations & future directions

This study has inherent limitations related to its retrospective design and reliance on data from the TriNetX network. The dataset includes only patients treated at participating healthcare organizations, limiting the capture of follow-up care at outside institutions and introducing potential selection bias. As a result, outcomes and complications occurring outside the network may have been missed. Variability in electronic health record systems and documentation practices across institutions also affects data standardization and reliability. Inconsistencies in variable definitions and ICD coding—due to clerical errors or omission of comorbidities—may lead to misclassification or incomplete data. Additionally, ICD codes lack the clinical granularity needed to represent patient complexity. Essential factors such as socioeconomic status and post-acute care, which may influence outcomes, were unavailable in the dataset and, therefore, could not be analyzed. We were also unable to determine if patients underwent preoperative MRSA colonization and whether it was identified via nasal swab, wound culture, or other modalities. Furthermore, the dataset lacked information on whether MRSA+ patients underwent decolonization or received targeted prophylactic antibiotics (e.g., vancomycin). These missing data limit our ability to fully contextualize the observed associations between MRSA colonization and postoperative complications. Since these were trauma-related fractures, follow-up visits were not tracked as consistently as they typically are for scheduled orthopedic procedures.

Given these limitations, future studies should prioritize prospective data collection using standardized MRSA screening protocols in orthopedic trauma patients. In particular, research should evaluate the effectiveness of preoperative nasal swabbing and decolonization in reducing postoperative complications in lower extremity trauma. Further investigation is also needed to determine the most appropriate prophylactic antibiotic regimen for MRSA+ patients, especially in light of potential nephrotoxicity and antimicrobial resistance. By incorporating more granular clinical variables, such as intraoperative details, postoperative care protocols, and long-term follow-up, future studies can validate our findings and support the development of standardized guidelines for MRSA screening and management in orthopedic trauma populations.

Conclusions

Our findings demonstrate that MRSA colonization is significantly associated with systemic complications—including wound dehiscence, venous thromboembolism, sepsis, pneumonia, and organ dysfunction—among orthopedic trauma patients. This pattern suggests that MRSA positivity may function more as a marker of underlying patient frailty and vulnerability than as a direct causal factor for wound infections. Preoperative MRSA screening may therefore serve as a valuable risk-stratification tool to anticipate complications and optimize perioperative management. Development of standardized screening and decolonization protocols in orthopedic trauma warrants further investigation to clarify their role in improving outcomes.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

A.A. developed the study concept and design. A.A. conducted cohort construction, statistical analyses, and data visualization. A.A. drafted the manuscript. H.H, P.S., L.A. critically reviewed and revised the manuscript. L.D. and J.D. provided overall supervision and final approval of the work. All authors approved the final version and agree to be accountable for all aspects of the work.

Funding

Not applicable.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Not applicable.