Extended oral antibiotic prophylaxis does not reduce periprosthetic joint infection after primary outpatient total shoulder arthroplasty: A matched cohort analysis

Abstract

Background

Over the last decade, total shoulder arthroplasty (TSA) has increasingly transitioned to the outpatient setting, where postoperative care pathways inherently limit the ability to deliver a full 24 hour course of intravenous antibiotic prophylaxis. Despite guideline recommendations, extended oral antibiotic prophylaxis is variably used after outpatient TSA, with limited evidence supporting this practice.

Methods

A retrospective cohort study using the TriNetX database identified patients undergoing primary outpatient TSA between 2015 and 2025. Patients were stratified by receipt of extended oral antibiotic prophylaxis. Propensity score matching yielded two cohorts of 2647 patients each. Outcomes included periprosthetic joint infection (PJI), surgical site infection (SSI), all-cause revision, wound disruption, and emergency department utilization at 90 days and 1 year. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.

Results

At 90 days, there were no significant differences in PJI (0.9% vs 0.5%; RR 1.20, 95% CI 0.96–3.84) or SSI (0.8% vs 0.5%; RR 1.67, 95% CI 0.82–3.40). At 1 year, PJI (1.6% vs 1.2%; RR 1.34, 95% CI 0.85–2.12) and SSI (1.1% vs 0.8%; RR 1.14, 95% CI 0.79–2.42) rates remained comparable between groups.

Discussion

Extended oral antibiotic prophylaxis did not reduce infection-related outcomes following primary outpatient TSA.

Level of evidence

III, Retrospective cohort study.

Keywords

Outpatient total shoulder arthroplasty periprosthetic joint infection surgical site infection antibiotic prophylaxis propensity score matching

Introduction

The rate of total shoulder arthroplasty (TSA) continues to rise as the prevalence of glenohumeral osteoarthritis and life expectancy increase.¹ One devastating complication following TSA is periprosthetic joint infection (PJI), which has been reported in up to 5% of cases.² PJIs following TSA are associated with substantial morbidity, functional decline, as well as significant financial burden on the healthcare system.^2,3

Over the last decade, TSA has increasingly transitioned to being performed as an outpatient procedure, whether performed at a hospital, ambulatory surgery center or other facility.⁴ In 2021, the Centers for Medicare & Medicaid Services removed TSA from the inpatient- only list, which led to rapid increases in outpatient utilization.⁵ Numerous studies have demonstrated that outpatient TSA yields similar, or even improved outcomes, when compared to inpatient procedures.⁶

Perioperative antibiotic prophylaxis remains a key component of infection prevention in shoulder arthroplasty.⁷ Although broader World Health Organization (WHO) surgical site infection (SSI) guidelines recommend against continuing prophylactic antibiotics after completion of surgery, many arthroplasty-specific consensus recommendations have historically supported weight-based intravenous cefazolin with postoperative dosing for up to 24 h.^8,9 In the outpatient setting, however, postoperative care pathways may limit the ability to deliver additional intravenous doses after discharge, contributing to variability in the use of extended oral prophylactic antibiotics.¹⁰ As a result, some surgeons may prescribe extended oral antibiotics as supplemental coverage after outpatient TSA, despite limited evidence supporting this practice.

Despite the growing adoption of outpatient TSA, there remains a paucity of evidence evaluating the effectiveness of oral antibiotic prophylaxis in this population. To our knowledge, this is the first large matched cohort analysis to examine the utility of extended oral antibiotics after outpatient primary TSA. The primary objective of this study was to compare the 90-day incidence of PJI and postoperative complications between matched cohorts undergoing outpatient TSA with or without administration of extended oral antibiotics following surgery. We hypothesized that extended oral antibiotic prophylaxis would not be associated with a reduction in infection-related outcomes following primary outpatient TSA.

Methods

Data source

This retrospective cohort study utilized data from the TriNetX database, a global federated health research network, to identify patients aged 18 and above who underwent primary TSA between 1 July 2015 and 1 July 2025. The TriNetX database Research Network comprises 108 participating healthcare organizations with over 131 million patient electronic medical records with data regarding procedures, diagnoses, medications, and laboratory values. This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for consistent reporting of observational data.¹¹

Cohort identification

The study population was established using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), and current procedural terminology (CPT) coding to identify patients over the age of 18 who underwent TSA. Two cohorts were established based on the use (or lack) of oral antibiotics postoperatively. Patients were included if they were at least 18 years old at the time of surgery and had a minimum of 90 days of follow-up. Patients were classified into the postoperative antibiotics group if the database had recorded an oral antibiotic prescription (cephalexin, cefadroxil, clindamycin, doxycycline, ciprofloxacin, trimethoprim-sulfamethoxazole, or amoxicillin-clavulanate) within 5 days prior to surgery or within 3 days postoperatively following their TSA. This exposure window was selected to capture all perioperative prescribing patterns, including preoperative prescription fills in anticipation of outpatient discharge, aligning with previously published methodology in arthroplasty literature.¹² Patients were excluded from analysis if they had a prior diagnosis of malignancy, which may have required immunosuppressive therapy. Additionally, patients were excluded if they had a history of a proximal humerus fracture or pathologic fracture of their humerus or shoulder. Patients with a history of recent illness were also excluded, which was defined as an antibiotic prescription or one of the following diagnoses within 6 months of surgery: influenza, pneumonia, urinary tract infection, cellulitis, sepsis, pharyngitis, or infection of an internal orthopedic prosthetic device, implant, or graft. Lastly, those who underwent inpatient TSA were excluded, which was defined by the presence of an inpatient encounter code within 24 h on or after the index surgery. Patients in the control group (no antibiotics) were identified as those who did not have an oral antibiotic prescription for at least 90 days postoperatively. All patients undergoing TSA would be expected to receive standard perioperative intravenous antibiotic prophylaxis according to institutional practice and current guidelines. However, the TriNetX database does not reliably capture the timing or administration of individual inpatient or perioperative intravenous antibiotic doses, including whether an additional postoperative intravenous dose was administered prior to discharge. Therefore, the exposure definition in this study was limited to extended oral antibiotic prophylaxis after outpatient TSA. Patients in the control cohort had no recorded oral antibiotic prescription within the postoperative exposure window or during the 90-day postoperative period, but may have received standard perioperative intravenous prophylaxis as part of routine surgical care. Medications that qualified for inclusion in the antibiotic cohort were oral clindamycin, amoxicillin-clavulanate, cephalexin, ciprofloxacin, cefadroxil, trimethoprim-sulfamethoxazole, or doxycycline. These antibiotics are cited to be the most commonly prescribed for postoperative infection prophylaxis after TSA.^8,13

Propensity score matching

We employed a methodology similar to that used in a recently published study evaluating outcomes of prophylactic antibiotic use in total hip arthroplasty.¹⁴ To minimize potential confounding, cohorts were matched by 1:1 propensity scoring based on age, sex, obesity class based on WHO classification, nicotine dependence, prior shoulder arthroscopy, and medical comorbidities defined by the Charlson Comorbidity Index. WHO Class I, Class II, and Class III obesity are defined as a body mass index of 30.0 to 34.9 kg/m², 35 to 39.9 kg/m², and greater than 40 kg/m², respectively. Propensity score matching within TriNetX first models the probability of treatment assignment via logistic regression based on selected covariates. The platform then applies greedy nearest neighbor matching without replacement, constrained by a caliper width of 0.1 pooled standard deviations—a threshold shown in the literature to optimize bias reduction and precision balance between matched cohorts.¹⁵ This method has been previously validated and employed across numerous studies using TriNetX and similar EHR-based datasets.

Outcomes of interest

The primary outcomes of interest were the risk of infection-related complications, including PJI and SSI within 90 days and 1 year of surgery. Secondary outcomes included the risk of all-cause revision, wound disruption, and ED utilization between groups. The ICD-10-CM and CPT codes used for cohort identification can be found in the Supplemental Table 1.

Statistical analysis

Chi-square tests were used to determine differences in categorical comorbidity variables, and Student's t-tests were used to analyze differences in continuous comorbidity variables, as indicated. Following Bonferroni correction for multiple comparisons, a p-value of <0.00046 was used to determine statistical significance for differences between cohort comorbidities. Rates of outcomes between groups were compared using risk ratios (RRs) with 95% confidence intervals (CIs). All statistical analyses were performed using the TriNetX database analysis software.

Results

A total of 5294 outpatients undergoing TSA met the inclusion and exclusion criteria, with 2647 prescribed oral antibiotic prophylaxis and 2647 not prescribed oral antibiotics. Propensity score matching produced two well-balanced outpatient cohorts of equal size (Supplementary Table 2).

Ninety-day complications and surgical outcomes

Within 90 days postoperatively, there was no statistically significant difference in the incidence of PJI between patients who received extended oral antibiotics compared with those who did not (0.9% vs 0.5%; RR 1.20, 95% CI 0.96–3.84). Rates of SSI were also similar between cohorts (0.8% vs 0.5%; RR 1.67, 95% CI 0.82–3.40). There was no significant difference in all-cause revision within 90 days (1.1% vs 1.0%; RR 1.13, 95% CI 0.66–1.93). ED utilization was comparable between groups (5.9% vs 5.8%; RR 1.03, 95% CI 0.83–1.27). Rates of wound disruption were too low to permit meaningful comparative analysis (Table 1).

Table 1.

Ninety-day outcomes and complications following outpatient primary TSA by extended oral antibiotic prophylaxis.

	Incidence
	Oral antibiotics N = 2647	No antibioticsN = 2647
Complication	Cumulative incidence (%)	Cumulative incidence (%)	RR (95% CI)
Periprosthetic joint infection	23 (0.9%)	12 (0.5%)	1.20 (0.96–3.84)
Surgical site infection	20 (0.8%)	12 (0.5%)	1.67 (0.82–3.40)
All-cause revision	28 (1.1%)	25 (1.0%)	1.13 (0.66–1.93)
Wound disruption	NR	NR	NR
ED visit	157 (5.9%)	153 (5.8%)	1.03 (0.83–1.27)

RR: risk ratio; CI: confidence interval; NR: not reported (outcomes with less than 10 instances within the given time window are not reported); TSA: total shoulder arthroplasty.

One-year complications and surgical outcomes

At 1 year postoperatively, there was no statistically significant difference in the incidence of PJI between patients who received extended oral antibiotics and those who did not (1.6% vs 1.2%; RR 1.34, 95% CI 0.85–2.12). Rates of SSI were similar between cohorts (1.1% vs 0.8%; RR 1.14, 95% CI 0.79–2.42). All-cause revision rates at 1 year did not differ significantly between groups (1.7% vs 2.2%; RR 0.76, 95% CI 0.51–1.13). Wound disruption rates were low and similar between cohorts (0.4% vs 0.4%; RR 1.00, 95% CI 0.43–2.30). ED utilization was comparable (13.8% vs 12.6%; RR 1.09, 95% CI 0.95–1.26) (Table 2).

Table 2.

One-year outcomes and complications following outpatient primary TSA by extended oral antibiotic prophylaxis.

	Incidence
	Oral antibioticsN = 2647	No antibioticsN = 2647
Complication	Cumulative incidence (%)	Cumulative incidence (%)	RR (95% CI)
Periprosthetic joint infection	43 (1.6%)	32 (1.2%)	1.34 (0.85–2.12)
Surgical site infection	29 (1.1%)	21 (0.8%)	1.14 (0.79–2.42)
All-cause revision	43 (1.7%)	57 (2.2%)	0.76 (0.51–1.13)
Wound disruption	11 (0.4%)	11 (0.4%)	1.00 (0.43–2.30)
ED visit	365 (13.8%)	334 (12.6%)	1.09 (0.95–1.26)

RR: risk ratio; CI: confidence interval; NR: not reported (outcomes with less than 10 instances within the given time window are not reported); TSA: total shoulder arthroplasty.

Discussion

In this outpatient-only cohort, extended oral antibiotic prophylaxis was not associated with a reduction in PJI or SSI at either 90 days or 1 year following outpatient primary TSA. No statistically significant differences were observed in infection-related outcomes between patients who received extended oral antibiotics and those who did not. The direction of the 90-day point estimates should be interpreted cautiously, as these non-significant findings may reflect residual confounding or confounding by indication rather than a causal effect of antibiotic exposure. Collectively, these results suggest that supplementing guideline-based perioperative intravenous prophylaxis with extended oral antibiotics in outpatient TSA does not confer a measurable protective benefit and may reflect underlying differences in surgeon preferences or patient risk.

Prior literature evaluating extended oral antibiotic prophylaxis in total joint arthroplasty has yielded mixed results, primarily from studies of hip and knee arthroplasty. While some studies have reported lower infection rates in select high-risk cohorts, other analyses and systematic reviews have demonstrated no association between prolonged prophylaxis and reduced infection risk.^16,17 Specifically regarding TSA, a recent retrospective cohort analysis found that extended oral antibiotic prophylaxis after primary TSA was associated with higher observed rates of PJI, even after adjustment for measured confounders. However, the authors suggest residual confounding rather than an antibiotic effect.¹⁸ These results are consistent with those of our outpatient-specific analysis, suggesting that extended prophylactic antibiotics did not confer a protective effect. Similar findings have also been reported in outpatient total hip and knee arthroplasty, supporting the broader principle that well-selected outpatient arthroplasty populations have low complication and infection rates, which we extend here to outpatient TSA.¹²

The interpretation of observational studies evaluating extended oral antibiotic prophylaxis after TSA warrants careful consideration and interpretation. It is plausible that these observations reflect differences in baseline patient risk rather than suggesting an adverse effect of antibiotic exposure.¹⁸ Prior work has demonstrated substantial variability in postoperative antibiotic prescribing that could be driven by surgeons’ assessment of infection risk rather than by standardized criteria.¹⁸ Extended antibiotic courses could be prescribed preferentially to patients perceived as being at higher risk of infection, based on factors not fully captured in propensity score-matched datasets. Although matching allowed adjustment for many measured variables, other clinically relevant factors, such as prolonged operative time or concerns for intraoperative contamination, were not available for inclusion and may have contributed to a higher risk cohort. Several of these factors have independently been associated with increased infection risk following shoulder arthroplasty, supporting the interpretation that the higher observed PJI rates in the extended antibiotic group are more likely attributable to residual confounding and confounding by indication rather than antibiotic-related harm.^14,16,19,20

The outpatient context is critical to interpreting the associations reported in this study. The rapid transition of TSA from inpatient to outpatient settings reflects advances in surgical technique, anesthesia, perioperative pain control, and patient selection, as well as cost efficiencies associated with ambulatory surgery.^4,5 Prior large database studies and meta-analyses have demonstrated that outpatient TSA is associated with similar rates of complications, infections, readmissions, and mortality compared with inpatient procedures.^4–6 However, outpatient care pathways inherently limit postoperative intravenous antibiotic administration, prompting some surgeons to prescribe extended oral antibiotics as a compensatory strategy. Evidence supporting an association between this practice and improved outcomes in outpatient TSA remains limited, and our findings do not demonstrate a protective effect. As outpatient TSA continues to expand following removal from the inpatient-only list, infection prevention strategies should be tailored to this generally lower risk population. Within this context, our findings indicated that postoperative oral antibiotic prophylaxis was not associated with additional protection against PJI or SSI.

Our findings demonstrated that extended oral antibiotics provided no reduction in infection risk following outpatient TSA, raising important implications for antimicrobial stewardship and patient safety. Prolonged antibiotic use carries the potential to select for resistant organisms, a particularly concerning issue in the management of PJI, where treatment already requires prolonged therapy and staged procedures. Prior work has shown that extended regimens after arthroplasty are associated with a two- to fivefold increase in gram-negative organisms, which are more difficult to eradicate and linked to inferior outcomes compared with gram-positive infections.^21–23 In addition to resistance, extended prophylaxis increases the risk of adverse drug events, including gastrointestinal complications and Clostridioides difficile colonization, which can be particularly detrimental in older patients.²⁴ Taken together and given that no benefit was observed in our outpatient TSA cohort, these results underscore the importance of adhering to guideline-based prophylaxis with the shortest effective duration to minimize preventable complications while preserving antimicrobial efficacy.

A strength of our study was the use of a large cohort drawn from the TriNetX database. The study's robustness was enhanced by employing propensity score matching, which reduces the effects of confounding variables on the outcomes of interest. While national collaborative databases enable extensive cohort investigations, there are inherent limitations to their use. The most noticeable limitation was the potential for coding inaccuracies, particularly with ICD and CPT codes, which may have affected the correct identification of patients and their associated complications. Additionally, the retrospective nature of this study may have introduced biases that we were unable to account for; although many patient-specific factors were controlled for by propensity score matching, risk factors not captured by the database, such as perioperative glycemic control, may have been more prevalent in one group than the other. Furthermore, because medication administration data for perioperative intravenous antibiotics are not reliably available in TriNetX, we were unable to determine the number of intravenous antibiotic doses received before discharge. As a result, this study specifically evaluates the association between extended oral antibiotic prophylaxis and postoperative outcomes, rather than differences in standard perioperative intravenous prophylaxis. Additionally, other perioperative infection prevention strategies, including skin preparation protocols, dilute betadine or peroxide lavage, topical vancomycin powder, glove-changing practices, hooded surgical attire, and institution-specific sterile technique protocols, were not available within the database. These factors may vary across surgeons and institutions and could influence infection risk independently of postoperative oral antibiotic use. Finally, this study did not report complications associated with extended antibiotic use following total joint arthroplasty, such as gastrointestinal or dermatologic side effects, which have been documented in the literature to range between 0% and 13.7%.²⁵

Conclusion

Extended prophylactic oral antibiotics did not significantly reduce the incidence of PJI, SSI, or all-cause revision after primary outpatient TSA. Despite adjustment for measured confounders through propensity score matching, no measurable protective benefit was observed, suggesting that extended oral antibiotic prophylaxis may not confer additional utility and value.

Supplemental Material

sj-docx-1-sel-10.1177_17585732261451169 - Supplemental material for Extended oral antibiotic prophylaxis does not reduce periprosthetic joint infection after primary outpatient total shoulder arthroplasty: A matched cohort analysis

Supplemental material, sj-docx-1-sel-10.1177_17585732261451169 for Extended oral antibiotic prophylaxis does not reduce periprosthetic joint infection after primary outpatient total shoulder arthroplasty: A matched cohort analysis by Bradley J Lauck, Nicholas C Bank, William R Davis, Charles B Colson, Stephen Himmelberg, Brian R Waterman and Alan W Reynolds in Shoulder & Elbow

Supplemental Material

sj-docx-2-sel-10.1177_17585732261451169 - Supplemental material for Extended oral antibiotic prophylaxis does not reduce periprosthetic joint infection after primary outpatient total shoulder arthroplasty: A matched cohort analysis

Supplemental material, sj-docx-2-sel-10.1177_17585732261451169 for Extended oral antibiotic prophylaxis does not reduce periprosthetic joint infection after primary outpatient total shoulder arthroplasty: A matched cohort analysis by Bradley J Lauck, Nicholas C Bank, William R Davis, Charles B Colson, Stephen Himmelberg, Brian R Waterman and Alan W Reynolds in Shoulder & Elbow

Supplemental Material

sj-docx-3-sel-10.1177_17585732261451169 - Supplemental material for Extended oral antibiotic prophylaxis does not reduce periprosthetic joint infection after primary outpatient total shoulder arthroplasty: A matched cohort analysis

Supplemental material, sj-docx-3-sel-10.1177_17585732261451169 for Extended oral antibiotic prophylaxis does not reduce periprosthetic joint infection after primary outpatient total shoulder arthroplasty: A matched cohort analysis by Bradley J Lauck, Nicholas C Bank, William R Davis, Charles B Colson, Stephen Himmelberg, Brian R Waterman and Alan W Reynolds in Shoulder & Elbow

Footnotes

ORCID iDs

Bradley J. Lauck

William R. Davis

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplemental material

Supplemental material for this article is available online.

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Supplementary Material

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