Extended antibiotic prophylaxis in primary total knee arthroplasty: A narrative review of current evidence and controversies

Table 1 Characteristics of included observational cohort studies evaluating antibiotic prophylaxis beyond 24 hours in primary total knee arthroplasty and related arthroplasty cohorts (2000 to 2025)

Ref.	Design	Setting/population	Arthroplasty type	Sample size	High-risk definition	Extended prophylaxis regimen	Comparator	Follow-up/endpoint	Primary outcome measure	Key finding	Limitations
Inabathula et al[13]	Retrospective cohort	Single system or multi-site cohort; high-risk primary arthroplasty patients	Primary TKA and THA	2181 primary TKAs	Composite: Obesity, diabetes, immunosuppression, prior infection, other comorbidities	Oral cephalexin 7 days after standard perioperative IV prophylaxis	Standard prophylaxis; no extended oral course	90 days	90-day PJI	Lower 90-day PJI reported in high-risk patients receiving 7-day EOA	Retrospective; confounding by indication; risk definition not universally validated; applicability to routine-risk patients uncertain
Veltman et al[14]	Registry-based observational cohort	Dutch Arthroplasty Register; hospital-level protocol comparison	Primary THA and TKA	242179 hip and knee arthroplasties	Not risk-stratified (population-level analysis)	Compared single-dose vs 24-hour vs multiple-dose IV perioperative protocols	Other duration protocols	1 year (revision for infection in registry)	Revision for infection (proxy for PJI)	Similar revision-for-infection risk across single-dose and multiple-dose strategies	Registry endpoint is revision, not all PJIs; limited microbiology and adherence detail; confounding by hospital-level practice
Kheir et al[15]	Prospective cohort (American Association of Hip and Knee Surgeons award study)	High-risk primary arthroplasty cohort	Primary TKA and THA	3855 total (TKA + THA)	High-risk composite (study-specific criteria)	Oral cefadroxil 500 mg twice daily for 7 days after standard perioperative IV prophylaxis	Standard prophylaxis; no EOA	1 year	1-year PJI	PJI decreased in high-risk patients receiving 7-day EOA (as reported)	Non-randomized; potential selection bias; generalizability depends on local baseline infection rate and perioperative pathway
Carender et al[16]	Retrospective cohort	Morbidly obese primary arthroplasty patients	Primary TJA (445 TKAs reported)	445 TKAs	Morbid obesity (body mass index ≥ 40)	Oral antibiotics 7-14 days (agent not standardised across all centres)	Standard prophylaxis; no EOA	Early postoperative period	Early PJI; wound complications	No significant reduction in early PJI or wound complications in morbidly obese subgroup receiving EOA	Limited power for rare events; heterogeneity in antibiotic selection and adherence; retrospective confounding
Kelly et al[12]	Cohort study (reimplantation context)	Two-stage exchange for PJI; not primary TKA prophylaxis	Reimplantation after PJI	Not applicable to primary TKA	Not applicable	Prolonged oral antibiotics after reimplantation	No prolonged antibiotics	Recurrence window per study	Recurrent PJI; resistance profile	Higher proportion of resistant organisms among recurrent PJIs in prolonged-antibiotic group (as reported)	Not primary TKA; included for resistance plausibility and stewardship implications only
Bundschuh et al[17]	Retrospective cohort (single-surgeon experience)	Universal extended prophylaxis in primary and aseptic revision cases; single-surgeon protocol	Primary and aseptic revision TJA (approximately 1250 primary TKAs)	Approximately 1250 primary TKAs	Not risk-stratified (universal protocol)	Oral cefdinir 7 days; concomitant intra-wound vancomycin powder	Historical or contemporary non-EOA comparator	3 months	3-month PJI	Lower short-term PJI reported with protocol; attribution to EOA vs vancomycin powder unclear	Strong confounding by co-intervention (vancomycin powder); single-surgeon external validity limits; before-after design vulnerable to secular trend
Flynn et al[9]	Retrospective institutional policy-change cohort	High-volume institutional transition to universal EOA	Primary TJA (> 4500 TJAs including TKA)	> 4500 primary TJAs	High-risk subgroup analyses performed (definition study-specific)	Oral cephalexin 10 days for all primary arthroplasty cases	Pre-policy standard prophylaxis (≤ 24 hours)	90 days and 1 year	PJI at 90 days and 1 year	No reduction in PJI overall or in high-risk subgroups (as reported)	Before-after design; adherence and outpatient completion difficult to verify; baseline PJI already low limits absolute benefit
Dhodapkar et al[18]	Administrative database cohort	United States claims/administrative dataset	Primary TKA	> 860000 TKAs	Not specified	Postoperative day-0 only vs day-0 plus day-1 IV dosing	Shorter duration	30 days	30-day SSI	No difference in 30-day SSI with extension to postoperative day 1; antibiotic choice influenced outcomes	Addresses intraoperative antibiotic choice rather than post-discharge duration; administrative dataset; limited clinical granularity

EOA: Extended oral antibiotic; IV: Intravenous; PJI: Periprosthetic joint infection; SSI: Surgical site infection; TJA: Total joint arthroplasty; TKA: Total knee arthroplasty; THA: Total hip arthroplasty.