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

Abstract

BACKGROUND

Periprosthetic joint infection (PJI) remains one of the most serious complications following primary total knee arthroplasty (TKA), associated with high morbidity, functional loss, and economic burden. Standard perioperative antibiotic prophylaxis – initiated pre-incision and discontinued within 24 hours – has long been considered optimal. However, extended oral antibiotic (EOA) prophylaxis administered for several days postoperatively has gained attention, particularly for high-risk patients.

AIM

To evaluate the current evidence and controversies surrounding extended prophylaxis.

METHODS

A comprehensive literature search of PubMed, EMBASE, and Scopus was conducted for studies published between 2000 and 2025. Eligible studies included randomized trials, cohort studies, registry analyses, systematic reviews, and meta-analyses assessing prophylaxis beyond 24 hours in primary TKA. Data extraction focused on regimen type, duration, patient risk stratification, infection outcomes, and antimicrobial resistance (AMR). Reference lists of included studies and prior reviews were manually screened to ensure completeness.

RESULTS

Eleven studies met the inclusion criteria. Extensive registry and meta-analysis data consistently showed no reduction in PJI with prophylaxis extended beyond 24 hours in unselected populations. Early retrospective studies suggested the benefit of 7-day oral cephalosporin regimens in high-risk patients, but subsequent larger institutional and population-level analyses failed to reproduce these findings. Evidence also indicates an increase in AMR with prolonged prophylaxis, while rates of Clostridioides difficile and drug toxicity remained low. No major guideline (Centres for Disease Control and Prevention, World Health Organization, American Academy of Orthopaedic Surgeons and American Association of Hip and Knee Surgeons, International Consensus Meeting) currently endorses routine EOA.

CONCLUSION

Extended antibiotic prophylaxis beyond 24 hours does not reduce the incidence of PJI in standard-risk primary TKA patients and may contribute to the development of AMR. While selective benefit in narrowly defined high-risk groups remains possible, current evidence is conflicting and limited by retrospective design. Routine use of EOA is not recommended; future multicenter randomized trials with standardized risk stratification are urgently needed to clarify its role. Until then, adherence to ≤ 24-hour prophylaxis as endorsed by international guidelines remains the most evidence-based and stewardship-aligned approach.

Keywords: Periprosthetic joint infection; Antibiotics; Extended spectrum; Antimicrobial resistance; Antibiotic stewardship

Core Tip: Extended oral antibiotic prophylaxis after primary total knee arthroplasty has not demonstrated consistent benefit in reducing periprosthetic joint infection compared with standard ≤ 24-hour regimens. While early retrospective data suggested possible value in high-risk patients, larger studies and meta-analyses show no advantage and highlight antimicrobial resistance concerns. Current international guidelines recommend limiting prophylaxis to 24 hours, with future randomized trials needed to clarify extended oral antibiotic’s role in selected populations.