The Case for Fewer Antibiotics in Joint Replacement Surgery

For anyone undergoing a total hip or knee replacement, the goal is a smooth recovery and a return to pain-free movement. However, a possible risk from these procedures is periprosthetic joint infection.

Infections are leading causes of joint replacement failures, often requiring additional surgeries, prolonged hospital stays, as well as emotional and financial strain on patients.

For higher risk patients, such as individuals with diabetes, chronic kidney disease, or a history of tobacco use, many orthopedic surgeons prescribe an extended course of oral antibiotics for an additional week after the patient leaves the hospital.

A Yale study published in The Journal of Arthroplasty found that this extra week of medication may not be needed.

A decade-long study tracking thousands of patients revealed that extended oral antibiotics did not significantly lower the risk of joint infections following hip or knee replacement surgery.

The research team found that the infection rates between those who received the regimen of oral antibiotics and those who did not were nearly identical at both the 90-day mark and one year after surgery. Even when researchers isolated the highest-risk patients, the extra medication provided no measurable benefit.

"For years, the instinct in medicine has often been to provide an extra layer of protection, assuming that more antibiotics equals less risk," says Daniel Wiznia, MD, an associate professor who specializes in hip and knee joint reconstruction and the study’s principal investigator. "However, this research prompts us to step back and re-evaluate our routine protocols. If an extra week of medication isn't moving the needle on infection rates, we need to identify other treatments that might have an impact."

Wiznia’s team looked back at existing medical records, tracking adult patients who underwent joint replacements between 2015 and 2025.

To ensure a fair comparison among patients, they used a statistical technique called propensity matching. Because surgeons usually give extended antibiotics to sicker or more vulnerable patients, comparing the two groups directly would skew the data. Propensity matching allowed the researchers to pair each patient who received extended antibiotics with four similar patients who did not, balancing them precisely by age, biological sex, and overall health status.

The findings remained consistent. Even when analyzing patients with morbid obesity, which is a condition that significantly raises the risk of surgical complications, the extended antibiotics failed to offer further protection.

This outcome challenges several previous, smaller studies suggesting that extended antibiotics were a cost-effective benefit for high-risk individuals, according to Wiznia. Instead, it aligns with recent national database trends indicating that standard, immediate post-operative care is already doing the heavy lifting.

Ilda Molloy, MD, MS, co-author on this research paper, assistant professor, and another Yale orthopedic surgeon who specializes in hip and knee joint reconstruction, agrees.

“At Yale, prosthetic joint infection management is a multidisciplinary effort that brings together orthopedic surgery, infectious diseases, microbiology, pharmacy, nursing, and other key clinical teams,” Molloy says. “These findings reinforce that infection prevention is about developing coordinated, evidence-based protocols that address risk before, during, and after surgery while using antibiotics thoughtfully and responsibly.”

In her role as director of prosthetic joint infection prevention and policy with Yale New Haven Health System, Molloy works across medical specialties to develop and evaluate infection prevention procedures, ensures that complex decisions incorporate the perspectives of multiple clinical disciplines, and refines protocols based on emerging evidence.

Standard care at Yale, where this study took place, includes thorough nasal screenings, antiseptic skin wipes, and precisely timed intravenous antibiotics right before and after the incision is made.

"What this tells us is that our primary, immediate infection-prevention measures are incredibly robust," Wiznia explains. "The work we do in the operating room and in the immediate hours following surgery is the real baseline of defense. Adding more oral antibiotics on top of that foundation later appears to offer diminishing returns."

While the study did not find a dramatic spike in immediate complications from the extra medication such as severe allergic reactions or kidney damage, the lack of benefit raises broader medical concerns. Public health experts and the Centers for Disease Control and Prevention have long warned about the dangers of over-prescribing antibiotics, which can lead to antibiotic resistance and impact healthy gut bacteria.

“Previous projections suggest that implementing extended antibiotics nationwide for all high-risk joint patients could add 50,000 years of cumulative antibiotic exposure annually,” Wiznia adds. “This massive inflation increases the risk of opportunistic infections like Clostridium difficile, a severe and painful bacterial infection of the colon.”

Fortunately, the patients in this study did not show a statistically significant surge in these adverse events. But as clinicians, researchers, and surgeons look at the big picture, prescribing a medication that offers no proven benefit introduces unnecessary long-term risk and cost.

The research team emphasized that, while these findings are powerful, they come from a retrospective look at data, which can occasionally be limited by missing administrative codes or variations in how patients actually take their pills at home as prescribed.

According to Wiznia, the medical community will need trials in which patients are randomly assigned to groups ahead of time to collect more conclusive data.

In the meantime, this research serves as a reminder that more medication does not always mean better outcomes.

"Every medication we prescribe should have a clear, proven purpose," Wiznia says. "Our goal shouldn't be to just give blanket prescriptions to everyone categorized as 'high-risk.' We need to refine our precision, looking at specific biomarkers like blood sugar control or nutritional levels, so we can treat the individual rather than the statistic."