Longer Antibiotic Courses After Heart Surgery May Backfire, Study Finds

For decades, surgeons have operated on a simple instinct: when it comes to antibiotics after open-heart surgery, more protection must mean less infection. A new retrospective cohort study from Saudi Arabia challenges that assumption with data suggesting the opposite may be true. Researchers at King Faisal Specialist Hospital and Research Center found that patients who received prophylactic antibiotics for more than 48 hours after cardiothoracic surgery developed surgical site infections at more than three times the rate of those whose antibiotic courses were stopped within 48 hours. The findings, published in BMC Infectious Diseases, add to a growing body of evidence that prolonged surgical antibiotic prophylaxis does not merely fail to help, but may actively harm patients.

The study team, led by Lana B. Fagih and Namareq Fahad Aldardeer, examined the records of 435 adult patients who underwent cardiothoracic surgery at the hospital’s Riyadh and Jeddah campuses between May 2023 and August 2024. All patients received postoperative prophylactic antibiotics for at least 24 hours, and the researchers excluded anyone with a pre-existing infection or antibiotic exposure within 48 hours before surgery, sharpening the focus on prophylaxis alone. The cohort split almost evenly: 216 patients received antibiotics for longer than 48 hours, while 219 received them for 48 hours or less. The patients were typical of a cardiac surgery population, with a mean age of 53.5 years and roughly two-thirds male.

The primary outcome was the incidence of surgical site infections within 90 days of surgery, a window that captures both early superficial wound problems and the deep sternal wound infections that cardiac surgeons fear most. The difference between the groups was striking. Infections occurred in 10.6 percent of patients who received prolonged prophylaxis, compared with just 3.2 percent of those whose antibiotics were stopped within 48 hours, a difference the authors report as statistically significant with a p-value of 0.002. With 30 infection events across the full cohort, the raw numbers are modest, but the direction of the effect runs counter to the protective logic that has long justified extended courses.

To rule out the possibility that sicker patients simply received longer antibiotics and also fared worse, the researchers built a multivariable model adjusting for age, diabetes, any coronary artery bypass grafting procedure whether conventional or robotic, and operative duration. Even after accounting for these confounders, prophylaxis lasting more than 48 hours remained independently associated with higher odds of surgical site infection, with an adjusted odds ratio of 3.09 and a 95 percent confidence interval of 1.22 to 7.84, and a p-value of 0.017. In plain terms, patients on prolonged prophylaxis had roughly three times the odds of developing a postoperative infection compared with otherwise similar patients on shorter courses.

The secondary outcomes add a troubling dimension to the story. Antibiotic resistance was detected more frequently in the prolonged-prophylaxis group, at 7.9 percent versus 3.2 percent in the shorter-course group, a difference that reached statistical significance with a Fisher exact p-value of 0.037. This pattern fits a well-established microbiological principle: extended antibiotic exposure exerts selective pressure on bacterial communities, favoring the survival and proliferation of resistant organisms. In a hospital setting, that selection pressure does not stay contained. Resistant strains colonizing surgical wounds can spread to other patients, complicate treatment for the individual, and erode the effectiveness of the antibiotic arsenal on which all of modern surgery depends.

Notably, mortality did not differ significantly between the two groups, with a p-value of 0.782, suggesting that the extra days of antibiotics neither saved lives nor cost them directly within the study period. But the absence of a mortality signal does not neutralize the findings. Surgical site infections drive morbidity, prolong hospital and intensive care unit stays, require additional procedures, and impose substantial costs on health systems. If longer courses increase infection rates while providing no survival benefit, the clinical calculus shifts decisively toward shorter prophylaxis.

The results land in the middle of a long-running international debate. Clinical guidelines, including those from major surgical and infectious disease societies, have increasingly recommended stopping surgical prophylaxis within 24 hours of wound closure, and some have argued that even shorter durations suffice. Yet practice varies widely, and cardiac surgery has been a stronghold of extended regimens, partly because of the perceived severity of deep sternal wound infections and the presence of foreign material such as sternal wires and prosthetic grafts. Observational studies like this one cannot prove causation with the certainty of a randomized trial, but they can reveal patterns in real-world practice that trial populations miss, and the consistency of this study’s signal with prior literature strengthens its plausibility.

Several mechanistic explanations could account for the association. Prolonged antibiotics disrupt the patient’s native microbiome, including the skin flora that normally occupies ecological niches and crowds out pathogens. Wiping out susceptible commensal bacteria can clear the way for resistant hospital strains such as methicillin-resistant Staphylococcus aureus or extended-spectrum beta-lactamase producing gram-negative organisms to colonize the surgical wound. Longer courses also increase the risk of Clostridioides difficile infection and other antibiotic-associated complications, and they contribute to the broader public health burden of antimicrobial resistance. Each additional day of drug exposure is a day of selection pressure with no demonstrated offsetting benefit beyond the first 24 to 48 hours.

The study’s limitations are worth keeping in view. As a retrospective cohort analysis at a single institution, it depends on the accuracy of medical records and the judgment of clinicians who chose antibiotic duration, and unmeasured confounding cannot be fully excluded. The number of infection events, 30 in total, is small enough that the confidence interval around the adjusted odds ratio is wide, spanning from just over one to nearly eight. The authors note that the article was shared early as an accepted, peer-reviewed version subject to further edits. Still, the institutional review board approved the study, the cohort was carefully defined to exclude confounding infections, and the statistical adjustment addressed the most obvious clinical confounders.

The implications for practice are nonetheless significant. Cardiothoracic surgery is performed hundreds of thousands of times each year worldwide, and even a modest reduction in infection rates from trimming antibiotic courses would translate into thousands of avoided complications, shorter hospital stays, and slower propagation of drug-resistant bacteria. The study, which received no specific external funding and declared no competing interests, adds a data point to the case that antibiotic stewardship in surgery is not about generosity with drugs but precision with them. As the authors conclude, prolonged prophylaxis beyond 48 hours after cardiothoracic surgery was associated with higher rates of surgical site infections and increased antibiotic resistance, a finding that should prompt surgeons and hospital antimicrobial stewardship programs alike to reexamine how long the drip keeps running after the chest is closed.

Subject of Research: Duration of prophylactic antibiotics after cardiothoracic surgery and its effect on surgical site infections and antimicrobial resistance

Article Title: The impact of prophylactic antibiotic duration on postoperative outcomes post-cardiothoracic surgery: a retrospective cohort study

Article References: Fagih, L. B., Alharbi, A. A., AlBalawi, S. A., Hejazi, R. A., Kamel, S. A., Dairi, M. S., Aljefri, D. M., Badawi, M. A., Alghunaim, R. M., Jamjoom, A. A., AlUthman, U., & Aldardeer, N. F. (2026). The impact of prophylactic antibiotic duration on postoperative outcomes post-cardiothoracic surgery: a retrospective cohort study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14546-2

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14546-2

Keywords: antibiotic prophylaxis, cardiothoracic surgery, surgical site infection, antimicrobial resistance, coronary artery bypass grafting, antibiotic stewardship, retrospective cohort study, deep sternal wound infection, infection control, cardiac surgery, hospital-acquired infection, BMC Infectious Diseases