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

Sirolimus, also known by its original brand name rapamycin, works by inhibiting mammalian target of rapamycin, or mTOR, a central cellular signaling hub that governs growth, proliferation and the response of lymphatic endothelial cells to injury. In vascular anomalies, particularly lymphatic and veno-lymphatic malformations, aberrant signaling through the PI3K-AKT-mTOR pathway drives the abnormal proliferation of lymphatic vessels, producing masses that can swell, leak, deform tissue and compress airways. By damping this pathway, sirolimus can shrink lesions and dramatically improve symptoms, which is why it has become a mainstay of medical therapy for complex vascular anomalies worldwide. But mTOR signaling is also indispensable to the immune system, where it coordinates T cell activation, lymphocyte proliferation and the coordination of innate and adaptive defenses. Immunosuppression is the pharmacological flip side of the drug’s therapeutic action, and it is the reason sirolimus has long been used to prevent organ transplant rejection.

The research team, led by Fadiah Alkhattabi and colleagues, assembled a cohort of 95 pediatric patients who received sirolimus between January 2019 and June 2025. The median age of the children was 12 years. Lymphatic malformations accounted for 46.3 percent of cases and veno-lymphatic malformations for 34.7 percent, reflecting the fact that these lymphatic-predominant lesions respond most reliably to mTOR inhibition. The investigators systematically collected every infection occurring within twelve months of therapy initiation, capturing outpatient episodes, emergency department encounters, hospital admissions and intensive care stays. This twelve-month window was chosen deliberately, since it spans the period of dose titration and steady-state immunosuppression during which clinicians most worry about opportunistic and community-acquired pathogens alike.

The headline number is striking: 63.2 percent of the children developed at least one infection during the observation period, and among those affected, the median count was three infections per patient. That is not a background rate of ordinary childhood illness; it is a sustained pattern of recurrent infection concentrated in a defined therapeutic window. The microbiological geography of these infections was also telling. Respiratory infections dominated, accounting for 80 percent of all infectious episodes, followed by skin and soft tissue infections at 11.7 percent and bloodstream infections at 5 percent. The respiratory predominance makes biological sense. The lung mucosa is a vast immunological interface, constantly patrolled by resident lymphocytes whose function depends on intact mTOR signaling, and lymphatic malformations themselves can compromise airway architecture and mucociliary clearance, compounding the vulnerability.

The clinical consequences were far from trivial. Infections drove emergency department visits in 70 percent of affected episodes and required hospitalization in 23.3 percent. Among children who were hospitalized, 28.6 percent deteriorated enough to require intensive care admission. One infection-related death occurred in the cohort, a sobering reminder that in children whose immune systems are pharmacologically dampened, common pathogens can occasionally follow malignant trajectories. Beyond the acute morbidity, the study documented a second, subtler cost: disruption of the treatment itself. Sirolimus doses had to be adjusted in 58.3 percent of infection episodes, and the drug was temporarily discontinued in 40 percent of cases. For a therapy whose benefit depends on continuous suppression of aberrant lymphatic growth, these interruptions risk lesion regrowth and symptom recurrence, creating a clinical dilemma in which the treatment of the infection and the treatment of the malformation pull in opposite directions.

One of the study’s most provocative findings concerns dosing. Children who developed infections had received a lower initial sirolimus dose than those who did not, with a median of 1.20 milligrams per square meter of body surface area compared with 1.60 in the infection-free group, a difference that reached statistical significance. At first glance this seems paradoxical: more drug, fewer infections. The authors’ data do not establish causation, and the retrospective design precludes firm mechanistic conclusions, but several explanations are plausible. Children prescribed higher initial doses may have been systematically different in ways the analysis could not fully capture, including the extent of their disease, their nutritional status or the intensity of monitoring they received. Alternatively, the association may reflect confounding by indication in reverse, with clinicians reserving more aggressive dosing for children they judged to be more robust. Whatever the mechanism, the finding underscores how little is known about the dose-response relationship between sirolimus exposure and infectious risk in this population, and it cautions against the assumption that lower doses are automatically safer.

Equally consequential is what the study found about antibiotic prophylaxis. Roughly a quarter to a third of children in both groups received prophylactic antibiotics, 28.3 percent of those who developed infections and 25.7 percent of those who did not, and the difference in infection rates between the two groups was not statistically significant. In other words, prophylactic antibiotics did not appear to protect the children who received them. This null result matters because prophylaxis is not a benign intervention. Chronic antibiotic exposure selects for resistant organisms, disrupts the microbiome and carries its own burden of side effects, all without demonstrated benefit in this cohort. The findings suggest that routine prophylaxis for all children on sirolimus cannot be justified by the current evidence, and that a more nuanced, risk-adapted approach is warranted, reserving preventive strategies for children with identifiable additional vulnerabilities such as profound lymphatic involvement of the airway, a history of recurrent pneumonia or coexisting immunodeficiency.

The study’s design imposes important limits on interpretation. As a single-center retrospective analysis, it depends on the completeness and consistency of clinical documentation over six years, and infection ascertainment may vary with how diligently clinicians recorded outpatient episodes. Without a control group of children with vascular anomalies who were not treated with sirolimus, the study cannot isolate the drug’s contribution to infection risk from the baseline susceptibility conferred by the malformations themselves. Children with lymphatic malformations are known to experience recurrent infections even without immunosuppressive therapy, because malformed lymphatic tissue impairs local immune surveillance and fluid drainage. The true attributable risk of sirolimus, therefore, likely lies somewhere below the raw 63.2 percent figure, though the recurrent and severe nature of the observed infections suggests the drug is a meaningful contributor.

Nevertheless, the practical implications for pediatric practice are immediate. Clinicians managing children with vascular anomalies on sirolimus should maintain a low threshold for evaluating respiratory symptoms, counsel families about early signs of infection, and coordinate care between dermatology, hematology-oncology, pulmonology and infectious disease specialists. Therapeutic drug monitoring, already standard practice for sirolimus, may need to be paired with a more explicit accounting of infection history when titrating doses, and treatment interruptions during acute illness should be weighed carefully against the risk of lesion progression. The authors argue that close monitoring and risk-adapted infection prevention strategies may help optimize sirolimus therapy, a formulation that acknowledges both the drug’s undeniable value and the infectious toll documented in their data.

As sirolimus and the newer generation of PI3K and mTOR pathway inhibitors expand into ever broader pediatric populations, studies of this kind become essential scaffolding for safe practice. The Riyadh cohort demonstrates that infections during sirolimus therapy are common, clinically significant and frequently disruptive to treatment continuity, while simultaneously showing that the reflexive answer of antibiotic prophylaxis does not work. What is needed next is prospective, multicenter surveillance with standardized infection definitions, pharmacokinetic correlates and, ideally, biomarkers of immune function that can identify which children truly need intensified protection. Until such data exist, the study stands as a clear signal that the benefits of mTOR inhibition in vascular anomalies must be actively balanced against a substantial and measurable infectious burden, one that deserves the same clinical attention devoted to the malformations themselves.

Subject of Research: Infection risk in pediatric patients with vascular anomalies treated with sirolimus

Article Title: The proportion of infections in patients with vascular anomalies treated with sirolimus: a retrospective study

Article References: Alkhattabi, F., Alsaleem, A., Aledaili, S., Alhuthil, R., & Alobieda, S. (2026). The proportion of infections in patients with vascular anomalies treated with sirolimus: a retrospective study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07707-4

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07707-4

Keywords: sirolimus, vascular anomalies, lymphatic malformations, pediatrics, mTOR inhibitor, infections, antibiotic prophylaxis, immunosuppression, respiratory infections, drug safety, retrospective study, BMC Pediatrics