Oral antibiotic step-down therapy for uncomplicated gram-negative bloodstream infections (BSIs) in solid-organ transplant recipients is safe and effective, and associated with fewer treatment-related adverse events, according to a recent study (Clin Infect Dis 2024;79[1]:208-214). Although a significant body of evidence has accumulated over the past several years to support the use of oral antibiotics to treat uncomplicated bacteremia in immunocompetent populations, this appears to be the first study to focus solely on the solid-organ transplant population.
In the retrospective analysis, investigators at Tufts University School of Medicine, Massachusetts General Hospital, and Brigham and Women’s Hospital identified all solid-organ transplant recipients within the hospital systems between 2016 and 2021 with uncomplicated gram-negative bacteremia involving an organism susceptible to an acceptably bioavailable oral antibiotic agent.
They identified 162 bacteremic events in 147 patients who met the inclusion criteria. Of this group, there were 120 bacteremic events in 107 patients treated with oral step-down therapy and 42 bacteremic events in 40 patients given IV therapy only. (Patients in the oral cohort had received an IV lead-in with a median duration of four days, before transitioning to oral.)
Primary outcomes for both groups were mortality within 30 days of treatment completion, bacteremia recurrence within 30 days of treatment completion and restart of IV antibiotics for the same underlying infectious process within 30 days of treatment completion. Secondary outcomes were development of Clostridioides difficile colitis within 30 days of treatment completion, other antimicrobial-related adverse events, catheter-associated adverse events, hospital length of stay from treatment initiation, need for new central IV access to facilitate treatment and need for tunneled central venous catheter placement.
The researchers did not find significant differences in mortality, bacteremia recurrence or restart of IV anti- biotics between the two groups. Patients transitioned to oral antibiotics had an average length of stay 1.97 days shorter (P=0.005) than those treated with IV therapy only. The odds of developing C. difficile and other treatment-associated complications were 8.4 times higher (P=0.015) and 6.4 times higher (P=0.002), respectively, in the IV group. Tunneled catheter placement was required in 55% of IV group patients.
“Until this work was done, we were unsure about the safety and efficacy and side effect profile of sending immunocompromised patients home on oral anti- biotics,” said the study’s lead author, Camille Nelson Kotton, MD, the clinical director of transplant and immunocompromised host infectious diseases at Massachusetts General Hospital, in Boston. All randomized controlled trials that have evaluated oral antimicrobial use for gram-negative bacteremia excluded highly immunocompromised hosts, and even previous retrospective studies have only included, at most, 10% immunocompromised patients (JAMA Intern Med 2019;179:316-323). “If we can safely send people home on orals, they will not need placement of either a PICC [peripherally inserted central catheter] line or a tunneled IV line, both of which are complicated, as well as home IV antibiotic administration, which is notoriously expensive. Some patients must go to nursing homes because their insurance doesn’t cover home IV antibiotics. These findings tell us that we have a safe, effective alternative for these patients to what we had previously been doing,” she said.
Lara Danziger-Isakov, MD, MPH, a professor of pediatrics and the director of the immunocompromised host infectious disease program at Cincinnati Children’s Hospital, who was not involved with the study, said the study opens a door for wider consideration for transitioning to oral antimicrobial therapy for this at-risk population of immunocompromised patients. “As a clinician, seeing no difference in the rates of bacterial recurrence or the need to restart IV therapies was very helpful,” she said. “Even more important is that there was a signal indicating that transplant patients transitioned to oral antibiotics are less likely to have other complications related to the administration of IV antibiotics. Reducing complications while retaining our ability to cure an infection is a significant benefit in this medically complex population.”
Josh Clement, PharmD, AAHIVP, BCIDP, who was also not involved in the research, called the study “a marked advancement and an important publication in this space. These are the data that we have been lacking when making decisions about when and if to transition to oral antibiotics in this population. Their sample size was robust and well balanced between the groups.”
Most patients in both oral and IV groups had received kidney transplants (70% and 69%, respectively), although the study also included liver, heart, lung and combined transplants, as well as one bowel transplant in the oral group. “The median time from transplant was 2.5 years in the IV group and three years in the PO [oral] group, so maybe you could say this was overall a lower risk population, but they still did well to be inclusive of a large mix of patients in terms of time post-transplant, with 15% in the first three months and 30% within the first six months,” Dr. Clement said.
Dr. Danziger-Isakov noted that some questions remain. “As the authors acknowledge, there are limitations in the size of the population, and these findings will need to be expanded to larger cohorts to ensure that the results are reproducible in a wider spectrum of the transplant patient population.”
The most common antibiotics included in the oral regimens were ciprofloxacin (68%) and levofloxacin (18%), while the most common antibiotic in the IV cohort was ceftriaxone (60%). “We tend to gravitate toward the more highly bioavailable agents, such as fluoroquinolones or Bactrim [sulfamethoxazole-trimethoprim],” Dr. Clement said. “Failing that, the oral beta-lactams have caused some concern because they don’t get as high bioavailability, but you can try to overcome that by pushing the dose a bit.”
One restriction in patient selection for oral versus IV antibiotic therapy would be the susceptibility profile of the organism, Dr. Kotton added. “As we see increasing antibiotic resistance, there will be a higher likelihood that we won’t have an oral option for some of these patients. I advise thoughtful and careful evaluation of the individual patient and their susceptibility test results.”
The sources reported no relevant financial disclosures.
This article is from the February 2025 print issue.