Study: Fluoroquinolones not linked to resistance in pediatric stem cell transplants
Key takeaways:
- Exposure to the antibiotics did not increase the risk for vancomycin-resistant Enterococcus colonization.
- Few patients tested positive for VRE overall, so the authors said more research is needed.
Fluoroquinolone exposure did not appear to increase the risk for developing vancomycin-resistant Enterococcus colonization following pediatric hematopoietic cell transplantation, a study found.
However, more research is likely needed because of the low volume of patients who were colonized, according to findings published in Journal of the Pediatric Infectious Diseases Society.
“Levofloxacin is used as a prophylactic antibiotic in certain populations, mainly children with leukemia or hematopoietic cell transplant recipients,” William R. Otto, MD, MSCE, assistant professor of pediatrics and attending physician in the division of infectious diseases at Cincinnati Children’s Hospital Medical Center, told Healio. “There is good evidence that levofloxacin helps to prevent bloodstream infections, but there are limited data about potential adverse effects of long-term levofloxacin prophylaxis, such as antibiotic resistance.”
The researchers cited a 2018 study of 455 patients that suggested longer exposure to antimicrobials like vancomycin, fluoroquinolones and meropenem increased patients’ risk for developing vancomycin-resistant Enterococcus (VRE) bacteremia.
Otto and colleagues performed a retrospective study of 799 patients aged younger than 25 years (58.6% boys; median age, 7.3 years; interquartile range, 3.2-14 years) who received hematopoietic cell transplantation at Cincinnati Children’s Hospital between Jan. 1, 2013, and Dec. 31, 2022. Each patient was screened for VRE colonization biweekly during their hospital stay.
The researchers investigated whether fluoroquinolone prophylaxis — including with levofloxacin or ciprofloxacin — was associated with an elevated risk for VRE colonization. They noted that levofloxacin was the preferred choice after 2018.
Overall, 55.3% of patients received levofloxacin or ciprofloxacin while hospitalized, and 6.9% were diagnosed with VRE colonization. Among patients who were exposed to fluoroquinolones, 6.3% developed VRE colonization, according to the researchers.
Otto and colleagues reported that fluoroquinolones prophylaxis did not affect the risk for developing VRE colonization (OR = 0.999; 95% CI, 0.982-1.017), but because few children screened positive for VRE overall, Otto said experts should study this further.
“Ultimately, continued research is needed to determine how often adverse effects of levofloxacin prophylaxis occur,” he said.
References:
- Gouliouris T, et al. J Antimicrob Chemother. 2018;doi:10.1093/jac/dky075.
- Murphy CR, et al. J Pediatric Infect Dis Soc. 2025;doi:10.1093/jpids/piaf010.
Perspective
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The authors are to be commended for performing a safety assessment evaluating whether receipt of fluoroquinolone antibiotics associated with the development of VRE colonization in hospitalized children without prior VRE colonization or infection. The authors performed systematic VRE screening before and every 2 weeks after HCT among a large cohort of 799 pediatric HCT recipients over a relatively long surveillance period (10 years). In total, 55 (7%) of 799 patients developed VRE colonization (28 patients out of 442 of whom had received fluoroquinolones) during the study period. Given the retrospective, observational cohort study design, the authors performed propensity analyses in an effort to reduce possible confounding and found no association between receipt of fluoroquinolone and subsequent development of VRE colonization (OR = 0.99; 95% CI, 0.981-1.017).
VRE rates across the institution are not reported; VRE incidence in this pediatric HCT cohort may have been underestimated given 1), the use of bacterial culture (of stool or rectal swab) as a less sensitive surveillance testing method than molecular testing (eg, by PCR for detection of van A and van B genes); and 2) a lack of more frequent surveillance testing (which decreases both the accuracy of the measurement and does not allow for precise assessment of timing of VRE acquisition).
Because screening and receipt of fluoroquinolones were dynamic processes over time during the study, overall low VRE colonization rates and lack of confirmation of timing of receipt of fluoroquinolone exposure preceding positive VRE screening impact the ability to definitively conclude that there is no association between receipt of fluoroquinolones and VRE acquisition.
Lastly, it is unclear what the clinical impact was for patients undergoing screening, from newly screening VRE positive, and receiving fluoroquinolone prophylaxis because clinical outcome data were not reported. Although likely beyond the scope of this study, it is unknown if newly colonized patients developed more VRE or fluoroquinolone-resistant invasive infections or had fluoroquinolone-associated perturbations to their gastrointestinal microbiome that affected other outcomes, including rates of Clostridioides difficile or contributed to the development of gastrointestinal graft-vs.-host disease post-HCT compared with patients who did not receive fluoroquinolones or develop VRE colonization.
The benefits of antimicrobial prophylaxis (fluoroquinolones or any antimicrobial agent) in possibly preventing invasive infections in at-risk individuals must continuously be weighed against possible unintended consequences, including the potential emergence of antimicrobial resistance and untoward clinical outcomes for patients.
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