Safety and Tolerability of Anti-Bacterial Prophylaxis during the Post-Engraftment Phase after Myeloablative Hematopoietic Stem Cell Transplantation.

Background: Bacterial infections, including infections with Gram-negative organisms, frequently complicate the post-engraftment phase after myeloablative allogeneic hematopoietic stem cell transplantation. In this pilot study, we investigated the safety and tolerability of administering antibacterial prophylaxis from the time of engraftment (absolute neutrophil count of >1500/mm3 for 2 days) through day +100. Moxifloxacin was chosen for its broad spectrum of bacterial coverage and for its ability to target both bacterial topoisomerase IV and DNA gyrase, limiting the development of antimicrobial resistance.

Methods: Twenty-three patients with engraftment after allogeneic transplantation at OHSU received moxifloxacin 400 mg po daily upon discontinuation of any antibiotics used for the treatment of pre-enrollment bacterial infection. Rates of bacterial infection, bacteremia, and colonization were recorded. Comparisons were made with a cohort of 60 consecutive patients undergoing myeloablative transplantation at OHSU without similar antibacterial prophylaxis from 2001–2002.

Results: The median duration of moxifloxacin prophylaxis was 77 days (range 7–87). Five patients had dose interruptions due to nausea associated with graft-versus-host disease and two patients elected not to restart study medication. Only 3 patients had dose interruptions during empiric antibiotic therapy for possible bacterial infection. Overall, moxifloxacin was well tolerated in this patient population, with 5 episodes of grade 3/4 toxicity felt possibly related to study drug (2 orthostatic hypotension in one patient, 2 nausea, and 1 hypertension). Five patients had episodes of transaminitis which were unlikely to be due to study medication, and which responded to discontinuation of antifungal therapy (4) or to treatment of liver GVHD (1). No cardiac arrhythmias or tendonopathy were observed. Compared to historic controls, a marked decrease in post-engraftment phase bacterial infections was observed. The control cohort, 16 patients experienced 17 episodes of Gram-negative and 22 patients had 25 episodes of symptomatic Gram-positive infections during the post-engraftment phase without prophylaxis. In contrast with moxifloxacin prophylaxis, 2 patients experienced 3 Gram-negative infections (χ2, p=0.079), 1 patient had an anaerobic infection, and 7 patients had 9 symptomatic Gram-positive infections.

Conclusions: Prophylactic moxifloxacin dosed throughout the post-engraftment phase has been well tolerated, safe, and associated with a fewer bacterial infections compared to historic controls. The efficacy of this prophylaxis strategy will best be determined in a planned randomized, placebo-controlled trial.