Decreased Gram Negative Bloodstream and C. Difficile Infections with Early Ciprofloxacin/Metronidazole Prophylaxis in Myeloablative Allogeneic Hematopoietic Stem Cell Transplant

Abstract

Topic Significance & Study Purpose/Background/Rationale: Allogeneic hematopoietic stem cell transplant (HSCT) patients are at high risk for infection during the pre-engraftment period. Current guidelines recommend fluoroquinolone prophylaxis for adults with anticipated neutropenia >6 days. This study was performed to determine optimal timing and antibiotic prophylaxis regimen for myeloablative allogeneic HSCT recipients. Methods, Intervention, & Analysis: An IRB-approved, singleinstitution retrospective study assessed patients undergoing myeloablative allogeneic HSCT with total body irradiation (TBI) between 3/2011 and 5/2016. Patients were grouped by antibiotic prophylaxis regimen. Early prophylaxis was defined as ciprofloxacin/metronidazole initiated in the first half of the preparative regimen. Late prophylaxis was defined as ciprofloxacin/metronidazole initiated in the latter half of the preparative regimen or on day of stem cell infusion. Ciprofloxacin-only early prophylaxis was defined as ciprofloxacin initiated in the first half of the preparative regimen. Neutropenia onset was defined as early (before Day −1), average (Day −1 to +1), or late (after Day +1). Microbiology results were reviewed from preparative regimen onset through 30 days post-transplant. Multiple logistic regression models compared effects of prophylaxis regimens adjusting for sex, Hematopoietic Cell Transplantation-Specific Comorbidity Index, Karnofsky performance status (KPS), prior BSI, and neutropenia onset. Findings & Interpretation: One hundred twenty-six patients met inclusion criteria (46 early, 50 late, 30 early ciprofloxacin-only prophylaxis). Groups did not differ significantly by sex, age, disease, KPS, allograft type, C. difficile history, BSI history, or neutropenia onset. Multiple logistic regression revealed significant differences in gram negative BSI and C. difficile infection rates. Gram negative BSI were less frequent with early versus late prophylaxis (adjusted OR .15, 95% CI .02-.78) and with early ciprofloxacin-only versus late prophylaxis (adjusted OR .12, 95% CI .006-.81). C. difficile infections were less frequent with early versus late prophylaxis (adjusted OR .13, 95% CI .02-.57) and early versus early ciprofloxacin-only prophylaxis (adjusted OR .18, 95% CI .02-.99). Total and Gram positive BSI rates did not differ significantly by prophylaxis regimen. Discussion & Implications: In this study, early prophylaxis with ciprofloxacin was associated with decreased Gram negative BSI. Metronidazole incorporation into early prophylaxis was associated with decreased C. difficile infection. These data support earlier antibiotic prophylaxis initiation with a fluoroquinolone and metronidazole.