Prospective Randomized Study of Prophylactic Ciprofloxacin Versus Levofloxacin in Hematopoietic Stem Cell Transplant Patients: An Interim Report
Farhan S, Marusca G, Bazydlo M, Neme K, Mikulandric N, Stephen J, Kortam N, Mayur R, Pelland D, Zagar N, Trapp MA, Henne E, Rohrer S, Szymanski S, Emole J, Peres E, and Janakiraman N. Prospective Randomized Study of Prophylactic Ciprofloxacin Versus Levofloxacin in Hematopoietic Stem Cell Transplant Patients: An Interim Report. Biology of Blood and Marrow Transplantation 2020; 26(3):S320.
Biol Blood Marrow Transplant
Infection is a serious complication of hematopoietic stem cell transplantation (SCT). However, the optimum oral agent for antibacterial prophylaxis in SCT recipients remains uncertain. Different antibiotics might affect incidence of blood stream infections, resistance, Clostridium difficile, gut microbiome, GVHD and relapse. To explore this we started this first clinical trial of levofloxacin (Levo) versus ciprofloxacin (Cipro) at our center. Methods: This is a single center prospective randomized study. Patients who meet the SCT program criteria to undergo autologous or allogeneic hematopoietic stem cell transplantation are eligible. Results: We present interim results. 111 consecutive patients were randomized since June 2018. At the time of the present report 102 of these patients have follow up for 60 days or more. There were 62 males and 40 females. Median age at time of SCT was 61. Fifty received Cipro and 52 received Levo. Fifty-six patients had autologous (27 Cipro and 29 Levo) while 46 patients had allogeneic SCT (23 Cipro and 23 Levo). For allogeneic SCT, 12 patients in each group had ATG. Time to engraftment and length of stay were similar in both groups. In the Cipro group 6 patients (12%) had bacteremia while in the Levo group 7 (13%) had bacteremia. Of patients with bacteremia, in the Cipro group none had Gram negative bacteremia while in the Levo group 4 had gram negative bacteremia (OR 9.37, p = 0.137). In the Cipro group 6 patients had gram positive bacteremia while in the Levo group 3 patients had gram positive bacteremia (OR 2.22, p = 0.277). In the Cipro group, 6 (12%) had clostridium difficile while in the Levo group only 1 (1.9%) had Clostridium difficile (OR 6.95, p = 0.078). Acute GVHD of all grades accrued in 17 patients (34%) in Cipro group and in 16 patients (30.7%) in the Levo group. Grade III-IV aGVHD occurred in 6 patients (12%) in Cipro group and in 3 patients (5.8%) in the Levo group (OR 2.23, p = 0.277). The hazard ratio for progression free survival was 0.67 (95% CI: 0.27, 1.67), p=0.395 for Levo vs. Cipro. The hazard ratio for overall survival, adjusted for auto/allo and age at transplant was 0.29 (95% CI: 0.09, 0.95), p = 0.041, for Levo vs. Cipro. However, 3 of deaths in the Cipro group were not related to type of antibacterial prophylaxis (listeriosis from contaminated food, fungal pneumonia in a wooden-house builder and stroke from intraventricular thrombus). So, unadjusted hazard ratio for overall survival (Levo vs. Cipro): 0.41 (95% CI: 0.13, 1.34), p = 0.142. Hazard ratio for overall survival (Levo vs. Cipro), adjusting for allo/auto and age at transplant: 0.39 (95% CI: 0.11, 1.33), p = 0.132. Conclusion: At this point, in this interim analysis, there seems to be a trend for Cipro to protect patients from gram negative bacteremia compared to levo. As a trade-off, there is higher trend for Clostridium difficile in the Cipro group compared to Levo group, but none is statistically significant so far.