Infectious Complications after High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Hematologic Malignancies in a 12-Year Period in Hospital Britanico, Uruguay
Authors: Oliver Ana Carolina , Riva Eloisa , Mosquera Ricardo Fabian , Pierri Silvia , Galeano Sebastian , Caneiro Ada , Bello Laura , Errecarte Carolina , Gai Regis , Miller Andrew , Muxi Pablo J. 
Published: October 2019

Abstract
Introduction: Autologous stem cell transplant (ASCT) plays a central role in the treatment of diverse diseases. Infection is one of the major causes of morbidity and costs of the procedure, representing the 2ndcause of death (24%) after primary disease (69%). Thus, preventing infections is a major goal.1There are no publications concerning infections in ASCT in our country.
Patients and Methods: Retrospective single center study.
Objectives: to compare the incidence of febrile neutropenia (FN) and characteristics of infections between 2 different antibacterial approaches. From January 2006 - December 2017, 279 ASCT have been done in our center. We included 266 patients with complete data: 249 received 1 ASCT and 17 received two. Anti-bacterial prophylaxis from 2006-2013 (Group 1) was ciprofloxacin from day 0 to neutrophil recovery. From 2013 to present (Group 2), levofloxacin was used. First febrile episode empirical treatment was Ceftazidime-Amikacin in Group 1 and Meropenem in Group 2.
Results: Median age was 56 years (18-72). MM and NHL (79,7%), 40% in complete remission, were the prevailing diseases. Median CD34+ cells transplanted was 4,87 x 106/kg (0,88-37). Median duration of neutropenia was 11 days (9-32). (Table 1)
Group 1: 28% had no FN episodes. Catheter-related and gastrointestinal were the most prevalent sites of infection. Positive cultures were 17,4%, 66,6% Gram+. 91% received Ceftazidime+Amikacine. A 2ndantibiotic was added in 52 patients (60%). Six patients required intensive care unit (ICU) admission (4.9%), due to pneumonia (3), sepsis (2) and viral encephalitis (1). Median days at discharge after ASCT was 17 (10-56); 20,6 for those who had FN episodes and 16,5 for those who did not (p= 0,004).
Group 2: 13,8 % had no FN episodes. Pneumonia and catheter-related infections were the most prevalent sites of infection. Positive cultures: 20 %; 69% Gram +. 70 patients received an additional agent (56%).Six patients required ICU admission (4,1%), 1 due to pneumonia, 1 sepsis, 1 alitiasic cholecystitis, 1 catheter-related infection and pneumonia, 1 bradyarrhythmia and 1 atrial fibrillation. Median days at discharge after ASCT was +16 (12-62), 19,8 for those who experienced FN and 17 for those who did not (p=0,184).
Incidence of FN was 72% in Group 1 and 86,2% in Group 2 (p=0,004). Culture-negativity was 82,6% in Group 1 and 80% in Group 2. In blood + cultures, Gram + agents represented 66.6% in Group 1 and 69% in Group 2 (p=0.68).
Discussion: FN is common in ASCT (63-94%)2,3, implying longer hospitalization, more diagnostic procedures and increase in morbidity and mortality. Significant differences in FN incidence between groups, in favor of Ciprofloxacin prophylaxis (72% vs 86,2% (p=0,004) were found. The incidence of positive cultures was similar in both groups. Gram+ agents were the most common isolation. Prophylaxis with quinolones leaded to a low Gram negative bacteria isolation, as reported by others.4Most infectious episodes were associated with fever of unknown origin: 53 % in Group 1 and 56.8 % in Group 2, with differences in sites of infection's frequency: catheter-related infection prevailed in Group 1 and pneumonia in Group 2. (Table 2)
We hypothesized that a better Gram+ coverage with Levofloxacin might have help to reduce the incidence of clinical catheter infections. A 2nd antibiotic was needed in 60% from Group 1 and 56% in Group 2 (p=0,47). Median to neutrophil recovery was shorter in Group 1 (+8 vs +10), (p=0,0001). ICU admission was mostly due to sepsis, similar in both groups (p=0,74). During hospitalization, 2 patients died of sepsis in Group 1 and 0 in Group 2. Mortality rate was 1,87 %, similar to international reports.5 Patients in Group 2 were older, with more advanced diseases and hypogammaglobulinemia, which may contribute to difference in favor of Ciprofloxacin group in terms of FN and days to hematopoiesis recovery. (Table 3)
Levofloxacin prophylaxis was not associated with an increase in resistant bacteria nor Clostridium difficile infection.
Conclusions: The incidence of FN in ASCT was high. Levofloxacin prophylaxis was associated with more FN episodes and later discharge. Epidemiology and severity of infections and 2nd antibiotic requirement were comparable in both groups. Patients admitted for ASCT in the last 7 years had additional risk features that may contribute to explain the differences found. Mortality rate was low in both groups.

Disclosures
No relevant conflicts of interest to declare.