Fluoroquinolone Prophylaxis After Hematopoietic Cell Transplantation: Results from a Retrospective Study Evaluating Infectious Risk Versus Benefit

Jaci Dudley, PharmD BCOP
Oncology Clinical Pharmacy Specialist
UPMC Pinnacle Hospital
Harrisburg, PA

Hematopoietic cell transplantation (HCT) poses a risk for infection because many factors can compromise immune function. Prolonged neutropenia, immunosuppressive therapies, compromised mucosal barriers, and indwelling catheters are the main risks that can contribute to infection. As a result, current national guidelines recommend that providers consider antibacterial prophylaxis with a fluoroquinolone (FQ) in HCT patients when the anticipated duration of neutropenia is at least 7 days. Prophylaxis usually starts at the time of stem cell infusion and continues until the neutropenia resolves or empirical antibacterial therapy for a febrile neutropenia event is initiated. Despite FQ efficacy in preventing gram-negative infection, results for patient mortality have been mixed. Providers must weigh the benefit of antibacterial prophylaxis against the risk of infection with Clostridium difficile or multi-drug-resistant bacteria.

To facilitate these decisions, Dr. Amber Clemmons and colleagues designed a retrospective study that evaluated risks versus benefits of FQ prophylaxis for HCT patients. Their research, “Impact of Fluoroquinolone Prophylaxis on Infectious-Related Outcomes After Hematopoietic Cell Transplantation,” was published online in October 2017 in the Journal of Oncology Pharmacy Practice.¹ Until winter 2013, prophylaxis with an FQ agent was standard practice for all adult HCT patients at their institution. Because of local susceptibility results, the institution ceased prophylaxis in HCT patients and restricted providers to the use of other FQ agents; levofloxacin was removed from the formulary. Clemmons and colleagues measured the effect of this change through retrospective analysis. The primary outcome found was the incidence of bacteremia in patients who received an autologous or allogeneic HCT from 2011 to 2015. Secondary outcomes included the incidence of febrile neutropenia, urinary tract infection (UTI), pneumonia, C. difficile infection, and susceptibility to bacteremia infections; they also examined time to discharge and 30-day mortality rates.

Two study groups were selected. The first (n = 105) received FQ prophylaxis with levofloxacin 500 mg by mouth daily from day +1 until engraftment or a febrile neutropenia event. The second (n = 74) received no FQ prophylaxis; patients were treated under the new institutional protocol. Additionally, granulocyte-colony stimulating factor (GCSF) was changed to day +5 for the non-FQ group, and the FQ group started GCSF on day +1. No other significant difference was reported in the demographics of the two groups. These two main groups were further divided into autologous (n = 115) and allogeneic (n = 56) subgroups. Results were provided for each of these groups.

The primary outcome of the study was a significant difference for microbiologically documented bacteremia between FQ and non-FQ groups (15.2% vs. 31.8%; p < .01). As a secondary outcome, the investigators found no statistical difference in rates of UTI. Rates of pneumonia when tested by sputum culture were not statistically significant; however, when tested by chest X-ray, a significant difference was found, with higher rates of infection in the non-FQ group. Incidence of C. difficile between the groups was not found to be significantly different. Febrile neutropenia rates were lower in the FQ group than in the non-FQ group (54% vs. 83%, p < .0001), and fewer patients in the FQ group met sepsis criteria than in the non-FQ group (33% vs. 53%, p < .01). No statistically significant differences were seen in median time to discharge or in 30-day mortality rates between the two groups.

In the autologous subgroup, the FQ and non-FQ cohorts had statistically significant differences in rates of febrile neutropenia (55% vs. 91%, p < .0001) and sepsis (25% vs. 52%, p < .0034). The number of microbiologically documented bacteremia patients was significantly lower in the FQ group (8.5% vs. 27.3%, p = .0069). The incidence of UTIs was not different between the groups. Rates of positive sputum culture pneumonia were not significantly different; however, positive chest X-ray pneumonia was statistically higher in the non-FQ group. The incidence of C. difficile (12.7% vs. 9.1%, p = 1), the median time to discharge, and the 30-day mortality rates were not significantly different.

In contrast to the autologous subgroup, in the allogenic subgroup, febrile neutropenia and sepsis were not statistically significantly different between the FQ and the non-FQ groups (52.9% vs. 68.2%, p = .4; 50% vs. 54.5%, p = .73). For the primary outcome, the number of microbiologically documented bacteremia patients was also not significant between the two groups (29.4% vs. 40.9%, p = .4). Positive sputum culture pneumonia, positive chest X-ray pneumonia, UTI, and incidence of C. difficile were not significantly different, nor were median time to discharge and 30-day mortality rates.

The investigators concede that the retrospective nature of the study created an imbalance in the number of patients in each group. They also concede that by combining the autologous and allogenic subgroups, they combined populations with different risk factors for bacterial infection, though this was in keeping with institutional practice. A last limitation was the protocol change of GCSF initiation from 1 day post-transplant to 5 days post-transplant; however, they conclude that it was unlikely this difference had an impact on outcomes.

As the authors of this article note, the use of prophylactic antibiotics continues to be contested because of the potential risk of the development of antibiotic-resistant bacteria. Despite these concerns, the results of this study indicate that the benefits of FQ prophylaxis outweigh possible risks.

Reference

1. Clemmons AB, Gandhi AS, Albrecht B, et al. Impact of fluoroquinolone prophylaxis on infectious-related outcomes after hematopoietic cell transplantation. J Oncol Pharm Practice. 2017 Oct 23. doi:10.1177/1078155217735153. [Epub ahead of print]