To the Editor—Despite the benefits observed in randomized trials, the role of fluoroquinolone prophylaxis in neutropenic patients warrants reassessment because of increasing fluoroquinolone resistance and increased recognition of adverse effects from fluoroquinolones [1–5]. Thus, we read with interest the observational study from Caldwell et al of the impact of ending ciprofloxacin prophylaxis in patients receiving intensive chemotherapy or hematopoietic cell transplantation (HCT) at their center [6]. They compared 30 patients who developed Escherichia coli bacteremia despite receiving ciprofloxacin prophylaxis to 29 patients who developed E coli bacteremia after discontinuation of ciprofloxacin prophylaxis. They found that 73% of E coli bloodstream infections were ciprofloxacin resistant in patients who received ciprofloxacin prophylaxis, compared with only 28% in patients who did not receive ciprofloxacin prophylaxis. There were no statistically significant differences in outcomes between the 2 groups. The authors conclude that these data support discontinuation of universal fluoroquinolone prophylaxis in neutropenic patients.
A major limitation of this study is that the denominator of neutropenic patients who were at risk of developing bacteremia was not reported, preventing a comparison of the risk of bacteremia between patients who did and did not receive fluoroquinolone prophylaxis. It is expected that breakthrough infections that occur despite fluoroquinolone prophylaxis will be more likely to be caused by fluoroquinolone-resistant bacteria than those that occur in the absence of fluoroquinolone prophylaxis. However, fluoroquinolone prophylaxis may still decrease the overall risk of bacteremia. We previously compared the risk of bacteremia in patients with multiple myeloma undergoing autologous HCT at our center before and after the initiation of levofloxacin prophylaxis [7]. We found that the proportion of Enterobacterales bloodstream isolates that were fluoroquinolone resistant increased from 9% to 73% after the initiation of levofloxacin prophylaxis. However, the risk of any bloodstream infection decreased from 41% to 15% after initiation of levofloxacin prophylaxis and patients who received levofloxacin prophylaxis were less likely to develop gram-negative bacteremia, gram-positive bacteremia, and fever and neutropenia. Thus, although infections that occur despite fluoroquinolone prophylaxis are more likely to be caused by fluoroquinolone-resistant bacteria, fluoroquinolone prophylaxis may still decrease the overall risk of infection and fever, which in turn may decrease the risk of sepsis and use of broad-spectrum β-lactam therapies.
Instead of universal adoption or cessation of fluoroquinolone prophylaxis in high-risk neutropenic patients, our recent publication suggests an individualized approach to prophylaxis may be preferred, where the decision to use fluoroquinolone prophylaxis is based on screening for carriage of fluoroquinolone-resistant Enterobacterales (FQRE) [8]. In this study of HCT recipients who received levofloxacin prophylaxis, only 1% of patients who were not colonized with FQRE at the time of transplantation had breakthrough gram-negative bacteremia, compared with 31% of patients colonized with FQRE, suggesting that the effectiveness of fluoroquinolone prophylaxis depends on pretransplant FQRE colonization. We are currently conducting a multicenter observational study to validate these findings at other medical centers and in a broader range of hematologic patients, with the goal of crafting an individualized approach to prevention of bacterial infections in neutropenic patients.
Notes
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (R03 AI146612 and K23 AI114994 to M. J. S; and R01 AI090155 to B. N. K.).
Potential conflicts of interest. M. J. S. has received grant support from Allergan, BioFire Diagnostics, and Merck, and has received consulting fees from Shionogi. C. B. S. has received grant support from GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics. L. F. W. has received grant support from Accelerate Diagnostics, Hardy Diagnostics, BioFire Diagnostics, and Roche Molecular Systems, and has received consulting fees from Roche Molecular Systems, Shionogi, and Talis Biomedical. T. J. W. has received grant support from Allergan, Medicines Company, Merck, Shionogi, and Tetraphase, and consulting fees from Allergan, Medicines Company, Merck, Shionogi, Pfizer, and ContraFect.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Contributor Information
Michael J Satlin, Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.
Liang Chen, Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA; Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
Claire Douglass, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA.
Michael Hovan, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA.
Emily Davidson, Cooper Medical School of Rowan University, Camden, New Jersey, USA.
Rosemary Soave, Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Marisa La Spina, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA.
Alexandra Gomez-Arteaga, Department of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York, USAand.
Koen van Besien, Department of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York, USAand.
Sebastian Mayer, Department of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York, USAand.
Adrienne Phillips, Department of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York, USAand.
Jing Mei Hsu, Department of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York, USAand.
Rianna Malherbe, Hardy Diagnostics, Santa Maria, California, USA.
Catherine B Small, Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Stephen G Jenkins, Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.
Lars F Westblade, Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.
Barry N Kreiswirth, Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
Thomas J Walsh, Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
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