Fluoroquinolone Prophylaxis in Autologous Stem Cell Transplantation: Worthy of a Second Look

Maakaron, Joseph; Liscynesky, Christina; Boghdadly, Zeinab El; Huang, Ying; Agyeman, Akwasi; Brammer, Jonathan E.; Penza, Sam; Efebera, Yvonne A.; Benson, Don M.; Rosko, Ashley; William, Basem M.; Jaglowski, Samantha

doi:10.1016/j.bbmt.2020.03.027

Cited by 8 publications

(6 citation statements)

References 13 publications

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“…The key finding of our study was lack of effect of levofloxacin prophylaxis on incidence of FN, bloodstream infections and TRM. This is in contrast to the findings of recent studies published from the countries with established transplant programs where levofloxacin prophylaxis was associated with significant reduction in the incidence of FN and bloodstream infections 26,27 . Although the rates of ESBL pathogens, MDR pathogens, and C. difficile infection were higher with levofloxacin prophylaxis, the differences were not statistically significant.…”

Section: Discussioncontrasting

confidence: 98%

“…This is in contrast to the findings of recent studies published from the countries with established transplant programs where levofloxacin prophylaxis was associated with significant reduction in the incidence of FN and bloodstream infections. 26,27 Although the rates of ESBL pathogens, MDR pathogens, and C. difficile infection were higher with levofloxacin prophylaxis, the differences were not statistically significant. Our findings could be informative for LMIC cancer centers that rely on widespread fluoroquinolone prophylaxis for their local protocols despite high rates of antimicrobial resistance.…”

Section: Discussionmentioning

confidence: 90%

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Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients

Jandial

Lad

Jain

et al. 2023

Transplant Infectious Dis

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BackgroundInfections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post‐AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries.Materials and methodsWe performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient‐specific, disease‐specific, and transplant‐specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen‐related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100.ResultsNinety‐five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33–68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4–144). Eighty‐nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile‐associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9–14) and 12 days (range 9–23), respectively. The median duration of hospital stay was 16 days (range 9–29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant‐related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10 vs. day +11) and platelet engraftment (day +11 vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression‐free survival of the study population at 5 years were 72.7% and 64.8%, respectively.ConclusionThis study shows that the incidence of infections and TRM are higher in MM patients from lower‐middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis. image

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Section: Discussioncontrasting

confidence: 98%

Section: Discussionmentioning

confidence: 90%

Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients

Jandial

Lad

Jain

et al. 2023

Transplant Infectious Dis

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“…Our analysis suggests similar efficacy of antibiotic prophylaxis and G-CSF support in preventing infections. Previously published studies investigating antibiotic prophylaxis plus G-CSF support in MM patients receiving HDT/ASCT show lower rates of febrile neutropenia and septicemia, reflecting that this strategy might be even more effective [ 8 , 11 ]. However, other studies comparing antibiotic prophylaxis plus G-CSF support versus antibiotic prophylaxis show that adding G-CSF enables a shortening of neutropenia, but there is no consistent benefit along studies in preventing febrile neutropenia, septicemia, need of antibiotics, and death [ 12 , 15 , 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, in our analysis, G-CSF support reduced the risk of emerging MDR bacteria compared to antibiotic prophylaxis. Similarly, Maakaron et al were able to demonstrate significant higher rates of MDR bacteria in MM patients receiving levofloxacin plus filgrastim after HDT/ASCT compared to lymphoma patients receiving only filgrastim after HDT/ASCT [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, a large prospective randomized trial examining levofloxacin prophylaxis versus placebo in cancer patients with expected neutropenia longer than seven days after chemotherapy, demonstrated no significant effect of antibiotic prophylaxis on mortality [ 9 ]. Due to the high prevalence of fluoroquinolone-resistant Gram negative bacteria and the increased risk of acquiring multidrug resistant (MDR) bacteria, even during short-term antibiotic prophylaxis, the value of antibiotic prophylaxis in patients with MM receiving HDT/ASCT remains controversial [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Antibiotic Prophylaxis or Granulocyte-Colony Stimulating Factor Support in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Klein

Sauer

Klein

et al. 2021

Cancers

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We compare, in this manuscript, antibiotic prophylaxis versus granulocyte-colony stimulating factor (G-CSF) support as anti-infective strategies, in patients with multiple myeloma (MM), undergoing high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT). At our institution, antibiotic prophylaxis after HDT/ASCT in MM was stopped in January 2017 and replaced by G-CSF support in March 2017. Consecutive MM patients who received HDT/ASCT between March 2016 and July 2018 were included in this single-center retrospective analysis. In total, 298 patients and 353 individual cases of HDT/ASCT were evaluated. In multivariate analyses, G-CSF support was associated with a significantly shortened duration of severe leukopenia < 1/nL (p < 0.001, hazard ratio (HR) = 16.22), and hospitalization (estimate = −0.19, p < 0.001) compared to antibiotic prophylaxis. Rates of febrile neutropenia, need of antimicrobial therapy, transfer to intensive care unit, and death, were similar between the two groups. Furthermore, antibiotic prophylaxis was associated with a significantly increased risk for the development of multidrug resistant bacteria especially vancomycin-resistant Enterococcus faecium compared to G-CSF support (odds ratio (OR) = 17.38, p = 0.01). Stop of antibiotic prophylaxis as an anti-infective strategy was associated with a reduction in overall resistance rates of bacterial isolates. These results indicate that G-CSF support should be the preferred option in MM patients undergoing HDT/ASCT.

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Host-microbe interactions and outcomes in multiple myeloma and hematopoietic stem cell transplantation

Pianko

Golob²

2022

Cancer Metastasis Rev

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Microbiota are essential to normal immune development and there is growing recognition of its importance to human health and disease and deepening understanding of the complexity of host-microbe interactions in the human gut and other tissues. Commensal microbes not only can influence host immunity locally through impacts of bioactive microbial metabolites and direct interactions with epithelial cells and innate immune receptors but also can exert systemic immunomodulatory effects via impacts on host immune cells capable of trafficking beyond the gut. Emerging data suggest microbiota influence the development of multiple myeloma (MM), a malignancy of the immune system derived from immunoglobulin-producing bone marrow plasma cells, through the promotion of inflammation. Superior treatment outcomes for MM correlate with a higher abundance of commensal microbiota capable of influencing inflammatory responses through the production of butyrate. In patients with hematologic malignancies, higher levels of diversity of the gut microbiota correlate with superior outcomes after hematopoietic stem cell transplantation. Correlative data support the impact of commensal microbiota on survival, risk of infection, disease relapse, and graft-versus-host disease (GVHD) after transplant. In this review, we will discuss the current understanding of the role of host-microbe interactions and the inflammatory tumor microenvironment of multiple myeloma, discuss data describing the key role of microbiota in hematopoietic stem cell transplantation for treatment of hematologic malignancies, and highlight several possible concepts for interventions directed at the gut microbiota to influence treatment outcomes.

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Fluoroquinolone Prophylaxis in Autologous Stem Cell Transplantation: Worthy of a Second Look

Cited by 8 publications

References 13 publications

Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients

Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients

Antibiotic Prophylaxis or Granulocyte-Colony Stimulating Factor Support in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Host-microbe interactions and outcomes in multiple myeloma and hematopoietic stem cell transplantation

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