Impact of Levofloxacin for the Prophylaxis of Bloodstream Infection on the Gut Microbiome in Patients With Hematologic Malignancy

Ziegler, Matthew J.; Han, Jennifer H.; Landsburg, Daniel J.; Pegues, David A.; Reesey, Emily; Gilmar, Cheryl; Gorman, Theresa; Bink, Kristen; Moore, Amy; Kelly, Brendan J; Program, Cdc Prevention Epicenters

doi:10.1093/ofid/ofz252

Cited by 27 publications

(21 citation statements)

References 43 publications

(48 reference statements)

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“…In our single-center cohorts, LEVO had no detectible detrimental effect on microbiota diversity, maintained beneficial taxa such as Blautia, and did not promote expansion of common culprits of complications, such as Enterococcus and Streptococcus. These results, along with those from a previous study [11], suggest that LEVO is associated with less disruption of the gut microbiome compared with broad-spectrum b-lactam antibiotics. Novel strategies to protect and restore the indigenous microbiota in addition to individualized prophylactic and therapeutic antibiotics can optimize the supportive care provided during curative-intent therapy.…”

Section: Discussionsupporting

confidence: 82%

“…In a previous study, in a cohort of patients with hematologic malignancies and NF, stool samples collected before LEVO exposure showed a lower rate of positivity on culture for quinolone-resistant coagulase-negative Staphylococcus and Enterococcus [19]. A previous study of stool samples collected from patients with acute myeloid leukemia or multiple myeloma for the evaluation of diarrhea did not find a difference in a diversity or in the relative abundance of Enterococcus and Clostridia between samples collected without versus with preceding LEVO exposure [11]. Samples with previous LEVO (only) exposure had a higher relative abundance of Blautia.…”

Section: Discussionmentioning

confidence: 81%

“…Antibiotics with potent antianaerobic activity have consistently shown the most detrimental impact on the gut microbiome [7][8][9][10]. Although a few previous analyses suggested that LEVO does not cause major disruptions to the gut microbiota [7,8,11], this issue has not yet been adequately addressed. We used our institutional biorepository to address this knowledge gap.…”

Section: Introductionmentioning

confidence: 99%

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Levaquin Gets a Pass

Rashidi

Kaiser

Holtan

et al. 2020

Biology of Blood and Marrow Transplantation

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Antibiotic-induced gut dysbiosis has been associated with poor outcomes after intensive therapy. We evaluated the effect of levofloxacin (LEVO), the most commonly used prophylactic antibacterial antibiotic during intensive chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT), on the gut microbiota in 2 cohorts of patients, 1 cohort comprising 20 patients with acute leukemia receiving intensive chemotherapy and the other cohort comprising 20 allo-HCT recipients. 16S rRNA gene sequencing of thrice-weekly collected stool samples permitted a comparison between intervals with no antibacterial antibiotic exposure and those with only LEVO exposure. In mixed-effects modeling, the only variables influenced by LEVO were the relative abundances of Parabacteroides (regression coefficient, -.063; 99% confidence interval [CI], -.102 to -.024) and Blautia (regression coefficient, .050; 99% CI, .004 to .095). Other taxa and microbiota diversity were unaffected. Overall, the effect of LEVO on the gut microbiota in these cohorts was mild.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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Levaquin Gets a Pass

Rashidi

Kaiser

Holtan

et al. 2020

Biology of Blood and Marrow Transplantation

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“…Levofloxacin was a fluoroquinolone prescribed to our patients. According to Ziegler et al, there was no association between DOT of levofloxacin and gut microbiome diversity [ 35 ]. However, we observed an association between DOT of fluoroquinolones (at <two weeks) and overall survival.…”

Section: Discussionmentioning

confidence: 99%

Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer

et al. 2021

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Antibiotic-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors. We investigated the impact of antibiotics on the clinical outcomes of nivolumab in patients with non-small cell lung cancer (NSCLC). Patients who received nivolumab for NSCLC between July 2015 and June 2018 and who were followed up until June 2020 were included in a retrospective cohort analysis. Of 140 eligible patients, 70 were on antibiotics. Overall survival (OS) was shorter in patients on antibiotics (ABX) compared to those not on antibiotics (NoABX) (p = 0.014). OS was negatively associated with piperacillin/tazobactam (PTZ) (HR = 3.31, 95% CI: 1.77–6.18), days of therapy (DOT) ≥ 2 weeks (HR = 2.56, 95% CI: 1.30–5.22) and DOT of PTZ. The defined daily dose (DDD) in PTZ (r = 0.27) and glycopeptides (r = 0.21) showed weak correlations with mortality. There was no difference in progression-free survival (PFS) between ABX and NoABX; however, PFS was negatively associated with the antibiotic class PTZ and DOT of PTZ. Therefore, the use of a broad-spectrum antibiotic, such as PTZ, the long-term use of antibiotics more than 2 weeks in total and the large amount of defined daily dose of specific antibiotics were associated with decreased survival in patients receiving nivolumab for NSCLC.

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“…Many transplant centers use fluoroquinolones for neutropenic antibiotic prophylaxis, and a report on the impact of fluoroquinolone prophylaxis in patients with hematologic malignancies at risk for neutropenic fever demonstrated minimal impact of this antibiotic on gut microbiota 81 . Further prospective testing in a randomized fashion is needed to definitively associate specific antibiotic interventions with gut microbiome changes and transplant‐related outcomes.…”

Section: Therapeutic Developmentmentioning

confidence: 99%

Clinical effects and applications of the gut microbiome in hematologic malignancies

D'Angelo

Sudakaran

Callander

2020

Cancer

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The gut microbiome and its effects on host immunity have exciting implications for cancer prognosis and therapy. Examples in allogeneic hematopoietic stem cell transplantation (allo‐SCT) demonstrate the role of the gut microbiome as a biomarker for clinical outcomes, and animal models demonstrate how microbiota manipulation may augment therapeutic responses. There are multiple mechanisms that gut microbiota may have in affecting distant tumor environments, including control of cytokine release, dendritic cell activation, and T‐cell lymphocyte stimulation. Recently, there has been a marked interest in understanding interactions between host and microbiome in hematologic malignancies. This review summarizes the current understanding of the gut microbiome and its impact on leukemia, lymphoma, multiple myeloma, and allo‐SCT and highlights several broad methods for targeting the gut microbiome in therapeutic trials.

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Impact of Levofloxacin for the Prophylaxis of Bloodstream Infection on the Gut Microbiome in Patients With Hematologic Malignancy

Cited by 27 publications

References 43 publications

Levaquin Gets a Pass

Levaquin Gets a Pass

Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer

Clinical effects and applications of the gut microbiome in hematologic malignancies

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