Effect of Azithromycin on Airflow Decline–Free Survival After Allogeneic Hematopoietic Stem Cell Transplant

Bergeron, Anne; Chevret, Sylvie; Granata, Angela; Chevallier, Patrice; Vincent, Laure; Huynh, Anne; Tabrizi, Reza; Labussière‐Wallet, Hélène; Bernard, Marc; Chantepie, Sylvain; Bay, Jacques‐Olivier; Thiébaut-Bertrand, Anne; Thépot, Sylvain; Contentin, Nathalie; Fornecker, Luc‐Matthieu; Maillard, Natacha; Risso, Karine; Berceanu, Ana; Blaise, Didier; Tour, Régis Peffault de la; Chien, Jason W.; Coiteux, Valérie; Socié, Gèrard

doi:10.1001/jama.2017.9938

Cited by 99 publications

(57 citation statements)

References 46 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antibiotic exposure and low microbiome diversity have been increasingly recognized as important risk factors for poor transplant outcomes including GVHD and bacterial infection [3,6,[8][9][10][11][12][13]40]. The potential adverse impact of antibiotic exposure on transplant outcomes is further highlighted by a recent randomized trial in which azithromycin prophylaxis given for 2 years post-transplantation resulted in worse airflow decline-free survival and higher rates of hematologic relapse when compared with placebo [7]. Altered microbiota induced by antibiotic use may play a role in immune modification and transplant outcomes [6,[8][9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

“…Prophylactic and empiric antibiotic use are part of standard care for high-risk patients, especially hematopoietic cell transplant (HCT) recipients, and reduce the risk of morbidity and mortality associated with life-threatening bacterial infections [1][2][3][4]. On the other hand, emerging data suggest that antibiotic exposure can affect other adverse transplant outcomes [5][6][7]. Although the exact mechanism remains elusive, the immunomodulatory effects of antibiotics via altered gut microbiota on the susceptibility to bacterial infection or graft-versus-host disease (GVHD) may be a plausible explanation [6,[8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

Ogimi

Krantz

Golob

et al. 2018

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Recent publications note an association between antibiotic exposure and respiratory viral infections (RVIs). Antibiotics affect microbiota and impair immune response against RVIs in mice, and low microbiome diversity is associated with pulmonary complications including viral lower respiratory tract disease (LRTD) in hematopoietic cell transplantation (HCT) recipients. In this study, we examined whether antibiotic exposure was associated with increased risk of disease progression in RVIs post-transplantation. We analyzed patients who underwent allogeneic HCT (June 2008 to February 2016) and had their first RVI due to parainfluenza virus (PIV), respiratory syncytial virus (RSV), or human metapneumovirus (MPV) during the initial 100 days post-transplantation. Antibiotic exposure in the 3 weeks before RVI onset was defined as (1) use of specific antibiotics versus none of these antibiotics and (2) number of antibiotic-days. Cox proportional hazards models were used to examine associations between antibiotic exposures and risk of viral disease progression to proven/probable/possible LRTD. Ninety HCT recipients (84 adults, 6 children) fulfilled study criteria; 33 progressed to LRTD. The number of antibiotic-days was associated with progression to LRTD after adjusting for neutropenia, steroid use, and either lymphopenia (hazard ratio, 1.41 [95% confidence interval, 1.04 to 1.92], P = .027) or monocytopenia (hazard ratio, 1.46 [95% confidence interval, 1.11 to 1.91], P = .006). Specific antibiotic classes was not associated with the outcome. Cumulative antibiotic exposure immediately before RVI onset is a risk factor for disease progression following PIV, RSV, and MPV infections post-transplantation. Larger cohort studies are needed to determine the impact of specific antibiotics or antibiotic classes on disease severity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

Ogimi

Krantz

Golob

et al. 2018

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…[4] However, a large prospective, placebo-controlled study which was evaluating its use in allogeneic hematopoietic cell transplant recipients was stopped early because of a higher rate of relapse of hematological malignancies in the azithromycin arm. [5] From the perspective of antiviral immunity, a robust immune response requires both a healthy immune system and adequate duration of exposure to the virus. Thus, immunization responses in immunosuppressed patients can be suboptimal.…”

Section: J O U R N a L P R E -P R O O F Hydroxychloroquine In Covid-1mentioning

confidence: 99%

Hydroxychloroquine in Covid-19: Does the end justify the means?

Yakoub‐Agha

2020

Current Research in Translational Medicine

View full text Add to dashboard Cite

“…The combination of inhaled fluticasone, azithromycin, and montelukast (FAM) appears to slow the decline in lung function with BOS [82] but has not yet been proven in a randomized controlled trial. While FAM is standard therapy for established BOS, recent data argue strongly against using azithromycin as prophylaxis against BOS due to decreased survival due to a higher rate of hematologic relapse [83]. Though FAM has been shown to decrease the progression of BOS, mortality due to progressive lung disease remains high, and patients typically present to the ICU with respiratory failure.…”

Section: Pulmonary Chronic Gvhdmentioning

confidence: 99%

ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease

Stephens

2020

Evidence-Based Critical Care

View full text Add to dashboard Cite

A 44 year-old woman with a history of acute myeloid leukemia (AML) underwent a non-myeloablative haploidentical peripheral blood hematopoietic stem cell transplant (HSCT) 10 days ago. She was admitted to the hospital with fevers to 39 °C. On examination, she is anxious-appearing, with a temperature of 38.9 °C, a heart rate of 120 beats/min, a respiratory rate of 28 breaths/min, a blood pressure of 98/64 mmHg, and an oxygen saturation of 94% on 4 L/min oxygen via nasal cannula. A tunneled central venous catheter is in situ in her right internal jugular vein. Her total white blood cell (WBC) count is <0.5 cells/mm 3 and platelet count is 8000 cells/mm 3 . A chest CT scan shows diffuse patchy bilateral infiltrates (Figure). She is started on empiric antibiotic coverage with piperacillin/tazobactam, and 3 L of crystalloid are administered. Several hours later, she is more hypotensive, with nadir systolic pressures of 80-88 mmHg, and is more hypoxic, now saturating 85% on 6 L/min nasal cannula oxygen. QuestionHow should this patient be managed?Answer Broad spectrum antibiotics and lung-protective respiratory support.All patients after HSCT are immunosuppressed, profoundly so in the early post-transplant period before engraftment has occurred. This patient is likely to have a pneumonia with secondary septic shock, but a central line-associated infection from her tunneled central line is possible, as are non-infectious complications of HSCT. Respiratory failure is the most frequent cause of intensive care unit (ICU) admission after HSCT, most frequently from an infectious cause. The patient was placed on high-flow nasal cannula (HFNC) for oxygenation support and started on a norepinephrine infusion for hemodynamic support. Antibacterial coverage was changed to meropenem, levofloxacin, and vancomycin, and voriconazole was added for antifungal coverage. Her central line was removed. Her respiratory status continued to decline, and endotracheal intubation and mechanical ventilation were required 24 h after admission. She was placed on volume assist-control with a tidal volume of 6 mL/kg predicted body weight, and bronchoscopy with bronchoalveolar lavage (BAL) was performed. The BAL fluid was initially bloody, but cleared with sequential aliquots. Microbiologic studies of the BAL fluid were positive for respiratory syncytial virus and Pseudomonas aeruginosa. She was maintained on low tidal-volume ventilation and vasopressors were weaned off. Her white blood cell count slowly began to recover, and her respiratory status began to improve. She was extubated on hospital day 12 and was discharged from the ICU on hospital day 14. Principles of ManagementHematopoietic stem cell transplant (HSCT) has become an essential therapeutic modality in the treatment of malignant and non-malignant hematologic disease. In 2016, more than 23,000 HSCTs were performed in the United States, including approximately 15,000 autologous HSCTs and more than 8500 allogeneic transplants [1]. Allogeneic transplants are associated with more morbidity and m...

show abstract

Effect of Azithromycin on Airflow Decline–Free Survival After Allogeneic Hematopoietic Stem Cell Transplant

Abstract: clinicaltrials.gov Identifier: NCT01959100.

Cited by 99 publications

References 46 publications

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

Hydroxychloroquine in Covid-19: Does the end justify the means?

ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease

Contact Info

Product

Resources

About