Successful systemic high‐dose ribavirin treatment of respiratory syncytial virus‐induced infections occurring pre‐engraftment in allogeneic hematopoietic stem cell transplant recipients

Gueller, Saskia; Duenzinger, Ulrich; Wolf, Timo; Alsuwaidan, Salem; Mousset, Sabine; Berger, Annemarie; Martin, Hans; Bug, Gesine

doi:10.1111/tid.12092

Cited by 38 publications

(51 citation statements)

References 30 publications

(55 reference statements)

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“…11,13,18 No studies with adenovirus, enterovirus, or rhinovirus met inclusion criteria. With the exception of the 2 MERS-CoV studies, all studies were in immunocompromised patient populations-primarily, studies with hematological malignancy/HSCT recipients (n = 9) 10,12,13,[16][17][18][19][20][21] or lung/heart-lung recipients (n = 4). 11,22,24,29 Of the 516 NIRVI cases, 380 were treated with oral ribavirin.…”

Section: Data Extractionmentioning

confidence: 99%

Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections

Gross

Bryson

2015

Ann Pharmacother

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Section: Data Extractionmentioning

confidence: 99%

Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections

Gross

Bryson

2015

Ann Pharmacother

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“…The small-particle aerosol generator-2 delivered a greater inhaled dose (20,196.4 Ϯ 9,093.9 g/mL) than the vibrating mesh micropump (16, 859.3 Ϯ 8,874.5 g/mL); however, the difference did not reach statistical significance (P ϭ .77).…”

Section: Drug Deliverymentioning

confidence: 91%

“…19 Although oral and intravenous preparations have been effective, they do not act directly on the respiratory mucosa and are associated with adverse effects, such as neutropenia. 20 A number of centers have been administering inhaled ribavirin to transplant patients, requiring prolonged delivery by mask or mouthpiece. This study establishes important groundwork for the administration of aerosolized ribavirin with an alternate aerosol delivery system, and although caregiver exposure remains a concern, the efficiency of the vibrating mesh micropump may permit shorter treatment durations.…”

Section: Clinical Impactmentioning

confidence: 99%

Characterization of Ribavirin Aerosol With Small Particle Aerosol Generator and Vibrating Mesh Micropump Aerosol Technologies

et al. 2016

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BACKGROUND: Ribavirin is an antiviral drug that can be administered by inhalation. Despite advancements in the oral delivery of this medication, there has been a renewed interested in delivering ribavirin via the pulmonary system. Although data are not conclusive that inhaled ribavirin improves outcomes, we set out to determine whether delivery by a newer generation nebulizer, the vibrating mesh micropump, was as effective as the recommended small-particle aerosol generator system. METHODS: We compared the physicochemical makeup and concentrations of ribavirin before and after nebulization with 0.9% NaCl and sterile water. An Andersen cascade impactor was used to determine particle size distribution and mass median aerodynamic diameter, and an absolute filter was used to measure total aerosol emitted output and inhaled dose during mechanical ventilation and spontaneous breathing. Ribavirin was analyzed and quantified using high-performance liquid chromatography with tandem mass spectrometric detection. RESULTS: Ribavirin was found to be stable in both 0.9% aqueous NaCl and sterile water with an r 2 value of 0.96 and identical coefficients of variation with no difference in drug concentration before and after nebulization with the vibrating mesh micropump. The small-particle aerosol generator produced a smaller mass median aerodynamic diameter (1.84 m) than the vibrating mesh micropump (3.63 m, P ‫؍‬ .02); however, there was no significant difference in the proportion of drug mass in the 0.7-4.7-m particle range. Total drug delivery was similar with the smallparticle aerosol generator and vibrating mesh micropump in both spontaneously breathing (P ‫؍‬ .77) and mechanical ventilation (P ‫؍‬ .48) models. CONCLUSIONS: The vibrating mesh micropump nebulizer may provide an effective alternative to the small-particle aerosol generator in administration of ribavirin using NaCl or sterile water, both on and off the ventilator. Further clinical studies are needed to compare efficacy.

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“…However, an effective role of oral ribavirin for RSV treatment has not been established by a larger randomized controlled trial. A recent observation of five allogeneic HSCT recipients with URD RSV infection had no progression to LRD when treated with oral ribavirin [45]. Similarly, in a study of 96 adults with PCR-proven RSV infection, 34 were moderately to severely immunocompromised and received oral ribavirin treatment (600-800 mg twice daily) with or without IVIG (500 mg/kg IV q48 h), the drug was well tolerated, and no RSV-related deaths were seen in the 34 patients described [44].…”

Section: Prevention and Treatmentmentioning

confidence: 99%

Respiratory Syncytial Virus in Hematopoietic Stem Cell Transplantation and Solid-Organ Transplantation

Neemann

Freifeld

2015

Curr Infect Dis Rep

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Respiratory syncytial virus (RSV), one of the most common causes of respiratory infections in immunocompetent individuals, can cause significant pulmonary morbidity and mortality in hematopoietic stem cell (HSCT) and less often in solid-organ transplant recipients. Early diagnosis and medical intervention prior to the progression from upper to lower respiratory tract viral involvement is essential to positively affect the clinical course. The greatest risk of disease progression from upper to lower respiratory tract disease is during the early posttransplant period for HSCT recipients, with lymphopenia being an important risk factor. Polymerase chain reaction has become the preferred method for rapidly diagnosing infection in this population because of higher sensitivity compared to traditional viral culture and direct viral antigen methods. Despite the lack of prospective randomized trials, retrospective pooled analyses have suggested that systemically delivered ribavirin (either aerosolized, oral, or IV; with or without immunomodulator therapy) can decrease the risk of progression of disease. Additionally, there are a number of clinical trials currently in process to evaluate several new agents that target RSV in the high-risk HSCT patient population.

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Successful systemic high‐dose ribavirin treatment of respiratory syncytial virus‐induced infections occurring pre‐engraftment in allogeneic hematopoietic stem cell transplant recipients

Cited by 38 publications

References 30 publications

Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections

Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections

Characterization of Ribavirin Aerosol With Small Particle Aerosol Generator and Vibrating Mesh Micropump Aerosol Technologies

Respiratory Syncytial Virus in Hematopoietic Stem Cell Transplantation and Solid-Organ Transplantation

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